Implementation of Quality by Design and PAT in the Pharmaceutical industry (INV-19)

Transcription

1 Implementation of Quality by Design and PAT in the Pharmaceutical industry (INV-19) Contract Manufacturing Organisation perspective Ian Flawn Orpana 9 Jun09 1

2 Ian Flawn Orpana Current Business & Technical Director QPharma AB, Sweden Contract Manufacturing Organisation Work experience: Glaxo (Aust), Baxter Healthcare (UK), Roche (UK), Bovis (UK), Ferring (DK) Roles Production Mgr, Technical Support, Consultant Qualifications: BSc (Hons) Applied Biology MSc Pharmaceutical Technology Membership Chartered Biologist Steering Committee member ISPE PAT 2

3 Agenda Define PAT & QbD CMO s attitude to PAT & QbD Potential implementation 3

4 1988: First experience of process understanding In-line measurement Geoff the lead granulator 4

5 Early pharmaceutical experiences Specifications set with limited understanding Tests based upon pharmacopoeia Little process control (mostly) Tripping on time, often equating to shift patterns/t breaks Amazing amount of non value adding documentation Quality by testing Little effort in continuous improvements due to regulatory efforts to support An art not science Limited openness Other departments Regulatory authorities 5

6 1995 SUPAC 2001 PAT Advisory Committee meetings 2002 FDA PAT teams selected & training begins 2003 Interactions with industry The Desired State is articulated Wall Street Journal More technology in make potato chips FDA joins ASTM International Technical Committee E55 on the pharmaceutical application of PAT Nov: EU PAT team formed Important events 2004 Mar: Critical path initiative Sept: Pharmaceutical cgmps for the 21st Century: A Risk-Based Approach. Sept: PAT Guidance document End of yr: EU PAT agreed with FDA guidance document 2005 Nov: Q8(R1): Pharmaceutical Development Nov: Q9: Quality Risk Management QbD 2008 Jun: Q10: Pharmaceutical Quality System 2009 Mar: Experiences by all parties with the implementation of the Q8, Q9 and Q10 guidelines 6

7 Desired state 7 QuestionsandAnswersonCurrentGoodManufacturingPracticescGMPforDrugs/ucm htm#desired

8 PAT Guidance for Industry.it is not a typical Agency guidance Scientific & risk-based framework Support innovation and efficiency: Pharmaceutical development, Manufacturing, Quality assurance Consists of: Set of scientific principles and tools supporting innovation Strategy for regulatory implementation 8

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11 JPI Interviews Moheb Nasr Director, Office of New Drug Quality Assessment (ONDQA), CDER, US FDA [2005] QbD is more global than Process Analytical Technology. PAT fits into QbD very nicely. Focus of PAT is on manufacturing as defined by the FDA guidance as a system to understand, monitor, and control pharmaceutical manufacturing. QbD is more global because it starts with the clinical, through development, formulation status which is not part of PAT, manufacturing, where PAT can be very helpful, and continuous improvement, which PAT advocates, and the quality system and all of that. So I think [QbD] it s much bigger than PAT. But PAT fits into QbD systems. I will also argue that you may not have to use all of the PAT tools to have QbD, but I think it would be of great benefit to use them. Source: 11Journal of Pharmaceutical Innovation Issue Volume 2, Numbers 3-4 / December, 2007

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13 PAT & QbD (1/2) Evolution caused some degree of confusion Srn management were briefed on top level PAT, then it evolved into QbD Source: 3 Oct

14 PAT & QbD (2/2) Caused a degree of misunderstanding Pilot plant objective By Q4 2008, a Pilot Plant is in operation to reduce COGS by increasing process understanding & facilitating continuous improvement PAT (Q8 definition) A system for designing, analyzing, and controlling manufacturing through timely measurements (i.e., during processing) of critical quality and performance attributes of raw and in-process materials and processes with the goal of ensuring final product quality. 14

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16 Current status QbD & PAT grouped together to maximise interest Desired state is the goal Consensus QbD is the higher level aspect of the two acronyms QbD underpinned in the ICH family of documents (Q8_R1,Q9 & Q10) Terminology within ICH documents ~ excellent glossary's 16

17 Fundamental documents to QbD 2005 Nov: Q8(R1) Pharmaceutical Development 2005 Nov: Q9: Quality Risk Management 2008 Jun: Q10: Pharmaceutical Quality System 2009 Mar: Q&A: Experiences by all parties with the implementation ASTM standards Journal of Pharmaceutical Innovation 17

18 A CMO s attitude QbD & its implementation 18

19 Level of implementation of QbD with CMO s Limited due to: Processes developed >10yrs Resources of product owner limited Processes have good safety data High investment cost Often small volumes Strategically like for like process by product owner CMO does not possess skill set to implement Not sufficient case studies to give confidence 19

20 Types of processes Technology transfer Sending & Receiving Units (SU to RU) Types of transfer R&D to Production Early Development to Late Development Late Development to Production Production to Production Relationships Friendly Guarded Hostile 20

21 CMO perspective Strategy 21 Proj Mgt Legal Risk mgt Case study

22 CMO role CMO with Development capabilities vital route Often based within pharmaceutical clusters Supporting small to medium sized pharmaceutical companies Message is strong from customers Processes will be designed with better science Processes will be more robust Facilitate technology transfer 22

23 Initial steps of QbD (1/2) Development Greatest demand Lowest capital investment Straightforward Existing skills Well educated & experience workforce Increased training on advanced statistics Design of experiments Moving from univariate trend analysis to multivariate 23

24 Initial steps of QbD (2/2) Increasing network Attending conferences Community of Practices (ISPE), Controlled Release Society, PDA ASTM E55 ( Consortiums (Chemometrics and Spectroscopy Group) Universities ISPE (PQLI) Product Quality Lifecycle Implementation Scope: Suggest ways to implement ICH guidelines 24

25 Q8 Pharmaceutical Development Quality Target Product Profile Delivery system, strength, container Iterative process Risk Assessments, DoE to assess Critical Quality Attributes & Critical Process Parameters Setting of: Design space Control strategy Monitoring technologies 25

26 Lifecycle approach to QbD Worry is that it will delay time to market Next few years data will be published show effort/costs of QbD New ways of working are needed Cannot go back to the scenario where..more technology in potato chips than.. Phased & iterative approach, end result delivery system showing process understanding 26

27 Issues and trends (1/2) Phased approach Essentially not all process information is needed immediately, but demonstration to authorities on how this will be attained should be shown Openness to authorities Huge variation in API & excipients Manufacturing process cannot manage variability of process Effort needed with QbD in API & excipients 27

28 Issues and trends (2/2) Need good business cases Move final testing wet chemistry into process High cost involved in monitoring equipment & control system associated to medium to low volume products. Tablet production high number of technology islands Continuous manufacturing popular (roller compaction). End 28