Revision of the EU GMP Guide: EU Commission Publishes Comments for Chapters 3, 5, 6 and 8

On 17 January 2013, the EU Commission published the drafts of 4 revised chapters of the EU GMP Guide. Responses to the public consultation have now been published on the EU Commission website.

What were the major changes?

Paragraph 6 of Chapter 3 Premise and Equipment has been revised and extended. It contains regulations on how to avoid cross-contamination. The changes made are tightly interlinked with the revised contents of Chapter 5 Production. The requirements expressed also refer to a new guideline on dedicated facilities which has been published recently by the EMA.

The revisions made in Chapter 5 Production can be found in the paragraphs 17 to 20. These revisions also refer the question of how to avoid cross-contamination. All the revisions now submitted as a draft have been intensively discussed between the EU authorities and the industry. In addition, paragraphs 26 to 28 on Qualification of Suppliers have also been modified. The changes take into consideration the new requirements according to which the manufacturer of a medicinal product has to ensure that the APIs have been manufactured in compliance with the GMP regulations. So-called "supply chain security" requirements have also been added. Now, the drug manufacturer must also ensure that all the starting materials used originate from controlled sources. Moreover, there are new requirements now with regard to the control of starting materials and the obligation to inform authorities when a medicinal product is no longer available for GMP reasons.

Chapter 6 Quality Control now provides new requirements on the transfer of analytical methods as well as new regulations about the handling of out-of-specification results.

Chapter 8 Complaints and Product Recall points out — among other things — 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.

Stakeholders such as pharmaceutical companies and industry organisations have now sent in their comments and concerns. Jean-Denis Mallet, member of the ECA Advisory Board has also sent in his point of view.

Some of the major challenges seem to be

Chapters 3 and 5:

• Need to be read in conjunction with the draft EMA guideline on setting health based exposure limits for use in risk identification
• Use of toxicologist specifically required to evaluate allowable limits of carryover
• Tighter allowable limits — use of dedicated equipment and facilities
• Supply chain security requirements for APIs

Chapter 8: Complaints, Quality Defects & Product Recalls

• Quality management system required to evaluate product defects