Until final regulations are finished, the US FDA has released draft guidance describing the agency’s expectations for outsourcing facilities and the cGMP requirements for them.
Under the Drug Quality and Security Act, a new section called 503B is added to the FD&C Act, under which a drug compounder can register as an outsourcing facility with the FDA.
This interim guidance reflects FDA’s intent to recognize the differences between compounding outsourcing facilities and conventional drug manufacturers, and to tailor cGMP (current good manufacturing practice) requirements to the nature of the specific compounding operations conducted by outsourcing facilities while maintaining the minimum standards necessary to protect patients.
The guidance lays out specifics on facility design, environmental and personnel monitoring, equipment, production and process controls, release testing, lab controls and other areas of potential concern.
The agency said it does not intend to take action against an outsourcing facility regarding the identification or testing of each lot if all of the following conditions are met:
• The component is an approved finished human drug product;
• The component was purchased directly from a manufacturer who has registered and listed with FDA without repacking or other alteration since initial manufacture, or was purchased from a distributor that certifies that the component has not been subject to repacking or other alteration since initial manufacture;
• The label of each lot of the component has been examined to verify that the component meets required specifications before use; and
• The shipment’s package integrity has been verified upon receipt before use.
FDA is also requesting public comment on possible alternative approaches that would enable an outsourcing facility to have confidence in the quality of incoming components without periodic laboratory testing following initial qualification testing to confirm the information in the supplier’s certificate of analysis (COA).
Under this potential alternative approach, FDA would not intend to take action against an outsourcing facility regarding additional testing to confirm the supplier’s COA if (1) the supplier submits to FDA a drug master file (DMF) containing the information outlined below, (2) FDA has reviewed the DMF and issued a letter to the DMF holder stating that FDA has no further comments, (3) the DMF holder has provided a copy of that letter to the outsourcing facility, and (4) the outsourcing facility maintains a copy of the letter that can be produced during an inspection.
Other Moves to Deal with Compounders
In addition to this proposed draft guidance, the FDA has issued a proposed rule that would revise the FDA’s current list of drug products that may not be compounded because the drug products have been withdrawn or removed from the market because they were found to be unsafe or not effective. The proposed rule would modify the description of one drug product on the list and add 25 drug products to the list.
Meanwhile, two Federal Register Notices note that the FDA is reopening the nomination process for two lists of active pharmaceutical ingredients that may be used to compound drug products. One list is for drug products compounded in accordance with section 503A , and the other list is for drug products compounded in accordance with section 503B of the FD&C Act.
The agency also has issued final guidance for individuals or pharmacies that intend to compound drugs.