Regional Training Course on Validation

Regional Training Course on Validation and Process Control

for Electron Beam Radiation Processing

Technical Cooperation Project RER/8/010 “Quality Control Methods and Procedures

for Radiation Technology”

Warsaw, Poland, 3-8 December 2007

Organizers: International Atomic Energy Agency

Institute of Nuclear Chemistry and Technology

Results of first RER/8010 comparison in technological

gamma ray dosimetry

Zofia Stuglik

Institute of Nuclear Chemistry and Technology, Laboratory for Measurement of Technological Doses, Warsaw, Poland

IAEA Training Course, 3-7 December 2007, Warsaw, Poland

Arrangement

of a comparison

• Before IAEA Training Course (April 2006, Warsaw) its participants were invited to bring for meeting some high dose dosimeters for irradiation in reference 60Co gamma field.

• Dosimeters should be a transfer-type. It means, they should not change their dosimetric signals during transportation between laboratories.

• Dose rate at a reference 60Co gamma field (INCT, Warsaw, Poland) has been traceable to a primary standard of absorbed dose maintained by National Physical Laboratory (NPL) Teddington, UK.


Arrangement of comparison

• Dosimeters were irradiated during the meeting by a staff of a reference laboratory (LMTD/INCT) and returned to the participants.

• Irradiated dosimeters were analyzed at the participants laboratories according to their own procedures.

• Participants were sent an information about dose values on the Information Sheets to IAEA Officer.

• The reference laboratory sent the protocol of irradiation to IAEA Officer.

• All the data has been treated as strictly confidential.


Why

our

laboratory

(Laboratory

for Measurements

of Technological

Doses

operated

in

the

Institute

of

Nuclear

Chemistry

and

Technology) was chosen

as organizer?

To be entitled to organize proficiency testing (PT) or interlaboratory comparisons (ILC) the organizer must demonstrate implementation of quality system according to at least one of the standards:

ISO/IEC 9001 ISO/IEC 17025 ISO/IEC Guide 43-1 ISO/Guide 34


Laboratory for Measurements of Technological Doses Institute of Nuclear Chemistry and Technology

(LMTD/INCT)

fulfil this requirement because it had implemented the quality system concordant with ISO/IEC 17025:2005

standard.

The accreditation number of LMTD is AB 461


LMTD/INCTwas accredited

by

Polish Centre for Accreditation

(PCA)

PCA

is a governmental body and cooperates with

European co-operation for Accreditation (EA) and

International Laboratory Accreditation Cooperation (ILAC)


On the ground of multilateral agreement signed between PCA and EA, PCA

accreditations are valid not only in Poland but

also in all countries associated with EA and/or ILAC



Our

logo

holders60Co, Issledovatel

Irradiation

conditions

• Because of different size of participant’s dosimeters two different holders were used.

• An expanded uncertainty of dose rate evaluation in standard polystyrene holder was equal 1,2% (k=1) and in PMMA holder 1,9% (k=1), (k=coverage factor).

• Dosimeters were irradiated at the approximate electron equilibrium conditions at temperature: 22±1°C.


The full results were known only to IAEA Officer M.H. de O.Sampa and two persons, chosen by her for data evaluation.

The individual results were known to their owner (the participant) and could be used by for evaluation and improving of his/her dosimetry system.

General information about state of art of high dose dosimetry in the countries participating in RER/8/010 were presented by me at June 2007 on RER/8/010 Meeting at Bran, Rumunia.


Information

obtained

from

the

Questionnaires sent by 17 participants

• High interest to high dose dosimetry comparisons (13 positive answers)

• Good level of experience in high dose dosimetry (11 positive answers)

• Insufficient attention to the question of traceability of dosimetric measurements (6 positive answers).

• Very low number of dosimetric laboratories accredited according to ISO/IEC 17025 standard (1 positive answer)


Dosimetry

systems

used

(2006) in

the

region(according to participants declaration)

6 standard liquid dosimeters: ECB, Fricke, cerric/cerous)

3 TLD 3 films (FWT, other ones) 3 alanine-EPR dosimetry3 semiconductor dosimeters, track dosimeters2 calorimeters2 ionization chambers2 plates (perspex, other ones)


Dosimetry

systems

for technological dosimetry

should

be:

– fast– cheap– accurate

Dosimeters

should

be:– rigid– easy-to-handle– non-toxic

– thin (for dose distribution measurements at electron beam irradiation)


Transfer dosimeters

Dosimetry Comparison Trials which are necessary element of QA/QC in the radiation processing and the transfer dosimeters

are necesary to perform comparisons.

Transfer dosimeter

= a dosimeter, often a reference-standard dosimeter suitable for transport between different locations, used to compare absorbed dose measurements (definition used in the ISO/ASTM standards)

Main properties of transfer dosimeter:- dosimetric signal should be stable (no post-effects)- dosimetric material should be safe (also for the point of view

of IATA rules)


Conclusion

• not all actually used dosimetry systems are suitable for technological purposes

• not all countries have dosimeters which can be used as transfer dosimeters



The problem

Many countries from our region use ECB dosimeters.

These dosimeters have very good dosimetric characteristics.

Their dosimetric properties allow to use them as transfer dosimeters.

Unfortunately, according the IATA rules they can not be sent by air.


So, many our actions with ECB dosimeters are non legal.

At the time of 2006 comparison two our participants lost their ECB dosimeters in the airports – ECB dosimeters were recognized by custom officers as „dangerous”.

It can not be sent by fast posts, as DHL.

Dosimeters

used

in

the

Comparison

Trial, Warsaw,

2006

• 3 EPR/alanine• 3 films• 1 plate (PMMA)• 1 ECB



Results

of

2006 comparisonThe

differences

between

reference

value

and

the

participants

read-out

(%)

ECB -1,0; -0,8

alanine-EPR +1,0; +0,5;

-2,6; -1,5; +1,5; +0,7

Films -5,3; +2,0; +40,8; +12,9;

+0,3; -11,0

Plate +16,8; +17,9

blue – accredited laboratory

amaranth – lack of traceability

Factors which had negative influence

on accuracy

of

high dose

measurement

in the comparison trial


1.

Lack

of

traceability

2.

Use

of

film and

plate

dosimeters

Factors

which had possitive

influence on an accuracy

of

high dose

measurement

in the

comparison trial

2006


1.

Acreditation

of dosimetry laboratory (Δ ≤ 1%)

2.

Traceability

(Δ

from

+2,0 % to -11%)

3.

Use

of

the

standard dosimetry

systems: EPR/alanine dosimetry (Δ

from +1,5% to -2,6%)

and ECB liquid

dosimeter (Δ ≤ 1%)

ALANINE-EPR DOSIMETRY SYSTEM. WHY WE LIKE IT?

Zofia

Stuglik

Institute of Nuclear Chemistry and Technology, Laboratory for Measurement of Technological Doses,

Warsaw, Poland

IAEA Training Course, 3-7 December 2007, Warsaw, Zofia Stuglik

What we should do to developa new high-dose dosimeter?

(1)

To find material

with

radiation effect monotonically (if possible lineary) dependent on an

absorbed

dose

(2)

To investigate its

dosimetric

characteristics

(sensitivity, dose range, repeatability, accuracy, post-efects)

(3)

To evaluate economical parameters

of

new

method

(cost and availability of dosimetric material, cost of analytical instrument and its services)

(4)

To evaluate operational features of

new

dosimeter

(sensitivity for environmental conditions, time from irradiation to the read-out, other ones..)

(5)

To perform a

calibration curve = functional

dependence

between radiation

effect

(dosimetric

signal) and

absorbed

dose


Short

history

of

EPR α-alanine

dosimetry(EPR ≡

ESR)

1960 -

ESR signals

in

single crystal

of

alanine

[I.Miyagawa and W.Gordy,J.Phys.Chem. 32 (1960) 255-264]

1962 –

First

use

of

alanine

as EPR dosimeter

[ W.W.Bradshaw, D.G.Cadena, G.W.Crafford, H.A.Spetzler, Rad.Res., 17 (1962) 11-21 ]

1982 –

Re-validation

of

alanine-EPR

dosimetry

system

[D.F.Regulla, U.Deffner, Int.J.Appl.Radiat.Isot., 33 (1982) 1101-1114]

1983 –

alanine-EPR

dosimeter

as transfer dosimeter

in

radiation

processing [D.F.Regula, U Deffner, Radiat.Phys.Chem. 22 (1983) 305-309]

1988 -

A polymer-alanine

film for dose

distribution

measurement

[I.Janovsky, J.W.Hansen, P.Cernoch, Appl.Radiat.Isot., 39 (1988) 651-659


Standard Practicefor Use

of

an

Alanine-EPR

Dosimetry

System

1/ 1994 E 1607 - 94 ASTM1a/ International

Standard ISO 15566:1998(E)

2/ 1996 E 1607 - 96 ASTM

3/ 2002 ISO/ASTM 51607:2002(E)

4/ 2004 ISO/ASTM 51607:2004(E)


IAEA Training Course, 3-7 December

2007, Warsaw, Zofia

Stuglik

What

is

alanine?

Simple

amino-acid

(C3

H7

O2

N) which

can exist

in

two

structural

forms: α

and

β

α-alanine: CH3

-CH(NH2

)-COOH dosimetric material

β-alanine: CH2

(NH2

)CH2

-COOH

unconvenient for dosimetry because low stability of radicals


α-alanine: CH3

-CH(NH2

)-COOH exist

in

three

structural forms:

•L-α-alanine

(optically

active, 557 Euro/kg)•D-α-alanine

(optically

active,

3220 Euro/kg)

•DL-α-alanine

(racemat, 113 Euro/kg)

All

forms

can

be used

in

technological

dosimetry

but because

of

economical

reasons

the

most suitable

is

DL-α-

alanine.DL : L : D = 1 : 5 : 28


Crystalline

α-alanine

CH3

-CH(NH2

)-COOH

CH3

-CH(NH3+)-COO-

zwitterionvery stable structure, melting point: 314,5 °C

FW 89,06

IAEA Training Course, 3-7 December

2007, Warsaw, Zofia

Stuglik

CH3

-CH(NH3+)-COO-

chemical

bond

energy

(eV)C-H

4,3

N-H

4,0C-O

3,6

C-C 3,5C-N

3,0

The

weakest

bond

is

C-N

and

it

is

broken

during

the radiolysis

giving

the

NH3 (amonium, stable molecule)

and

SAR

radical



CH3

-CH(NH3+)-COO-

e-

fast

electron

CH3

-C*H-COO- + NH3

SAR

Stable

Amonium

Radical

(paramagnetic

specie)

AMMONIUM

stable

chemical

molecule

microcrystalline

α-alanine

On the base of this very stable (years) SAR radical

generated

in

crystalline

α-

alanine

it

is

established an

alanine-EPR

dosimetry

system.



Date: 3 .0 6 .1 9 0 7 Time: 1 2 :0 2

Fi l ename: F:\WIDMAE~1 \MORDAL~2 \mor1 .spc

[]3400 3425 3450 3475 3500 3525 3550 3575

- 250

- 200

- 150

- 100

- 50

0

50

100

150

200

*10^ 3]

EPR signal

in

microcrystalline

α-alanine

ΔH dosimetric

signal

magnetic

field [mT]


Dosimetric

signal

EPR signal

presented

before

is

the

first

derivative

of the

absorption

band.

The

quantity

proportional

to an

absorbed

dose

is number

of

radicals. Number

of

radicals

is

proportional

to double integral

of

presented

before EPR signal.

Nevertheless, double integration

of

EPR signal

is

not accurate

procedure

and

in

dosimetry

practice

an

amplitude

of

the

highest

line

of

EPR signal

is

used

as dosimetric

signal.

EPR measurementsThe

method

was developed

at

1941 year

by

Zavojskijand

is

connected

with

Zeeman

effect.


Zeeman

effect

Unpaired

electron

(for instance in radical) has

a magnetic moment (spin).

In a magnetic

field Bo the

moment of

electron

µ•

can

be aligned

to the

magnetic

field (a state

with

lowest

energy),•

can

be aligned

against

to the

magnetic

field (a state

with

highest

energy)

The

difference

between

them

depends

linearily

on the magnetic

field.


EPRWhen

we use

not only

magnetic

field but also

microwave

field with

the

frequency

~10 GHz

(X range, λ~3cm) we can observe

an

absorption

of

microwave

energy

by spin

population

with

lower

energy EPR signal generation.


1.

Radiation

sensitive

material

=dosimeter2.

Analytical

instrument for dosimetric

signal

measurement3.

Calibration

curve

= signal-to-dose

dependence


What

is

necessary

to establish

dosimetry system ?

Different

kinds

of

alanine-EPR

dosimeters


Kodak alanine-EPR

film dosimeter



Spectrometer

of

Electron

Paramagnetic

Resonance

(EPR

≡

ESR)

magnet

Microwave cavity with a sample

Microwave generatorwaveguide


2 4 6 8 10

20

40

60

80

100

Inte

nsity

of E

SR si

gnal

(a.u

.) ΔH

Calibration curve for Alanpol-27 dosimeter

Dose, kGy

2-10 kGy


Dozymetr Alanpol 27 - krzywa wzorcowa (zakres: 0,4 - 60kGy)

y = -0,0007x2 + 0,1159x + 0,0267R2 = 0,9997

0,0

0,5

1,0

1,5

2,0

2,5

3,0

3,5

4,0

4,5

5,0

0 10 20 30 40 50 60 70Dawka pochłonięta, kGy

ΔH

, j. u

.

0,4 kGy

–

60 kGy

Advantages

of

alanine-EPR

dosimetry

system

•

dosimetric

signal

is

stable

during

very

long

time

(years)•

wide dose detection range (1Gy -

100 kGy)

•

linear

signal-to-dose

dependence

(≤

10 kGy)•

Dosimetric

signal

is

energy

and

dose

rate independent

(gamma and electron beams)•

accuracy

•

non-destructive and

fast

detection method •

low temperature coefficient of

irradiation

•

different

shapes

of

dosimeters, also

films•

dosimeters

are

not very

expensive

•

easy to handle•

non-toxic

•

chemical composition of

dosimetric

material

is

similar to the chemical

composition

of

organic

matter

•

environmental

conditions•

1expensive 2.

energy and dose


Disadvantages

of

alanine-EPR

dosimetry

system

EPR signal

•

Sensitive

to light

(for long

time

illumination)•

Sensitive

to water

and

humidity

EPR spectrometer

•

Expensive•

Market monopolized

by one producer

Small

EPR spectrometers

for dosimetry

(20 000 -

60 000 Euro)


Alanpol

dosimeter


Characteristic

features:

•Low

concentration

of

DL-α-alanine

(10 -

30%)

•Hydrofobic

polymer

as a matrix

Alanpol

dosimeter



An

experiment

After

lunch we will have

small

experiment

with

different kinds

of

alanine-EPR

dosimeters

We will started

with

9 alanine-EPR

dosimeters

Alanpol

and 9 film dosimeters

from

Gamma Service, East

Germany

All

dosimeters

were

irradiated

with

10 MeV

electrons

to the same dose

25 kGy

Each

group

will have

3 dosimeters

of

each

kind

Group

I

is

going

with

me to EPR Laboratory

to observe EPR measurement

of

dosimetric

signal


An experiment

Group II

is going with Mr. S.Fabisiak

to LMTD. This group will place its dosimeters in exicator

(humidity

~100%) (1/2 h)

Group III

is also going with Mr. S.Fabisiak

to LMTD. This group will put its dosimeters to glass of water ( ½

h)

After half of hour the dosimeters both groups will go with Mr. Fabisiak

to Department VII, to EPR Laboratory for

EPR measurements

EPR measurements will be done by Dr. Jarosław

Sadło


The results of all measurements will be given to the participants today or tomorrow.

You will able

to observe that the sensitivity of different alanine

dosimeters for environmental condition is different

We expected that signal in Alanpol

will be practically the same for all dosimeters.

EPR

signals

in GS films will strongly depend on the storage conditions.

SelectionSelection ofof materialsmaterials ((polymerspolymers) for ) for radiationradiation sterilizationsterilization

GraGrażżyna Przybytniakyna Przybytniak

International Atomic Energy AgencyDecember 3 – 7, 2007

Regional Training Course on Validation and Process Controlfor Electron Beam Radiation Processing

Progress Progress inin radiationradiation processingprocessingSubstantial fraction of cable insulation is crossSubstantial fraction of cable insulation is cross--linked using radiation (flame retardant wirelinked using radiation (flame retardant wires s and and cables cables –– for for safsafeetyty and to reduce the total and to reduce the total weight).weight).Nylons for automobilesNylons for automobiles..RotomoldedRotomolded drums (transportation of hazardous drums (transportation of hazardous chemical wastes).chemical wastes).Application in rubber tires.Application in rubber tires.Radiation vulcanization of rubber latexRadiation vulcanization of rubber latex..Radiation crossRadiation cross--linked linked SiCSiC fiber.fiber.Polymer recycling.Polymer recycling.HydrogelsHydrogels –– wound dressing, soft contact lenses, wound dressing, soft contact lenses, controlledcontrolled––release drug deliveryrelease drug delivery..

RadiationRadiation chemistrychemistry ofof polymerspolymers

polymerizationcrosslinking

degradation grafting

Criterion of the estimation of Criterion of the estimation of polymer radiation resistancepolymer radiation resistance

HI

-CH2 –C-IR n

R1I

-CH2 –C-IR2 n

If in the main chain each carbon atom is bonded with at least one hydrogen atom, the polymer can be radiation cross-linked

Polymers containing in main chain some carbonatoms substituted with four substituentsundergo only degradation

Some polymers in order of Some polymers in order of decreasing radiation resistancedecreasing radiation resistance

-CH-CH2 -

-N-CH2 -

-CH=CH-

-CH2 -CH2 -

OII-C-NH-

-Si(CH3 )2 -O-

CH2 -OH

-R-O-C-O-IIO

polystyrene

Aniline form-aldehyde resin

polyethylene

elastomers

polyamide

siloxane

Phenyl form-aldehyde resin

polycarbonate

Internal protection effectInternal protection effect

Such an effect is possible when Such an effect is possible when protection groups are in structure of protection groups are in structure of polymer macromolecules.polymer macromolecules.Protection effect is not limited only to Protection effect is not limited only to direct surrounding of the direct surrounding of the mermer but is but is spread over further fragments of the spread over further fragments of the chain.chain.

Cyclohexane G(R) = 6,5 Benzene G(R) = 0,75

CH=CH2

Styrene G(R) = 0,69

/100eV

PolymersPolymers inin dosimetrydosimetry

Polystyrene Polystyrene calorcaloriimetmeterer

Ca. 95% of radiation energy converts Ca. 95% of radiation energy converts into heatinto heat

Polystyrene

Thermistor

Polystyrenefoam

CCH2 CH2CHH

H

C CH C CH2

330 335 340 345 350 355 360 365

after 1 day

after 1 h

directly upon irradiation

PS

Magnetic field / mT

RT, 25 kGy, electron beamair atmosphere

RadicalsRadicals inin polystyrenepolystyrene

ChemicalChemical processesprocesses inin polymerspolymers irradiatedirradiated withwith ionizing ionizing radiationradiation

CrossCross--linkinglinking..Degradation of the main chains of Degradation of the main chains of macromolecules.macromolecules.Changing in the number and type of Changing in the number and type of double bonds. double bonds. Emission of low molecular gaseous Emission of low molecular gaseous productsproducts..Polymer oxidation.Polymer oxidation.

Heat of polymerizationHeat of polymerization

PolymerPolymer EffectEffect HeatHeat ofof polymerizationpolymerization

PolyethylenePolyethylenePolypropylenePolypropylenePolystyrenePolystyrenePolyisobutylenePolyisobutylenepolymethylmethacrylatepolymethylmethacrylate

CrosslinkCrosslinkCrosslinkCrosslinkCrosslinkCrosslinkChainChain scissionscissionChainChain scissionscission

22 kcal/mol22 kcal/mol16.5 kcal/mol16.5 kcal/mol17 kcal/mol17 kcal/mol13 kcal/mol13 kcal/mol13kcal/mol13kcal/mol

DegradationDegradation ofof polypropylenepolypropylene

CH3 H CH3 H CH3 HI I I I I I-C – C – C – C – C – C –I I I I I IH H H H H H

PolypropylenePolypropylene -- gaseous gaseous productsproducts

95% hydrogen95% hydrogen2,7% methane2,7% methane1,9% water1,9% water0,048% butane0,048% butane0,01% carbon 0,01% carbon

dioxidedioxide

0,02% carbon oxide0,024% pentane0,013% heptane0,01% ethane0,01% pentene

Only 6% of consumed oxygen is presentin gaseous compounds

AlkylAlkyl radicalsradicals ofof polypropylenepolypropylene

-CH2 C•(CH3 )CH2 -

-CH2 C•HCH2 --CH(CH3 )C•HCH(CH3 )-

-CH(CH3 )CH2 C•H

-CH(CH3 )CH2 C•(CH3 )

-CH2 CHCH2-I

•CH2

RadicalsRadicals inin polypropylenepolypropylene

3350 3400 3450 3500 3550 3600

DPPH

magnetic fie ld / G

-CH2 – C(CH3 ) – CH2 -

-CH2 – C(CH3 ) – CH2 -

OO

PREFERENCESPREFERENCES

RADICALS BOND DISSOCIATION ENERGY CH3 CH2

•

422 kJ/mol

CH3 CH•

CH3 413(CH3 )3 C•

397CH2 =CHCH2

•

359

OxidativeOxidative degradationdegradation

R•

Ionising radiation

R-OO•

R-OOH

O2

R-H

R-OOH

O O OHII II I-C-OH -C- -CH-

Scission of main chain macromolecules – decrease in molecular weight

Abstraction of gaseous productsFormation of polar molecular groups Loss of transparencyYellowing of the materialDeterioration of mechanical properties

IoniIonizzinging radiation induces in PP radiation induces in PP free radicals what results in:free radicals what results in:

Radiation degradation of Radiation degradation of polypropylene polypropylene –– protection agentsprotection agents

Because of polymer degradation, also during Because of polymer degradation, also during processing, stabilizers and antioxidants are added to processing, stabilizers and antioxidants are added to the plastic the plastic Processes induced by Processes induced by phphotolysisotolysis and radiation (also and radiation (also thermally) proceed according to the same thermally) proceed according to the same mechanisms. mechanisms. Radical processes Radical processes –– initiation, propagation, branching, initiation, propagation, branching, termination. termination. Protection agents Protection agents –– phenol antioxidantsphenol antioxidants,, amine amine stabilizers, HALS, stabilizers, HALS, mercaptansmercaptans..Primary antioxidants Primary antioxidants –– inhibit propagation of radical inhibit propagation of radical processes. processes. Secondary antioxidants Secondary antioxidants –– limit decomposition of limit decomposition of polymers by polymers by peroxyperoxy groups.groups.

Comparison of spin trapping by Comparison of spin trapping by various agentsvarious agents

O

H

O. O

ROO ROO..

OOR

N

H

N

O.O.

R.

N

ORROO.

