PDA: A Global. Association. Matrix Approach to Media Fills. (c) 2012 Catalent Pharma Solutions. All rights reserved.

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Tobias Brown
6 years ago
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PDA: A Global Matrix Approach to Media Fills Association

2 Overview Guidance Overview Matrix Introduction Why Matrix Media Fills Sample Matrix New Products & Technologies Biologics Scheduling Media Fills Handling Matrix Media Fill Failures Innovations in Media Fills 2

3 Guidance Criteria PDA EU FDA Selection Numer of runs & frequency Matrix Considerations Incubation temperature Qualification of staff 3 runs for validation routine 2/Y Risk assessment to set worst case No worst case, run at extremes of range C for 14 days Initial, then once per year 3 runs per shift for validation routine 2/Y Evaluate # of interventions C for 7 days followed by C for 7 days Frequency not specified 3 runs for validation routine 2/Y Evaluate: range of speeds # of interventions # of personnel C for 14 days. If 2, incubate at lower temp first Initial, then once per year 3 runs per shift for validation routine 2/Y Use largest container with widest mouth at slowest speed and smallest vial with highest speed C for 7 days followed by C for 7days Frequency not specified 3

4 Reason for matrix approach Most efficient compliant method validating multiple products. Best Coverage: Microbiological assurance confirmed by worst case conditions Systematic program including Risk Assessment forces examination of all products and parameters annually Cost Savings: Raw Materials Indirect Costs - Testing, Disposal and Clean up Equipment costs: purchase and maintenance of incubators Additional capacity for production Manpower costs 4

5 Introduction of matrix Risk Assessment utilized to determine critical to sterility parameters Risk Assessment determines worst case value for critical to sterility parameters (fill duration, # of interventions, # of personnel, # of aseptic connections during set up) Where a worst case value can not be justified, the extreme values of the range are used to bracket the parameter (container size, closure size, fill speed) 5

6 Example of a simple matrix Filling Line is used for 3 products Reduction of 67 % Conventional Media Fill Schedule Product Vial Size Closure Size fill speed staff Fill time interventions # of Media Fills Initial Routine 1 2mL 13mm 200/min 3 6 hour /yr 2 5mL 20mm 150/min 2 7 hour /yr 3 20mL 20mm 120/min 2 8 hour /yr Matrix Media Fill Schedule # of Media Fill required without using matrix approach 9 6/yr 1 2mL 13mm 200/min 3 8 hour /yr 2 20mL 20mm 120/min 3 8 hour /yr # of Media Fill required using matrix approach 6 2/yr 6

New products & technologies New Product is compared to current limits to determine fit If not covered within existing limits a separate media fill is required If covered by the existing limits, the

7 New products & technologies New Product is compared to current limits to determine fit If not covered within existing limits a separate media fill is required If covered by the existing limits, the Generic Validation Protocol is updated to include new products placement, including risk assessment completion & documentation New Technology requires risk assessment; most likely will require separate matrix 7

Biological products Due to Biologics process variability, no single / standard process set up is possible It may be more practical to validate the various

8 Biological products Due to Biologics process variability, no single / standard process set up is possible It may be more practical to validate the various segments of the process individually The frequency of revalidation should relate to the process of regular, commercial production determined to use worst case conditions 8

9 Schedule Foundation of schedule is worst case condition Program schedule reviewed and approved annually Schedule updates for new products deployed through risk assessments and implemented via change control Different approaches can be used : Alternate to cover each end of the set limits Randomize to cover each end of the set limits and mid level processes 9

10 Media fill myths Fence determination via brackets can lead to larger potentially impacted population Frequency of media fills within the fence actually increases, reducing risk to any specific product MYTHS Human error failures impact larger population TRUTH Human failures should always be treated with full CAPA, fence should be the same in matrix vs. non-matrix program 10

11 Innovations in media fill Irradiated Dehydrated Media Eliminates Bioburden & Mycoplasma risks Reduced contamination risk Cold Filterable Media Filterability Formulation in facility Safety (no hot WFI) Mimics process No pre-use sterilizing/testing Vegetable Based Media Optimized performance with non-animal origin Eliminates TSE risk Available irradiated Available with color indicator Possible recovery for anaerobic media fill use CONSIDERATIONS Validation in use (eg. Recovery vs. TSB) Maturity in use Fit for purpose for individual needs Supplier Qualification 11

12 Summary Matrix approach to Media Fills A systemic, risk based method utilizing worst case conditions Meets guidance requirements for equipment and validation of staff Provides coverage at lowest cost A structured way to review new products, and technologies; including Biologics 12

13 Thank you for your attention Acknowledgements - Catalent Pharma Solutions: G. Delestrait, D. Diels-Vandepoel, E. Hoppenbrouwers, H. Jeffreys, J. Krewer, K. Schmidt, J. Spiers 13

Hot Topics in Drug Product Process Validation: A Reviewer s Perspective

Hot Topics in Drug Product Process Validation: A Reviewer s Perspective Colleen Thomas, Ph.D. Quality Assessment Lead (Acting) FDA/CDER/OPQ/OPF Division of Microbiology Assessment CASSS CMC Strategy Forum