ROUTINE PROCESS CONTROL

Good management

Processing record

Qualified and experienced

operators

Quality Manual

A Radiation processing facility should have the following vital components

RADIATION PROCESSING FACILITY

Processing record

Should contain information ofReception and inspection of productUnique code identifying each productStorage environmentScheduling the irradiationLoading the product onto the irradiator systemUnloading the irradiated product from the systemInspectionchecking of routine dosimetry, process parametersSign-off of any non-conformancesApproval for release and dispatchDispatch to the customer

Specifications of the process

The product covered by the specification The product pattern and relationship

between dose at the monitoring position and the dose at the maximum and minimum dose position

The routine dosimeter monitoring position(s) For gamma irradiation, the relationship

between product density, dose and source strength

For electron beam, the relationship between characteristics, conveyor speed, product configuration and dose

Description of the product

The dimensions and density of package

A description of the irradiation container

A description of the conveyor path

Process Control

Receipt and inspection of the product

Product Storage

Product Processing

Post irradiation Inspection

Routine Dosimetry

Product Release

Receipt and inspection of the product

Check for any obvious signs of damage.Check that the identity of the product matches the description in the documentationCheck that the amount of material to be irradiated matches with the amount described in the paperwork (purchase orders or delivery note).Check the product that has been sent for routine irradiation has been validated for that process.

Product Storage

Store unirradiated product in an area isolated from any irradiated product.Physical separation such as barrier is most appropriate.Keep storage conditions appropriate for the product being irradiatedPest control if requiredRecord the storage environment as a part of the processing records for the product

Product Processing

Product processing-Documentation

Document should be maintained for each consignment of product and it should be signed off at each stage of processing through the irradiator for

Reception and inspection of productScheduling the irradiatorLoading the product onto the irradiator systemUnloading the irradiated product form the systemFinal inspection including checking of routine

dosimetry and other stored process parametersRecording of any non-conformancesApproval for release and dispatchDispatch to the customer or their courier.

Product loading for irradiation

Use approved loading configurations specified in approved and documented proceduresPlace controlled identification labels

• location • date of processing, • Unique codes identifying the irradiation

conditions and batch/lot numbers.

Use of Radiation sensitive indicators

Radiation sensitive indicators may be used to show that the product containers have been irradiated.Radiation sensitive indicators should be used as only qualitative indicators of irradiation.Routine dosimetry of each and every run is essential in order to certify the dose to the product.

Placement of Routine dosimeters

Place routine dosimeters at predetermined routine monitoring positionPlace routine dosimeters at least at the beginning, end of an irradiation lot, in order that it may be demonstrated that the irradiation process was under controlThe frequency of dosimeter placement should be sufficient to verify that the process is in control.

For Gamma Irradiator

Dosimeters are typically placed at the beginning and at the end of each run of a particular processing category.

Additionally, dosimeters may be placed so at least one dosimeter is within the irradiator cell at all times.

For Electron beam irradiator

Dosimeters are typically placed at the beginning and at the end of each run of a particular category utilizing a specific set of processing parameters.

Bulk-flow irradiators

For fluids and grains continuously flow during irradiation, add several dosimeters to the product stream at the beginning and during the production run.From the statistical distribution of the dose measurements, the absorbed dose is estimated with statistical confidence.

Product Processing

Process control

Process interruptions

Dose monitoring

Analysis

Process control

For gamma irradiators,

Record date and time of processingSet the operating parameters as established during process qualificationControl and record the dwell time and conveyor speed of the product

Process control

For Electron Beam irradiators,

Record date and time of processingSet the operating parameters as established during process qualificationMeasure and record machine variables

• beam current• scan width• conveyor speed• Beam energy

Process interruptions

If the parameters deviate outside the processing limits prescribed from process qualification, interrupt the process to evaluate and correct the cause of the deviationsEffect on the quality of the product

Dose monitoring

The dose measurements at the routine monitoring position provides a measure of the process that is independent of any other control or measurement system of the irradiator. The minimum frequency of dose measurement should be chosen based on the particular requirement of the irradiator or process

Separate location for irradiated product

The identification as irradiated may best be achieved by ensuring that product is unloaded from an irradiator to a separate location from the one which is used for unirradiated product. This, together with the use of unique identification labels, ensures a full trail of traceable records for the product.

Routine Dosimetry

Dosimetry

The key quantity that determines the process is the absorbed dose.Dosimeters are the devices that are capable of providing a quantitative and reproducible measurement of dose.Various dosimetry techniques are available for measuring absorbed dose in a quantitative manner.Relevant ISO/ASTM standard practices and guides are available for dosimetry in radiation processing facilities

Dose Measurement

It has to be demonstrated thatDose measurement is traceable to a national or international standard. The uncertainty of measurement is known.The Influence of temperature, humidity and other environmental considerations on dosimeter response is known and taken into account