-ROOR

Piperydinederivatives

Phenol derivatives

VitamineVitamine as as antioxidantantioxidant

O CH3CH3

CH3

CH3

C16 H31

HOROO

OCH3

CH3

CH3

C16 H31

O

OCH3

CH3

CH3

C16 H31

O

+ ROOH

OCH3

CH3

CH3

C16 H31

O

CH3

CH3 CH33200 3250 3300 3350 3400 3450 3500

240 K

210 K

180 K

150 K

120 K

77 K

pole magnetyczne / G

PolymericPolymeric dosimetersdosimetersPoly(vinylPoly(vinyl chloride) free from chloride) free from plastificatorsplastificators and and other other additadditiviveses

G(HClG(HCl) = 5,4 /100eV ) = 5,4 /100eV -- 2323ooC;C;22/100eV 4022/100eV 40ooCC

Poly(methylPoly(methyl metacrylatemetacrylate))

-CH-CH2 -CH- HCl + -CH=CH-CH-I I ICl Cl Cl

-CH=CH-CH- HCl + -CH=CH-CH=CH-ICl

PolymericPolymeric dosimetersdosimeters -- PVCPVC

RadiationRadiation yieldyield ofof hydrogenhydrogen

PolymerPolymer G(HG(H22 ) / ) / μμmol/Jmol/J SupplierSupplier

PP PP freefree fromfrom additivesadditivesPP PP freefree fromfrom additivesadditivesPP PP isotacticisotacticPP PP sydiotacticsydiotacticParafilmParafilm

0.400.400.370.370.260.260.330.330.340.34

F401 (F401 (isotacticisotactic) PKN ORLEN S.A.) PKN ORLEN S.A.MoplenMoplen HP 400H HP 400H BasselBassel PKN ORLEN S.A. PKN ORLEN S.A. AldrichAldrich ChemicalChemical Company Company IncIncAldrichAldrich ChemicalChemical Company Company IncIncPARAFILMPARAFILMRR MM

PEPE

UHMWPEUHMWPE

0.420.420.450.450.460.460.410.410.490.490.460.460.430.430.510.51

MalenMalen FGNX 23DFGNX 23D--022022BorealisBorealis FT 3030FT 3030BorealisBorealis RB 0323RB 0323BorealisBorealis FA 3220FA 3220BorealisBorealis FT 5230FT 5230LupolenLupolen 2012d2012dLitenLiten PL10PL10GURGUR

PSPS 0.0360.036 GPPS GPPS -- OwispolOwispol 525 0001TH525 0001TH PKN PKN

OrlenOrlen

RadiationRadiation crosslinkingcrosslinking

330 335 340 345 350 355 360 365

Magnetic field / mT

9 '

1h

5.5h

27h

48h

a

b

c

d

e

CC

CC

CC

H

H2

H2H2

H2

H2

alkyl radical

CC

CC

CC

H

H2

H2H2

H

H

H

CC

CC

CC

H

H2

H2H2 H

allyl radical

n

polyenyl radical

RT, 25 kGy, electron beamneutral atmosphere

RadicalsRadicals inin polyethylenepolyethylene

PrimaryPrimary and and secondarysecondary processesprocesses inin polyethylenepolyethylene

CH2

CH2

++

CH

CH

++ H2

CH

CH

+

+ H2

HCH2+

CH+ e + H

Types of polyethylene Types of polyethylene crosslinkingcrosslinking

Type Y

Type X ICH2I

HCICH2I

ICH2ICHICH2I

Radical recombination

Ending bond

ICH2I

-CH2 -CH=CH2 + CHICH2I

ICH2I

-CH2 -CH-CH2 -CHICH2I

Unsaturated bonds after Unsaturated bonds after irradiationirradiation

-CH=CH2

-CH=CH-

RadiationRadiation crosscross--linkinglinking inin polyethylenepolyethylene

HICIH

HICIH

HICIH

HICIH

Radiation chemistry of amorphous Radiation chemistry of amorphous and crystalline phases of PEand crystalline phases of PE

Alkyl radicals are produced in both Alkyl radicals are produced in both phases.phases.CrossCross--linking is limited to amorphous linking is limited to amorphous phase.phase.Oxidation proceeds only in amorphous Oxidation proceeds only in amorphous phase.phase.Residual radicals in crystalline phase Residual radicals in crystalline phase migrate towards surface between both migrate towards surface between both phases.phases.

Influence of radiation crossInfluence of radiation cross--linking on linking on macroscopic propertiesmacroscopic properties ofof polymerspolymers

Increase in strength at breaking.Instead melting they undergo softening as thermosets.They are unresolved in organic solvents but undergo swelling.Increase Young modulus.Decrease elongation at break.Improve resistance on creep and friction.Enhance resistance on aggressive chemicals, fats, corrosive substances.Change in thermal properties - thermal dimensional stability, decrease in ability towards thermal distortion.

AgentsAgents influencinginfluencing radiationradiation stabilitystability ofof polymericpolymeric materialsmaterials::

•Less defects in crystalline domains - higher radiation stability

•Chemical changes induced by ionizing radiationcan be divided on two stages. At first stage reactions proceed directly during irradiation, at second stage upon exposure, in post-radiation effects.

AgentsAgents influencinginfluencing radiationradiation stabilitystability ofof polymerspolymers

Significant diffusion of oxygen throughSignificant diffusion of oxygen throughoutoutpolymer facilitates oxidative degradation and polymer facilitates oxidative degradation and enhances enhances radiosensitivityradiosensitivity. Polymers in . Polymers in thethe form form of films and fibres have intensive contact with of films and fibres have intensive contact with oxygen due to large ratio of oxygen due to large ratio of thethe surface to surface to weight.weight.

Fast irradiation with large doses results in Fast irradiation with large doses results in inhibition of oxidation effects (likewise in neutral inhibition of oxidation effects (likewise in neutral gas atmosphere) because of short time of gas atmosphere) because of short time of oxygen diffusion inward material. Therefore oxygen diffusion inward material. Therefore inside of the object polymer preserves initial inside of the object polymer preserves initial properties properties andand even undergoes crosslink.even undergoes crosslink.

Oxygen permeability through Oxygen permeability through polymerspolymers

PolymerPolymer constantconstant KKDimethylsiloxaneDimethylsiloxane rubberrubberPoly(siliconePoly(silicone––coco-- carbonatecarbonate))FluorosiliconeFluorosiliconeRubberRubber latexlatexPolystyrenePolystyrenePolyethylenePolyethylene HDHDCelluloseCellulose acetateacetateMethylMethyl cellulosecellulosePoly(vinylPoly(vinyl chloridechloride))Poly(vinylPoly(vinyl alcoholalcohol))Polyamide(nylonPolyamide(nylon 6)6)TeflonTeflon

50,050,016,016,011,011,02,42,40,120,120,100,100,080,080,070,070,0140,0140,0110,0110,0040,0040,00040,0004

Polymers applied in radiation Polymers applied in radiation sterilized medical devicessterilized medical devices

•Acrylonitryle/butadiene/styrene (ABS)•Polystyrene•Polystyrene-acryl nitryle•Polyethylene of various density•Polyamide•Polyurethane•Poly(ethylene–vinyl acetate)•Poly(ethylene-acryl)•Polypropylene

Examples of radiation doses for Examples of radiation doses for medical productsmedical products

ProductsProducts DoseDose / / kGykGy

GloversGloversSwabsSwabsSpecimen containersSpecimen containersElectrodesElectrodesSyringeSyringeGownGownCatheterCatheterScrub bushScrub bushBandageBandageVascular graftVascular graftSutureSutureOrthopedic prosthesesOrthopedic prostheses

88--151588--151588--151588--15151515--20201515--20201515--2020

25252525252525252525 K. Burg,

S. Shalaby

SterilizationSterilization StabilityStability ofof MaterialsMaterials www.eldonjames.comwww.eldonjames.com//framesframes//strilize.htmlstrilize.html

MATERIAL GAMMA RADIATION ETHYLENE OXIDE AUTOCLAVE

Polycarbonate Compatible to 10 M-Rad dose with little loss of physical properties. Will discolor to light yellow- green hue.

Highly compatible with 100% EtO; may stress crack if sterilized in EtO/ CFC mix, due to molding stresses.

Not recommended. May craze or stress crack due to molding stresses.

Radiation Stable Polycarbonate Excellent up to 10 M-Rad dose with little loss of physical properties. Light violet hue turns clear upon sterilization.

Highly compatible. Withstands normal EtO sterilization conditions, but multiple exposures can reduce tensile elongation properties.

Not recommended.

Polypropylene Excellent up to commonly used sterilization doses (approximately 6 M-Rad).

Fair; may stress crack in EtO/CFC mix due to molding stresses.

Poor. Parts may distort due to low heat deflection temperature.

Stainless Steel see additional notes below**

Excellent Excellent Excellent

Nylon and Glass Filled Nylon Physically compatible with commonly used sterilization doses, but may discolor to brownish hue.

Very Good. Some susceptibility to oxidizing agents.

Very Good. Components may swell slightly due to water absorption.

ABS Compatible to 10 M-Rad dose with some loss of impact strength, but increased tensile strength. Some discoloration to slight brownish hue.

Excellent retention of properties for at least 5 sterilization cycles.

Poor. Parts may distort due to low heat deflection temperature.

Polyurethane (Tubing) Excellent. Some discoloration may occur, but reverses over time. No significant effect on physical properties.

Excellent. No noticeable effect on material properties.

Not Recommended. Hydrolysis of polyurethane may create aromatic amine impurities.

Polyethylene (Tubing) Excellent. Tensile strength increases and modulus of elasticity decreases due to cross-linking of polymer.

Excellent Not Recommended. Tubing may distort at common autoclave temperatures.

ExamplesExamples ofof radiationradiation--stablestable materialsmaterials inin sterilizingsterilizing dosedose rangerange

goodgood poorpoorAcrylonitrileAcrylonitrile//butatienebutatiene//styrenestyrenePolystyrenePolystyrenePolystyrenePolystyrene--acrylonitrileacrylonitrilePolyethylenePolyethylenePolyamidesPolyamidesPolysulfonesPolysulfonesPolyimidesPolyimidesPolyurethanePolyurethanepolyphenylenepolyphenylene-- sulfidesulfidePolyestersPolyestersPoly(ethylenePoly(ethylene--vinylvinyl acetateacetate))Poly(ethylenePoly(ethylene--acrylateacrylate))SiliconeSiliconeNatiralNatiral rubberrubber

PolyvinylchloridePolyvinylchloridePolyvinylidenePolyvinylidene chloridechloridePolyvinylPolyvinyl formalformalPolyvinylbutyralPolyvinylbutyralPolycarbonatePolycarbonateStyreneStyrene//AcrylonitrileAcrylonitrile

PolypropylenePolypropyleneFluoropolymersFluoropolymersPolytetrafluoroethylenePolytetrafluoroethylenePolychlorotrifluoroethylenePolychlorotrifluoroethylenePolyvinylPolyvinyl fluoridefluoridePolyvinylidenePolyvinylidene fluoridefluorideEthyleneEthylene-- tetrafluoroethylenetetrafluoroethyleneFluorinatedFluorinated ethyleneethylene-- propylenepropyleneCellulosicsCellulosics ––estersesters celulosecelulosePolyacetalsPolyacetals

ANSI/AAMI/ISO 11137 – 1995Annex A

FactorsFactors influencinginfluencing

ChemicalChemical structurestructure•• CrystallinityCrystallinity•• IsomersIsomers•• PolydispersityPolydispersity•• AdditivesAdditives•• ComponentsComponents•• AtmosphereAtmosphere•• RadiationRadiation raterate

30 years

of

PVC dosimetry in

INCT

Zofia

Stuglik

Institute of Nuclear Chemistry and Technology, Laboratory for Measurement of Technological Doses, Warsaw, Poland


History1972

Instalation

of linear electron accelerator LAE 13/9

9 kW, 7 ÷

13 MeV, (Jefremov

Institute,

Leningrad, USSR)

two

regimes:straight electron

beam –

for pulse radiolysis

scanned electron

beam –

for technological studies



LAE 13/9 deflection magnet (270 deg)

Pulse radiolysis apparatus, horizontal beam

Vertical, scanned beam for technological experiments

(1 meter below)

HistoryResponsible persons for electron beam dosimetry

systems

were:

Dr. Przemysław

Panta

(water and graphite quasi-adiabatic calorimeters)

Dr. Zofia

Bułhak

(film dosimeters)


At 60-ties and 70-ties PVC films were intensively investigated by a lot of scientists

(C.Artandi, A.A.Miller, A.Chapiro,

S.Onishi, Y.Nakayama…).

Mrs. Bułhak

joined to this group at the beginning of 70-ties. Dosimetric

applications of PVC films was a subject

of Mrs.

Bułhak

dissertation and because of that they were investigated very carefully.

Some results of these experiments will be presented today

and were compared with the results of the last studies done in Laboratory for Measurement of Technological Doses.



PVC production, method

I

PVC = polyvinyl

chloride

ethylene + chlorine vinyl chloride

vinyl chloride polyvinyl chloridePCV

catalyst

polymerization

n

dichlorethane


PVC production, method

IIPVC = polyvinyl

chloride

acetylene + hydrochloride vinyl chloride

vinyl chloride polyvinyl chloridePCV

catalyst

polymerization

n


How

much of

PVC is

in

the

PVC ?

It

depends……

PVC

hard

(%)

soft (%)

PVC

> 90

40-80

Plasticizer

≤

5

20-60

Stabilizer

0,5 –

0,5 0,5-4

Lubricant ≤5

≤

1

(Fillers)

?

?


The PVC film from Kunstoffwerke, Staufen

which has been used in our Institute for electron beam dosimetry

applications was produced for pharmacy.

It may contain some amounts:

• plasticizers (probably phthalates)

• thermal stabilizers (probably Sn

(stannum) compounds)

• lubricants

The main component is

PVC


Radiolysis

For the simple chemical system as Fricke dosimeter it is possible to establish exact scheme of radiation reactions, to measure their orders, rate constants and G-values.

For PVC it is impossible.

The system is too complicated. We have some information about radiolytical

processes going in

PVC but we are still far for the full knowledge.


What we know?EPR experiments of Ohnishi and Nakayama showed that irradiation of PVC generate 3 types of radicals:

-CH2

C*H-CH2

-

-CHCl-C*H-CHCl-

-CH2

C*Cl-CH2

-

These reactive species initiate chemical reactions leading to more stable structures, for instance -

double bonds systems

C=C.


What else we know?

It is known from many years that the main gaseous product of PVC radiolysis is hydrochloride (HCl).

High G-value of HCl

formation (~26) points to the chain reactions involved in its production.

It is also known that HCl

initiate autocatalytic decay of PVC polymer.


So, among products of PVC radiolysis there are at least two types of species: radicals

and hydrochloride (HCl)

which will destabilize the PVC polymeric system.

But we want to use PVC as dosimeter. So, we should find factors which will stabilize it.

There are two such factors: •time•temperature

In dosimetry

we have not plenty of time,

so we use temperature.

.


At higher temperatures the chemical reactions go faster, the concentration of active species go down and irradiated PVC is going to the more stable state.

Of course, the temperature should be below the softening point

of PVC because very high temperature also lead to

destruction of polymer.


The temperature is

a factor which

can

put in order an

intrinsic

structure of irradiated PVC

films.

Probably

the double bond

of carbon

systems

change

to

carbon couple bond

which

are

known as chromophores

wavelength nm

Dosimetric signal

A396

Electronic

optical

absorption

in

irradiated

PVC films


Optical spectra observed in irradiated PVCThe optical absorption spectra observed in irradiated and

heated

PVC films are ascribed in literature to the coupled carbon bonds

C=C-C=C-C=C-C=C-C=C

The short structures (a number of the coupling bonds ≤

3) absorb the UV light.

The long structures (number of the coupling bonds from 4 to 9) –

absorb the visible light (less energy is necessary to

excite them)


Now, we are

going

to the

results

obtained

in

our

Institute 30-ty years

ago.


Optical

spectra observed

in

different

PVC films

after

irradiation

and

heating

D=30 kGy

Staufen, type

N


After

irradiation

and

heating

After

irradiation

Before

irradiation

PCV from

Kunstoffwerke, Staufen

ΔA396

= dosimetric

signal


Calibration

curves

for different

PVC films

(5 –

50 kGy, gamma)


Calibration

curves

for different

PVC films

(5 –

50 kGy, 10 MeV

electrons)


Vessels

with water

at

different temperature

PVC films

Experimental

scheme

for measurement

of

temperature coefficient of irradiation

40 kGyelectron

beam


Temperature coefficient of irradiation

k=0,25 % per 1°C [Z.Bułhak]


Irradiated

PVC film, probably

Staufen, type

N Influence of

temperature

and

heating

duration

on dosimetric

signal

(A396

)

80 °C

30 min

70 °C

60 °C


Post-effects

(=changes

in

dosimetric

signal

amplitudes) observed

in irradiated

PVC film Staufen, type

N for D=40kGy without

heating

and

after

30min heating

at

different

temperatures

80 °C

70 °C without

heating

50

°C

10 days 20 days


The best stability of dosimetric

signal was obtained for 30min heating at 80°C.

However

So high temperature was near the softening point of PVC film used in this experiment and because of that 70°C was selected for dosimetric

applications.


The protocol of dosimetric

signal measurement

with non-plasticized PVC film from Staufen, Type N

1975

1.

Irradiation

2.

Heating: 30 min at 70°C (oven with water jacket)

3.

Cooling 30 min at room temperature

4.

Absorbance measurement at 396nm

5.

Read-out the dose from a calibration curve ΔA396

=f(D) (performed at the same conditions as dose measurement ones)


On the base of Dr. Z.Bułhak

work INCT bought some tons of non-plasticized PVC film from Kunststoffwerke, Staufen

and used this film for

dose distribution measurements during more than 30 years.

The same film is used also today.

Two years ago LMTD started the experiments to re- validate dosimetric

characteristics of PVC films

which still are using at INCT Sterilization Plant.


Results

•There were observed some differences between sensitivity of different scrolls

of

PVC film.

• No correction for film thickness was necessary.

• CV-values and calibration curves were acceptable.

• Resistance for environmental conditions was excellent.


Calibration curve for PVC (scroll IV) (mean values)


Calibration curve for PVC (scroll IV) (6 dosimeters)


The protocol from 1975 is still valid

However, we observed

that

actually

used PVC films are much more sensitive to

any deviation from the

protocol

because

of

strong

post-effects


Post-effects

in

PVC films

irradiated

with

gamma and high energy

electrons

to 22 kGy

time, h

gamma

electrons


Post-effects

in

PVC films

irradiated

with

gamma and high energy

electrons

to 7 kGy

gamma

electrons


[Z.Peimel-Stuglik, S.Fabisiak, Appl.Radiat.Isot., 2007, in

press]

and heating


What is a reason of such situation?

There were at least three possibilities:

(a) PVC films changed their properties during 30 years

(b) The films which endured to our time are not type N from Kunststoffwerke, Staufen, chosen for dosimetric

application by Dr. Bułhak


(c) The results dealing post-effects and presented in work done at 1975 were obtained for PVC films irradiated to doses ~ 40 kGy.

For such high doses the post-effects in irradiated and heated PVC films are negligible and were omitted.


Advantages

of PVC films

• Very low price

• High sensitivity to ionizing radiation

•

High tolerance (nonsensitivity) to environmental conditions (air humidity, liquid water, visible, UV and Cherenkov light)

• Negligible film thickness variations

•

Slow ageing, significant rigidity, availability in large sheets and the possibility of rough visual dose evaluation

•

Cheap and simple analytical instrument for dosimetric

signal measurements

(spectrofotometer

for visible light)


Disadvantagesof

PVC films

• Significant and complicated post-effects

• Dependence of the post-effects on dose.

•

Repeatability (CV, % ) on the level 2 –

6% (from batch to batch).

•

Chemical composition of PVC films different that mean chemical composition of organic matter (high content of Cl and some amounts (1-3%) of Ca or Sn). Exact chemical composition of PVC film is known only to its producer.


Disadvantagesof

PVC films

• Be careful to use them for low doses (up to 20 kGy)

•

Take attention for technical parameters of oven -

dosimetric signal obtained after heating in oven with ventilation will be

different than after heating in oven with water jacket (for the same dose).

• Each batch should be carefully validated.

•

The protocol of measurement (timing, heating) should be establish and the staff shall follow it.


You

can

use

PVC film for high dose electron

beam

dosimetry

if

you

are

very

accurate

and

carefull


What will be if you are not very accurate

Practical Aspects of IQ and OQ

Electron Radiation Processing

A. KovácsInstitute of Isotopes

Hungarian Academy of Sciences

Budapest, Hungary

Validation and process controlThe steps of validation as described in the EN

ISO 11137 Standard:

- Process definition- Installation qualification- Operational qualification- Performance qualification

In addition:- Routine process control

Dosimetry procedures - validation

Installation qualification:- to demonstrate that the irradiation facility has been supplied and installed according to its specifications:

To determine beam No specific dosimetric requirements,characteristics by dosimetry; to verify operation within specification;


Operational qualification:- carried out by irradiating appropriate test material (of

homogeneous density) to demonstrate the capability of the equipment to deliver appropriate doses, i.e. the irradiation process that has been defined;

- provides baseline data to show consistent operation of the irradiation facility (i.e. within established and defined limits);

- OQ should be repeated to show consistent operation, i.e. the results obtained are within established and defined limits

Operational qualificationAim:

To characterize the irradiation facility relating plant parameters to absorbed dose (measured in a reference product);

Gamma facility: nominal dose vs. irradiation time or dwell time and dose distribution;

Dichromate, ECB, ceric-cerous, Gex (B3), FWT- 60, Perspex, Sunna, alanine;

Electron beam facility:nominal dose vs. conveyor speed,beam characteristics, dose map;

Calorimeters, ECB, Sunna, alanine,Gex (B3), dichromate;

Operational Qualification I.

1. Determination of absorbed dose and conveyor speedrelationship:

Absorbed dose vs:

- Conveyor speed;- Electron current;- Scan width;

0,0 0,2 0,4 0,6 0,8 1,0 1,2 1,4 1,6 1,8 2,0 2,20

2

4

6

8

10

12

14

16

18

20

Abs

orbe

d do

se, k

Gy

1/conveyor speed, min/m

Tasks and Tools1. Dosimeters to use:

Calorimeters (PS, graphite);(other possibilities: ECB, Sunna, alanine,etc);

2. Tasks:- To irradiate calorimeters at two conveyor speeds and at two electron current settings (separately);- To establish conveyor speed and electron current vs. absorbed dose relationship;

Process calorimeters

Water, graphite, polystyrene calorimeters: 1.5 – 10 MeV.

Other possibilities: ECBECB in polystyrene phantom:

Other possibilities: Alanine, Sunna film

Sunna film in phantom:

Operational Qualification II.

2. Measurement of scan width and homogeneity:

Tasks and Tools1. Dosimeters to use:

PVC film strip;

(other possibilities: FWT-60, B3, alanine, Sunna, etc);

• Tasks:

- To irradiate PVC films at various scan widths – scanning direction;

Operational Qualification III.

