04 qualification and validation overview - DCVMN

1 qualification and validation - an overview - by Dr. Ingrid Walther May 2015, page 1. Definitions qualification . Action of proving that any equipment works correctly and actually leads to the expected results. The word validation is sometimes widened to incorporate the concept of qualification .. EU-GMP- guide , Glossary qualification Action of proving that any premises, systems and items of equipment work correctly and actually lead to the expected results. The meaning of the word validation is sometimes extended to incorporate the concept of qualification . WHO Technical Report Series, No. 961, 2011. qualification is something that has to be done additionally to GEP. It is done for those systems that have a direct impact on product quality. ISPE Baseline Volume 5. May 2015, page 2. Definitions qualification provides documented evidence that equipment is designed and works as it should: qualification equipment-related validation provides documented evidence that processes lead to product of the desired quality and safety: validation process-related Example: baking oven / car May 2015, page 3.

2 Regulatory Background ! WHO-Guideline, WHO Technical Report Series, No. 961, 2011 Section 4. ! EU guide to Good Manufacturing Practice Part 1, Chapters 5 + 6. Annex 11: Computerised Systems Annex 15: qualification and validation , current Version 2001, new version October 2015. Part 2: GMP for Active Pharmaceutical Ingredients ! US-FDA Regulations FDA 21 CFR Parts 210 and 211: CGMP-Regulations Process validation , General Principles and Practice, January 2011. Guides for Inspection ! GAMP 5 (Computerised Systems). ! ..further national regulations and laws May 2015, page 4. Regulatory Background Guidelines (no legal obligation, but should be followed): ! PIC-Document PI 006-3 (Title: validation Master Plan, Installation and Operational qualification , Non-sterile Process validation , Cleaning validation , 25 September 2007). ! ISPE Baseline, Vol. 5, Commissioning and qualification , 2001. January 2008 Draft for comments no new version published yet! Common understanding in all Regulations and Guidelines: " qualification and validation activities are needed to achieve the target of reliable product quality and safe products!

3 May 2015, page 5. Regulatory overview VMP RA DQ IQ OQ PQ PV CV Comp. Val. EU-GMP- guide x x x x x x x x x WHO x x x x x x x x PIC. Document x - x x x x x - PI 006-3. FDA- guide - lines x - - x x x x x x Identi- EU-GMP- fication validation of guide Policy critical x x x x x x x Part 2 para- meters En- ISPE- Commis- Impact hanced Baseline sioning Plan / VMP. Assess- ment Design Review x x x - - - (EDR). GAMP 5 x x x x x x New: URS is expected in EU-GMP- guide ! May 2015, page 6. Different interest groups in qualification qualification shall be done by interdisciplinary teams team members have different attitudes! Eng inee ring p liers Sup QA qualification Supplier Seite 7 May 2015, page 7. Basic Idea of the Guideline: GEP GMP. from: ISPE Baseline guide on Commissioning and qualification , 2000. GEP GMP. Engineers ./. Pharmacists . May 2015, page 8. Different Regulations with different focuses! GEP. ISPE Baseline, Vol. 5, Commissioning and qualification , 2001. GAMP 5 (Computerized Systems).

4 ASTM E2500-7, Standard guide for specification , Design, and Verification of Pharmaceutical and Biopharmaceutical Manufacturing Systems and Equipment, 2007. Common understanding of the GEP and GMP Regulations GEP GMP. " qualification and validation activities are needed to achieve the target of reliable product quality and safe products! May 2015, page 9. qualification and validation overview Impact Assessment VMP. qualification Computer-Val. validation Risk Analyses Risk Analyses Risk Analyses DQ DQ Method validation IQ IQ Process validation Cleaning validation OQ OQ. PQ PQ. May 2015, page 10. Separate responsibilities and target! Entirety of functions of an equipment technical documents /. Technical Acceptance Testing GMP-relevant qualification (only a part of the Functions technical acceptance testing!). Seite 11 May 2015, page 11. Why does the split between GEP and GMP make sense? Pharmaceutical responsibility lies with a pharmacist: He / she is obliged to ensure that all quality relevant process parameters and conditions are under control Approval of qualification documents " pharmacist / biotechnologist may not be able to evaluate ALL technical requirements Technical equipment is often very complex " Fokusing on GMP-aspects in qualification allows the view on the essential In case of authority inspections: " GMPrequirements must be fulfilled and THIS must be documented (the amount of paper does NOT GMP-compliant?)

5 Count!). In production routine: " Formal Change Control is only required for GMP-relevant aspects Reduce documentation effort by separating GEP from GMP! May 2015, page 12. qualification and validation Documents during the Life-Cycle Combined effort between GEP and GMP " What has successfully passed the technical (GEP) testing is considered acceptable for GMP-testing! Basis RA Detail RA. Manufa- Transport/ Process- Routine Engineering Start-up Optimi- cturing Installation Production zation URS FDS / DQ FAT SAT / IQ OQ PQ-Phase PV / RV Re-Val. Change Control / Re- qualification Good Engineering Practice - GEP. May 2015, page 13. What is the basis of ASTM E2500-7? Risk- und science-based approach ICH Q9. - Risik evaluations are based on technical expertise and always target at patient safety - Level of effort, formalty and documentation of the QR process must be commensurate with the risk for the patient critical / relevant aspects of a system must be understood Quality by Design.