Dosimetry Standards – Measurement

•ASTM E2628 “Standard Practice for Dosimetry in Radiation Processing”•ASTM E2701 “Standard Guide for Performance Characterization of Dosimeters and Dosimetry Systems for Use in Radiation Processing” •ISO/ASTM 51261 “Standard Guide for Selection and Calibration of Dosimetry Systems for Radiation Processing”•ISO/ASTM 51707 “Standard Guide for Estimating Uncertainties in Dosimetry for Radiation Processing”

Dosimetry Standards - Application

•ISO 11137-3:2006 “Sterilization of health care products – Radiation – Part 3:Guidance on dosimetric aspects”•ASTM E2303 “Standard Guide for Absorbed Dose Mapping in Radiation Processing Facilities”•ISO /ASTM 51608 “Standard Practice for Dosimetry in an X-ray (Bremsstrahlung) Facility for Radiation Processing”•ISO/ASTM 51649 “Standard Practice for Dosimetry in an Electron BeamFacility for Radiation Processing at Energies Between 300 keV and 25MeV”•ISO/ASTM 51702 “Standard Practice for Dosimetry in Gamma Irradiation Facilities for Radiation Processing”

Dosimetry Standards - individual dosimetry system

•ISO/ASTM 51205 Practice for Use of a Ceric-Cerous Sulfate Dosimetry System•ISO/ASTM 51275 Practice for Use of a Radiochromic Film Dosimetry System•ISO/ASTM 51276 Practice for Use of a Polymethylmethacrylate Dosimetry System•ISO/ASTM 51310 Practice for Use of a Radiochromic Optical Waveguide Dosimetry System•ISO/ASTM 51401 Practice for Use of a Dichromate Dosimetry System•ISO/ASTM 51538 Practice for Use of the Ethanol-Chlorobenzene Dosimetry System

Dosimetry Standards - individual dosimetry system

•ISO/ASTM 51540 Practice for Use of a Radiochromic Liquid Dosimetry System•ISO/ASTM 51607 Practice for Use of the Alanine-EPR Dosimetry System•ISO/ASTM 51631 Practice for Use of Calorimetric Dosimetry Systems for Electron Beam Dose Measurements and Dosimeter Calibrations•ISO/ASTM 51650 Practice for Use of Cellulose Acetate Dosimetry Systems•ISO/ASTM 51956 Practice for thermoluminescence Dosimetry (TLD) Systems for Radiation Processing •ASTM E1026 Practice for Using the Fricke Reference Standard Dosimetry System•ASTM E2304 Practice for Use of a LiF Photo-Fluorescent Film Dosimetry System

Dosimetry Standards - any process deviation

•ISO/ASTM 51707 Guide for Estimating Uncertainties in Dosimetry for Radiation Processing•ASTM E2232 Guide for Selection and Use of Mathematical Methods for Calculating Absorbed Dose in Radiation Processing Applications

Analysis of the dose measurement

Dosimetric measurements are subject to sizeable uncertaintiesCalibration of the dosimetry systemReproducibility of individual dosimetersReproducibility of the positions of dosimeters in dose mapping experiments, and of the product being irradiated near those dosimeters;Stability of the irradiator (beam current, beam energy, scanning width, conveyor speed for electron beams; variations in tote properties for gamma irradiators, or in positioning of product within the totes, for gamma irradiators)Effects of influence quantities such as temperature, humidity, dose rate, time between irradiation and measurement the dosimeters.

For a controlled process

For a process under control, the measured values of the routine dose will be distributed statistically about a target dose value.Use statistical process control techniques to confirm that the process delivered to the product meets the conditions established during the validation exercise.

The irradiated product

The radiation process is mainly governed by the minimum absorbed dose achieved in the dose distribution within a given product. If the required minimum is not applied, the intended effect may not be achieved. There are also situations where high dose would damage the quality of the product

Post irradiation inspection

Post irradiation inspection

Inspect if the product suffered any damage as a result of the process

• Irradiation damage (discoloring as a result of a significant overdose)

• Machine damage (tearing of the cartons on the irradiation conveyor system)

Examine and report routine dosimetry resultsIf any product cartons suspected of receiving a non-conforming process are stored in the segregated area, isolated from the rest of the product.

Post irradiation inspection

Any cartons identified from the irradiation records as having had a non-conforming irradiation (for example, with interruption to the process) should be held and only released once investigations have confirmed the process was under control.Routine dosimetry obtained along with records of the machine variable during the irradiation process are compared with expected and validated range.

Non Conforming product

As a result ofRoutine dosimetry measurement indicating the

process was not correctEvident damage to the carton.

Product Release

PRODUCT RELEASE

Once the product, irradiation process records including routine dosimetry, and other records from the manufacturing process have been approved as conforming to the requirements, the product may be released.

References

Guidelines for the Development, Validation and Routine Control of Industrial Radiation Process. IAEA Radiation Technology Series No.4 (2013)Trends in radiation Sterilization of Health Care Products. IAEA, STI/PUB/1313 (2008)ISO 11137:2006 “Sterilization of Healthcare Products – Radiation”

Part 1: Requirements for development, validation and routine control of a sterilization process for medical devicesPart 2: Establishing the sterilization dosePart 3: Guidance on dosimetric aspects