3. To measure dose distribution in reference product:

Tasks and Tools

1. Dosimeters to use: B3 windose – in depth;PVC strip - in width;

(other possibilities: FWT-60, alanine, Sunna, etc);

2. Tasks:

- To irradiate reference product with dosimeters- To measure irradiated B3 films and PVC strips;- To draw isodose curves;

Operational Qualification IV.

4. To measure beam spot (pulsed machines):

To check, if necessary overlap between pulses is achieved.

scanning frequencypulse repetation frequencyconveyor speed

Tasks and Tools

1. Dosimeters to use:PVC and B3 strips;

(other possibilities: CTA, etc).

2. Tasks:

To irradiate PVC and B3 strips on polystyrene sheet under the scanner in „standing” mode.

Operational Qualification V.

5. To measure „process interruption”.

To use PVC strips (in conveyor move direction).

Other possibilities:

CTA film, B3 strip.

Operational qualification (EB)General requirements:Dose mapping:

- over a range of operating parameters covering the operational limits;- density within the range of use (more is better);- at least three irradiation containers to be dose mapped;- to place dosimeters in a three dimensional array including surface;- mathematical modelling to optimize the positioning of dosimeters;- to establish the effect of process interruption on the dose;- to determine relationships between characteristics of the beam, theconveyor speed and the magnitude of dose at a defined locationwithin or on a container or in a fixed geometry travelling with, butseparately from the irradiation container (e.g. PS calorimeter);

- separate dose map to check the effect of changing to product ofdifferent density;

CALIBRATION OF DOSIMETRY SYSTEM

• Calibration of dosimeter• Calibration of equipment

CALIBRATION OF DOSIMETERS (1)• Irradiation of dosimeters

• Measurement (analysis) of dosimeters (with calibrated instrument)

• Generation of calibration curve or response function

• Initial calibration verification, and periodically confirmation of validity

• Traceability chain

CALIBRATION OF EQUIPMENT (2)

• All measurement equipment must be calibrated and be traceable to national standards.

• Certain measurement equipment cannot be calibrated (e.g. signal amplitude from an EPR spectrometer)

therefore⇓

• the stability of the equipment has to be demonstrated by the use of measurement standards (e.g. stable EPR spin standards).

CALIBRATION OF EQUIPMENT (2)

- Spectrophotometer:absorbance and wavelength scale with calibrated optical filters;

- Thickness gauge:calibrated gauge blocks;

-Thermometers:calibrated thermometers;

- Resistance measurement (Ohm-meter for calorimeters):calibrated reference resistor;

- Humidity meters:saturated salt solutions;

THANK YOU FOR YOUR ATTENTION!

Accuracy

Precision

Principles and Practical Aspects of

Performance Qualification

A. Kovács

Institute of IsotopesHungarian Academy of Sciences

Budapest, Hungary

Validation and process control

The steps of validation as described in the sterilization standard EN ISO 11137:



Performance qualification

Aim:To measure dose map in real product in order to locate

Dmin and Dmax and to establish irradiation conditions according to

required specifications, i.e.:

D(product) > D(required, e.g. sterilization dose)and D(product) < D(acceptable)

Mathematical modelling to optimize the positioning ofdosimeters;

Gamma / Electron Interaction with Matter

Electron radiation – metals: scatter

Gamma / EB: Dose Distribution

EB Processing Aspects

Single and double sided irradiation:

• Electron energy (surface sterility; single layer);• Product box dimensions;• Product density;• Product loading pattern;

Education of manufacturer!

Electron Irradiation Possibilities

Performance qualificationDetermination of dose distribution in products:

- Homogeneous products;

- Non-homogeneous products;

- Bulk products, flow systems;

Performance qualificationThe role of film dosimeters – resolution!

Performance qualificationInterface effects:

X-Ray Machines

X-Ray Dosimetry• Dosimeters applied in gamma processing seems

to be suitable;

• IAEA dosimetry check in Takasaki, Japan:Alanine, ECB, dichromate, ceric-cerous tests;(Anthrax case).

• Gamma and X-ray similarities in interaction with matter;

Electron Accelerator Facilities

Zbigniew Zimek, Sylwester BułkaDepartment of Radiation Chemistry and Technology

Institute of Nuclear Chemistry and Technology

Dorodna 16, 03-195 Warsaw, Poland

Regional Training Course on Validation and Process Control

for Electron Beam Radiation Processing

Technical Cooperation Project RER/8/010

“Quality Control Methods and Procedures for Radiation Technology”Warsaw, Poland, 3 - 8 December 2007

03 - 08 December 2007

Zbigniew ZIMEK, Sylwester BUŁKA,

INCT, Warsaw, POLAND 2

Aspects of progress in development of

industrial accelerators

� Adaptation of accelerators primary built for scientific experiments

� Electron energy and beam power increase in certain accelerator

constructions

� Computer control system managing accelerator start-up, routine

operation and technological process, maintenance (diagnostics)

� Accelerator technology perfection (electrical efficiency, operation

cost)

� Compact and more efficient accelerator constructions

� Reliability improvement according to industrial standards

� Accelerators for MW power levels

� Accelerators tailored for specific use

03 - 08 December 2007



Penetration [g/cm2] =

0.37(Energy [MeV] - 0.2)

for one side treatment

and equal entrance

and exit doses

Productivity [kg/h] =

3600 x Power [kW] x

Utilization efficiency /

Dose [kGy]

Average beam power

Although there are many different types of accelerators offering

a wide range of performances ratings, only few would be suitable

for particular application (Marshall R. Cleland, 1992).

Electron energy

03 - 08 December 2007



General considerations

� Product to be irradiated dimensions, densities, position

� Vetical or horizontal EB direction

� Operation schedule and seasonal requirements

� Reliability of accelerator

� Control system compatible with facility automation standarts

� Remote accelerator operation and diagnostics

� Accelerator external supply service

� Factory assembling tests

� Warranty conditions and post-warranty service

� Staff training

� Facility qualification

03 - 08 December 2007



Criterions for accelerator selection

Criterion of selection

Basic accelerator parameters� Electron energy

� Average beam powerAuxiliary accelerator parameters

� Scan characteristics

� Control system compatibility� Accelerator external supply service

Terms of accelerator purchase� Price

� Manufacturer

� Terms of delivery and installation� Warranty conditions

� Exploitation cost

Remarks

The main requirements which

define technological abilities

and facility throughput

The parameters which may

characterize accelerator for

facility design

Economical aspects which define

investments and exploitaton

costs

03 - 08 December 2007



Accelerator/Facility external supply service

� Safety installations (personnel, radiation, high voltage, fire,

TV surveillance system)

� Electricity consumption, grounding, mains frequency

compatibility

� UPS system or additional power line

� Stand-by conditions (vacuum and temperature regime)

� Water cooling system(s)

� Compressed air or other gases provided

� Air cooling and ozone ventillation

03 - 08 December 2007



ADVANTAGES

� Proven accelerator technology

� Simplicity of construction

� Long life power components

� High parameters stability

� High beam power

� Narrow energy spread

� Wide range of power adjustment

� Computer supported control system

� Low exploitation cost

� High quality maintenance service

03 - 08 December 2007



DISADVANTAGES

� Prototype accelerator construction (limited exploitation

experience)

� Parameters on the edge of present limits

� Some power components with limited lifetime (magnetron)

� High electric energy demands

� Poor accelerator availability

� Small company with limited resources

� High total cost

� Difficulties in spare parts availability

03 - 08 December 2007



Radiation process effectiveness

Acceptable price of 1 W electron beam power

Type of radiation process

Product characteristics

100-250 $/W Semiconductors

modification

Low dose Small scale

High unit price

100-50 $/W Radiation sterilization Medium dose Large scale

Medium unit price

<2.5 $/W Flue gas treatment Low dose

Very large scale No commercial value

03 - 08 December 2007



Accelerators for radiation processing

Direct accelerator Single cavity Linear accelerator

HV cable from Coaxial cable from Waveguide from

DC power RF generator source of microwaves

03 - 08 December 2007



Accelerators for radiation processing(achievements)

Type of Accelerator Parameter

Direct DC

RF 100 - 200 MHz

Linear microwave 1.3–9.3 GHz

Av. beam current Energy range Beam power In future Electrical efficiency

<1.5 A

0.05 – 5 MeV

~500 kW

1 MW

60 – 80 %

<100 mA

0.3 – 10 MeV

700 kW

1 MW

20 – 50 %

<100 mA

2 – 10 MeV

50 kW

100 kW

10 – 20 %

03 - 08 December 2007



DIRECT ACCELERATORS

transformer type

03 - 08 December 2007



List of transformer accelerator producers

� ESI - Energy Science, USA

� RPC Technologies, USA

� RDI - Radiation Dynamics, USA (IBA)

� Wasik Associates, USA

� NHV - Nissin High Voltage, Japan

� SHI - Sumitomo Heavy Industries, Japan

� High Voltage Engineering Europe, Netherlands

� INP - Institute of Nuclear Physic, Russia

� SIEA - Sci. Inst. of Electrophysical Apparatus, Russia

� Vivirad, France

� Res. Inst. of Automation for Machine-Building, China

� Inst. of Nuclear Studies, Establishment for Nuclear Equipment, Poland

03 - 08 December 2007



Capability of D.C. Power Supplyfor transformer accelerators

Accelerator Power line transformer

Cockckroft- Walton

HF Transformer

Dynamitron

Ratings 150-1000kV 10-1000 mA

300-5000 kV 30-1000 mA

500-1000 kV 30 mA

500-5000 kV 1-70 mA

Frequency 50/60 Hz 1-3 kHz 20-50 kHz 50-100 kHz

Insulation Oil/SF6 SF6 SF6 SF6

Efficiency >90 % 70-80 % 85 % 30-60 %

Remarks Low energy High power

High energy High power

Large

High energy Low power Compact

High energy Low eff.

03 - 08 December 2007



CASCADE ACCELERATOR

EPS-4 type

NISSIN HV, Japan

PARAMETERS:

ENERGY 1-5 MeV

STABILITY ± 2%

BEAM CURRENT 30 mA

STABILITY ± 2%

BEAM POWER 150 kW

SCANNER 1400 mm

HOMOGENEITY <± 5%

03 - 08 December 2007



K. Mizusawa,

M. Kashiwagi,

Y. Hoshi

Radiat. Phys. Chem. Vol.

52, Nos 1-6,

Pp 475-477, 1998

5 MeV, 150 kW Electron Beam FacilityRadia Industry, Japan

03 - 08 December 2007



High Power EB for Flue Gas Treatment

1 MW, 800 kV Power Supply 0.8 MeV, 300 kW Accelerator

NHV, Japan

03 - 08 December 2007



ELV 12 coreless transformer acceleratorElectron energy 1 MeVBeam power 400 kWFrequency 1000 HzOne power supply Three scanners

INP, Russia

03 - 08 December 2007



SINGLE CAVITY ACCELERATORS

single pass or multi-pass systems

03 - 08 December 2007



RF accelerator producers

(100 - 200 MHz)

� INP - Institute of Nuclear Physic, Russia

� IBA - Ion Beam Application, Belgium

� Denki Kogyo Co, Japan

� KAPRA – Research Association, Korea

03 - 08 December 2007



SINGLE CAVITY SINGLE PASSACCELERATORS

IŁU 6

energy 1,2-2,5 MeV

beam power 20 kW

frequency 127 MHz

IŁU 8

energy 1 MeV

beam power 20 kW

IŁU 10

energy 2-5 MeV

beam power 50 kW

frequency 115 MHz Scanner

Resonator IŁU 6

INP, Russia

03 - 08 December 2007



ILU 12 ELECTRON ACCELERATOR

Electron energy 5 MeVBeam power 300 kWFrequency 176 MHzRF power 450 kW

Auslender V.L. et all.,

EPAC 2002, Paris, France

Accelerating structure

03 - 08 December 2007



10 MeV ELECTRON

ACCELERATOR

RHODOTRON TYPE

1. Resonator2. Tetrode3. Water cooling system4. Support5. Electromagnet6. Vacuum pump

Frequency 107.5 MHz

03 - 08 December 2007



TT 1000:

up to 700 kW; 7 MeV (100 mA)

up to 500 kW; 5 MeV (100 mA)

TT 300:

up to 200 kW; 10 MeV (20 mA)

up to 135 kW; 5 MeV (27 mA)

TT 200:

up to 100 kW; 10 MeV (10 mA)

up to 100 kW; 5 MeV (20 mA)

TT 100:

35 kW; 10 MeV (3.5 mA)

IBA, Belgium

ELECTRON ACCELERATORS

RHODOTRON TYPE

M. Abs et all.,

Rad. Phys. Chem., 2004

03 - 08 December 2007



MULTI PASS

ACCELERATOR

FANTRON 1

Energy 10 MeV

Beam power 100kW

Frequency 160 MHz

RF power 220 kW

Bending magnets 16

Hyeok-jung Kwon et all

EPAC 2000, Vienna, Austria

03 - 08 December 2007



LINEAR ELECTRON

ACCELERATORS

03 - 08 December 2007



Linear electron accelerator producers

(microwave 1.3-9.3 GHz)� Varian, USA

� Titan Beta, USA

� RPC Technologies, USA

� American Science & Engineering, Inc., USA

� Mitsubishi Heavy Industries, Japan

� Technical Systems Ltd, UK

� Thomson CSF, France

� Res. Inst. of Electrophysical Apparatus, Russia

� RIA TORYI, Russia

� Res. Inst. of Automation for Machine-Building, China

� Inst. of Nuclear Studies, Establishment for Nuclear Equipment,

Poland

03 - 08 December 2007



Accelerator for medical sterilization

� Electron energy

5 – 12 MeV

� Beam power

10 – 45 kW

P.J. Cracknell

Radiat. Phys. Chem.

46 (1995) 469-472

03 - 08 December 2007



Accelerator UEL-10-10S; 10 MeV, 10 kW

03 - 08 December 2007



10 MeV ELECTRON ACCELERATOR WITH

LOCAL SHIELD (TOP VIEW)K.G. Carlson, C. B.

Williams, B. Lambert,

Fuh-Wei Tang

Radiat. Phys. Chem.

57 (2000) 619-623

03 - 08 December 2007



10 MeV ELECTRON ACCELERATOR WITH LOCAL SHIELD

ELECTRON ENERGY 10 MeV DOSE 10-50 kGyBEAM POWER 3-5 kW PRODUCTIVITY up to 50 000 m3/y

03 - 08 December 2007



COMPACT

ACCELERATOR

MeVAc

Energy 3 MeVBeam power 3 kWScanning 30 to 50 cmHeight 1 mWidth 0,3 m

THOMSON-CSF

LINAC

03 - 08 December 2007



LINEAR ELECTRON ACCELERATOR

Mitsubishi Heavy Industries Ltd.

Electron energy 4 MeV; Length 60 cm; Weight 20 kg

03 - 08 December 2007



American Science & Engineering, Inc.

Energy 4 MeV; X-band 9303 MHz; control interface PLC;Acceleration section RF length 40 cm

03 - 08 December 2007



OUTPUT AND BEAM

SCANNING DEVICES

03 - 08 December 2007



BEAM SCANNING DEVICES

ELEKTRONIKA 10/10 IŁU 6

03 - 08 December 2007



Double beam path scanning horn

Golubenko Y. et all., INP

97-7, Russia

03 - 08 December 2007



90° Dual Beam,

Multiple Pass

Technique

550 keV

HV-Trans-

former

550 keV

HV-Trans-

former

HUBER + SUHNER, Switzerland

03 - 08 December 2007



ELECTRON-10 (0.5-0.75 MeV; 50 kW)

1 – Primary winding; 2 – Secondary winding; 3 – Pressure vessel;

4 – Electron source; 5 – Accelerating tube; 6 – Scanning device;

7 – Vacuum pump; 8 – Vacuum chamber; 9 – Outlet window;

10 – Turning magnet; 11 – Radiation shielding.

A.S. Ivanov, V.P. Ovchinnikov,M.P. Svinin, N.G. Tolstun,PAC 1993, Washington, USA

03 - 08 December 2007



LINEAR SCANNING SYSTEM

CAARI 2002

Denton, Texas

November 13, 2002

VACUUM CHAMBER

ELECTRON BEAM

ELECTROMAGNET TITANIUM FOIL

03 - 08 December 2007



COMPUTER CONTROL

SYSTEMS

03 - 08 December 2007



Measurement and control

� Parameters measurement and accelerator control

(energy, beam current, pulse repetition, scan width,

cooling and vacuum status, and others)

� Recording parameters

� Calculating parameters for further use

� Technological data processing and recording

03 - 08 December 2007



CONTROL ROOM IN INDUSTRIAL FACILITY FOR

FLUE GAS TREATMENT

03 - 08 December 2007



X-RAY CONVERSION

03 - 08 December 2007



X-RAY CONVERSION DEVELOPMENT

60

200150

5080

700

6020

150 150

20200

100

200

300

400

500

600

700

800

1980 1985 1990 1995 2000 2005

YEARS

BE

AM

PO

WE

R [

kW

]

03 - 08 December 2007



NFI : Irradiation Room with EB

and X-ray Ports

03 - 08 December 2007



Conveyor

Control

Truck

Yard

X-rayEB

Accelerator

Automated Storage

NFI:Irradiation Facility

03 - 08 December 2007



Remarks� A meaningful steps can be recognized in the past of accelerator development.

Present stage of accelerator technology perfection includes: cost

effectiveness, reliability, compactness, very low energy and introduction of

MW beam power level,

� Major industrial accelerator producers are located in USA, Russia, Japan

and Belgium. Several other countries including China and Poland are

capable to produce accelerators at limited scale,

� Any practical accelerator construction must be compromise between size,

efficiency and cost,

� The progress in accelerator technology is not a quick process but can be

easily noticed in longer time scale,

� Appropriate accelerator selection should be performed to meet all technical

and economical conditions for successful process implementation,

03 - 08 December 2007



� Highly trained personnel is not required to run modern accelerators because

of simplicity of their operation under computer support,

� Spare parts and major maintenance service should be available from the

manufacturer of the accelerator during the machine lifetime,

� New accelerators constructions can frequently offer better economic and

technical characteristics but only long time operation can reveal weak points

of certain construction in practical industrial conditions.

03 - 08 December 2007



THANK YOU FOR ATTENTION...THANK YOU FOR ATTENTION...

Validation and Process Control for EB Radiation Processing 1

Establishment of a sterilization dose

Iwona KaluskaInstitute of Nuclear Technology and Chemistry

Warsaw, Poland


Radiation sterilization processing -

responsibilities

Product manufacturer

Operator of the radiation sterilization facility


Approaches to reduce the total number of products to be tested for establishing the sterilization dose

Establishing and maintaining product families for the selection and auditing of a sterilization dose;Sampling plans for verification dose experiments and sterilization dose audits;Frequency of sterilization dose audits.


Bioburden

Population

of

viable

microorganisms

on or

in

product

and/or

sterile

barrier

system


Variables that impact on product bioburden

Raw materials,Components,Product design and size,Manufacturing process,Manufacturing equipment,Manufacturing environment,Manufacturing location.


For product manufactured in different locations, consideration shall be given to the impact on bioburden of:

Geographic and climatic differences between locations,Any differences in the control of the manufacturing processes or environment, andSources of raw materials and processing adjuvants

(e.g.water).


A product familly shall be represented by:

•

The master product, or•

An equivalent product, or

•

A simulated product.


A documented assessment, to decide which of the three potential representative products is appropriate, should considerate:

Number of microorganisms comprising the bioburden,Type of microorganisms comprising the bioburden,Size of product,Number of components,Complexity of product,Degree of automation during manufacture,Manufacturing environment.


Master product

A member of the product family shall only be considered a master product, if assessment indicates that this product requires a sterilization dose that is greater than that of all other product family members. In some situations there may be several products within the product family that could be considered as the master product. In such circumstances any one of these products may be selected as the master product to represent the product family.


Equivalent product

A group of product shall only be considered equivalent if assessment indicates that group members require the same sterilization dose. Selection of the equivalent product shall either be

at random, or according to a planned schedule

to include different

members of the

product family. The

manufacturing volume and availability of product

should be considered in the selection of the equivalent product to represent the product family.


A simulated product may be:

One which is similar to the actual product in terms of materials and size, and subjected to similar manufacturing processes; orA combination of components from products within the product family that would not typically be combined for use.


Maintaining product families

Assessment/Periodic reviews;Modifications to product and/or manufacturing processes;Records.


Selection and testing of product for establishing the sterilization dose

Nature of the productproduct for sterilization may consist of:

an individual health care product within its primary package,a set components presented in a primary package which are assembled at the point of use to form the health care product, together with accessories required to use the assembled product,a number of identical health care products within a primary package,a kit comprising a variety of procedure-related health care products.


Nature of item for establishing the sterilization dose

Product typeItem for bioburden

estimation, verification and/or incremental dose experiment

Rational

a) Individual health care product within its primary package

Individual health care product Each health care product is used independently in clinical practice

b) Set of components within primary package

Combination of the components of the product

Components are assembled as a product and used together in clinical practice

c) Number of identical health care products within primary package

Single health care product taken from the primary package

Each health care product is used independently in clinical practice

d) Kit of procedure-

related

health care productsEach type of health care product

Each health care product is used independently in clinical practice


Selection and testing of product for establishing the sterilization dose

Sample

item

portion

(SIP)

Examples for SIP calculation

Basis for SIP calculations

Product examples

Surface area Implants (non- absorbable)

Mass PowdersGownsImplants (absorbable)

Length Tubing (consistent diameter)

Volume Fluid in water cup


Sterilization dose

Minimum absorbed dose required to achieve the specified assurance level


Sterilization dose selection

Selection of sterilization dose using either:Bioburden informationInformation obtained by incremental dosing

Selection of a sterilization dose of a 25 kGy or 15 kGy following

substantiation

of the appropriateness of this dose


If a product-specific sterilization dose is selected, it shall be set by one of the

following methods

a) Methods 1 for multiple and single batches

b) Method 2A

c) Methods 2B

d) A method providing equivalent assurance to that of a), b) or c) above in achieving the specified

requirement for sterility


The sterilization dose shall be substantiated by one of the following methods (1/2)

a)

for product with an average biodurden in the range 0,1 to 1000 inclusive, by

1)

Method VD25max

2)

Method 1, subjected to the derived sterilization dose taking a value equal to or less than 25 kGy,

3)


4)

A method providing equivalent assurance to that of 1), 2), or 3) above in achieving maximally an SAL of 10-6.


The sterilization dose shall be substantiated by one of the following methods (2/2)

b)

for product with an average

bioburden

in the range 0,1 to 1,5 inclusive,

1)

Method VD15max

2)

Method 1, subjected to the derived sterilization dose taking a value equal to or less than 15

kGy,

3)


4) A method providing equivalent assurance to that of 1), 2), or 3) above in achieving maximally an SAL of 10-6.


Procedure for Method 1 for multiple batches (1/4)

Select the appropriate SAL and obtain samples of product unitsDetermine the bioburden level using ten final packaged products from three different batchesDetermine the batch average of each of the three batchesCalculate the overall batch average



Select the verification dose from the dose table using either the highest batch average or the overall batch average;Perform the verification dose experiment using 100 final packaged products;



Sterility test the 100 units (Soybean Casein Digest Broth, incubated at (30±2)°C for 14 days);Acceptability of the experiment

≤ 2 positive sterility tests = acceptable> 2 positive sterility tests = method is not valid, the alternative method should be used (Method 2).