6 GEP in this sense serves GMP. Subject Matter Experts (SMEs) participate in the entire process Supplier documentation is available continuous improvement process " reduced qualification effort without compromising patient safety! May 2015, page 14. 1. Step in Risk Assessment: Impact Assessment = Separation into GEP and GMP. Impact Spectrum (ISPE). non-critical no impact . idenfity critical systems " GEP. explain, why non-critical system have been identified as such - non-critical systems are under GEP-control for critical systems: explain the scope of qualification critical direct impact . " GMP. ISPE Baseline: Figure 2-1. May 2015, page 15. 1. Step in Risk Assessment: Impact Assessment = Separation into GEP and GMP. identify systems Commissioning &. develop system boundaries Commissioning qualification yes Impact on product qualify? no yes Indirect Impact Direct Impact . Linkd to DI-System? System System no No Impact System develop supporting rationale GEP GEP and GMP.

7 According to: ISPE Baseline guide on Commissioning and qualification , 2000. May 2015, page 16. Zusa mmenha ng zwis chen de r tec hni sche n und der Qua lifizie rungsdokume nta ti on Tec hnis che D okum ente K onzept st udie Quali fiz ier ungsdok um ente B asic Engineer ing ink l. V alidier ungs mas ter plan H y gienekonz ept +. ( ev. D r uc ks t ufenk onzept ). Good Engineer ing Pr ac ti ces / C hange C ontr ol ( 3). R +I- S chem ata C omput er - Quali fiz ier ungs- V alidier ungs - R ahmenplan ( 3). D etai l-Lay out s R ahmenplan Complex structure of ( 3). P roz e ablauf pl ne E influ auf t echn. ( 3) D ok umente R is ik oanalys en Funk ti onsdiagr am me qualification and validation ( 3). Las tenhef t D et. Z. E ng. E. Leis tungs v erz eic hnis se / D es ignqualif izi erungs - I. Tec hnis che A nfr agespez if ik ation P l ne work and flow of information in g T. f un P r ese n di gege umen te D ok P rot ok olle A ngebots ver handlungen A barbei tung ( ggf.)

8 Nder ungen der D Q- Pl ne projects! A nfor der ungen). B est ellung D Q- Ber ic ht P flic ht enheft ( FS ). B eginn GM P- C hange- C ontr ol " Organization required Quali t t splan L S DS / HD S. i e f ( 2) R ahmenplan R ahmenplan Modul tes t PV RV. e r a I ntegr ations t est n t S ATS / HA TS. K onst r ukt ion / T echn. I Q-P l ne D ok umentat ion ( 1). FA T OQ- P l ne R is ik oanalys e R is ik oanalys e A barbei tung Quali fiz ier ung I nst allat ion der A s- built - P l ne P l ne analy t . P l ne A nlage D ok umentat ion Pr P roz e - Met hoden- R einigungs - - n ac f un g V alidier ung V alidier ung V alidier ung hA. bsc I Q- hlu P rot ok olle ( 1). I BN / S A T. Z. Pr f ung A barbei tung E. nach Abs A bnahme chlu OQ- I. P rot ok olle T. A nalyt . Met hoden- Quali fiz ier ungs- v alidier ung A bsc hlu ber ic ht P. h a S tabili t t s- P roz e - R einigungs - r c hargen v alidier ung m v alidier ung a u n t A bsc hlu - A bsc hlu - e ber ic ht ber ic ht r n e h m A bsc hlu - A bsc hlu - e ber ic ht ber ic ht n A bsc hlu - ber ic ht A pprov al ( FD A / E U ).

9 ( 1) event uell teilw . A bar beitung IQ/ OQ. (V er meidung von D oppeltes t ung QA - Genehmigung ( 2) ber pr fung bei Liefer anten- A udit not wendi g ( 3) kein z eitli cher A blauf , wi cht ige t ec hnisc he Dok ument e ( B eis piele). May 2015, page 17. The validation Master Plan validation work needs to be organised! Implement a validation Project Manual . the validation Master Plan VMP. WHO-Requirement The key elements of a qualification and validation programme of a company should be clearly defined and documented in a validation master plan. May 2015, page 18. The validation Master Plan Annex 15 EU-GMP- guide The VMP or equivalent document should define the qualification validation system and include or reference information on at least the following: i. qualification and validation policy;. ii. The organisational structure including roles and responsibilities for qualification and validation activities;. iii. Summary of the facilities, equipment, systems, processes on site and the qualification and validation status.)

10 Equipment to be qualified processes to be validated summarised and compiled in a matrix format iv. Change control and deviation management for qualification and validation ;. v. Guidance on developing acceptance criteria;. " will be presented in the presentation on Risk Analyses vi. References to existing documents;. vii. The qualification and validation strategy, including requalification, where applicable. May 2015, page 19. The validation Master Plan Possible VMP / QP / VP Structure Valididation Master Plan ( validation Policy). Plant 1 / Line 1 Plant 2 / Line 2 Plant 3 / Line 3 .. qualification qualification qualification Plan Plan Plan validation validation validation Plan Plan Plan Everything described in the VMP / QP / VP must be done! May 2015, page 20. The validation Master Plan i. qualification and validation policy (firm s policy, general description), : Targets Validity (for which Project - how long?). Basic Guidelines (WHO, EU- and US-FDA-cGMP-Guidelines).