EC Releases Revisions of GMP Guidelines

The European Commission (EC) has released the draft revision for four chapters of its good manufacturing practice (GMP) guidelines-chapters 3, 5, 6 and 8.  A public consultation was launched earlier this year with comments due on 18 July 2013. The EC stated that these revisions were needed to reflect the latest thinking relating to best practices.

The proposed changes, available at the EC’s website, are summarised below:

Chapter 3 Premises and Equipment: Section 6 has been revised to address the prevention of cross-contamination in facilities that manufacture multiple products lines. This topic is also addressed in chapter 5. Manufacturers are advised to follow quality-risk-management principles to assess and control all present or inherent risks in the facility.

Reference is made to a new complementary guidance on toxicological assessments relative to setting carryover limits in shared facilities and equipment. The chapter states that risk assessment should include among other parameters a toxicological evaluation of the products being manufactured.

In cases where cross-contamination cannot be adequately controlled by operational or technical measures, the facility will not be allowed to manufacture multiple product lines. The same applies to cases where scientific data does not support threshold values or if threshold values are too difficult to detect.

Chapter 5 Production: The chapter contains several new revisions, including refined guidance on where products should and should not be manufactured (i.e., not in the presence of non-medical products) and the use of technical poisons like pesticides or herbicides (which should not be used in the presence of medical products). Revisions of sections 17–20 are intended to address cross-contamination and refer to toxicological assessment guidance.

Sections 26–28 on the qualification of supplies have been revised to reflect the legal obligation of manufacturing authorisation holders to ensure that active substances are produced in accordance with GMP. The changes also address supply chain traceability in agreement with requirements set out in the 2011 Falsified Medicines Directive.

The chapter states that supporting evidence for each supplier/material approval should be maintained. Staff involved in these activities should have a current knowledge of the suppliers, the supply chain and the associated risks involved. Where possible, starting materials should be purchased directly from the manufacturer of the starting material.

This requirement applies to APIs and excipients which are considered topose a particular risk to the quality of the medicinal product, as explained in the chapter. All starting materials used in the production of medicines should be tested, as should the finished product.

Section 33 has been incorporated to provide clarification on the testing of starting materials as well as to harmonise expectations of manufacturers in this aspect. Section 68 introduces guidance on notification of regulatory authorities of potential drug shortages.

Chapter 6 Quality Control: A new section has been included to address technical transfer of analytical testing methods and other items including out-of-specification results. The chapter states that test methods should be verified to ensure that they are the same as those validated in the original marketing authorisation dossier. Technology transfer between testing facilities must be documented and tested to ensure that 1) it is the same technology, 2) operators are adequately trained, 3) standards are maintained and 4) acceptance criteria is established.

Chapter 8 Complaints, Quality Defects and Product Recalls: Changes have been made to incorporate quality-risk-management principles when investigating quality defects/complaints and when making decisions on product recalls or other risk-mitigating actions; to stress on the need to determine the cause(s) of quality defects/complaints so that necessary actions can be put in place to prevent or minimise recurrence; and to clarify expectations and responsibilities regarding the investigation and reporting of quality defects/complaints to the proper authority.