Establish sterilization dose by finding the closest biodurden number in the dose table equal or greater than the average bioburden and the selected SAL level.


Product with an average bioburden in the range 0,1 to 0,9 inclusive, for

multiple or single batchesThe procedure for dose establishment using Method 1 shall be followed, except:

An entire product shall be used for testing,A correction factor shall be employed in the determination of bioburden,Use values given in another table for radiation dose required to achieve a given SAL for an average bioburden in the range 0,1 to 0,9 inclusive having the standard distribution of resistances.


Method 2

Two procedures are available for validation of Method 2

Method 2A for products with bioburden as would be expected from normal manufacturing processMethod 2B for products with consistent and very low bioburden.


Procedure for Method 2ASelect SAL and obtain product samples;Select 280 product samples from each of the three production batches;Perform incremental dose experiments irradiating 20 product units from each of the three batches at one of the series of not less than nine doses, starting at

2 kGy, then

increasing in

2 kGy increments, i.e., 4 kGy, 6 kGy, 8 kGy, etc.


This dose may vary from the nominal incremental dose by ±

1,0 kGy or ±

10%

whichever is greater.


Procedure for Method 2A

The products are then sterility tested to determine a verification dose expected to yield a SAL of 10¯². The results of the sterility test are used to make an estimate of the D10

value, and this

estimate is used for extrapolation to SAL below 10¯².


A kGy and First Fraction Positive (FFP) kGy

For each of the three batches, determined the lowest dose (FFP kGy) where at least one of the twenty tests is negative. Find the median value. Determine A kGy from the table using the number of positive sterility tests at the median FFP kGy dose.


Designate D* kGy (the initial estimate of the dose

required to achieve an SAL of 10¯²)

If the highest batch d* kGy exceeds the median batch d* kGy less than 5 kGy, the median batch d* kGy becomes D* kGy; orIf the highest batch d* kGy exceeds the median batch d* kGy by 5 or more, the highest batch d* kGy becomes D* kGy.


D* kGy

For each of the three batches, determine the d* kGy by either finding the lowest dose of two consecutive doses at which all tests are negative, followed by no more than one further positive test, or by finding the lowest dose at which one positive in twenty tests occurs, immediately preceded and followed by incremental doses at which all tests are negative.


CD* batch

Establish the batch in which the d* kGy equals the D* kGy and designate in the CD* batch.


First No Positives (FNP) kGy

If CD* ≤

2, FNP kGy= DD* kGyIf 10<CD*>2, FNP kGy = DD* +2,0 kGy

•

If 16<CD*>9, FNP kGy = DD* +4,0 kGy•

If CD*>15 D* kGy should be redetermined

DD* kGy, the actual dose delivered


Establish sterilization dose

Determine DS kGy (dose required to inactive 90% of the organism surviving DD* kGy) from FFP kGy and FNP

•

When (FNP-FFP)<

10 kGy, then DS kGy = 2+0,2(FNP-FFP) kGy

•

When (FNP-FFP)≥

10 kGy, then DS kGy = 0,4+(FNP-FFP) kGy

•

EstablishD** kGy = DD*kGy + [log(CD*)] (DS) kGy


Verification dose experiment

Irradiate 100 products from CD* batch at the dose of D* kGy. Designate the delivered dose as DD* kGy.Test the irradiated products at 30°C±2°

for 14 days.


Sterilization dose

Sterilization dose = D**kGy +[-log(SAL) – log(SIP)-2] (DS) kGy

WhereD**

kGy is the estimate of the dose that will provide a 10ֿ²SAL for the test samples

SAL

is the preselected sterility assurance level for the productSIP

is the portion of product unit used for determining D** kGy and DS kGy

DS kGy

is an estimate of the dose required to inactivate 90% of the organisms surviving D** kGy


Procedure for Method 2B

The entire product shall be utilized (i.e., SIP = 1,0)Series of at least 8 doses, starting at 1 kGy

and

increasing in nominal increments of 1 kGy. This dose may vary from the nominal incremental dose by ±

0,5

kGy or ±10% whichever is greater.After irradiation at any of the incremental doses, the number of positive tests of sterility observed shall not exceed 14, andFNP shall not exceed 5,5 kGy


Method VDmax

This method is for substantiation of a selected sterilization dose.In carrying out substantiation, the method verifies that

bioburden

present on product prior to sterilization is less resistant to radiation than a microbial population of maximal resistance consistent with the attainment of an SAL of 10-6

at the selected sterilization dose.

Verification is conducted at a SAL of 10-1

with 10 items irradiated in the performance of the verification dose experiment. The dose corresponding to this SAL is characteristic of both the bioburden level and the associated maximal


Method VDmax

The

VDmax methods given in ISO 11137-2 are for selected sterilization doses of 25

kGy

and 15

kGy. The method for 25

kGy

is applicable to product having an average

bioburden

in the range 0,1 to 1000 inclusive, whereas that for 15

kGy

applies to a limited

range of

bioburden

only extending from 0,1 to 1,5.


Procedure for Method VD 25max

1.

Obtain samples of product units (at least 10 items from each of 3 independent production batches);

2.

Determine average bioburden

3.

Obtain VDmax

For SIP=1,0, if the average bioburden is not given in the table,

use the closest tabulated average bioburden greater than the calculated average bioburden

For SIP<1, calculate the average bioburden for the entire item by dividing the SIP average bioburden by the SIP decimal value.

SIP VD 25max

= (SIP = 1,0 VD25max

)

+ (SIP Dose Reduction Factor

x log SIP)

4.

Perform the verification dose experiment (irradiate 10 products at the VDmax

5.

Interpretation of results

If there is

no

more than

1 positive test –

verification is accepted,

If 2 positive tests

–

perform confirmatory

verification dose experiment,

If >

2

positive tests

-

verification is not accepted.


Confirmatory verification dose experiment

Select at least 10 product itemsIrradiate the 10 product items at VD 25

max

Subject the irradiated products to test of sterilityInterpretation of results

No positive tests – verification is acceptedIf the are any positive tests -verification is not accepted.



General

1.

The average bioburden of product shall be determined by applying a correction factor.

2.

An entire product (SIP=1) shall be used



1.

Obtain samples of product units (at least 10 items from each of 3 independent production batches);

2.

Determine average bioburden

3.

Obtain VDmax

the highest batch average, if

one or more batch averages is equal

to or greater than two times the overall average bioburden, or

the overall average bioburden, if each of the batch averages is

less than two times the overall average bioburden

4.

Perform the verification dose experiment (irradiate 10 products at the VD 15

max

obtained from the table

)

5. Interpretation of results

If there is

no more than

1 positive test –

verification is accepted,

If 2 positive tests

–

perform confirmatory

verification dose experiment,

If >

2

positive tests

-

verification is not accepted.


Values of VD 15max

for average bioburden in the range from 0,1 to 1,5

Average Bioburden

SIP=1VD15

max (kGy)Average Bioburden

SIP=1VD15

max (kGy)

0,10 0,0 0,50 1,8

0,15 0,5 0,60 2,0

0,20 0,9 0,70 2,2

0,25 1,1 0,80 2,3

0,30 1,3 0,90 2,2

0,35 1,5 1,0 2,1

0,40 1,6 1,5 1,7

0,45 1,7


Comparison of the Dose Setting Methods

Method 1 Method 2 VDmax

A and B 25 kGyRational Estimate dose

for SAL=10-2, extrapolate to required SAL

Determine dose by incremental dosing, calculate dose required for SAL

Assume 25 kGy produces SAL= 10-6

Production batch size All Medium –Large AllProduction rate Any Frequent AnyBioburden limit 1,000,000 None ≤1000

Method 2A-840Method 2B-780(200 can be returned to inventory)

Samples for testing 130 units 40


Procedure for auditing the sterilization dose established using Method 1 or Method 2 (1/3)

Obtain product samples (at least 110 product items from a single batch of product)Determine average bioburden of each of at least 10 product items and calculate the average bioburdenPerform verification dose experiment (irradiate 100 products at the verification dose or D**, found in the original dose setting exercise)



Interpretation of resultsIf there are no more than 2 positives –verification acceptedIf there are 3 ÷ 4 positive tests - augment the sterilization dose; to resume the use of the original sterilization dose, repeat the sterilization dose audit, using a further 100 items and the same verification dose as that used in the original audit.



Interpret results of the repeat audit as follows:If no more than 2 positive tests are obtained in the 100 tests and review of environmental and manufacturing controls and bioburden estimates indicates no value outside established specifications, use of the original sterilization dose may be resumed.If 3 or more positive tests of sterility are obtained, the sterilization dose shall be reestablished immediately. Continue the use of augmented dose until the sterilization dose is reestablished.

If 5 or more positive tests of sterility are obtained, the sterilization dose is inadequate; the sterilization dose shall be augmented immediately.


Procedure for auditing the sterilization dose substantiation using VD max

Obtain product samples (at least 20 product items from a single batch of product)Determine average bioburden (of each of at least 10 product items)Perform verification dose experiment (irradiate 10 product items

at VD 25max

or VD 15max

, whichever is applicableInterpretation of results

Accept audit if no more than 1 positive test of sterility is obtainedPerform a confirmatory verification dose experiment if there are 2 positive test of sterilityIf there are 3 or more positive tests of sterility are obtained, the sterilization dose is not adequate. The sterilization dose shall be immediately augmented and the sterilization dose shall be re-established with an alternative method.


Confirmatory sterilization dose audit

Select 10 product itemsIrradiate them at VD 25

max

or VD 15max

, whichever is applicableInterpretation of results

If no positive tests of sterility – sterilization dose has been confirmedIf any positive tests of sterility are obtained- the sterilization dose shall be immediately augmented and re-established.


Augmentation of sterilization dose substantiated

using Method VD 25max or VD 15

max

Augmented sterilization dose (kGy) = 25 kGy + dose augmentation value

Augmented sterilization dose (kGy) = 15 kGy + dose augmentation value

Dose augmentation values are given in the tables.

The Role

of

Influence

Factors

on

the

Performance

of

Dosimetric

Systems

A.

Kovács

Institute

of

IsotopesHungarian

Academy

of

Sciences

Budapest, Hungary

Master

Course

on

Nuclear

and

Ionising

Radiation

Technology

Dosimetry

– principles

•

In radiation processing, validation and process control (e.g. sterilization, food irradiation) depend on the measurement of absorbed dose.

•

Determination

of

absorbed

dose

in

product

specific* dosimetry

systems.

•

Accurate, traceable

dose

measurements

provide independent, inexpensive

means

for

quality

control

in

radiation

processing.

Dosimetry

–

applications

and

systems

•

Fields

of

application:

-

installation

qualification;-

operational

qualification;

-

performance

qualification;-

process

control;

•

Dosimetry

provides

documentation

in

the

processes, if

-

the

measurement

is traceable

to

a national

standard,-

the

uncertainty

of

the

system

is known.

•

Applied

systems:-

primary-, secondary-, transfer

standards;

-

routine

systems;

Selection

criteriaQuality

control

has to

be based

on

the

assurance

that

the

process

was

carried

out within

prescribed

dose

limits.

↓

This

requires

proper

use

and

selection

of

dosimetry

system.

↓

Selection

criteria:

-

according

to

the

process

to

be controlled

(i.e. dose

range);

-

according

to

dosimeter

characteristics;

(dose, dose

range, energy, cost, reproducibility, resolution, stability, etc);

Dosimetry

principlesDose measurements are based on various methods:

-

Temperature

increase

(calorimetry)

-

Colour

change

(radiochromic

systems)

-

Free

radical

concentration

(alanine)

-

Conductivity

change

(ECB, aqueous-alanine

solution)

-

Radiation

chemical

oxidation

(Fricke)

-

Radiation

chemical

reduction

(ceric-cerous, dichromate)

-

Crystal

lattice

modification

(semiconductors)

-

Measurement

of

optically

stimulated

luminescence

(Sunna

film)

Dosimetry

systems

in

present

practiceDosimeter

system Method

of

analysis Useful

dose

range, Gy

Nominal

precision

limits References

Fricke

solutionUV –

spectro-photometry

3x10 –

4x102 1 %ASTM E 1026 -

04

Ceric – ceroussulphate

UV –

spectro-photometry

103

– 106 3 %ISO/ASTM

51205

Potassiumdichromate

UV-VISspectrophoto.

5x103

–

4x104 1 %ISO/ASTM

51401

Ethanol-mono-chlorobenzene

Titration,orHF oscillometry

4x102

–3x105 3 %ISO/ASTM

51538

L -

alanine EPR 1 –

105 0.5 %ISO/ASTM

51607

Perspex

systemsVIS -

spectro-photometry

103

– 5x104 4 %ISO/ASTM

51276

FWT –

60film

VIS -

spectro-photometry

103

- 105 3 %ISO/ASTM

51275

B 3film

VIS -

spectro-photometry

103

- 105 3 %ISO/ASTM

51275

Cellulosetriacetate

UV –

spectro-photometry

104

- 106 3 %ISO/ASTM

51650

CalorimetryResistance/temperature

1.5x103

–5x104 2 %

ISO/ASTM51631

Factors

Affecting

Dosimeter

AccuracyCalibration and practical irradiation conditions are different:

•

Energy

dependence

(gamma, X-ray, electron)

•

Geometrical

factors

(product

type, dose

gradients)

•

Dose-rate effects (EB – gamma)

•

Environmental

effects

(light, temperature, etc)

•

Instrumental

errors

(scattered

light, OD/λ

scale)

•

Storage

conditions

(before

and

after

irradiation)

Characteristics

of

gamma and

electron radiation

•

Gamma

Electron-

high

penetration

-

low/medium

penetration

-

low

dose

rate

-

high

dose

rate-

longer

irradiation

time:

-

short

irradiation

time:

hours/days

seconds/minutes

Radiation

Interaction

Energy dependence

•

Calibration

in

a Gammacell

type

facility

and

routine

use

in

an

industrial

facility

– energy

spectrum

degradation

-

Fricke

„G”

value

decreases

by

about

15 % when

photon

energy

decreases

from 1 MeV

to

about

50 keV;

•

Importance

of

selection

of

suitable

dosimeters

–

radiation

absorption characteristics

should

be similar

to

that

of

absorbing

medium

(dosimeters

consisting

of

higher

atomic

number

–

products

consisting

of

low

atomic

number)↓

•

Cavity

theory

applications

(to

calculate

dose

in

product):

-

use

of

photon

mass

energy

absorption

coefficients

(gamma radiation) or -

electron

mass

collision

stopping

powers

(electron

radiation)

Geometrical

Factors•

Dose

distributions

in

bulk

products

•

Dose

gradients

within

product

and

dosimeter

•

Homogeneous

vs. inhomogeneous

products

•

Interface

effects

–

use

of

thin

dosimeters

Dose Distributions

Dose

rate

effects•

In

radiation

processing

applications

the

absorbed

dose

rates

may

vary

from

mGy/s up

to

about

109

Gy/s resulting

in

dosimetry

errors

in

the

case of

dose

rate

dependent

dosimeter

response.

•

The reason: radiation-induced

intermediate

species –

ions, radicals

- (formed

in

higher

concentrations

at

higher

dose

rates) interfere

with

the

development

of

the

ultimate

dosimeter

response.

•

In

physical

systems

(ionization

chambers) the

high

dose

rate

effect

is the recombination

of

ions.

•

In

chemical

systems

(solutions) due

to

high

dose

rate

effect

the

radicalradical

reactions

in

the

solvent

compete

with

the

primary

solute

scavenging

reactions

(Fricke

system).

•

Dose

rate

dependence

is usually

coupled

with

other

influences (temperature, oxygen

diffusion), therefore

corrections

are

difficult

(in-plant

calibration).

Dose Rate Effect

Environmental

EffectsTemperature

effects:

1. Irradiation

temperature

–

the

most important

environmental

factor

contributing

to dose

estimation

errors.

-

The solution:

temperature coefficient to apply → mean

temperature

during irradiation

is required;

-

The temperature

dependence

relationship

can

vary

from

linear

to

anything;

-

The temperature

coefficient

may

be a function

of

dose;

2. Temperature

after

irradiation

–

FWT-60, B3 and

Sunna

films: post

irradiation temperature

treatment

to

stabilize

response;

3. Temperature

during

read-out

–

Fricke

and

ECB solution;

Irradiation Temperature Effects

Temperature

effects

-

calorimetry

Relative

Humidity

Effects

•

Many

dosimeters

may

absorb

water

resulting

in

different

dose

response function.

•

Careful

packaging

to

protect

dosimeters

–

especially

some

plastic

and radiochromic

systems.

•

Investigation

of

humidity

effects

on

dosimeter

response

by

using

various salt

solutions.

•

Pre-irradiation

adjustment

of

dosimeter

moisture

content

–

in

sealed pouches.

Packaging

Humidity

„meters” (saturated

salt

solutions)

Salt Temperature(oC)

Relative

humidity(%)

CH3

COOK 20 20

CaCl2

. 6 H2

O 24.518.5

3135

K2

CO3

. 2 H2

O 24.518.5

4344

NaHSO4

. H2

O 20 52

PackagingPackaging

of

films, perspex, etc.:

Three

layers

„plastic”

bag:

-

outside: 15 μm polyamideprotects

Al

layer

-

middle: 12 μm Alprotects

dosimeter

-

inside: 75 μm PEfor

sealing

Effect

of

Oxygen

Content

•

Oxygen

is a reactive

molecule

which

reacts

with

radiation-induced unstable

species and

free

radicals

(radical

scavenger) thus

affecting

the

final

concentration

of

certain

products

used

for

dosimetry, i.e. the

dose response.

•

The role

of

oxygen

in

the

Fricke

system

–

effects

the

dose

range.

•

Oxygen

diffusion

into

plastic

film dosimeters

at

low

dose

rates

–

e.g. in CTA film higher

response

is due

to

more efficient

double

bond

formation

as

a result

of

oxygen

diffusion

during

irradiation.

•

Post

irradiation

effect: oxygen

diffusion

into

dosimeter

material

after irradiation

results

in

fading

of

the

dosimeter

signal.

Light

Effects

•

Many

dosimeters

are

sensitive

to

light

effects

before, during

and

after irradiation

–

sometimes

even

during

read-out.

-

Solutions

(e.g. Fricke, ECB), radiochromic

films

(e.g. FWT-60, B3);

•

To

avoid

it: packaging

and

careful

handling.

•

To

avoid

UV light

during

storage

(solutions, films).

Effect

of

Impurities

•

Impurities

react

with

radiation-induced

intermediate

species thus effecting

dosimeter

response.

•

To

avoid

it:

-

to

use

suitable

purity

chemicals;

-

addition

of

impurities

in

larger

concentration

(ECB);

-

pre-irradiation

of

dosimeter

solution

(dichromate);

Conclusions•

Differences

between

irradiation

conditions

during

calibration and

practical applications can

result

in

serious

dosimetric

errors.

•

The influence

of

combinations

of

environmental

factors

on

the

dosimeter response

can

result

in

instabilities.

•

Therefore:

-

these

effects

have

to

be investigated;

-

packaging

and

proper

handling

to

be used;

-

temperature

effects

are

most critical

ones;

•

If

possible, in-plant

calibration

and/or

verification

to

be applied!

Environmental

effects

on

dosimetry

systems

Dosimeter Measurement time

after

irr.

Humidity Dose

rate(Gy

s-1)

Irradiation

temp. coeff., (oC)-1

Alanine immediately yes < 108 + 0.25 %

Dichromate 24 hours no 0.7 –

5x102 -

0.2 %

Ceric-cerous immediately no < 106 conc. dep.

ECB immediately no < 108 + 0.05 %

Calorimeters immediately no < 108 -

Perspex 24 hours yes < 105 + 1 %

FWT-60 5 min/60 oC yes < 1013 + 0.2 %

B3 5 min/60 oC yes < 1013 + 0.3 %

Sunna 20 min/70 oC no < 1013 + 0.2 %

Thank you for your attention!

ValidationValidation ofof radiationradiation sterilizationsterilization processprocess

Iwona KaluskaInstitute of Nuclear Chemistry and Technology

QualityQuality systemssystems

Quality management systems -Requirements

EN ISO 9001:2000supersedes EN ISO 9001:1994EN ISO 9002:1994EN ISO 9003:1994

Medical devices-Quality management systems-Requirements for regulatory purpose

EN ISO 13485:2003supersedesEN ISO 13485:2002 EN ISO 13488:2002

WhyWhy ISO 13 485 ?ISO 13 485 ?

The standards for quality management systems recognize that, for certain processes used in manufacturing, the effectiveness of the process cannot be fully verified by subsequent inspection and testing of the product. Sterilization is an example of such a process. For this reason, sterilization processes are validated for use, the performance of sterilization process is monitored routinely and the equipment is maintained.

Particular requirements for sterile medical devicesParticular requirements for sterile medical devices

7.5.1.3.The organization shall maintain records of the process parameters for the sterilization process which was used for each sterilization batch (see 4.2.4). Sterilization records shall be traceable to each production batch of medical devices (see 7.5.1.1.)7.5.2.2 The organization shall establish documented procedures for validation of sterilization processes. Sterilization processes shall be validated prior to initial use.Records of validation of each sterilization process shall be maintained (see 4.2.4)

ISO 14937:2000ISO 14937:2000

Sterilization of health care products –General requirements for characterization of a sterilizing agent and the development, validation and routine control of a sterilization process

ValidationValidation

The purpose of validation is to demonstrate that the sterilization process established in process definition can be delivered effectively and reproducibly to the sterilization load. Validation consists of a number of identified stages: installation qualification, operational qualification, and performance qualification.

InstallationInstallation qualificationqualification (IQ)(IQ)

IQ is undertaken to demonstrate that the sterilization equipment and any ancillary items have been supplied and installed in accordance with their specification.

OperationalOperational qualificationqualification (OQ)(OQ)

OQ is carried out either with unloaded equipment or using appropriate test material to demonstrate the capability of the equipment to deliver the sterilization process that bas been defined.

Performance Performance qualificationqualification (PQ)(PQ)

PQ is the stage of validation that uses product to demonstrate that equipment consistently operates in accordance with predetermined criteria and the process yields product that is sterile and meets specified requirements.

ManagementManagement responsibilityresponsibility

The development, validation and routine control of a sterilization process is likely to involve a number of separate parties, each of whom is responsible for certain elements.

In order to illustrate the variety of possible allocations, three sample o scenarios are presented.

Scenario 1 – Health care facilityScenario 2 –Medical device manufacturer using in-house facilitiesScenario 3 – Medical device manufacturer using a sterilization subcontractor.

Medical device manufacturer using Medical device manufacturer using a a sterilization subcontractorsterilization subcontractor

In this scenario, the user of the sterilization process is a manufacturer of single-use medical devices who is using sterilization subcontractor to deliver the sterilization process. Additionally, the medical device manufacturer is using a contract laboratory to undertake defined testing as part of the product release procedures. The parties involved are the medical device manufacturer, the sterilization subcontractor, and the contract laboratory.

