Pharmaceutical Quality Systems ICH Q 10 Concepts Implementation

Pharmaceutical Quality Systems (ICH Q 10) Concepts & Implementation SAPRAA Meeting 19 th 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 Q 10 ? • Implementation advice • Summary

What is the Objective of any System? (Using ICH Q 10 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?

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 Quality System Production System Facilities & Equipment System Laboratory Controls System Materials System Packaging & Labeling System

FUNDAMENTALS OF ICH Q 10 FDA for the 21 st Century approach provides the road map for Q 10

ICH Q 10 OBJECTIVES Product Realization State of Control Continual Improvement (Compliance)

Fundamentals of Q 10 Development Commercial Tech Transfermanag Supply Discontinue GMP

Fundamentals of Q 10 Monitoring Systems Development Commercial Tech Transfermanag Supply Discontinue GMP

Fundamentals of Q 10 Monitoring Systems Development CAPA Systems Commercial Tech Transfermanag Supply Discontinue GMP

Fundamentals of Q 10 Monitoring Systems Development CAPA Systems Commercial Tech Transfermanag Supply Discontinue GMP Change Management

Fundamentals of Q 10 Monitoring Systems Development CAPA Systems Commercial Tech Transfermanag Supply Discontinue GMP Management Review Change Management

Fundamentals of Q 10 Monitoring Systems Development Quality Risk Management Commercial Tech Transfermanag Supply CAPA Systems Discontinue GMP Management Review Change Management

Q 9 Risk Based Approach (2005) Initiate Quality Risk Management Process Risk Assessment T eam foc us ed Risk Identification Risk Analysis S takeho lder involvement Internal consu ltation unacceptable Risk Control Risk Reduction Risk Acceptance Output / Result of the Quality Risk Management Process Risk Review Events R is k Ma nag e m ent too ls R is k C o m m u n ic ation Risk Evaluation

Fundamentals of Q 10 Monitoring Systems Development Quality Risk Management Commercial Tech Transfermanag Supply CAPA Systems 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 Q 10 SENIOR MANAGEMENT RESPONSIBILITY Monitoring Systems Development Quality Risk Management Commercial Tech Transfermanag Supply CAPA Systems Discontinue GMP Management Review Knowledge Management Change Management

Q 10 Management Responsibilities for a Pharmaceutical Quality System (P 4 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 Q 10 is not intended to create any new expectations beyond current regulatory requirements", and anything within ICH Q 10 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 Q 10 requires an understanding of FDA for the 21 st Century, ICH Q 8 (Design), ICH Q 9 (Risk) as well as ISO 9000 (2005) to maximize benefit • ICH Q 10 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 • GMP for the 21 st century www. fda. gov/cder/gmp 2004/GMP_finalreport 2004. htm • International Conference on Harmonisation, ICH Q 8: Pharmaceutical Development, November 2005. http: //www. ich. org/ • International Conference on Harmonisation, ICH Q 9: Quality Risk Management, November 2005. http: //www. ich. org/ • International Conference on Harmonisation, Draft Consensus Guideline, ICH Q 10: 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 2008 By: Adrian Kirk. Pharmaceutical Technology Europe