Derek Murphy,

Director, R&D Biologics QA

Astra Zeneca Global Operations

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.

Introduction

• Why introduce QbD?

• The role of the Qualified Person

• Definition of the Qualified Person

• The role of the QP

Background

• Process understanding

• Process control and oversight

• QP certification

• Audit

• Product Quality Review

The impact on QA and the QP

New challenges and opportunities

Summary

Why introduce QbD?

Shift from Quality by Testing to Quality by Design – why?

Better product?

Better understanding of product and control of manufacturing

processes?

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

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 51

– 1. 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.

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 3.5.4 – 3.5.22.

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!

The impact on QA and the QP

Process transfer

Process control and oversight

QP certification

Audit

Product Quality Review

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

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

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

Audit

Scope of inspection will not change. But…

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

QbD

Development Design Space

Supporting data

Knowledge management

Controls?

QbT

Manufacturing Control Strategy

Information exchange

Understanding

Change management

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?

New challenges/opportunities

Developing the skill sets and knowledge within

functions

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

Product Specification File

Clinical Supply Tech Transfer Development Commercial Retirement

GMP ?

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!

Thank you!