The allocation of responsibilities might The allocation of responsibilities might be be as as followsfollows: : (1/ 5)(1/ 5)

Quality management system elements– Each party has its own quality management system.

The limits of responsibility of each party are laid down in formal contracts.

Sterilizing agent characterization– The sterilization subcontractor has licensed the

sterilization process from a separate organization who characterized and developed the sterilization process. The process developer has undertaken the sterilizing agent characterization and made the resultant data available to the sterilization subcontractor and the medical device manufacturer.

The allocation of responsibilities mightThe allocation of responsibilities might be be as as followsfollows: : (2/ 5)(2/ 5)

Process/equipment characterization– The sterilization subcontractor has developed an

equipment specification, including a control system for the equipment, which is capable of being programmed to deliver a predefined process. A sterilizer manufacturer has been contracted to manufacture and install the specified equipment.

Product definition– The medical device manufacturer is responsible for

specification of the product and its manufacture.


Process definition– The medical device manufacturer defines a process for the

particular medical device(s) to be sterilized. The medical device manufacturer undertakes the biological safety assessments and product compatibility studies. In this case, these studies are conducted using experimental sterilization equipment.

Validation– The sterilization subcontractor undertakes installation qualification

and operational qualification in accordance with documented procedures. The medical device manufacturer then undertakes performance qualification using the installed sterilization equipment conforming that the equipment is capable of delivering the defined sterilization process. The medical device manufacturer reviews and approves the validation exercise. A contract laboratory might perform microbiological testing in accordance with methods agreed with the medical device manufacturer.


Routine control and monitoring– This is carried out by the sterilization subcontractor

laboratory in accordance with documented procedures agreed with the medical device manufacturer.

Product release from sterilization– This is carried out by medical device manufacturer in

accordance with documented procedures, on the basis of records provided by the sterilization subcontractor and the contract laboratory.


Maintaining process effectiveness– The sterilization subcontractor carries out

equipment maintenance and calibration in accordance with documented procedures. The medical device manufacturer maintains the quality of product prior to sterilization and takes responsibility for requalification; the sterilization subcontractor carries out any necessary repetition of part or all of installation qualification or operational qualification.

EN ISO 11137 : 2006EN ISO 11137 : 2006

Sterilization of health care products - Radiation

IrradiatorIrradiator operator operator responsibilitiesresponsibilities

Installation qualificationOperational qualificationControlling the irradiation processChange control of the irradiatorCertification of the radiation dose

Primary manufacturer responsibilities

• Establishing the sterilization dose• Developing product families• Establishing the maximum acceptable dose• Performance qualification• Controlling the manufacturing process including the

specifications for products submitted to the irradiator operator, i.e., product density, orientation, dimensions

• Revision of specifications submitted to the irradiator operator

• Change control of the product to include a review of product-related variables that impact processing categories

• Product release

Installation Qualification

Equipment documentation (describing the design

and installation requirements; it should include

drawings and details of all the construction materials,

the dimensions and tolerances of the equipment,

support services and power supplies)

Any modification made to the irradiator installation

Records should include the following:

For gamma irradiators, the activity of the source and description of the location of individual components of the source

For electron beam and X-ray irradiators, the characteristics of the beam (electron energy, average beam current, scan width and scan uniformity.

Operational qualificationOperational qualification

Equipment calibration (including test

instrumentation used for monitoring,

controlling, indicating or recording)

Irradiator dose mapping


• Determination of product loading pattern

• Product dose mapping

RisRisøøScanScan, a new software , a new software package package for for analysis of analysis of

radiochromic radiochromic film film dosimetersdosimeters

Jakob HeltJakob Helt--HansenHansenArne MillerArne Miller

High High Dose Reference Dose Reference LaboratoryLaboratoryRisRisøø National National LaboratoryLaboratory

The ideaThe idea……

Replace spectrophoto-meter with scanner and PC.

RisRisøøScanScan is:is:

A software package for image analysis of A software package for image analysis of dosimeter films. dosimeter films. Not only RisNot only Risøø B3 film, but other dosimeter B3 film, but other dosimeter systems using color change can be used.systems using color change can be used.Emphasis on calibration, depth dose curves Emphasis on calibration, depth dose curves and surface dose profiles.and surface dose profiles.Developed at the High Dose Reference Developed at the High Dose Reference Laboratory at RisLaboratory at Risøø National Laboratory.National Laboratory.Using Using LabViewLabView programming language from programming language from National Instruments.National Instruments.

Scanner Scanner ≠≠

spectrophotometerspectrophotometer

A scanner is not a precision instrument- 255 grey-scale levels.- one scan can differ from the nextdue to different lamp temperature etc.

Expect that scanners are not comparable.

Scans are not comparable if scanner settings are not kept constant.

CalibrationCalibration

Ideally one would make a calibration for every Ideally one would make a calibration for every image.image.Calibration for each dosimeter type.Calibration for each dosimeter type.Use reference to link calibration to subsequent Use reference to link calibration to subsequent images.images.

We use laminated B3 film dosimeter irradiated to 12, 25 and 50 kGy.


Scan imageRisø B3 dosimeters

Reference

Make sure scanner settings are kept constant.


Scan image

Select color channel

Every pixel has an RGB

value.

To enhance signal to noise ratio we only use the green value for Risø B3 dosimeters.

Risø B3 dosimeters

Reference


Scan image


Every pixel has an RGB value.

To enhance signal to noise ratio we only use the green value for Risø B3 dosimeters.

Risø

B3 dosimeters

Reference


Scan image

Record scanner settings


Name of scanner.Brightness, contrast, gamma value.Scan resolution.

Manual procedure.


Scan image


Select polynomial fitCheck residuals



Scan image



Measurement of reference values


Item name Response

A 98.89B 142.18C 184.30


Scan image





Save Calibration

Measurement of Measurement of ddoseose

Scan image



Scan image

Measurement ofMeasurement of ddoseose

Scan image


Load

calibration


Compare image and calibration settings

Scan image


Scan image


Load

calibration



Typical correction: <1%Typical standard deviation on a reading: 1-2%


Scan image


Load

calibration



Compare image and calibration

reference

MeasurementMeasurement of doseof dose Reference correctionReference correction

∑=

=′n

i

iipixel xaDr

0

)(

0

50

100

150

200

250

0 25 50 75 100Dose, kGy

Pix

el re

spon

se


∑=

−=n

ipixel

iipixel rxarD

0

)root()(

-150

-100

-50

0

50

100

0 25 50 75 100

Dose, kGy


∑= ′

′⋅−=

n

i pixel

ncalibratiopixel

iipixel r

rrxarD0

)root()(

-150

-100

-50

0

50

100

0 25 50 75 100

Dose, kGy


Scan image


Load

calibration


Write to log file



Surface Surface dose dose profileprofile..EE--beam energy beam energy measurement based on measurement based on depth depth dose dose analysisanalysis..

Scan image


Load

calibration



Calculate dose as function of pixel

intensity

Surface dose profile analysisSurface dose profile analysis

Energy measurement based on Energy measurement based on ddepthepth dose analysisdose analysis

Average and most probable electron energy can beAverage and most probable electron energy can be calculated based on the descending slope.calculated based on the descending slope.

Energy measurement based on Energy measurement based on ddepthepth dose analysisdose analysis

Determination of Determination of offsets: depth & dose.offsets: depth & dose.Calculation of L.R. of Calculation of L.R. of the descending slope.the descending slope.Calculation of RCalculation of R5050, R, Rexexand Eand E5050, , EEexex based on based on user defined user defined equations. equations. (ISO/ASTM).(ISO/ASTM).Manual and Manual and automated procedure.automated procedure.

Energy measurement based onEnergy measurement based on ddepthepth dose analysisdose analysis

Calculation of beam energy: scanner versus photospectromete

Difference in calculated beam energy: <1%

GAFGAF dosimeters and dosimeters and RisoeScanRisoeScan

Use Red and Green color channel

11

DosimetryDosimetryfor for

electron beam electron beam sterilization sterilization

Arne MillerRadiation Research DepartmentRisø National LaboratoryTechnical University of Denmark DK-4000 RoskildeDenmark

22

Absorbed dose:Absorbed dose:

Energy absorbed per unit massEnergy absorbed per unit mass

1 Gray (Gy) = 1 J/kg1 Gray (Gy) = 1 J/kg

Dose range for sterilization: 10 Dose range for sterilization: 10 -- 5500 kGykGy

Dose range for dose setting: 1 Dose range for dose setting: 1 -- 10 kGy10 kGy

Realization by Realization by calorimetrycalorimetry::

dose = dose = ΔΔT*CpT*Cp

related through basic physical properties and related through basic physical properties and definitionsdefinitions

33

Dosimeter systemsDosimeter systems

Response based on physical or chemical changesResponse based on physical or chemical changesin a materialin a material

temperaturetemperaturecolour (UV colour (UV –– VIS VIS –– IR)IR)luminescence (TL luminescence (TL –– OSL)OSL)radical concentration (EPR)radical concentration (EPR)viscosityviscosityelectrical conductivityelectrical conductivityoptical rotationoptical rotation

44

Dosimeter propertiesDosimeter properties

response functionresponse function

temperature effectstemperature effects

humidity effectshumidity effects

dose rate influencedose rate influence

stability before and after stability before and after

irradiationirradiation

55

Examples of dosimeter systems for eExamples of dosimeter systems for e--

beambeam

calorimeterscalorimeters

radiochromicradiochromic film dosimetersfilm dosimeters

alanine / EPRalanine / EPR

66

Calorimeter for dose measurement at electron acceleratorCalorimeter for dose measurement at electron accelerator

77

Graphite Graphite calorimetercalorimeter

OnOn--line irradiationline irradiation

Change of Change of temperature as a temperature as a function of timefunction of time

88

Graphite Graphite calorimetercalorimeter

Conveyor Conveyor irradiationirradiation


99

Polystyrene Polystyrene calorimetercalorimeter

Conveyor Conveyor irradiationirradiation


1010

CalorimeterCalorimeter

Measures change in temperatureMeasures change in temperature

Dose range:Dose range:

Graphite 1.5 Graphite 1.5 ––

15 kGy15 kGy

Polystyrene 3 Polystyrene 3 ––

40 kGy40 kGy

Stable signal for 10 minutes (polystyrene)Stable signal for 10 minutes (polystyrene)

Reproducibility less than 1%, 1.s.dReproducibility less than 1%, 1.s.d

Measurement instrument: DGVMMeasurement instrument: DGVM

1111

Change of colourChange of colour

ExampleExample

RisRisøø B3 dosimeterB3 dosimeter

Visible absorption Visible absorption spectrumspectrum

RadiochromicRadiochromic film dosimetersfilm dosimeters

1212

RadiochromicRadiochromic film film dosimetersdosimeters


Calibration curve of B3 Calibration curve of B3 dosimeter filmdosimeter film

(OD = Absorption)(OD = Absorption)

1313

RadiochromicRadiochromic film dosimetersfilm dosimeters


Response function of Response function of B3 dosimeter filmB3 dosimeter film

Risø B3-06 Gamma UV4

y = 1,2080E-06x3 - 4,3548E-04x2 + 8,0201E-02x + 2,6373E-01R2 = 9,9958E-01

0,0000

1,0000

2,0000

3,0000

4,0000

5,0000

6,0000

0 20 40 60 80 100 120 140

Dose, kGy

A/t

1414

RdiochromicRdiochromic

film dosimetersfilm dosimeters

Measures change absorptionMeasures change absorption

Dose range:Dose range:

RisRisøø

B3B3

3 3 ––

100 kGy100 kGy

GEX WinDose GEX WinDose ––

DoseStix 3DoseStix 3--

100 kGy100 kGy

Far West Technology FWTFar West Technology FWT

1 1 ––

80 kGy80 kGy

CTA 10 CTA 10 ––

300 kGy300 kGy

1515

RdiochromicRdiochromic

film dosimetersfilm dosimeters

Measures change absorptionMeasures change absorption

Response change with time after irradiationResponse change with time after irradiation

RisRisøø

––

GEX GEX ––

FWT stable FWT stable --

almost almost --

after after heating heating

Reproducibility less than 3%, 1.s.dReproducibility less than 3%, 1.s.d

Measurement instrument:Measurement instrument:

Spectrophotometer or ScannerSpectrophotometer or Scanner

1616

RisRisøøScanScan A new measurement systemA new measurement system

1717

Dose mapping Dose mapping --

RisRisøøScanScan

Dosimeter film

Dose alongX-axis

Dose alongY-axis

1818

Alanine dosimeterAlanine dosimeter

Alanine Alanine pellets or pellets or filmsfilms

for electron or for electron or gamma gamma reference reference dosimetrydosimetry

1919

Alanine DosimetryAlanine Dosimetry

Radical concentrationRadical concentration

EPR = ESREPR = ESR

Electron Paramagnetic Electron Paramagnetic

Resonance spectrumResonance spectrum

of irradiated alanine pelletof irradiated alanine pellet

2020

Alanine Alanine

DosimetryDosimetryAH587B recalib measured

y = -1,0856E-07x4 + 4,8485E-05x3 - 9,4523E-03x2 + 1,0961E+00x + 5,7123E-03

R2 = 9,9998E-01

0,000

10,000

20,000

30,000

40,000

50,000

60,000

70,000

0 20 40 60 80 100 120 140

Response

Dos

e, k

Gy

ResponseResponse functionfunction

DoseDose as a as a functionfunction ofof

EPR signalEPR signal

2121

Alanine Alanine

DosimetryDosimetry

ResponseResponse as a as a function of function of irradiation irradiation temperaturetemperature

AH592A Gamma temp (normalized)

y = 1,46E-03x + 9,63E-01R2 = 9,29E-01

0,96

0,98

1,00

1,02

1,04

1,06

0 10 20 30 40 50 60 70

Irradiation temp C

Npr

mal

ized

res

pons

e

2222

Alanine DosimetryAlanine Dosimetry

Measures free radical concentrationMeasures free radical concentration

Pellets or filmsPellets or films

Dose range: 10 Gy Dose range: 10 Gy ––

100 kGy100 kGy

Stable signal for more than one yearStable signal for more than one year

Reproducibility less than 0.5%, 1.s.dReproducibility less than 0.5%, 1.s.d

Measurement instrument:Measurement instrument:

EPR spectrometerEPR spectrometer

2323

Other dosimetersOther dosimeters

GAFchromic (com)GAFchromic (com)Visible absorptionVisible absorption

< 1 Gy < 1 Gy ––

50+ kGy50+ kGy

PE PE ––

PolyethylenePolyethylene

IR absorptionIR absorption

10 10 ––

100 kGy100 kGy

PVC PVC --

polyvinylchloridepolyvinylchlorideVisible absorptionVisible absorption

5 5 ––

50+ kGy50+ kGy

2424


2525


ISO 11137ISO 11137--1, sect 4.3.41, sect 4.3.4

““Dosimetry used in the development, Dosimetry used in the development, validation and routine control of validation and routine control of the sterilization process shall have the sterilization process shall have measurement traceability to measurement traceability to national or international national or international standards and shall have a known standards and shall have a known level of uncertainty.level of uncertainty.””

Can only be obtained through Can only be obtained through calibrationcalibration

2626


Dosimeters used in radiation processingDosimeters used in radiation processing

must be calibrated.must be calibrated.

MethodMethod::

1.1.

IrradiateIrradiate

dosimetersdosimeters

to to knownknown

dosesdoses

2.2.

MeasureMeasure

responseresponse

3.3.

EstablishEstablish

responseresponse

functionfunction

2727

Calibration Example: Calibration Example: AlanineAlanine

MathematicalMathematical fitfit betweenbetween dosedose and and responseresponse

Dose = f(R)Dose = f(R)

oror

R = f(dose)R = f(dose)

AnyAny functionfunction cancan bebe used.used.Example:Example:3rd order3rd orderpolynomialpolynomial

AH592A gamma 3rd

y = 2,5366E-05x3 - 7,8383E-03x2 + 1,0437E+00x + 1,4037E-01

R2 = 9,9995E-01

0,000

10,000

20,000

30,000

40,000

50,000

60,000

0 20 40 60 80 100 120

Dose, kGy

Res

pons

e

2828

Calibration Example: AlanineCalibration Example: Alanine

MathematicalMathematical fitfit betweenbetween dosedose and and responseresponse

AnyAny functionfunction cancan bebe usedused..

Example:Example:

4th order4th order

PolynomialPolynomial

AH592A gamma 4thy = -1,9061E-07x4 + 6,4366E-05x3 - 1,0256E-02x2 +

1,0891E+00x + 5,9504E-03R2 = 9,9998E-01

0,000

10,000

20,000

30,000

40,000

50,000

60,000

0 20 40 60 80 100 120

Dose, kGy

Res

pons

e

2929


SelectionSelection ofof functionfunction basedbased onon evaluationevaluation ofof residualresidual plotplot

This plot This plot contains a contains a function function –– the the residuals are residuals are not randomnot random

AH592 gamma 3rd residual

-12,00-10,00-8,00-6,00-4,00

-2,000,002,004,00

0 20 40 60 80 100 120

Dose, kGy

Res

idua

l, %

3030


SelectionSelection ofof functionfunction basedbased onon evaluationevaluation ofof residualresidual plotplot

This plot This plot contains no contains no function function –– the the residuals residuals randomrandom

AH592A gamma 4th residual

-1,50

-1,00

-0,50

0,00

0,50

1,00

1,50

0 20 40 60 80 100 120

Dose, kGy

Res

idua

l, %

3131

MethodsMethods

ofof


RecommendedRecommended

methodmethod::

InIn--plant calibrationplant calibration

CalibrateCalibrate

by by irradiationirradiation

at at thethe

facilityfacility wherewhere

thethe

dosimetersdosimeters

areare

usedused..

DoseDose

measuredmeasured

by reference by reference dosimeters.dosimeters.

This method allows environmental This method allows environmental influence factors to neglected influence factors to neglected ––

almost!almost!

3232

MethodsMethods

ofof


InIn--plant calibrationplant calibration

ImportantImportant

The routine dosimeter and the reference The routine dosimeter and the reference dosimeter must receive the same dose.dosimeter must receive the same dose.

Use phantoms.Use phantoms.

3333

MethodsMethods

ofof


ElectronElectron

beambeam

phantophanto mmRef dosimeter

Routine dosimeter

3434

MethodsMethods

ofof


AlternativeAlternative

methodmethod

CalibrateCalibrate

by by irradiationirradiation

at at calibrationcalibration laboratory.laboratory.

When using this method, verification of When using this method, verification of dosimeter response in plant must be dosimeter response in plant must be carried out.carried out.

3535

MethodsMethods

ofof


RecommendedRecommended

reference:reference:

CIRMCIRM--29 (August 1999)29 (August 1999)

Guidelines for the Calibration of Guidelines for the Calibration of Dosimeters for use in Radiation Dosimeters for use in Radiation ProcessingProcessing

3636

MeasurementMeasurement

TraceabilityTraceability

--

an often misused terman often misused term

ISO vocabulary 6.12:ISO vocabulary 6.12:

the property of a result of a measurement the property of a result of a measurement whereby it can be related to appropriate whereby it can be related to appropriate standards, generally international or national standards, generally international or national standards, through an standards, through an

unbroken chain of comparisonsunbroken chain of comparisons

Measurement Traceability is documented through Measurement Traceability is documented through 3rd party 3rd party accreditationaccreditation

3737

Measurement traceability chainMeasurement traceability chain

MeasurementMeasurement TraceabilityTraceability

National standardNational standard

Reference fieldReference field

Transfer dosimeterTransfer dosimeter

22ndnd Lab ref fieldLab ref field

Transfer dosimeterTransfer dosimeter

Irradiation facilityIrradiation facility

Routine dosimeterRoutine dosimeter


Irradiation facilityIrradiation facility


3838

Reference Reference radiation radiation

fieldfield

Risøgammacell

3939

AccreditationAccreditation

Measurement Traceability is documented through 3rd party Measurement Traceability is documented through 3rd party accreditationaccreditation

International standard for accrediting calibration International standard for accrediting calibration laboratories:laboratories:

EN IEC ISO 17025:2005EN IEC ISO 17025:2005

General requirements for the competence of testing General requirements for the competence of testing and and calibration laboratoriescalibration laboratories

ContainsContains

ISO 9001 quality management requirementsISO 9001 quality management requirements

Technical requirementsTechnical requirements

4040



is granted by national accrediting is granted by national accrediting organizations.organizations.

In Denmark: DANAKIn Denmark: DANAK

The national accreditations must be evaluated by The national accreditations must be evaluated by international organizations. In Europe: European international organizations. In Europe: European organization for Accreditation, EA.organization for Accreditation, EA.

Wider international network based on multinational Wider international network based on multinational recognition agreements.recognition agreements.

4141


Why accreditation?Why accreditation?

Customer requirementCustomer requirement

Regulatory requirementsRegulatory requirements

3rd party evaluation strengthens technical competence 3rd party evaluation strengthens technical competence of laboratoryof laboratory

4242

Measurement UncertaintyMeasurement Uncertainty

ReferencesReferences

GUM: Guide to the expression of GUM: Guide to the expression of Uncertainty in Measurement (1993) Uncertainty in Measurement (1993) (ISO)(ISO)

Guide for Estimating Uncertainties in Guide for Estimating Uncertainties in Dosimetry for Radiation ProcessingDosimetry for Radiation Processing

ISO / ASTM 51707ISO / ASTM 51707

4343


UncertaintyUncertainty

OneOne

classificationclassification::

RandomRandom::

ObservedObserved

duringduring

measurementmeasurement

NonNon--randomrandom::

Not Not observedobserved

duringduring measurementmeasurement

BothBoth

contributecontribute

to to thethe


uncertaintyuncertainty

4444


UncertaintyUncertainty

BIPM classificationBIPM classification::

Type A:Type A:

Uncertainties that are evaluated by applying Uncertainties that are evaluated by applying statistical methods to a series of repeated measurementsstatistical methods to a series of repeated measurements

Type B:Type B: Uncertainties that are evaluated by other means Uncertainties that are evaluated by other means

BothBoth

contributecontribute

to to thethe



4545

The use of an The use of an ““uncertainty budgetuncertainty budget””::

1.1. Evaluate all sources contributing to the uncertainty of the Evaluate all sources contributing to the uncertainty of the measurement, Type A measurement, Type A -- BB•• Type A:Type A:

Uncertainties that are evaluated by applying statistical Uncertainties that are evaluated by applying statistical methods to a series of repeated measurementsmethods to a series of repeated measurements

•• Type B:Type B:Uncertainties that are evaluated by other meansUncertainties that are evaluated by other means

2.2. Combine all sources by taking the square root of the sum of the Combine all sources by taking the square root of the sum of the squaressquares

S=S=

3.3. Carry out measurement and calculate uncertaintyCarry out measurement and calculate uncertainty4.4. Compare Compare ““budgetbudget”” value and measured value value and measured value

Example!Example!

