GTP Scenario # 1GTP Scenario # 1

September 17,2005September 17,2005

Scenario # 1Scenario # 1 J Smith is 10 months old with J Smith is 10 months old with

leukemia in remission. He is leukemia in remission. He is scheduled to receive a PBPC scheduled to receive a PBPC transplant from transplant from HLA matched, HLA matched, ABO major incompatible siblingABO major incompatible sibling..

Product has excessive RBCs and Product has excessive RBCs and CD34CD34++ cells. cells.

Lab is to:Lab is to: Perform a density gradient Perform a density gradient

separation in 50 ml conical tubes.separation in 50 ml conical tubes. Freeze ‘excess’ cells.Freeze ‘excess’ cells.

Laboratory InformationLaboratory Information

Cell Therapy Laboratory:Cell Therapy Laboratory: Unclassified facility.Unclassified facility. BSC cleaned with an appropriate BSC cleaned with an appropriate

cleaning agent before use (1 product cleaning agent before use (1 product per BSC).per BSC).

BSC is certified annually.BSC is certified annually. Centrifuge cleaned as part of preventive Centrifuge cleaned as part of preventive

maintenance (not before use).maintenance (not before use). What level of EM and Cleaning is What level of EM and Cleaning is

required?required?

What should be considered?What should be considered?

Evaluate the conditions.Evaluate the conditions. The process is ‘open’.The process is ‘open’. The product is a 361 GTP product.The product is a 361 GTP product. The laboratory is an unclassified The laboratory is an unclassified

room.room. Cell manipulations occur in the Cell manipulations occur in the

BSC.BSC.

Product MonitoringProduct Monitoring

Sterility: Pre & Post Sterility: Pre & Post processing?processing? RecommendedRecommended

Periodic audit review of sterility Periodic audit review of sterility results?results? RecommendedRecommended

BSC Environmental MonitoringBSC Environmental Monitoring

Settle plates during processing?Settle plates during processing? Recommend performing as part of Recommend performing as part of

process validation. Review data and process validation. Review data and determine need based on risk determine need based on risk assessment.assessment.

Surface sampling after cleaning?Surface sampling after cleaning? Perform as part of validation and as Perform as part of validation and as

periodic check of cleaning procedure.periodic check of cleaning procedure. Airborne sampling during Airborne sampling during

processing?processing? Only perform if settle plate data Only perform if settle plate data

inconclusive or trending upward.inconclusive or trending upward.

Facility MonitoringFacility Monitoring

Perform air particle counts Perform air particle counts during processing?during processing? Recommend periodic checks Recommend periodic checks

during laboratory ‘working hours’ during laboratory ‘working hours’ (dynamic monitoring).(dynamic monitoring).

Centrifuge MonitoringCentrifuge Monitoring

Perform EM sampling of the Perform EM sampling of the surfaces (buckets)?surfaces (buckets)? Recommend performing as part of Recommend performing as part of

process validation.process validation. Recommend performing after Recommend performing after

preventive maintenance.preventive maintenance. Recommend performing during Recommend performing during

processing only if products begin processing only if products begin to have positive sterility results.to have positive sterility results.

Personnel MonitoringPersonnel Monitoring

Perform on day of processing Perform on day of processing after the staff completes the after the staff completes the process?process? Recommend performing as part of Recommend performing as part of

process validation and/or process validation and/or employee training.employee training.

Recommend performing during Recommend performing during processing only if products begin processing only if products begin to have positive sterility results.to have positive sterility results.

EM & PM Result ReviewEM & PM Result Review

How often?How often? Recommend monthly review.Recommend monthly review.

Does this need to be done Does this need to be done before product release?before product release? Review cannot be part of product Review cannot be part of product

release; the product is infused release; the product is infused immediately after processing immediately after processing (fresh).(fresh).

CleaningCleaning

BSC?BSC? Centrifuge?Centrifuge? Lab benchtops?Lab benchtops? Lab floors?Lab floors? Control rate freezer?Control rate freezer? Document Review?Document Review?

Cleaning RecommendationsCleaning Recommendations

BSC: BSC: Clean before & after use Clean before & after use with an appropriate cleaning with an appropriate cleaning agent.agent. Unless validation EM/PM results Unless validation EM/PM results

indicate this is not adequate.indicate this is not adequate. Unless post-processing cultures Unless post-processing cultures

become positive (investigation become positive (investigation outcome).outcome).

Unless there is a spill.Unless there is a spill.

Cleaning RecommendationsCleaning Recommendations

Centrifuge & Benchtops:Centrifuge & Benchtops: Clean before & after use with appropriate Clean before & after use with appropriate

cleaning agent.cleaning agent. Control Rate Freezer: Control Rate Freezer:

Clean on a periodic basis as per manufacturer’s Clean on a periodic basis as per manufacturer’s instructions. instructions.

Floors: Floors: Clean on a periodic basis.Clean on a periodic basis.

Unless validation EM/PM results indicate Unless validation EM/PM results indicate this is not adequate.this is not adequate.

Unless post-processing cultures become Unless post-processing cultures become positive (investigation outcome).positive (investigation outcome).

Unless there is a spill.Unless there is a spill.

Cleaning Document ReviewCleaning Document Review

How often?How often? Recommend periodic document Recommend periodic document

review.review. Does this need to be done Does this need to be done

before product release?before product release? Review should not be part of Review should not be part of

product release. product release.

VariationVariation

Would you do anything Would you do anything differently if the donor were HCV differently if the donor were HCV positive?positive? Consider whether cleaning agent Consider whether cleaning agent

in use is viricidalin use is viricidal