Half way through the year 2014 - 04 Jul 2014
It is now middle of the year in 2014 and so feels appropriate to see what changes are in the horizon with respect to Good Manufacturing Practices (GMP) changes. It is universal truth that the only constant is change. And even the conservative GMP regulated environment is not immune to change.
In the EU environment, the following changes are afoot with respect to EU GMP guide:
Changes to Chapter 3 (Premises and Equipment) and Chapter 5 (Production) of the EU GMP guide.
With regards to chapter 3, this is concerned with the revision and expansion of paragraph six of the chapter focusing on controlling cross contamination. The changes made are inter-woven with the revision on Chapter 5. The revision to chapter 5 are reflected in paragraphs 17 to 20 and designed to address issues on cross contamination. Further revisions in paragraphs 26 to 28 addresses issues on the Qualification of Suppliers and supply chain integrity which places the onus on drug manufacturers to ensure that all starting materials utilised originate from controlled sources.
Finalisation of the revision of Chapter 8 (Complaints, Quality Defects and Product Recalls) of the EU GMP Guides
The revision of this chapter highlights the significance of a quality management system for the evaluation of quality defects in relation to product recalls and likewise clarifies the requirements regarding the reporting (when and how) of quality defects to the authority. The revision further stresses the importance of applying the principles of Quality Risk Management in the investigation and assessment of quality defects and to the decision making process in relation to product recalls and other risk-reducing actions.
The revised chapter also details the requirements for written procedures. For instance, there should be established written procedures in relation to recall activities or the implementation of any other risk reducing actions, so that recall operations can be initiated promptly and efficiently. In addition, Mock Recalls are also now described in detail. Evaluation of the effectiveness of the recall procedure should be assessed both during and out of office hour situations. This evaluation should be documented and justified.
In summary, whilst the current Chapter 8 of the guide has less than 2 pages and focuses on complaints and recalls only, the revised guide is six pages long with clearly defined expectations for:
- Personnel and Organisation
- Procedures for handling and investigating complaints including possible quality defects
- Investigation and Decision Making
- Root Cause Analysis and Corrective and Preventative Actions
- Product Recalls and other potential risk-reducing actions
- Finalising the revision of Annexes 15 (Qualification and Validation), 16 (Certification and Batch Release by a QP) and 17 (Parametric Release) of the EU GMP Guide
With respect to Annex 15, the revision clearly reflects the concepts of ICH Q8, 9, 10 and 11. The concept of ‘Design Space’ is now also addressed in the area of Process Validation; Concepts of Risk Management (Q9) are now expected; life cycle concept and process knowledge (Q10) are also embodied in the document.
The revision of annex 16 of the EU guide is expected to clarify which duties have to be performed by a QP and which duties may be delegated.
The revision of Annex 17 is intended to clarify to what extent Q8, Q9 Q10 and Q11 should be followed in order to implement Real Time Release Testing (RTRT). It should also detail how to design a system of release that provides assurance that the product or active substance is of the intended quality.
Chapter 6 on Quality Control
The revision of Chapter 6 (Quality Control) of the EU GMP guide has been finalised. The new chapter will become effective on the 1st October 2014. The main changes include the addition of a new chapter on transfer of analytical methods; requirements to address accidental cross contamination; and the need for all Out of Trend (OOT) and all Out of Specification (OOS) to be investigated.