.....ssss 24

23

22

21 ++++


4646

Uncertainty in radiation Uncertainty in radiation

processingprocessing

Rules of thumb:Rules of thumb:

•• 1 s.d. < 5% is an obtainable value1 s.d. < 5% is an obtainable value•• 5% < 1s.d. < 10% should be 5% < 1s.d. < 10% should be

improvedimproved•• 1 s.d. > 10% is poor and efforts 1 s.d. > 10% is poor and efforts

should be made to improveshould be made to improve

Knowledge of the measurement uncertainty is used for setting proKnowledge of the measurement uncertainty is used for setting process limits.cess limits.


4747

temperaturetemperaturehumidityhumiditydose ratedose rate

are difficult to correct for and may act differently at are difficult to correct for and may act differently at different dosesdifferent doses

ThereforeTherefore

calibrate using processing conditionscalibrate using processing conditionscalibrate by irradiation in plantcalibrate by irradiation in plantif calibration is carried out in calibration laboratory, if calibration is carried out in calibration laboratory, verify response by irradiation in plantverify response by irradiation in plant

Environmental influence factorsEnvironmental influence factors

11

ValidationValidationandand

routine control ofroutine control ofsterilization by irradiationsterilization by irradiation

Arne MillerRisø

National LaboratoryTechnical University of Denmark DK-4000 RoskildeDenmark

22

Content of presentation:Content of presentation:FollowingFollowing outlineoutline in EN ISO in EN ISO 1113711137--1:20061:2006

Equipment characterizationEquipment characterization (6)(6)

Product definitionProduct definition (7)(7)

ProcessProcess definitiondefinition (8)(8)

InInstallationstallation Qualification Qualification (9.1)(9.1)

Operational Operational QualificationQualification (9.2)(9.2)

••

Performance QualificationPerformance Qualification (9.3)(9.3)

Process Control and MonitoringProcess Control and Monitoring (10)(10)

33

6 Equipment characterization6 Equipment characterization

1. Description of irradiation facility1. Description of irradiation facility

2. Software2. Software

(6.2.2) Software used to control and/or (6.2.2) Software used to control and/or monitor the process shall be prepared in monitor the process shall be prepared in accordance with a quality management accordance with a quality management system that provides documented evidence system that provides documented evidence that the software meets its design intentionthat the software meets its design intention

= = software software validationvalidation

44

7 Product definition7 Product definition

7.17.1

Product to be sterilized, including Product to be sterilized, including packaging materials, shall be specified.packaging materials, shall be specified.

55

8 Process definition8 Process definition

(8.2)(8.2)

Establishing sterilization doseEstablishing sterilization dose

Using dose setting or dose substantiation Using dose setting or dose substantiation methods (11137methods (11137--2).2).

Note:Note:

Product samples shall be irradiated to Product samples shall be irradiated to defined and uniform doses.defined and uniform doses.

66

8 Process definition8 Process definition

(8.1)(8.1) Establishing maximum acceptable doseEstablishing maximum acceptable dose

““When treated with the maximum acceptable dose, When treated with the maximum acceptable dose, product shall meet its specified functional requirements product shall meet its specified functional requirements throughout its defined lifetimethroughout its defined lifetime””

Product or material samples are irradiated to Product or material samples are irradiated to uniform doses.uniform doses.

Irradiation of product samples to known doses, Irradiation of product samples to known doses, usually 1usually 1--22--3 x sterilization dose.3 x sterilization dose.

77

ProductProduct--specific testing specific testing -- No international standard No international standard

for product testingfor product testing

General information General information about materials for about materials for radiation sterilizationradiation sterilization

AAMI TIR 17AAMI TIR 17

88

9.1 Installation qualification9.1 Installation qualification

(A.9.1) (A.9.1) --

is carried out to demonstrate that the is carried out to demonstrate that the sterilization equipment and any ancillary sterilization equipment and any ancillary items has been supplied and installed in items has been supplied and installed in accordance with their specification.accordance with their specification.

Whether or not data are Whether or not data are ““in accordance with in accordance with their specificationtheir specification””

depends on agreement depends on agreement

between supplier and userbetween supplier and user

MeasurementsMeasurements

are oftenare often

thethe

same as forsame as forOperationalOperational

QualificationQualification

99

9.2 Operational qualification9.2 Operational qualification

Operational qualificationOperational qualification

(9.2.2) (9.2.2) ––

shall be carried out by irradiating shall be carried out by irradiating appropriate test material to demonstrate appropriate test material to demonstrate the capability of the equipment to deliver the capability of the equipment to deliver the sterilization process that has been the sterilization process that has been defined.defined.

--

provides baseline data to show consistent provides baseline data to show consistent operation of the facilityoperation of the facility

1010

Operational qualification Operational qualification

GammaGamma

••

dosedose

distribution in reference distribution in reference product(sproduct(s))

••

dosedose

as as functionfunction

ofof

dwelldwell

timetime••

processprocess

interruptioninterruption

••

mixmix

ofof

productsproducts

1111

OQ gamma cont..OQ gamma cont..

Gamma FacilityGamma FacilityLayoutLayout

1212

OQ OQ gammagammacont..cont..

Placement of dosimeters

1313

Dose distributionDose distribution in reference productin reference product

IsodoseIsodose curvescurves

OQ Gamma cont..OQ Gamma cont..

1414

Dose maps must be made with fully loaded irradiation Dose maps must be made with fully loaded irradiation chamberchamber

Range of densities of reference product must cover Range of densities of reference product must cover extremes of products to be irradiatedextremes of products to be irradiated

Additional measurement:Additional measurement:

−−

effect of process interruptioneffect of process interruption

Dose mappingDose mapping


1515

Dose mapping shall be carried out on a sufficient number of Dose mapping shall be carried out on a sufficient number of irradiation containers to allow determination of the irradiation containers to allow determination of the distribution and variability of dose between containersdistribution and variability of dose between containers

Dose mapping must be repeated when significant changes Dose mapping must be repeated when significant changes of the irradiation plant are made, of the irradiation plant are made, e.g. e.g. source changesource change

Dose mappingDose mapping


1616

Operational qualification Electron Operational qualification Electron beambeam

Measurements to be carried outMeasurements to be carried out

––

dosedose

distribution reference distribution reference productproduct––

scan scan widthwidth

––

energyenergy––

dosedose

as as functionfunction

ofof

speed, speed, currentcurrent, scan , scan

widthwidth––

beambeam

spotspot

––

processprocess

interruptioninterruption

1717

OQ EOQ E--beam cont..beam cont..

Placement of Placement of dosimeters in dosimeters in reference productreference product

1818

Dose Dose distribution in distribution in reference reference productproduct

Limits for Limits for acceptable acceptable variations can bevariations can bedefineddefined.


1919

Scan widthScan width


Limits for acceptable variations can bedefined.

2020

EnergyEnergy

Wedge and stack for energy measurementWedge and stack for energy measurement


2121

Typical depthTypical depth--dose curvedose curve

EnergyEnergy –– range range relationshipsrelationships


2222

Energy Energy –– range relationshipsrange relationships

ISO / ASTM 51649ISO / ASTM 51649

AluminiumAluminium

Most probable energy Most probable energy EEpp

= 5.09 x = 5.09 x RRpp

+ 0.2 (+ 0.2 (MeVMeV))

Average energy EAverage energy Eaa

= 6.2 x R= 6.2 x R5050

Other equations for water and polymersOther equations for water and polymers


2323

Dose as a function Dose as a function of of

-- beambeam currentcurrent-- conveyor speedconveyor speed-- scan scan widthwidth


Dose = f(I/V*Sw)

y = 1129,8x - 0,1538R2 = 0,9996

01020304050607080

0,000 0,010 0,020 0,030 0,040 0,050 0,060 0,070

I/(V*Sw)

Dose

, kG

y

2424


Beam spot patternBeam spot pattern

2525


Process interruptionProcess interruption

2626

(12.4.1)(12.4.1) ““RequalificationRequalification of a sterilization process shall of a sterilization process shall be carried out be carried out ………… at defined intervalsat defined intervals……

““RequalificationRequalification of a sterilization process shall be carried out of a sterilization process shall be carried out ………… after the assessment of any changeafter the assessment of any change……

The extent to which The extent to which requalificationrequalification is carried out shall be is carried out shall be justified.justified.

Recommendation:Recommendation: Repeat OQ at regular intervals, e.g. Repeat OQ at regular intervals, e.g. annually in order to demonstrate consistent operation.annually in order to demonstrate consistent operation.

Different elements of OQ can be done at different intervalsDifferent elements of OQ can be done at different intervals


2727

Performance qualificationPerformance qualification

2828

(9.3.1)(9.3.1) Concerns dose mapping of real productConcerns dose mapping of real product

to identify the location and magnitude of minimum and to identify the location and magnitude of minimum and maximum dosesmaximum doses

andand

to determine the relationship between the min and max to determine the relationship between the min and max doses and the routine dosedoses and the routine dose

Performance qualificationPerformance qualification

2929

Purpose of dose mappingPurpose of dose mapping

-- to demonstrate that: to demonstrate that:

••

D (min) D (min) >>

D (Steril) and D (max) D (Steril) and D (max) <<

D (acceptable)D (acceptable)

••

D (min) determined by sterilization requirementsD (min) determined by sterilization requirements

••

D (max) determined by radiationD (max) determined by radiation--induced changes in productinduced changes in product

Performance qualification ..cont..Performance qualification ..cont..

3030

Strategies for dose mappingStrategies for dose mapping-- based on:based on:

OQ measurementsOQ measurementsInhomogeneous product distribution, orientation, voids, interfacInhomogeneous product distribution, orientation, voids, interfaces.es.ExperienceExperience

Processing categoriesProcessing categories

Limitations of dose mappingLimitations of dose mapping

Ability to measure Ability to measure ““the truethe true”” value of D(min) or D(max)value of D(min) or D(max)Location of dosimeterLocation of dosimeterResolution of dosimeter systemResolution of dosimeter system


3131


Examples from real life Examples from real life ……....

3232

DoseDose

mapmap

Plastic tubePlastic tube

Diameter:Diameter: 11 cm11 cm

WallWall

thicknessthickness: 10 : 10 mmmm

10 10 MeVMeV

electronselectrons

OneOne--sideside


3333

DoseDose

mapmap

tubetube Single and double side Single and double side irradiationirradiation

3434

DoseDose

mapmap

tubetube Single and double side Single and double side irradiationirradiation

3535

DoseDose

mapmap

Tube Tube withwith

AgAg--sensorsensor

10 10 MeVMeV

electronselectrons

A: Single side A: Single side irradiationirradiation

B: Double side B: Double side irradiationirradiation

AA

BB

3636

DoseDose

mapmap Metal Metal implantimplant, 10 , 10 MeVMeV

electronselectrons, double , double sidedsided

irradiationirradiation RisRisøø

B3, RisB3, Risøø

ScanScan

3737


(9.3.5) Dose mapping shall be carried out using representative i(9.3.5) Dose mapping shall be carried out using representative irradiation containers rradiation containers sufficient in number to determine the variability of dose betweesufficient in number to determine the variability of dose between containersn containers

Practical approach:Practical approach:

Either dose map in detail 3Either dose map in detail 3--10 containers10 containers

oror−−

dose map in detail one containerdose map in detail one container−−

repeat measurement of D (min) and D (max) in several (e.g. 10) repeat measurement of D (min) and D (max) in several (e.g. 10) containers containers

−−

evaluate measurement uncertainty taking into account all evaluate measurement uncertainty taking into account all uncertainty components.uncertainty components.


3838

Setting Process LimitsSetting Process LimitsSelect process parametersSelect process parameters

Conveyor speedConveyor speedBeam currentBeam currentScan width Scan width

so that so that D(minD(min) will exceed ) will exceed D(sterileD(sterile) and ) and so that so that D(maxD(max) will not exceed ) will not exceed D(acceptableD(acceptable))

Select process limits based on the measured uncertainty.Select process limits based on the measured uncertainty.

Practical approachPractical approachselect process parameters so that D(min) is 2 standard deviationselect process parameters so that D(min) is 2 standard deviations higher than s higher than D(sterilD(steril))


3939

Selection of uncertainty Selection of uncertainty limits for process controllimits for process control

Normal distribution

0

0,2

0,4

0,6

0,8

1

-4 -3 -2 -1 0 1 2 3 4

Standard deviations

Prob

abili

ty


2.5 %

4040

Strategies for dose mapping based onStrategies for dose mapping based on

-- information from Operational Qualificationinformation from Operational Qualification

-- inhomogeneous product distribution, orientation, voids, interfainhomogeneous product distribution, orientation, voids, interfacesces

-- experienceexperience

Limitations of dose mappingLimitations of dose mapping

-- ability to detect correctly the locations of min and max dosesability to detect correctly the locations of min and max doses

-- location of dosimeterlocation of dosimeter

-- measurement resolution of dosimetermeasurement resolution of dosimeter

Process categoriesProcess categories

product that can be processed product that can be processed –– irradiated irradiated –– in the same wayin the same way


4141

Repeat of Performance QualificationRepeat of Performance Qualification

Only needed if product is changedOnly needed if product is changedor if facility is changedor if facility is changed

review of documentation at defined intervals is review of documentation at defined intervals is recommended, e.g. every 3 yearsrecommended, e.g. every 3 years


4242

Routine monitoring and controlRoutine monitoring and control

4343

Dosimetry Dosimetry

(10.6)(10.6) Dosimeters shall be placed on routine monitoring Dosimeters shall be placed on routine monitoring positionspositions

(10.7)(10.7) The frequency of dosimeter placement shall be The frequency of dosimeter placement shall be sufficient to verify that the process is in control. The frequensufficient to verify that the process is in control. The frequency cy and its rationale shall be documented and its rationale shall be documented


4444

Monitoring of parametersMonitoring of parameters

ElectronsElectrons

Electron energyElectron energyBeam currentBeam currentScan widthScan widthConveyor speedConveyor speed


4545

Statistical Process controlStatistical Process control

Action limit

Warning

limit

4646

(11.2)(11.2) Procedures shall define the requirements for Procedures shall define the requirements for designating the sterilization process as conforming, designating the sterilization process as conforming, taking into account the uncertainty of thetaking into account the uncertainty of the measurement system.measurement system.

Product release from sterilizationProduct release from sterilization

4747

Audit issuesAudit issues Installation / operation qualificationInstallation / operation qualification

GammaGamma••

Is dose map detail sufficient?Is dose map detail sufficient?

••

Was a suitable range of densities for reference Was a suitable range of densities for reference products used?products used?

••

Was effect of process interruption Was effect of process interruption demonstrated?demonstrated?

••

Was OQ repeated after latest source reloading?Was OQ repeated after latest source reloading?••

Was consistent plant operation demonstrated?Was consistent plant operation demonstrated?

••

Was dosimeter system calibrated with Was dosimeter system calibrated with traceability?traceability?

4848

Audit issuesAudit issues Installation / operation qualificationInstallation / operation qualification

ElectronsElectrons••

Is dose map detail sufficient?Is dose map detail sufficient?

••

Is there a procedure for the frequency of OQ?Is there a procedure for the frequency of OQ?••

Was effect of process interruption Was effect of process interruption

demonstrated?demonstrated?••

Documentation for pulseDocumentation for pulse--toto--pulse overlap?pulse overlap?

••

Was beam energy measured?Was beam energy measured?••

Was consistent plant operation demonstrated?Was consistent plant operation demonstrated?

••


4949

Audit issuesAudit issues Performance qualificationPerformance qualification

Dose map.Dose map.••


••

Was measurement traceability maintained Was measurement traceability maintained during dose map?during dose map?

••

Is dose map detail sufficient?Is dose map detail sufficient?••

Was measurement uncertainty established?Was measurement uncertainty established?

••

Is there a procedure for review of PQ? Is there a procedure for review of PQ?

5050

Audit issuesAudit issues Performance qualificationPerformance qualification

GammaGamma••

Are procedures for change of product Are procedures for change of product established?established?

••

Were partially filled containers considered?Were partially filled containers considered?

ElectronsElectrons••

Is it demonstrated the Is it demonstrated the ““first boxfirst box””

is adequately is adequately

irradiated?irradiated?••

Were partially filled containers considered?Were partially filled containers considered?

5151

Audit issuesAudit issues Process ControlProcess Control

Measurement of routine doseMeasurement of routine dose••

Is dosimeter system calibrated with Is dosimeter system calibrated with traceability?traceability?

••

Is measurement traceability maintained?Is measurement traceability maintained?••

Were results of routine dose measurement Were results of routine dose measurement within acceptable limits?within acceptable limits?

Measurement of facility parametersMeasurement of facility parameters••

Were key parameters measured?Were key parameters measured?

••

Were the measurement results within Were the measurement results within acceptable limits?acceptable limits?

International Standards for Radiation Sterilization of

Medical Devices

ArnArnee

MillerMillerRisRisøø

National LaboratoryNational Laboratory

Technical University of DenmarkTechnical University of DenmarkDK 4000 DK 4000 RoskildeRoskildeDenmarkDenmark

22

Sterilization of Medical DevicesSterilization of Medical Devices

Medical Device Directive Medical Device Directive 93/42/EEC93/42/EECHas been implemented for CE marking in national legislation Has been implemented for CE marking in national legislation since 1998. since 1998. A new Medical Device Directive was issuedA new Medical Device Directive was issued12 October 2007: 2007/47/EC12 October 2007: 2007/47/EC

It amends the old directive It amends the old directive It must be implemented in national laws by end of 2008It must be implemented in national laws by end of 2008Manufactures must comply by March 2010Manufactures must comply by March 2010

Nothing is changed with respect to sterilizationNothing is changed with respect to sterilization

33

Sterilization of Medical DevicesSterilization of Medical Devices

Medical Device Directive Medical Device Directive 93/42/EEC 93/42/EEC -- 2007/47/EC2007/47/EC

Essential requirements must be fulfilled in order for CEEssential requirements must be fulfilled in order for CE--marking of products marking of products Annex 1: Essential requirementsAnnex 1: Essential requirements8.48.4::

““Devices delivered in a sterile state must have been Devices delivered in a sterile state must have been manufactured and sterilized by an appropriate, validated manufactured and sterilized by an appropriate, validated method.method.””

How to comply with essential requirements? How to comply with essential requirements?

Follow mandated standardsFollow mandated standards

44

The old standardsThe old standardsEN 552:1995EN 552:1995 Sterilization of Medical devices Sterilization of Medical devices ––Validation and Process control of Sterilization by Validation and Process control of Sterilization by IrradiationIrradiation..

CEN/TC 204 Sterilization of Medical DevicesCEN/TC 204 Sterilization of Medical Devices

ISO 11137:1996ISO 11137:1996 Sterilization of Health Care Sterilization of Health Care Products Products –– Requirements for validation and routine Requirements for validation and routine control control –– Radiation sterilizationRadiation sterilization..

ISO/TC 198 Sterilization of Health Care ProductsISO/TC 198 Sterilization of Health Care Products

EN 556EN 556--1:2001 1:2001 Sterilization of medical devices Sterilization of medical devices --Requirements for medical devices to be designated Requirements for medical devices to be designated 'STERILE' 'STERILE' -- Part 1: Requirements for terminally Part 1: Requirements for terminally sterilized medical devicessterilized medical devices

CEN/TC 204 Sterilization of Medical DevicesCEN/TC 204 Sterilization of Medical Devices

55

The new standardThe new standard

EN ISO 11137:2006 Sterilization of health care EN ISO 11137:2006 Sterilization of health care products products –– RadiationRadiation

-- has replaced the two old standardshas replaced the two old standards

When the standard is followed, compliance with EU When the standard is followed, compliance with EU Medical Device Directive is presumedMedical Device Directive is presumedThe standard is accepted as an American standardThe standard is accepted as an American standardThe standard is accepted worldwideThe standard is accepted worldwide

EN 556EN 556--1:2001 1:2001 Sterilization of medical devices Sterilization of medical devices -- Requirements for medical devices to be Requirements for medical devices to be

designated 'STERILE' designated 'STERILE' --

Part 1: Requirements for Part 1: Requirements for terminally sterilized medical devicesterminally sterilized medical devices

66

EN 556EN 556--11

EN 556EN 556--1:2001 1:2001 Sterilization of medical devices Sterilization of medical devices --

Requirements for Requirements for medical devices to be designated 'STERILE' medical devices to be designated 'STERILE' --

Part 1: Requirements for Part 1: Requirements for

terminally sterilized medical devicesterminally sterilized medical devices

Requirement:Requirement:

For a terminally sterilized medical device to be designated For a terminally sterilized medical device to be designated ””STERILESTERILE””, , the theoretical probability of there being a viable microthe theoretical probability of there being a viable micro--organism organism present on/in the device shall equal to or less than 1 x 10present on/in the device shall equal to or less than 1 x 10--66..

77

Standards providing background for Standards providing background for new EN ISO standardnew EN ISO standard

ISO 9001:2000, ISO 9001:2000, Quality management systems Quality management systems ––RequirementsRequirements

ISO 13485ISO 13485 Medical devices Medical devices -- Quality Quality management systems management systems -- Requirements for Requirements for regulatory purposesregulatory purposes

ISO 14937 ISO 14937 Sterilization of medical devices Sterilization of medical devices --General requirements for characterization of a General requirements for characterization of a sterilizing agent and the development, validation sterilizing agent and the development, validation and routine control of a sterilization process for and routine control of a sterilization process for medical devicesmedical devices

88

Other standards that are incorporated Other standards that are incorporated into the new ISO EN standardsinto the new ISO EN standards

ISO/TR 15843 Product families, ISO/TR 15843 Product families, dose audit frequency and dose dose audit frequency and dose audit sample sizesaudit sample sizes

ISO/TR 15844 Radiation ISO/TR 15844 Radiation sterilization of one batchsterilization of one batch

AAMI TIR 27 VDAAMI TIR 27 VDmaxmaxsubstantiationsubstantiation ofof 25 kGy25 kGy

99

EN ISO 11137:2006EN ISO 11137:2006

Three Parts:Three Parts:

Part 1: Part 1: Requirements for the development, Requirements for the development, validation and routine control of a validation and routine control of a sterilization process for medical devicessterilization process for medical devices

Part 2: Establishing the sterilization dose Part 2: Establishing the sterilization dose

Part 3: Guidance on Part 3: Guidance on dosimetricdosimetric aspectsaspects

Covers gamma, electron beam and xCovers gamma, electron beam and x--rayray

It is in principle limited to medical devicesIt is in principle limited to medical devices-- but can be used for other productsbut can be used for other products

1010

EN ISO 11137EN ISO 11137--11

ContentContent1 Scope1 Scope2 References2 References3 Terms and definitions3 Terms and definitions4 Quality management system4 Quality management system5 Sterilizing agent characterization5 Sterilizing agent characterization6 Process and equipment characterization6 Process and equipment characterization7 Product definition7 Product definition8 Process definition8 Process definition9 Validation9 Validation10 Routine monitoring10 Routine monitoring11 Product release11 Product release12 Maintaining process effectiveness12 Maintaining process effectiveness

1111

EN ISO 11137EN ISO 11137--11


Definitions 3.37: Definitions 3.37: documented procedure for obtaining, documented procedure for obtaining, recording and interpreting the results recording and interpreting the results required to establish that a process will required to establish that a process will consistently yield product complying with consistently yield product complying with predetermined specifications. predetermined specifications.

