Contract Manufacturing as a Topic in a new Warning Letter

The topics of supplier qualification, contracts and Quality Oversight  are not new. They are part of the Pharmaceutical Quality System (PQS). Also in other industries these tasks are an indispensable part of supplier management and co-operation. It is therefore surprising that this still leads to observations in GMP inspections. This has now happened at a company in the USA which was inspected by the US Food and Drug Administration FDA. The FDA has now published a so-called Warning Letter.

The inspected company Sircle Laboratories, like many other companies, works with contract manufacturing organisations (CMOs). However, according to the FDA, the company lacks the necessary overview and procedures for dealing with CMOs.

For example, the FDA criticizes the company for failing to follow "established quality unit (QU) procedures" as well as" commitments documented in quality agreements (QAs)". Examples are:

Inadequate Quality Oversight

CMOs were not adequately supervised and controlled, resulting in "sub-standard CMOs" being appointed. A CMO has received a Warning Letter because of "failure to establish appropriate time limits for each stage of production" and in investigating out-of-specification (OOS) results. However, Sircle Laboratories had not responded adequately and had not conducted a retrospective review.
The FDA now expects a comprehensive evaluation plan " to ensure that suppliers are suitably qualified and appropriate oversight is maintained".

Inadequate instructions and compliance

There was a failure to establish adequate written responsibilities and procedures for the review of batches manufactured by CMOs. Relevant production records of the CMO were not reviewed even though this was supposed to be done. How the release of medicines from CMOs should be done was not defined.

Non-compliance with the change control procedures

In the same Warning Letter, the FDA also criticized the change control procedures in the company, e.g. in the case of complaints and labelling of medicinal products, etc.