EC Updates Guidance to Ensure Supplier Compliance

The European Commission has updated its GMP guidance to notify manufacturing authorization holders (MAHs) of their legal obligation to ensure that active substances are produced in accordance with GMP.

Through audits of active substance manufacturers and distributors, MAHs are now required to ensure that their suppliers meet GMP and good distribution practice standards. Excipients “should be given similar attention to those for active substances,” according to the updated guidance released last week.

The commission’s revisions are related to four different chapters on GMP guidance for drug production, quality control, equipment and premises, as well as complaints, quality defects and product recalls.

Under the guidance on production, MAHs are now required to ensure supply chain traceability and notify competent authorities at least two months before constraints in manufacturing operations will cause either a temporary or permanent shortage.

In addition, the revised guidance calls for manufacturers’ quality requirements to be discussed and agreed with suppliers. The agreement should incorporate aspects of the production and control processes, including handling, labelling, packaging and distribution requirements, complaints, recalls and rejection procedures, according to the commission.

Manufacturers can use partial or full test results from the approved starting material manufacturer ”but must, as a minimum, perform identification testing of each batch themselves,” according to the new guidance.

The supply chain and traceability records for each active substance should be available and retained by the EEA-based manufacturer or importer of the drug, the guideline says. And if possible, the commission recommends that “starting materials should be purchased directly from the manufacturer of the starting material.”

Other revisions include:

  • A new section in chapter six of the GMP guidance on the technical transfer of testing methods and other items such as out of specification results;
  • Additional emphasis in chapter eight on the need for the cause(s) of quality defects/complaints to be investigated, and so appropriate preventative actions are put in place; and
  • Further integrations with the new European Medicines Agency guidance on ways to prevent cross-contamination from multiple drugs produced at shared facilities.

 Comments on the revised GMP guidelines are due July 18 and they are expected to come into operation soon after the comments are received.

Meanwhile, the European Commission has set a Jan. 31 deadline for finalizing its amended first chapter on the GMP guidelines, which is part of plans to align quality system guidelines with the International Conference on Harmonisation’s Q10 guidance.

The US Food and Drug Administration is also expected to issue guidance sometime soon on what drugmakers are required to share with CMOs and other suppliers, officials said in September.