The draft guidance released in May called on CMOs (contract manufacturing organizations) and pharma companies to create quality agreements delineating responsibilities between the contractors and the owners of the products.
Although the FDA does not require such quality agreements by law, warning letters have been issued because of a lack of an agreement, so companies seem weary to let the legal status of the guidance affect how seriously they take it.
Among the 34 comments posted to the draft guidance docket, most sought more clarity on the FDA’s thinking on the quality agreements.
For instance, Sanofi’s head of regulatory policy, Linda Bowen, seeks clarity on the scope of the guidance, noting that a quality agreement “should only make reference to issues related to quality (testing results, sampling, etc.) and should not refer to financial or purely business related disagreements.”
Pfizer begins its comments by noting that an ICH (International Conference on Harmonization) working group is preparing a Q&A that will address a number of the same issues addressed in the guidance and the company suggests waiting on that Q&A to ensure alignment.
SOCMA’s (Society of Chemical Manufacturing Association) Bulk Pharmaceutical Task Force echoes Pfizer’s and Sanofi’s pleas for clarity and says the FDA should provide a definition for the term “contract manufacturing” as it applies to the manufacture of APIs, finished dose forms, combo products and biologics.
Quality Agreement Details
Pfizer also seeks more information from the FDA on whether it expects firms that manufacture drug substances and drug products to maintain quality agreements with raw material suppliers.
“This draft Guidance Document does not appear to include as contracted/outsourced activities the routine supply of raw materials to a firm that holds a BLA and internally performs all manufacturing activities for both” drug substance and product, Pfizer says. “If there is such an expectation, it is not clear how a firm’s routine supplier management controls, such as on site supplier audits, supply channel surveys and periodic reassessment of supplier performance, would mitigate the potential need for quality agreements between a firm and a raw material supplier.”
It is also not clear, according to Pfizer, if drug manufacturers need to establish quality agreements with excipient suppliers or other suppliers that help with the manufacturing process.
In addition, the guidance says that CMOs need to provide notification of each activity at a facility to the owner of the drug, but the BPTF says that cross-notification of each CMO activity across a facility “could violate the confidentiality agreements of other customers.”
Celgene similarly questions the scope of what should be included in an agreement, as it “is critical that the Product Owner and Contracted Facility understand how cross-contamination is prevented and traceability maintained and the respective responsibilities should be in any Quality Agreement, but the communication of that information is a very detailed topic to be included in a Quality Agreement.”
GlaxoSmithKline also notes a few instances where details that the guidance says should be in a quality agreement might be better suited for a supplier agreement.