1212

EN ISO 11137EN ISO 11137--11


Definitions 3.37: Definitions 3.37: documenteddocumented66

procedureprocedure55

for obtaining, for obtaining,

recording and interpreting the results recording and interpreting the results required to establish that a required to establish that a processprocess22

will will

consistentlyconsistently44

yield yield productproduct11

complying with complying with predetermined predetermined specificationsspecifications33. .

1313

EN ISO 11137EN ISO 11137--11

ValidationValidationInstallation Qualification Installation Qualification -- IQIQ

Agreement supplier Agreement supplier –– customercustomer

Operational Qualification Operational Qualification -- OQOQshow consistent operationshow consistent operation

Performance Qualification Performance Qualification -- PQPQspecify how product shall be irradiatedspecify how product shall be irradiated

Routine Process ControlRoutine Process Controlshow that the process runs within specificationsshow that the process runs within specifications

1414

EN ISO 11137EN ISO 11137--1 Requirements1 Requirements

Documentation is in all steps based on Documentation is in all steps based on ability to measure doseability to measure doseSect. 4.3.4:Sect. 4.3.4:

““Dosimetry used in the development, Dosimetry used in the development, validation and routine control of the validation and routine control of the sterilization process shall have sterilization process shall have measurement traceability to national or measurement traceability to national or international standards and shall have a international standards and shall have a known level of uncertainty.known level of uncertainty.””

1515

EN ISO 11137EN ISO 11137--1 Requirements1 Requirements

Documentation in all steps based on Documentation in all steps based on ability to measure doseability to measure doseSect. 4.3.4:Sect. 4.3.4:

““Dosimetry used in the development, Dosimetry used in the development, validation and routine control of the validation and routine control of the sterilization process sterilization process shallshall have have measurement traceability to national or measurement traceability to national or international standards and international standards and shallshall have a have a known level of uncertainty.known level of uncertainty.””

1616

ISO 11137ISO 11137--1 Requirements1 Requirements Revision issues 1Revision issues 1

The use of Biological IndicatorsThe use of Biological Indicators••

and Tests and Tests forfor Sterility are not requiredSterility are not required

Sterilizing agent characterizationSterilizing agent characterization•• Radiation energy levels are Radiation energy levels are not restrictednot restricted. .

--

but assessment is but assessment is required required for potentially for potentially induced radioactivity at energy levelsinduced radioactivity at energy levels

higher higher

than 5 than 5 MeVMeV

xx--rays and 10 rays and 10 MeVMeV

electronselectrons

1717


Process and equipment characterizationProcess and equipment characterization

Product definitionProduct definitionProcessing categoriesProcessing categoriesGrouping for processingGrouping for processing

Process definitionProcess definitionEstablishing the maximum acceptable doseEstablishing the maximum acceptable doseEstablishing the sterilization doseEstablishing the sterilization dose

detailed in 11137detailed in 11137--22

Transference of established dosesTransference of established dosesbetween between ““similarsimilar”” facilities: No additional testingfacilities: No additional testing

1818


Product release Product release taking into account the uncertainty of the taking into account the uncertainty of the measurement systemmeasurement system

Maintaining process effectivenessMaintaining process effectivenessFrequency of bioburden determinationFrequency of bioburden determination

Quarterly (generally)Quarterly (generally)

Frequency of sterilization dose auditsFrequency of sterilization dose auditsQuarterly Quarterly →→ bibi--annually annually →→ annuallyannually

1919


GuidanceGuidanceFormat of EN 552 followed with guidance Format of EN 552 followed with guidance

for each sectionfor each sectionAnnex AAnnex A

Includes tables on recommended IQ / Includes tables on recommended IQ / OQ actions for facilities OQ actions for facilities

2020

ISO 11137ISO 11137--2 2 Establishing the Sterilization DoseEstablishing the Sterilization DoseRevision Issues 1Revision Issues 1

1.1. Product FamiliesProduct Familiesdefinition and maintenancedefinition and maintenancegrouping for bioburden, dose establishment grouping for bioburden, dose establishment and dose auditsand dose audits

2.2. Designation of product to Designation of product to represent familyrepresent family

master master equivalentequivalentsimulatedsimulated

2121

Revision Issues 2Revision Issues 23.3. Method 1 Method 1

change in table to reflect whole bioburden change in table to reflect whole bioburden numbersnumbersincluded table for bioburden 0.1 to 1.0 included table for bioburden 0.1 to 1.0 cfucfusingle batch proceduresingle batch procedure

4.4. Method 2 Method 2 remains essentially unchangedremains essentially unchanged

ISO 11137ISO 11137--2 2 Establishing the Sterilization DoseEstablishing the Sterilization Dose

2222

Revision Issues 3Revision Issues 35.5.

VDVDmaxmax

2525

Substantiation of 25 kGySubstantiation of 25 kGymethodmethod is based upon VDis based upon VDmaxmax

bioburden bioburden ≤≤ 1,000 1,000 cfucfu/product/product

single batchsingle batch procedureprocedure

6.6.

VDVDmaxmax

1515

Substantiation of 15 kGySubstantiation of 15 kGymethodmethod is based upon VDis based upon VDmaxmax

bioburden bioburden ≤≤ 1.5 1.5 cfucfu/product/productsingle batch proceduresingle batch procedure


2323

Revision Issues 4Revision Issues 4Dose auditDose audit

audit procedures expanded and clarifiedaudit procedures expanded and clarifieddose augmentation expandeddose augmentation expanded

allow processing to continue in case of dose audit allow processing to continue in case of dose audit failurefailure


2424

ISO 11137ISO 11137--3 3 Guidance on Guidance on DosimetricDosimetric

AspectsAspects

Specific guidance on dosimetry as Specific guidance on dosimetry as used in parts 1 and 2used in parts 1 and 2

ReferenceReference

to ISO/ASTM standards to ISO/ASTM standards onon

Dosimetry for Radiation Dosimetry for Radiation

ProcessingProcessing

AnnexAnnex

A:A:

MathematicalMathematical

modellingmodellingPoint Point KernelKernelMonteMonte

CarloCarlo

2525


AspectsAspectsISO/ASTMISO/ASTM

standards standards onon

Dosimetry for Radiation Dosimetry for Radiation

ProcessingProcessing

Presently 31 standards and guides Presently 31 standards and guides Dosimetry systemsDosimetry systems

AlanineAlanineCalorimetersCalorimetersetcetc

Dosimetry methodsDosimetry methodsCharacterization of gamma plantsCharacterization of gamma plantsCharacterization of electron acceleratorsCharacterization of electron acceleratorsDose mappingDose mappingetcetc

2626


AspectsAspectsIssues:Issues:

Dosimeter calibrationDosimeter calibration

Guidance on practical use of dosimetryGuidance on practical use of dosimetry

Application of measurement uncertainties.Application of measurement uncertainties.

Use of statistical evaluation of PQ dose Use of statistical evaluation of PQ dose map data.map data.

2727

Present statusPresent status

ISO standards published April ISO standards published April 20062006EN standards parts 1 and 3 EN standards parts 1 and 3 published April 2006published April 2006

Errors discovered in part 2Errors discovered in part 2

Revised ISO 11137Revised ISO 11137--2:20062:2006EN ISO 11137EN ISO 11137--2:20072:2007

QA/QC Reflected in ISO 11137

(The Role of Dosimetry in the Validation Process)

András Kovács

Institute of IsotopesHungarian Academy of Sciences

Budapest, Hungary

Quality assurance•

In established radiation technologies implementation of international standards guarantee the safety of the procedure to public health authorities:

In case of sterilization of medical devices:

- EN ISO 11137 (Sterilization of Health Care Products)

•

Standardized dosimetry (ISO/ASTM standards) – as a tool of QC - has got key role for the validation of the sterilization and food irradiation processes, as well as to control the radiation processing of polymer products.

The importance and role of dosimetry

•

In radiation processing validation and process control (e.g. sterilization, food irradiation) depend on the measurement of absorbed dose.

•

Measurements of absorbed dose shall be performed using a dosimetric system or systems having a known level of accuracy and precision (European standard EN552:1994).

•

The calibration of each dosimetric system shall be traceable to an appropriate national standard.

Dosimetry – principles and requirements

•

Determination of absorbed dose in product specific dosimetry systems.

•

Dosimetry – as part of the total quality system - provides quality assurance and documentation that the irradiation procedure has been carried out according to specifications.

•

Accurate, traceable dose measurements provide independent, inexpensive means for quality control in radiation processing.

Dosimeter system Method of analysis Useful dose range, Gy

Nominal precision limits References

Fricke solutionUV – spectro-photometry

3x10 – 4x102 1 %ASTM E 1026 - 04

Ceric – ceroussulphate

UV – spectro-photometry

103 – 106 3 %ISO/ASTM

51205

Potassiumdichromate

UV-VISspectrophoto.

5x103 – 4x104 1 %ISO/ASTM

51401

Ethanol-mono-chlorobenzene

Titration,orHF oscillometry

4x102 –3x105 3 %ISO/ASTM

51538

L - alanine EPR 1 – 105 0.5 %ISO/ASTM

51607

Perspex systemsVIS - spectro-photometry

103 – 5x104 4 %ISO/ASTM

51276

FWT – 60film

VIS - spectro-photometry

103 - 105 3 %ISO/ASTM

51275

B 3film

VIS - spectro-photometry

103 - 105 3 %ISO/ASTM

51275

Cellulosetriacetate

UV – spectro-photometry

104 - 106 3 %ISO/ASTM

51650

CalorimetryResistance/temperature

1.5x103 –5x104 2 %

ISO/ASTM51631

Validation and process control

The steps of validation as described in the EN ISO 11137 Standard:



Process definition1. Establishing maximum acceptable dose:

-

Assurance of the quality, safety and performance of product throughout defined

lifetime

should

begin

with

the

selection

of

appropriate

materials.

-

Product

or

material

(and

packaging

material)

samples are irradiated to uniform doses

greater, than

expected

during

actual

processing

↓after

that

product

shall

meet

its

specified

functional

requirements

throughout

its

defined

lifetime.

-

Transference

of

maximum acceptable

dose

to

other

radiation

source:

dose rate and product temperature should be considered!

Process definition

2. Establishing the sterilization dose:

-

Using dose setting methods, product samples are irradiated to defined doses

within

specified

tolerance

levels.

The dosimetry

system

used

must be

capable

of

providing

accurate

and

precise

measurements

in

the

entire

range

-

The distribution

of

dose

applied

to

product

must be known. Dose

mapping exercises

can

be

performed

at

higher

doses

than

used

for

dose

setting.

-

Irradiation

for

dose

setting

(γ) is carried

out in

a special

facility

or

outside

of the

normal

product

path

in

a sterilization

facility. In

case

of

EB it

is performed

in

the

sterilization

facility.

-

Methods

2A and

2B each

require

an

incremental

dose

experiment

–

each incremental

dose

must be measured

independently.


Installation qualification:- to demonstrate that the irradiation facility has been supplied and installed according to its specifications:

To determine beam No specific dosimetric requirements,characteristics by dosimetry; to verify operation within specification;


Operational qualification:- carried out by irradiating appropriate test material (of

homogeneous density) to demonstrate the capability of the equipment to deliver appropriate doses, i.e. the irradiation process that has been defined;

- provides baseline data to show consistent operation of the irradiation facility (i.e. within established and defined limits);

- OQ should be repeated to show consistent operation, i.e. the results obtained are within established and defined limits

Operational qualificationAim:

To characterize the irradiation facility relating plant parameters to absorbed dose (measured in a reference product);

Gamma facility: nominal dose vs. irradiation time or dwell time and dose distribution;

Dichromate, ECB, ceric-cerous, Gex (B3), FWT- 60, Perspex, Sunna, alanine;

Electron beam facility:nominal dose vs. conveyor speed,beam characteristics, dose map;

Calorimeters, ECB, Sunna, alanine,Gex (B3), dichromate;

Operational qualification (γ)- Dose distribution in reference product

- Limits for acceptable variations can be defined.

Operational qualification (γ)

General requirements:-

Dose mapping:

- density within the range of use (two densities);- at least three irradiation containers;- for requalification mathematical modelling to optimise the positioning of dosimeters;

- dose mapping data to determine relationshipbetween timer setting and dose at e.g. Dmin location;mathematical models can give approximate values.

- separate dose mapping for assessing theeffect of process interruption;

- to check the effect of changing to product of differentdensity (sequentially processing the two materials);

Operational qualification (EB)•

Dose distribution in reference product:

Operational qualification (EB)

Measurement of electron energy:

Operational qualification (EB)

Measurement of beam spot(pulsed machines):To check, if necessary overlap between pulses is achieved.

scanning frequencypulse repetation frequencyconveyor speed

Operational qualification (EB)Measurement of scanning width and homogeneity:

Operational qualification (EB)General requirements:Dose mapping:

- over a range of operating parameters covering the operational limits;- density within the range of use (more is better);- at least three irradiation containers to be dose mapped;- to place dosimeters in a three dimensional array including surface;- mathematical modelling to optimize the positioning of dosimeters;- to establish the effect of process interruption on the dose;- to determine relationships between characteristics of the beam, theconveyor speed and the magnitude of dose at a defined locationwithin or on a container or in a fixed geometry travelling with, butseparately from the irradiation container (e.g. PS calorimeter);

- separate dose map to check the effect of changing to product ofdifferent density;


Aim:1.

To

measure

dose

map

in

real product in

order to locate

Dmin

and

Dmax

and to

establish

irradiation conditions

according

to

required

specifications, i.e.:

D(product) > D(required, e.g. sterilization dose)and D(product) < D(acceptable)

2.

To

determine

relationship

between

Dmin

and

Dmax

and

the

dose

at

the routine

monitoring position;

Mathematical modelling to optimize the positioning of dosimeters during dose mapping;

Process control1. Measurement of process parameters:

To measure dose at the monitoring position to verify that theirradiation process is within established/required limits

⇓knowing the relationship between Dmin , Dmax and Dmonitoring .

Dose measurement frequency: at beginning and end of run (minimum)

2. Control and monitoring of operating parameters.

Controlled parameters:Electron beam facility: Gamma facility:

–

Electron energy - Timer setting–

Beam current - Other type of products present

–

Scanned beam width - Routine dose–

Conveyor speed

–

Routine dose

THANK YOU FOR YOUR ATTENTION

IDEAL DOSIMETRY SYSTEMIDEAL DOSIMETRY SYSTEM

DOSIMETRY SYSTEMS IN CURRENT DOSIMETRY SYSTEMS IN CURRENT USEUSE

A. KOVA. KOVÁÁCSCS

InstituteInstitute

ofof

IsotopesIsotopesHungarianHungarian

AcademyAcademy

ofof

SciencesSciences

HH--1525. Budapest, P.O.B. 77. Hungary1525. Budapest, P.O.B. 77. Hungary

BACKGROUNDBACKGROUND

In radiation processing validation and process control In radiation processing validation and process control (sterilization, food irradiation, etc.) depend on the (sterilization, food irradiation, etc.) depend on the measurement of absorbed dose.measurement of absorbed dose.

Measurements of absorbed dose shall be performed Measurements of absorbed dose shall be performed using a dosimetric system or systems having a known using a dosimetric system or systems having a known level of accuracy and precision (European standard level of accuracy and precision (European standard EN552:1994).EN552:1994).

The calibration of each dosimetric system shall be The calibration of each dosimetric system shall be traceable to an appropriate national standardtraceable to an appropriate national standard..

DosimetryDosimetry –– principlesprinciples

andand requirementsrequirements

DeterminationDetermination ofof absorbedabsorbed dosedose inin productproduct specificspecificdosimetrydosimetry systemssystems –– similaritysimilarity inin radiationradiation absorptionabsorptioncharacteristicscharacteristics..

DosimetryDosimetry –– asas part part ofof thethe totaltotal qualityquality systemsystem -- providesprovidesqualityquality assuranceassurance andand documentationdocumentation thatthat thethe irradiationirradiationprocedureprocedure has has beenbeen carriedcarried out out accordingaccording toto specificationsspecifications..

AccurateAccurate, , traceabletraceable dosedose measurementsmeasurements provideprovideindependentindependent, , inexpensiveinexpensive meansmeans forfor qualityquality controlcontrol ininradiationradiation proessingproessing..

DosimetryDosimetry

––

applicationapplication

andand

systemssystems

FieldsFields ofof applicationapplication::--

installationinstallation

qualificationqualification;;

--

operationaloperational

qualificationqualification;;--

performanceperformance

qualificationqualification;;

--

processprocess

controlcontrol;;

DosimetryDosimetry providesprovides documentationdocumentation inin thethe processesprocesses, , ifif

--

thethe


is is traceabletraceable

toto

a a nationalnational

standard,standard,--

thethe


ofof

thethe

systemsystem

is is knownknown..

AppliedApplied systemssystems::--

primaryprimary--, , secondarysecondary--, , transfertransfer

standardsstandards;;

--

routineroutine

systemssystems;;

DosimetryDosimetry systemssystems

inin radiationradiation processingprocessing

PrimaryPrimary

standard standard systemssystems::

--

DosimeterDosimeter

ofof

thethe

highesthighest

metrologicalmetrological

qualityquality, , establishedestablished

andand

maintainedmaintained

asas

anan

absorbedabsorbed

dosedose

standard standard byby

a a nationalnational

oror

internationalinternational

standardsstandards organizationorganization

forfor

calibrationcalibration

ofof

radiationradiation

environmentsenvironments

((fieldsfields););

--

ApplicationApplication

is is basedbased

onon


ofof

basicbasic physicalphysical

quantitiesquantities;;

--

Most Most commoncommon

systemssystems: : ionizationionization

chamberschambers, , calorimeterscalorimeters;;



ReferenceReference


--

DosimeterDosimeter

ofof

highhigh


qualityquality

usedused

asas

a standard a standard toto provideprovide

measurementsmeasurements

traceabletraceable

toto

measurementsmeasurements

mademade

byby

primaryprimary

standardstandard

systemssystems;;--

TheseThese

systemssystems

requirerequire


andand

areare

usedused

toto

calibratecalibrate

radiationradiation

environmentsenvironments

andand

routineroutine

dosimetersdosimeters;;--

SolidSolid

phasephase

dosimetrydosimetry

systemssystems

::

alaninealanine

((pelletpellet, , rodrod, film);, film);--

LiquidLiquid

phasephase

dosimetrydosimetry

systemssystems

: :

FrickeFricke

solutionsolution;;potassiumpotassium

dichromatedichromate

solutionsolution;;

ethanolethanol--monochlorobenzenemonochlorobenzene

solutionsolution;;cericceric--cerouscerous

solutionsolution;;

--

CalorimetersCalorimeters;;

AlanineAlanine

dosimetrydosimetry

(ISO/ASTM 51607)(ISO/ASTM 51607)

--

ESR ESR analysisanalysis; ; MeasuresMeasures

freefree

radicalradical

concentrationconcentration;;

-- DoseDose

rangerange: 10 : 10 GyGy

––

100 100 kGykGy;;

-- ReproducibilityReproducibility

<< 0.5 %;0.5 %;

DichromateDichromate

dosimetrydosimetry


-- ColourColour

changechange

byby

spectrophotometryspectrophotometry;;

-- DoseDose

rangerange: 10 : 10 ––

50 50 kGykGy;;

-- ReproducibilityReproducibility

<< 0.5 %;0.5 %;



TransferTransfer


--

IntermediaryIntermediary

systemsystem

withwith

highhigh


qualitiesqualities, , suitablesuitable

forfor transferringtransferring

dosedose

informationinformation

fromfrom

anan

accreditedaccredited/standard /standard

laboratorylaboratory

toto

anan


facilityfacility

toto

establishestablish

traceabilitytraceability;;

--

TheseThese

systemssystems

requirerequire


andand

postpost


stabilitystability;;

--

DosimetryDosimetry

systemssystems::

--

alaninealanine; ;

--

ECB, ECB, cericceric--cerouscerous, , potassiumpotassium


solutionssolutions;;



RoutineRoutine

systemssystems::

--

DosimetryDosimetry

systemssystems

usedused

inin

radiationradiation

processingprocessing

facilitiesfacilities

forfor absorbedabsorbed

dosedose

mappingmapping

andand

processprocess

monitoring;monitoring;

--

SystemsSystems,,capablecapable

ofof

givinggiving

reproduciblereproducible

signalssignals

--

TheseThese

systemssystems

requirerequire

calibrationcalibration;;--

DosimeterDosimeter

systemssystems::

--

PerspexPerspex

((redred--, , amberamber--, , GammachromeGammachrome););--

radiochromicradiochromic

filmsfilms

(FWT(FWT--60, B3, 60, B3, GafchromicGafchromic););

--

ECB, ECB, cericceric--cerouscerous

solutionssolutions;;--

ProcessProcess

calorimeterscalorimeters

((waterwater, , graphitegraphite, , polystyrenepolystyrene););

PerspexPerspex

dosimetrydosimetry


ColourColour

changechange

--

spectrophotometryspectrophotometry;;DoseDose

rangerange: 0.5 : 0.5 ––

50 50 kGykGy;;

ReproducibilityReproducibility

<<

3 %;3 %;PostPost


changechange

ofof

signalsignal;;

RadiochromicRadiochromic

dyedye

filmsfilms

(ISO/ASTM 51275) (ISO/ASTM 51275)

ColourColour

changechange

--

spectrophotometryspectrophotometry;;FWTFWT--

6060: : 33

––

1150 50 kGykGy;;

B3: 2 B3: 2 ––

100 100 kGykGy;;GafChromicGafChromic: 1 : 1 GyGy

––

40 40 kGykGy;;


inin presentpresent practicepractice

DosimeterDosimeter

systemsystem MethodMethod

ofof

analysisanalysisUsefulUseful

dosedose

rangerange, , GyGy

NominalNominal

precisionprecision

limitslimits

ReferencesReferences

FrickeFricke

solutionsolutionUV UV ––

spectrospectro--

photometryphotometry2x10 2x10 ––

4x104x1022 1 %1 %ASTM E ASTM E

1026 1026 --

0404

CericCeric

––

cerouscerous

sulphatesulphate

UV UV ––

spectrophotomspectrophotom././

PotentiometryPotentiometry101033

––

101066 3 %3 %ISO/ASTMISO/ASTM

5120551205

PotassiumPotassium


UVUV--VISVIS

spectrophotomspectrophotom..5x105x1033

––

4x104x1044 1 %1 %ISO/ASTMISO/ASTM

5140151401

EthanolEthanol--monomono

chlorobenzenechlorobenzene

TitrationTitration,,oror

HF HF oscillometryoscillometry4x104x1022

––3x103x1055 3 %3 %ISO/ASTMISO/ASTM

5153851538

L L --

alaninealanine EPREPR 1 1 ––

101055 0.5 %0.5 %ISO/ASTMISO/ASTM

5160751607

PerspexPerspex

systemssystemsVIS VIS --

spectrospectro--

photometryphotometry101033

––

5x105x1044 4 %4 %ISO/ASTMISO/ASTM

5127651276

FWT FWT ––

6060

filmfilm

VIS VIS --

spectrospectro--


--


5127551275

B 3B 3

filmfilm

VIS VIS --

spectrospectro--


--


5127551275

CelluloseCellulose

triacetatetriacetate

UV UV ––

spectrospectro--


--


5165051650

CalorimetryCalorimetryResistanceResistance//

temperaturetemperature

1.5x101.5x1033

––

5x105x10442 %2 %

ISO/ASTMISO/ASTM

5163151631

EnvironmentalEnvironmental

effectseffects

onon

dosimetrydosimetry

systemssystems

DosimeterDosimeter MeasurementMeasurement

timetime

afterafter

irrirr..

