Regulatory and Monetary Drivers for Real-Time Analytics
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This document discusses regulatory and monetary drivers for implementing real-time analytics in biotech processes. Regulatory drivers include enabling quality by design approaches through continuous process monitoring and improvement. Real-time data collection allows for better design space definition and linking of critical process parameters to critical quality attributes. Monetary benefits include fewer lost batches through higher quality, faster processing times, and potential transition to continuous manufacturing with higher facility utilization.
Regulatory and Monetary Drivers for Real-Time Analytics
- 1. SME Biotech Consulting Regulatory and Monetary Drivers for Real Time Analytics Barry Rosenblatt, PhD SMEbiotech1@comcast.net
- 2. SME Biotech Consulting Outline Introduction: Defining Real Time Analytics In-Process vs Quality Attributes Regulatory Drivers QBD Continuous Process Improvement Real Time vs Batch Release Monetary Drivers Facility Utilization Continuous Processing Process Improvements/optimization
- 3. SME Biotech Consulting Defining Real-Time Analytics The FDA Guidance on Process Analytical Technology Describes Real-Time Analytics as: Nondestructive measurements that contain information related to biological, physical, and chemical attributes of the materials being processed. These measurements can be: at-line: Measurement where the sample is removed, isolated from, and analyzed in close proximity to the process stream. on-line: Measurement where the sample is diverted from the manufacturing process, and may be returned to the process stream. in-line: Measurement where the sample is not removed from the process stream and can be invasive or noninvasive
- 4. Defining Real-Time Analytics Use of RTAs Defining/developing design space Operating parameters CPP vs pCPP vs nCPP In-process checks Critical quality attributes Process and Product SME Biotech Consulting
- 5. Defining/Developing Design Space Current Paradigm (Off line analysis) Early development Define edge of Failure Platform approach Usually built for Speed Mid development Narrow operating parameter Gain full scale experience Late Development/PQ FEMA analysis DOE Set Specifications SME Biotech Consulting
- 6. SME Biotech Consulting Current Paradigm Phase 0 Phase 1 Phase 2 Phase 3 Develop Apply Analyze Specs? Comparability?Comparability? PQ FEMA DOE
- 7. Current Paradigm SME Biotech Consulting Bioreactor Harvest Capture Inputs/Ops Polishing Combination of at Line On-line and In-Line Seeding, pH, Temp, dO2 Agitation at Line testing VCD, Titer, Gly, PTM, Structure, Micro, AVA Outputs/OpS BDS Flow rate/TMP Volume, Mass Titer, Volume Flow Rate, Mass pH, Cond Titer, Vol, Turbidity, Filt Int. Micro Titer, Volume, Mass, pH, Cond, PTM/structure Purity, Micro Titer, Volume Flow Rate, Mass pH, Cond Titer, Volume, Mass, pH, Cond, PTM/structure, Purity, Micro Flow rate/TMP Volume, Mass BDS Release
- 8. Relationship of Operating Parameters to CQA SME Biotech Consulting CQA
- 9. Design Space Studies: DOE SME Biotech Consulting Adapted from A Mab: a Case Study in Bioprocess Development CMC Biotech Working Group
- 10. Quality By Design the desired state of pharmaceutical manufacturing and regulation may be characterized as follows: Product quality and performance are ensured through the design of effective and efficient manufacturing processes Product and process specifications are based on a mechanistic understanding of how formulation and process factors affect product performance Continuous real time quality assurance SME Biotech Consulting
- 11. QBD Paradigm Early Development o Define Design space o DOE o Linkage of CPP to CQA Mid Development/Late Development o Continuous Process Improvement SME Biotech Consulting
- 12. QBD Paradigm SME Biotech Consulting Bioreactor Harvest Capture Inputs/Ops Polishing Combination of On-line and In-Line Seeding, pH, Temp, dO2 Agitation Combination of On Line and In Line testing VCD, Titer, Gly, PTM, Structure, Micro, AVA Outputs/OpS BDS Flow rate/TMP Volume, Mass Titer, Volume Flow Rate, Mass pH, Cond Titer, Vol, Turbidity, Filt Int. Micro Titer, Volume, Mass, pH, Cond, PTM/structure Purity, Micro Titer, Volume Flow Rate, Mass pH, Cond Titer, Volume, Mass, pH, Cond, PTM/structure, Purity, Micro Flow rate/TMP Volume, Mass BDS Release X CQA testing In line
- 13. SME Biotech Consulting QBD Paradigm Phase 0 Phase 1 Phase 2 Phase 3 Develop Apply Analyze Specs? Continuous PQ FEMA DOE
- 14. Monetary Drivers Better definition of Platform processes Fewer lost lots (Higher quality) Shortened Processing Quicker TAT of analytics Lot release is instantaneous Possible transition to continuous Processing Higher utilization of plant SME Biotech Consulting
- 15. Reference Documents ICH Q8 ICH Q9 ICH Q10 ICH Q11 Guidance for Industry: PAT- A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance 2004 Questions and Answers on Design Space Verification (Joint FDA/EMA)24 October 2013 EMA/603905/2013 o A Mab: a Case Study in Bioprocess Development CMC Biotech Working Group Ver2 Oct 2009 SME Biotech Consulting