Pharmaceutical Quality Systems (ICH Q10) Concepts

Pharmaceutical Quality Systems (ICH Q10) Concepts & Implementation SAPRAA Meeting 19th June 2009 Chris Stubbs

Presentation Outline What is the objective of any System ? What is expected of us in terms of Quality Systems? Fundamentals of ICH Q10 ? Implementation advice Summary ICH Q10

What is the Objective of any System? (Using ICH Q10 as an example) ORGANIZATIONAL OPTIMIZATION Development Tech transfer Commercial Discontinuation Product Realization State of Control Continual Improvement System Boundaries ie full Life Cycle Compliance “Quality is a side effect of a system that is running well”

What is expected of us in terms of Quality Systems?

MCC Guide MEDICINES CONTROL COUNCIL GUIDE TO GOOD MANUFACTURING PRACTICE FOR MEDICINES IN SOUTH AFRICA

SA Guide to GMP (Common to all GMP Guides) CHAPTER 1 QUALITY MANAGEMENT 1.1 PRINCIPLE 1.1.1 The holder of a manufacturing licence must manufacture medicinal products so as to ensure that they are fit for their intended use, comply with the requirements of the medicine registration and do not place patients at risk due to inadequate safety, quality or efficacy. 1.1.2 The attainment of this quality objective is the responsibility of senior management and requires the participation and commitment by staff in many different departments and at all levels within the company, by the company's suppliers and by the distributors. 1.1.3 To achieve the quality objective reliably, there must be a comprehensively designed and correctly implemented system of Quality Assurance, Incorporating Good Manufacturing Practice and thus Quality Control and Quality Risk Management.

GMP – MCC/PICs Guide QUALITY UNIT PRODUCTS & MATERIALS PEOPLE PRODUCTION MNGMENT QUALITY MANAGEMENT EQUIPMENT FACILITIES

FDA – 6 Systems Approach FDA Quality Systems Quality System Production System Facilities & Equipment System Laboratory Controls System Materials System Packaging & Labeling System

FUNDAMENTALS OF ICH Q10 FDA for the 21st Century approach provides the road map for Q10

ICH Q10 OBJECTIVES Product Realization State of Control Continual Improvement (Compliance)

Fundamentals of Q10 Development Tech Transfer manag Commercial Supply Discontinue GMP

Fundamentals of Q10 Monitoring Systems Development Tech Transfer manag Commercial Supply Discontinue GMP

Fundamentals of Q10 Monitoring Systems Development CAPA Systems Tech Transfer manag Commercial Supply Discontinue GMP

Fundamentals of Q10 Monitoring Systems Development CAPA Systems Tech Transfer manag Commercial Supply Discontinue GMP Change Management

Fundamentals of Q10 Monitoring Systems Development CAPA Systems Tech Transfer manag Commercial Supply Discontinue GMP Management Review Change Management

Fundamentals of Q10 Monitoring Systems Development Quality Risk Management Tech Transfer manag CAPA Systems Commercial Supply Discontinue GMP Management Review Change Management

Q9 Risk Based Approach (2005) Initiate Quality Risk Management Process Risk Assessment Team focu sed Risk Identification Risk Analysis Risk Evaluation Internal consultation Stakeholder involvement Ri s k Co m m u n ic ation Risk Control Risk Reduction Risk Acceptance Output / Result of the Quality Risk Management Process Risk Review Review Events R i s k Ma nag e m ent tool s unacceptable

Fundamentals of Q10 Monitoring Systems Development Quality Risk Management Tech Transfer manag CAPA Systems Commercial Supply Discontinue GMP Management Review Knowledge Management Change Management

Knowledge Management Example: Quality By Design Christopher Sinko, Ph.D. Pfizer Global Research & Development Integrity Uniformity Weight Control In vitro Dissolution Chemical Purity API, Excipients, Manufacturing Process Pharmaceutics Profile Chemical Compatibility Process Simulation API Particle Size API Salt Selection Design Degradation Pathway Prediction Material Property Characterization

Fundamentals of Q10 SENIOR MANAGEMENT RESPONSIBILITY Monitoring Systems Development Quality Risk Management Tech Transfer manag CAPA Systems Commercial Supply Discontinue GMP Management Review Knowledge Management Change Management

Q10 Management Responsibilities for a Pharmaceutical Quality System (P4 Section 2) Senior Management has ultimate responsibility Have to participate Demonstrate strong & visible support Effective communication to appropriate levels of management Define roles, responsibilities authorities & inter-relationships Conduct Management reviews of product Quality, Process performance & Pharmaceutical Quality System performance Advocate continual improvement Commit appropriate resource Why do we need more guidance when the is all covered in GMP – refer section 1.1.2 & 1.1.3 of the GMP Guide ?

IMPLEMENTATION ADVICE FOR Q 10

IMPLEMENTATION REALITIES The guidance specifically states that: "ICH Q10 is not intended to create any new expectations beyond current regulatory requirements", and anything within ICH Q10 that is additional to current GMP requirements is "optional" rather than obligatory Implementation of these initiatives on top of current “rules based Quality Management Systems” will drown your Company in additional Resources and associated expenses Re-implementation of your Quality Management System based on these initiatives can create innovative ways to explore the latest efficiency improvements while still complying to GMP

Advice on how NOT to start High Management Team will See Value and Integrate Into Daily Performance Management Team Leadership Kick Off Fanfare Get System Ready Low Quality System Implementation Start End

Advice on What Works High Management Team see Value and have Integrated Into Daily Performance Management Team Leadership Integrate into Business Objectives STOP Get System Ready Kick Off Fanfare Low Quality System Implementation Start End

Advice on approaches that work The Head of the Unit and not the QA Manager/RP has to be seen as the driver of any implementation (think like a fox!) Always have a separate meeting (called by Head) to discuss the status of your QMS until implementation is complete: paradox- NOT at normal management meetings as QMS issues will be diluted by “more important issues” STOP and wait if you have to – Sub optimization leads to negative perceptions of value & results in management doubts A good Quality System should eventually be the backbone of a “Business Excellence System” but if it gets weighed down too early it will breakdown – Allow it to get strong before adding additional “modules” - irony: As the management team get excited they will want to use it for more (and break it) so you have to defend the system until the entire system is strong enough (and mature enough) to take on more processes

Summary ICH Q10 requires an understanding of FDA for the 21 st Century, ICH Q8 (Design), ICH Q9 (Risk) as well as ISO 9000 (2005) to maximize benefit ICH Q10 is an ISO SYSTEMS approach to GMP NOT additional to GMP but integral to GMP Covers full life Cycle of a Product Objectives: Product Realization, Control & Improvement DEMANDS Management Team to lead Quality System Seek compliance only and you will get compliance only The toughest implementation battles are internal so look for internal Allies before going outside for support

THANK YOU Selected References follow

References References GMP for the 21st century www.fda.gov/cder/gmp/gmp2004/GMP finalreport2004.htm International Conference on Harmonisation, ICH Q8: Pharmaceutical Development, November 2005. http://www.ich.org/ International Conference on Harmonisation, ICH Q9: Quality Risk Management, November 2005. http://www.ich.org/ International Conference on Harmonisation, Draft Consensus Guideline, ICH Q10: Pharmaceutical Quality System, May 2007. http://www.ich.org/ FDA, Guidance for Industry: Quality Systems Approach to Pharmaceutical CGMP Regulations, September 2006. http://www.fda.gov/ 01 January 2008By:Adrian KirkPharmaceutical Technology Europe