HumidityHumidity DoseDose

raterate

((GyGy

ss--11))

IrradiationIrradiation

temptemp. .

coeffcoeff., (., (ooCC))--11

AlanineAlanine immediatelyimmediately yesyes << 101088 + 0.25 %+ 0.25 %

DichromateDichromate 24 24 hourshours nono 0.7 0.7 ––

5x105x1022 --

0.2 %0.2 %

CericCeric--cerouscerous immediatelyimmediately nono << 101066 concconc. . depdep..

ECBECB immediatelyimmediately nono << 101088 + 0.05 %+ 0.05 %

CalorimetersCalorimeters immediatelyimmediately nono << 101088 --

PerspexPerspex 24 24 hourshours yesyes << 101055 + 1 %+ 1 %

FWTFWT--6060 5 min/60 5 min/60 ooCC yesyes << 10101313 + 0.2 %+ 0.2 %

B3B3 5 min/60 5 min/60 ooCC yesyes << 10101313 + 0.3 %+ 0.3 %

SunnaSunna 20 min/70 20 min/70 ooCC nono << 10101313 + 0.2 %+ 0.2 %

NEW APPROACHESNEW APPROACHES

New New requirementsrequirements::standardizationstandardization ofof existingexisting dosimetrydosimetrymethodsmethods;;increasedincreased reliabilityreliability toto encourageencourage industryindustry forforwiderwider useuse ofof ionizingionizing radiationradiation;;newnew technologiestechnologies ((maymay) ) requirerequire newnewdosimetrydosimetry methodsmethods;;introductionintroduction ofof improvedimproved calibrationcalibrationproceduresprocedures;;

New New approachesapproaches –– novelnovel

dosimetrydosimetry systemssystems

RequirementsRequirements::

New New technologiestechnologies ((environmentalenvironmental processesprocesses, , foodfoodirradiationirradiation atat lowlow temperaturestemperatures, , anthraxanthrax, , pharmaceuticalspharmaceuticals, , XX--rayray technologiestechnologies, , highhigh dosedose controlcontrol););

AchievedAchieved byby::

ImprovementImprovement ofof existingexisting dosimetrydosimetry systemssystems;;IntroductionIntroduction ofof newnew systemssystems;;

SystemsSystems basedbased

onon conductivityconductivity

evaluationevaluation

EthanolEthanol--monochlorobenzenemonochlorobenzenesolutionsolution (1 (1 –– 300 300 kGykGy))((nonnon--destructivedestructive

methodmethod))

AqueousAqueous –– alaninealanine solutionsolution(1 (1 –– 100 100 kGykGy))

PolyanilinePolyaniline basedbased polymerpolymercompositescomposites (5 (5 –– 150 150 kGykGy))


onon fluorimetryfluorimetry

PrinciplesPrinciples::AbsorbedAbsorbed energyenergy is is emittedemitted asas fluorescentfluorescent lightlight duedue toto opticalopticalexcitationexcitation (OSL (OSL –– opticallyoptically stimulatedstimulated luminescenceluminescence););FluorescenceFluorescence appearsappears micromicro-- oror nanosecondsnanoseconds afterafter excitationexcitation;;

AdvantagesAdvantages::Wide Wide dynamicdynamic rangerange;;HighHigh sensitivitysensitivity;;PassivePassive andand realreal timetime dosimetrydosimetry;;VariableVariable geometriesgeometries;;InexpensiveInexpensive detectorsdetectors;;MultipurposeMultipurpose applicationsapplications ((medicalmedical diagnosticdiagnostic, , radiationradiationprocessingprocessing, , radiationradiation protectionprotection, , spacespace studiesstudies, , etcetc); );


onon fluorimetryfluorimetry

ApplicationApplication possibilitiespossibilities::

RadiationRadiation inducedinduced decaydecay ofoforiginallyoriginally fluorescentfluorescentmoleculesmolecules ((anthraceneanthracene, , fluoresceinfluorescein derivativesderivatives, , etcetc););

AppearanceAppearance ofof radiationradiationinducedinduced fluorescencefluorescence duedue totoformationformation ofof newnewfluorescentfluorescent radiolysisradiolysisproductsproducts ((SunnaSunna film);film);

The The SunnaSunna dosimeterdosimeter

PrinciplesPrinciples::

LiFLiF disperseddispersed uniformlyuniformly ininPE (1 cm x 3 cm x 0.4 cm);PE (1 cm x 3 cm x 0.4 cm);

ColourColour centerscenters (F(F--, M, M--, N, N--, , R R centerscenters) ) formform duedue totoionizingionizing radiationradiation;;

RedRed, , greengreen oror IR OSL IR OSL ororUV UV absorptionabsorption usedused forfordosimetrydosimetry;;

Net Fluorescence for Sunna 0399-20 Dosimeter

01020304050607080

400 500 600 700 800 900 1000 1100Wavelength (nm)

Perc

ent T

rans

mis

sion

or In

tens

ity

Excitation Spectrum GREEN FluorescenceRED Fluorescence

insert infraredspectra

The The SunnaSunna dosimeterdosimeter

ApplicationApplication possibilitiespossibilities::

EvaluationEvaluation ofof greengreen OSL OSL (50 (50 GyGy –– 250 250 kGykGy););

EvaluationEvaluation ofof UV UV absorbanceabsorbance (5 (5 –– 100 100 kGykGy););

EvaluationEvaluation ofof IR OSL IR OSL (10 (10 GyGy –– 10 10 kGykGy););

0

100

200

300

400

500

600

700

800

900

1000

0 50 100 150 200 250 300 350

Absorbed Dose (kGy)

Net S

igna

l (fs

u)

4.5 MeV E-beam, 25 kGy per pass Co-60, continuous


onon opticaloptical

absorptionabsorption ((tetrazoliumtetrazolium

saltssalts))TetrazoliumTetrazolium saltssalts studiedstudied::

CompoundCompound

ProductProduct

λλ

maxmax..

DoseDose

rangerange::

tetrazoliumtetrazolium

violetviolet

(TV)(TV)

525 525 nmnm

0.01 0.01 ––

30 30 kGykGytetrazoliumtetrazolium

redred

(TTC)(TTC)

490 490 nmnm

0.01 0.01 ––

100 100 kGykGy


blueblue

(TB)(TB)

520 520 nmnm

0.01 0.01 ––

10 10 kGykGynitronitro

blueblue


(NBT) (NBT) 522 522 andand

612 612 nmnm

0.01 0.01 ––

25 25 kGykGy

--

heterocyclicheterocyclic

organicorganic

compoundscompounds, , whichwhich

uponupon


yieldyield

highlyhighly colouredcoloured

waterwater

insolubleinsoluble

formazansformazans

duedue

toto

radiolyticradiolytic

reductionreduction..


ofof

absorbedabsorbed

dosedose

byby

measuringmeasuring opticaloptical

absorptionabsorption

ofof

oror

reflectedreflected

lightlight

fromfrom

NBT NBT --

PVA filmPVA film

InstrumentInstrument toto measuremeasure

reflectedreflected lightlight

ReflectometerReflectometer::

CalorimetricCalorimetric systemssystems

4 4 –– 10 10 MeVMeV: : --

graphitegraphite, , waterwater, PS , PS calorimeterscalorimeters;;

--

calibrationcalibration, , nominalnominal

dosedose measurementsmeasurements;;

1.5 1.5 –– 4 4 MeVMeV::--

PS PS calorimetercalorimeter;;

--

calibrationcalibration, , nominalnominal

dosedose determinationdetermination;;

80 80 –– 120 120 keVkeV::--

graphitegraphite

calorimetercalorimeter;;

--

toto

developdevelop

a a primaryprimary

standard standard systemsystem;;--

calibrationcalibration;;

NovelNovel approachesapproaches

-- methodologymethodologyDosimetryDosimetry automationautomation –– toto reducereduce humanhuman errorserrors

--

AutomatedAutomated

evaluationevaluation

systemssystems

((AerialAerial, , BrukerBruker, , etcetc.);.);--

AutomatedAutomated

scanningscanning

ofof

imagesimages

((dosedose

distributiondistribution) ) ––

RisRisøøScanScan;;

RealReal timetime dosimeterdosimeter applicationapplication

--

ToTo

determinedetermine

combinedcombined


temperaturetemperature

––

dosedose

raterate

effectseffects;;

MathematicalMathematical methodsmethods (RPSMUG (RPSMUG –– forfor modelingmodeling andand simulationsimulation))ToTo assistassist productproduct design;design;ToTo determinedetermine dwelldwell timetime settingsetting;;Rapid Rapid estimationestimation ofof dosedose distributiondistribution;;Parallel Parallel irradiationirradiation ofof complexcomplex productsproducts;;

SelectionSelection criteriacriteria

QualityQuality controlcontrol has has toto be be basedbased onon thethe assuranceassurance thatthat thethe processprocesswaswas carriedcarried out out withinwithin prescribedprescribed dosedose limitslimits

ThisThis

requiresrequires

properproper

useuse

andand

selectionselection

ofof

dosimetrydosimetry

systemssystems

SelectionSelection

criteriacriteria::--

accordingaccording

toto

thethe

processprocess

toto

be be controlledcontrolled

((sterilizationsterilization, ,

polymerpolymer

modificationmodification, , foodfood

processingprocessing, , etcetc.); .); dosedose

rangerange: 50 : 50 GyGy ––

300 300 kGykGy;;

--

accordingaccording

toto

dosimeterdosimeter

characteristicscharacteristics;;

SelectionSelection criteriacriteria

ReliableReliable calibrationcalibration andand standardizationstandardization;;BroadBroad absorbedabsorbed dosedose rangerange;;Limited Limited oror no no dependencedependence ofof responseresponse withwith dosedose, , dosedose raterate, , energyenergy;;RadiationRadiation absorptionabsorption characteristicscharacteristics similarsimilar toto productproduct;;StabilityStability, , reproducibilityreproducibility, , simplicitysimplicity, , lowlow costcost, , availabilityavailability;;SmallSmall sizesize –– goodgood resolutionresolution capabilitiescapabilities;;KnownKnown environmentalenvironmental ((influenceinfluence) ) factorsfactors;;SimpleSimple handlinghandling andand readread--outout procedureprocedure;;Limited Limited variationvariation withinwithin andand amongamong batchesbatches;;LongLong shelfshelf lifelife;;RuggednessRuggedness;;PortabilityPortability;;

""IdealIdeal

dosimetrydosimetry

systemsystem""

W.L. W.L. McLaughlinMcLaughlin: : „„ IfIf youyou havehave oneone dosimeterdosimeter youyou thinkthink youyou knowknow thethe dosedose. . IfIf youyou havehave twotwo dosimetersdosimeters youyou start start toto wonderwonder…”…”

Optimum Optimum conditionsconditions: : -- widewide dosedose rangerange –– gamma/EB/gamma/EB/XX--rayray-- no no environmentalenvironmental effectseffects-- immediateimmediate evaluationevaluation afterafter irradiationirradiation-- lowlow priceprice-- multiplemultiple useuse-- automatedautomated, , nonnon--destructivedestructive evaluationevaluation

PresentlyPresently availableavailable systemssystems::-- processprocess calorimeterscalorimeters-- ESR ESR alaninealanine-- oscillometricoscillometric ECBECB-- ((SunnaSunna film)film)

FACTORS AFFECTING DOSIMETER FACTORS AFFECTING DOSIMETER ACCURACYACCURACY

1.1.

IrradiationIrradiation

conditionsconditions

areare

differentdifferent

fromfrom


conditionsconditions::

--

temperaturetemperature, , dosedose

raterate, , relativerelative

humidityhumidity, , energyenergy

spectrumspectrum, , irradiationirradiation

geometrygeometry, , etcetc..

2.2.

StorageStorage

conditionsconditions::

--

beforebefore

andand

afterafter


3.3.

InstrumentalInstrumental

errorserrors::

--

absorbanceabsorbance

andand

wavelengthwavelength

scalescale, , scatteredscattered

lightlight, , transfertransfer

ofof calibrationcalibration

curvecurve

fromfrom

oneone

instrumentinstrument

toto

anotheranother

oneone, , etcetc..

Accuracy and PrecisionAccuracy and Precision

AIM OF CALIBRATIONAIM OF CALIBRATION

Determine relationship Determine relationship between response of a between response of a dosimeter and absorbed dosimeter and absorbed dose.dose.

Influence factors:Influence factors:--

dose ratedose rate

--

temperaturetemperature--

timetime

--

humidity, etc. humidity, etc.

Minimize effects of Minimize effects of influence factors by influence factors by optimum calibration optimum calibration conditions.conditions.

DosimetryDosimetry calibrationcalibration

–– newnew trendstrends

InIn--plantplant calibrationcalibration::

CalibrationCalibration phantomsphantoms(Gamma, (Gamma, electronelectron););

Internet Internet calibrationcalibration(NIST):(NIST):

protectedprotected software;software;alaninealanine dosimetrydosimetry;;

CALIBRATION OF DOSIMETRY CALIBRATION OF DOSIMETRY SYSTEMSYSTEM

Calibration of dosimeterCalibration of dosimeterCalibration of equipmentCalibration of equipment

CALIBRATION OF EQUIPMENT (1)CALIBRATION OF EQUIPMENT (1)

All All measurement equipmentmeasurement equipment must be calibratedmust be calibrated and be traceable to and be traceable to national standards.national standards.

Certain measurement equipment cannot be calibrated (e.g. signal Certain measurement equipment cannot be calibrated (e.g. signal amplitude amplitude from an EPR spectrometer) from an EPR spectrometer)

thereforetherefore⇓⇓

the the stability of the equipment has to be demonstratedstability of the equipment has to be demonstrated by the use of by the use of measurement standards (e.g. stable EPR spin standards).measurement standards (e.g. stable EPR spin standards).

CALIBRATION OF EQUIPMENT (2)CALIBRATION OF EQUIPMENT (2)

--

Spectrophotometer:Spectrophotometer:absorbance and wavelength scale with calibrated optical filters;absorbance and wavelength scale with calibrated optical filters;

--

Thickness gauge:Thickness gauge:calibrated gauge blocks;calibrated gauge blocks;

--Thermometers:Thermometers:calibrated thermometers;calibrated thermometers;

--

Resistance measurement (OhmResistance measurement (Ohm--meter for calorimeters):meter for calorimeters):calibrated reference resistor;calibrated reference resistor;

--

Humidity meters:Humidity meters:saturated salt solutions;saturated salt solutions;

CALIBRATION OF DOSIMETERS (1)CALIBRATION OF DOSIMETERS (1)

Irradiation of dosimetersIrradiation of dosimeters

Measurement Measurement ((analysisanalysis) ) of dosimeters (with calibrated instrument)of dosimeters (with calibrated instrument)

Generation of calibration curve or response functionGeneration of calibration curve or response function

Initial Initial ccalibrationalibration verification, and periodically confirmation of validityverification, and periodically confirmation of validity

TraceabilityTraceability chainchain

CALIBRATION OF DOSIMETERS (2)CALIBRATION OF DOSIMETERS (2)--

Dose range:Dose range:Larger dose range than intended use;Larger dose range than intended use;

--

Number of dose points: Number of dose points: (4 dosimeters at each point)(4 dosimeters at each point)Dose range less than one decadeDose range less than one decade: : 5 points (at least)5 points (at least)--

arithmetically (10 arithmetically (10 --

20 20 --

30 30 --

40 40 --

50 50 kGykGy););

Dose range greater than one decadeDose range greater than one decade: : 5 points (at least) per decade5 points (at least) per decade--

geometricalgeometricallyly

(1 (1 --

1.5 1.5 --

2.3 2.3 --

3.4 3.4 --

5.1 5.1 --

7.6 7.6 --

11.4 11.4 --

17 17 --

26 26 --

38 38 --

58 58 --

87 kGy);87 kGy);

--

Batch calibration:Batch calibration:Each new batch must be calibrated (annual checks);Each new batch must be calibrated (annual checks);DonDon’’t use manufacturers`s calibration curve t use manufacturers`s calibration curve --

unless verified;unless verified;

--

Post irradiation stability:Post irradiation stability:

to control! to control!

IRRADIATION OF DOSIMETERSIRRADIATION OF DOSIMETERS1. 1. Irradiation at a Irradiation at a calibration calibration facilitfacilityy

Irradiation of dosimeters in the reference radiation field of a Irradiation of dosimeters in the reference radiation field of a calibration laboratory calibration laboratory ((oror

ofof

anan

inin--househouse


facilityfacility) ) followed followed

by by ““calibration verificationcalibration verification””

in the irradiation plant.in the irradiation plant.

a./ advantagesa./ advantages--

easy to obtain full dose range;easy to obtain full dose range;

--

irradiation to accurately known doses under controlled and irradiation to accurately known doses under controlled and documented conditions;documented conditions;

b./ disadvantages:b./ disadvantages:--

different conditions from real use (uncertainties);different conditions from real use (uncertainties);

--

transport of dosimeters (pretransport of dosimeters (pre--

and postand post--irradiation storage irradiation storage effects effects --

uncertainties);uncertainties);

CCalialibrationbration

facilityfacility

Calibration

holder ↓

IRRADIATION OF DOSIMETERSIRRADIATION OF DOSIMETERS22..

Irradiation Irradiation in plantin plant

Routine dosimeters are irradiated together with reference or traRoutine dosimeters are irradiated together with reference or transfer standard nsfer standard dosimeters in dosimeters in ““calibration phantomscalibration phantoms””

in the irradiation plant.in the irradiation plant.

a./ advantages:a./ advantages:--

calibration and production conditions are similarcalibration and production conditions are similar(environmental conditions); (environmental conditions);

b./ disadvantages:b./ disadvantages:--

difficult to obtain full dose range in certain plants;difficult to obtain full dose range in certain plants;

c./ care must be taken:c./ care must be taken:--

to ensure that all dosimeters irradiated together receive the to ensure that all dosimeters irradiated together receive the same same

absorbed doseabsorbed dose

GAMMA IRRADIATION PHANTOMGAMMA IRRADIATION PHANTOM

--

To be placed in a regionTo be placed in a regionof low dose gradient;of low dose gradient;

--

The effect of irradiationThe effect of irradiationtemperature on the referencetemperature on the referencedosimeters must be considered:dosimeters must be considered:

TTeffeff

= = TTminmin

+ 2/3 (+ 2/3 (TTmaxmax

--

TTminmin

););

--

Use of temperature labels;Use of temperature labels;

ELECTRON BEAM PHANTOMELECTRON BEAM PHANTOM--

It is irradiated separately,It is irradiated separately,not in e.g. dummy product;not in e.g. dummy product;

--

Specific location on the depthSpecific location on the depthdose curve should be chosen;dose curve should be chosen;

-

The effective irradiation temperature can be considered:

Teff

= (Tmin

+ Tmax

) / 2;

IMPORTANCE OF TRACEABILITYIMPORTANCE OF TRACEABILITY

The The abilityability

toto

show show thatthat

a a measurementmeasurement

is is consistentconsistent

withwith

thethe

appropriateappropriate

nationalnational

oror

internationalinternational

standardsstandards

throughthrough

anan

unbrokenunbroken

chainchain

ofof

comparisoncomparison

((primaryprimary

standard standard lablab. . →→ secondarysecondary

standard standard lablab. . →→ routineroutine

lablab.).)

((verificationverification

is is neededneeded))

CALIBRATION VERIFICATIONCALIBRATION VERIFICATION

--

Calibration curves prepared for routine dosimeters in a Calibration curves prepared for routine dosimeters in a calibration facility (or incalibration facility (or in--house calibration facility) must be house calibration facility) must be verified for the actual conditions of use in the production verified for the actual conditions of use in the production irradiation facility;irradiation facility;

--

Routine dosimeters have to be irradiated together with Routine dosimeters have to be irradiated together with reference or transfer standard dosimeters to at least three reference or transfer standard dosimeters to at least three different absorbed doses.different absorbed doses.

--

Absorbed dose results originating from the two types of Absorbed dose results originating from the two types of dosimeters must be analyzed with respect to any systematic dosimeters must be analyzed with respect to any systematic trends for potential corrections if neededtrends for potential corrections if needed..

ANALYSISANALYSIS

1. Analysis of dosimeters1. Analysis of dosimeters--

use of calibrated instrumentation;use of calibrated instrumentation;

--

time of analysis after irradiation (potential changes oftime of analysis after irradiation (potential changes of

dosimeter dosimeter responseresponse

after irradiation);after irradiation);

2. Analysis of calibration data2. Analysis of calibration data--

mean response and sample standard deviation;mean response and sample standard deviation;

--

calculation of coefficient of variation;calculation of coefficient of variation;

3. Preparation of calibration curve3. Preparation of calibration curve

--

signal = f(dose)signal = f(dose)--

evaluation of mathematical expression (e.g. calculation of "perevaluation of mathematical expression (e.g. calculation of "percentage centage

residuals")residuals")

toto

selectselect

bestbest

fitfit;;

EXAMINATION OF RESIDUALSEXAMINATION OF RESIDUALSSelectSelect thethe mathematicalmathematical expressionexpression forfor thethe dosedose=f(=f(signalsignal) ) relationshiprelationship((e.ge.g. . lowestlowest

orderorder

polynomialpolynomial););

DetermineDetermine thethe coefficientscoefficients ofof thethe polynomialpolynomial ((useuse individualindividualdosimeterdosimeter pointspoints););

CalculateCalculate thethe dosedose forfor eacheach calibratedcalibrated dosimeterdosimeter;;

CalculateCalculate ""percentagepercentage residualsresiduals""::

((DDcalculatedcalculated

––

DDdelivereddelivered

) / ) / DDdelivereddelivered

x100x100

PlotPlot ""percentagepercentage residualsresiduals"" againstagainst dosedose andand examineexamine datadata forforanyany systematicsystematic trendstrends;;

EXAMINATION OF RESIDUALSEXAMINATION OF RESIDUALS ((exampleexample))

Calibration

curve

and

function

→ Percentage

residual

↓ ↓

Harwell AH 4thy = -1,6466E-07x4 + 5,3813E-05x3 - 8,2926E-03x2 + 8,5069E-01x -

7,1433E-03R2 = 9,9999E-01

0,0

5,0

10,0

15,0

20,0

25,0

30,0

35,0

40,0

45,0

0 20 40 60 80 100 120

Dose kGy

Resp

onse

AH 4th order

-1

-0,8

-0,6

-0,4

-0,2

0

0,2

0,4

0,6

0,8

1

1 10 100

Dose kGy

Res

idua

l %

THANK YOU FOR YOUR ATTENTION!THANK YOU FOR YOUR ATTENTION!

Accuracy

Precision

Regional Training Course on Validation

Documents

Transcript of Regional Training Course on Validation