GTP Scenario # 1

1. GTP Scenario # 1 September 17,2005

2. Scenario # 1 • J Smith is 10 months old with leukemia in remission. He is scheduled to receive a PBPC transplant from HLA matched, ABO major incompatible sibling. • Product has excessive RBCs and CD34+ cells. • Lab is to: • Perform a density gradient separation in 50 ml conical tubes. • Freeze ‘excess’ cells.

3. Laboratory Information • Cell Therapy Laboratory: • Unclassified facility. • BSC cleaned with an appropriate cleaning agent before use (1 product per BSC). • BSC is certified annually. • Centrifuge cleaned as part of preventive maintenance (not before use). • What level of EM and Cleaning is required?

4. What should be considered? • Evaluate the conditions. • The process is ‘open’. • The product is a 361 GTP product. • The laboratory is an unclassified room. • Cell manipulations occur in the BSC.

5. Product Monitoring • Sterility: Pre & Post processing? • Recommended • Periodic audit review of sterility results? • Recommended

6. BSC Environmental Monitoring • Settle plates during processing? • Recommend performing as part of process validation. Review data and determine need based on risk assessment. • Surface sampling after cleaning? • Perform as part of validation and as periodic check of cleaning procedure. • Airborne sampling during processing? • Only perform if settle plate data inconclusive or trending upward.

7. Facility Monitoring • Perform air particle counts during processing? • Recommend periodic checks during laboratory ‘working hours’ (dynamic monitoring).

8. Centrifuge Monitoring • Perform EM sampling of the surfaces (buckets)? • Recommend performing as part of process validation. • Recommend performing after preventive maintenance. • Recommend performing during processing only if products begin to have positive sterility results.

9. Personnel Monitoring • Perform on day of processing after the staff completes the process? • Recommend performing as part of process validation and/or employee training. • Recommend performing during processing only if products begin to have positive sterility results.

10. EM & PM Result Review • How often? • Recommend monthly review. • Does this need to be done before product release? • Review cannot be part of product release; the product is infused immediately after processing (fresh).

11. Cleaning • BSC? • Centrifuge? • Lab benchtops? • Lab floors? • Control rate freezer? • Document Review?

12. Cleaning Recommendations • BSC: Clean before & after use with an appropriate cleaning agent. • Unless validation EM/PM results indicate this is not adequate. • Unless post-processing cultures become positive (investigation outcome). • Unless there is a spill.

13. Cleaning Recommendations • Centrifuge & Benchtops: • Clean before & after use with appropriate cleaning agent. • Control Rate Freezer: • Clean on a periodic basis as per manufacturer’s instructions. • Floors: • Clean on a periodic basis. • Unless validation EM/PM results indicate this is not adequate. • Unless post-processing cultures become positive (investigation outcome). • Unless there is a spill.

14. Cleaning Document Review • How often? • Recommend periodic document review. • Does this need to be done before product release? • Review should not be part of product release.

15. Variation • Would you do anything differently if the donor were HCV positive? • Consider whether cleaning agent in use is viricidal