1. CBER Irradiated Blood Components Jennifer Jones Consumer Safety Officer CBER, OBRR, DBA September 16, 2009

2. CBER 2 Outline Irradiation Source Radiation Dose Submission Contents – Standard Operating Procedures (SOPs) – Records – Labeling

3. CBER 3 Irradiation Source Cesium-137 – sealed source irradiator Cobalt-60 – sealed source irradiator Linear accelerator X-ray – irradiator

4. CBER 4 Radiation Dose 2500 cGy targeted to container’s central portion 1500 cGy minimum dose at any other point of the container If product is irradiated more than once, document total (additive) dose An indicator should be used with each batch that is irradiated – Follow manufacturer’s instructions for use, including temperature control

5. CBER 5 Submission Contents Cover letter Form FDA 356h SOP for manufacturing irradiated blood products Typically, SOPs for equipment maintenance and personnel training

6. CBER 6 Submission Contents (cont.) Labels for each product with Form FDA 2567 Two months of irradiation records Most recent dosimetry map Contractor information, if applicable – Contractor who performs irradiation must register with FDA

7. CBER 7 SOPs Description of the irradiator (e.g., radiation source) Description of the dose delivered to the center of the container Length of time required to deliver irradiation Maximum irradiation dose limits Description of procedures for re-irradiation, if applicable

8. CBER 8 SOPs (cont.) Indication of the maximum number of units to be irradiated at one time Description of procedures for monitoring to determine actual dose delivered Validation – Initially – Annually for Ce-137 – Semi-annually for Co-60 – After mechanical repairs – Use Thermoluminescent Dosimeter (TLD) chips or other direct methods of measurement

9. CBER 9 SOPs (cont.) Dating period for Red Blood Cell products – Not more than 28 days from the date of irradiation but no more than the dating period of the original product Dating period for platelets remains unchanged

10. CBER 10 SOPs (cont.) Maintenance of irradiator Procedure for personnel training Staff safety If contract facility used for irradiation, your SOPs should: – Describe what steps are performed by you and by the contractor – Ensure manufacturing steps are performed according to your specifications and are in compliance with all applicable regulations

11. CBER 11 SOPs (cont.) Quality control (QC) (review considerations) Irradiator – Daily QC (e.g., check of turntable rotation) – Monthly comparison of irradiator timer and back-up timer, if available, with certified stop watch Irradiation indicators – Shipping and storage temperature checks – Expected results of each new lot – Investigation of failures and corrective actions

12. CBER 12 Records Strength of source Irradiation Records QC Equipment maintenance

13. CBER 13 Irradiation Records/QC Operator ID Site of irradiation Date and time of irradiation Duration of irradiation

14. CBER 14 Irradiation Records/QC (cont.) Level/dose of irradiation Documentation of QC for irradiator and irradiation indicators

15. CBER 15 Labeling Container Label (21 CFR 606.121) – Container label must include proper name of product, and modifier, if applicable (e.g., RBCs, Irradiated) – Change expiration date for RBCs if appropriate Circular of Information should include : – Indications for use in treating patients at risk of transfusion- associated GVHD – Side effects and hazards of irradiating RBCs Higher supernatant potassium levels than non-irradiated RBCs due to cell membrane damage

16. CBER 16 Labeling (cont.) Circular of Information (cont.) – Removal of residual supernatant plasma prior to transfusion may reduce risks associated with elevated plasma potassium License Number should not appear on the container unless the product has been licensed by the FDA

17. CBER 17 Where to obtain information FDA Memorandum, July 22, 1993: Recommendations Regarding License Amendments and Procedures for Gamma Irradiation of Blood Products – http://www.fda.gov/BiologicsBloodVaccines/GuidanceCo mplianceRegulatoryInformation/default.htm http://www.fda.gov/BiologicsBloodVaccines/GuidanceCo mplianceRegulatoryInformation/default.htm

18. CBER 18 Where to obtain information (cont.) “For the Submission of Chemistry, Manufacturing and Controls and Establishment Description Information for Human Blood and Blood Components Intended for Transfusion or for Further Manufacture and for the Completion of Form FDA 356h” (May 1999) – http://www.fda.gov/BiologicsBloodVaccines/GuidanceComp lianceRegulatoryInformation/default.htm http://www.fda.gov/BiologicsBloodVaccines/GuidanceComp lianceRegulatoryInformation/default.htm