New Annex 15 Updated Requirements & Approach to Validation. Presented by Ashley Isbel 10 th August 2015

Transcription

1 New Annex 15 Updated Requirements & Approach to Validation Presented by Ashley Isbel 10 th August 2015

2 EU GMP Guide Annex 15 Qualification & Validation 2001 Current version of Annex 15 published Nov 2012 Concept paper from the EMA outlined various reasons for the revision of Annex 15. Feb 2014 Draft Annex was released for public comment Mar 2015 Final version released Oct 2015 Implementation in EU and automatic PIC/S adopters??? TGA implementation has not yet been announced Slide 2 PharmOut 2015

3 Drivers for the revision Key drivers: ICH Q8, Q9, Q10, and Q11 Indirectly, FDA process validation guidance Advancements in manufacturing technology (eg. PAT) Changes to other Chapters, Sections and Annexes Industry standard practice Slide 3 PharmOut 2015

4 Drivers for the revision Slide 4 PharmOut 2015

5 Overview of changes Slide 5 PharmOut 2015

6 Overview of changes Key Updates: Significant additional guidance on Planning and documentation Added information on the qualification stages for equipment, facilities Major revision for Process Validation Major revision for Cleaning Validation New topics added, including verification of transport and method validation Slide 6 PharmOut 2015

7 Planning & Documentation for Qualification & Validation 8 clauses expanded to 18 in new Annex 15 Focus on clarity and removal of ambiguity Explicit permission to utilize vendor and third party testing and documentation provided appropriate personnel at the manufacturing site confirm suitability and compliance Risk management approach mandated, including life cycle approach to risk assessment Data integrity is also mentioned were appropriate checks needs to be built into qualification and validation tasks to ensure the integrity of all data obtained Slide 7 PharmOut 2015

8 Documentation & Qualification stages Now Mandatory Now expected For complex/novel systems Slide 8 PharmOut 2015

9 Process Validation Annex 15 required to be used with relevant PV guidelines Explicit reference to all three phases described in FDA PV guidance (although little information on process development phase) Detailed information on various aspects of PV batch sizes, tech transfer, bracketing, use of CQA and CPP, etc. New section on Ongoing Process Validation included (equivalent to Continued Process Verification in FDA guidance. Clear instructions on retrospective validation (no longer acceptable) and concurrent validation Slide 9 PharmOut 2015

10 Process Validation Slide 10 PharmOut 2015

11 Process Validation Design Space Slide 11 PharmOut 2015

12 New sections Entirely new sections: Ongoing Process Verification during Lifecycle (phase 3) Verification of Transportation Validation of Packaging Qualification of Utilities Validation of Test Methods Slide 12 PharmOut 2015

13 Cleaning Validation The cleaning procedure should be performed an appropriate number of times based on a risk assessment and meet the acceptance criteria in order to prove that the cleaning method is validated Risk Assessment Appropriate Number Proof Meet Acceptance Criteria Slide 13 PharmOut 2015

14 Cleaning Validation Limits for the carryover of product residues should be based on a toxicological evaluation. The justification for the selected limits should be documented in a risk assessment which includes all the supporting references. Visually clean not generally acceptable on its own Limits should be based on a toxicological evaluation and refers to the EMA Guideline on setting health-based exposure limits. Slide 14 PharmOut 2015

15 Cleaning Validation Therapeutic macromolecules and peptides are known to degrade and denature when exposed to ph extremes and/or heat, and may become pharmacologically inactive. A toxicological evaluation may therefore not be applicable in these circumstances. If it is not feasible to test for specific product residues, other representative parameters may be selected, e.g. total organic carbon (TOC) and conductivity. Also where a cleaning process is ineffective or is not appropriate for some equipment, dedicated equipment or other appropriate measures should be used for each product. Slide 15 PharmOut 2015

16 Cleaning Validation It is recognised that a cleaning validation programme may take some time to complete and validation with verification after each batch may be required for some products No longer looks for 3 consecutive batches Concurrent validation not acceptable for process, but may be acceptable, in some form, for cleaning validation. Slide 16 PharmOut 2015

17 Take Home Points New Annex 15 is more descriptive and has been developed with current industry behaviors in mind Approach is easily aligned with 3 stage FDA PV guidance, while remaining easily relatable for current Annex 15 users. For most companies, new requirements should not pose a dramatic shift Instruction now available for activities previously not addressed Cleaning validation implementation is a significant challenge We are one step closer to harmonization Slide 17 PharmOut 2015

18 Thank you for your time. Questions? Ashley Isbel Lead Consultant Slide 18 PharmOut 2015