Globalisation and outsourcing of manufacturing, as well as the rise of quality-by-design (QbD), have increased technology transfer within and between companies and countries. In light of these changes the European Medicines Agency (EMA) believes its Chapter 6 guidance needs revising.
The EMA is acting after good manufacturing practice (GMP) inspectors identified lack of test method validation, in the context of transfer of analytical methods, as the cause of a number of suspected out-of-specification (OOS) results.
Action to address the situation, which frequently occurs at contract quality control laboratories, has now been initiated by the EMA. A concept paper for the revised Chapter 6 was accepted in September, and published online this week , with a February 2011 deadline for comments.
The new Chapter 6 will consider: guidance in Annexes 16,19 and 20; ICH Q8, Q9 and Q10; the ICH Q11 draft; ongoing changes to Chapters 4,7 and Annex 11; and development of near infrared spectroscopy (NIR) for raw material identification and process analytical technology (PAT).
Specific guidance for endotoxin and microbiological testing will also be considered. Having considered all these elements and comments the EMA intends to create guidance on transfer of analytical methods between laboratories to support industry and inspectors.
A draft document will be prepared for September 2011 and then discussed, with a final draft being adopted in February 2012. This will be followed by a public consultation lasting a minimum of three months with the final document being adopted towards the end of 2012.
Impact on industry
The EMA expects the adoption of clear requirements for transfer of analytical methods will place additional burden on some companies that are yet to implement such a process. Changes to clarify guidance to harmonise regulatory policy would not have resource implications.
Finally, the EMA will also consider the affect on Annex 8 in the context of raw material identification as part of its anticipated impact assessment.
Chapter 5 & 7 revisions
Revisions to Chapter 6 are part of broader changes by the EMA. For instance, proposed revisions to Chapter 5 will ensure documentation reflects “the legal obligation of manufacturing authorisation holders to ensure that active substances are produced in accordance with GMP”.
Furthermore, the revisions introduce supply chain traceability for starting materials. This obliges manufacturers to record where each active substance is “manufactured, propagated, processed and handled”.
Revisions to Chapter 7 have also been proposed. These changes provide guidance on “outsourced GMP regulated activities beyond the current scope of contract manufacture and analysis operations”.