The impact of QbD on Quality Assurance and the Qualified Person

Transcription

1 The impact of QbD on Quality Assurance and the Qualified Person Managing the impact of adopting a QbD approach upon the roles and responsibilities of Quality Assurance and the Qualified Person. Derek Murphy, Director, R&D Biologics QA Astra Zeneca Global Operations

2 Introduction Background Why introduce QbD? The role of the Qualified Person Definition of the Qualified Person The role of the QP The impact on QA and the QP Process understanding Process control and oversight QP certification Audit Product Quality Review New challenges and opportunities Summary

3 Why introduce QbD? Shift from Quality by Testing to Quality by Design why? Better product? Better understanding of product and control of manufacturing processes?

4 Why introduce QbD? Shift from Quality by Testing to Quality by Design why? Better product? Better understanding of product and control of manufacturing processes? More efficient delivery of quality medicines to patients Both through development and in-market supply

5 Definition of the Qualified Person (QP) 2001/83/EC, articles, 48, 49, 50, 51 (2001/20/EC article 13 for IMPs) 2001/83/EC Article Member States shall take all appropriate measures to ensure that the qualified person referred to in Article 48, [ ], is responsible,[ ], for securing: (a) in the case of medicinal products manufactured within the Member States concerned, that each batch of medicinal products has been manufactured and checked in compliance with the laws in force in that Member State and in accordance with the requirements of the marketing authorization; (b) in the case of medicinal products coming from third countries, [ ] that each production batch has undergone in a Member State a full qualitative analysis, a quantitative analysis of at least all the active substances and all the other tests or checks necessary to ensure the quality of medicinal products in accordance with the requirements of the marketing authorisation. UK Code of Practice for QPs 13.2 Qualified Persons have duties not only to their employer but also to the Competent Authorities of the Member States and its inspection service.

6 The role of the QP EU guide to GMP, Annex 16, 2.3.2: The certification of the finished product batch performed by a Qualified Person signifying that the batch is in compliance with EU GMP and the requirements of its marketing authorisation (MA) (Product Specification File and CTA for Investigational Medicinal Products). The QP as part of QA: Annex 16; 3.5.3: Certification is recorded in a register or equivalent document. In addition the QP has responsibility for ensuring the following points These may be delegated to appropriately trained personnel or third parties. It is recognised that the QP will need to rely on a quality management system. The QP should have on-going assurance that this reliance is well founded. And do not forget the patient!

7 The impact on QA and the QP Process transfer Process control and oversight QP certification Audit Product Quality Review

8 Process transfer Do the GMP boundaries change? Annex 15 redraft, Quality Standards in Development? Reliance on design space and not classic process validation approach Changes in key information, tools, technologies, ownership. Change in how we validate raw materials. and what about QbD for method validation? New knowledge needed to comment intelligently on QbD documentation

9 Process control and oversight New language to learn and new ways of thinking Raw materials control Shift from end of process checks to in-line checks and Real Time Release Testing Lot release Deviations and Change Management And the Positives! Partner rather than Police! Pro-active v reactive Quicker lot release processes Specifications and controls based upon CQAs QA lot release decisions based on science

10 QP certification Positives Transparency, Better understanding Scientifically based specifications based on scientific justifications related to patient need Core data will change The balance between the QP s role and Competent Authority oversight QP Discretion - EU Guide to GMP, Annex 16: Balanced view but the line is drawn at specification failures

11 Audit Scope of inspection will not change. But QbD Development Design Space Supporting data Knowledge management Controls? QbT Manufacturing Control Strategy Information exchange Understanding Change management Increased liaison between Inspectors and reviewers? Increased liaison between inspectors and reviewers QA as a bridge between functional groups? The role of the QP in the audit

12 Product Quality Review Small but significant changes! Change to data sources Change in who is involved? Change in emphasis? Move to Real Time PQR Within the development cycle and beyond! Challenge is to maintain focus on the patient needs not science?

13 New challenges/opportunities Developing the skill sets and knowledge within functions Product Specification File Defining quality standards in Development Use of Quality System tools in Development QA s central position as an enabler Understanding regulatory expectations with regards to deviations and changes? GMP Development Clinical Supply Tech Transfer Commercial Retirement

14 Summary How to manage the changes There will be changes Changes are prompted by: Changes in expectations (QbT to QbD) Changes to input information Changes to outputs Changes can be managed By planning By education By communication By cooperation. We need to work together to deliver the benefits to the patient!

15 Thank you!