Contract manufacturing has become the norm in pharmaceutical industry, and it is necessary that a sponsor and contract manufacturing organization (CMO) make the best use of each other’s experience and facilities for maximum profit to product and patients. As the product manufacture and its release depends on the efforts of two parties, it is essential to have clarity among two parties regarding their roles and responsibilities. Therefore, FDA has issued draft guidance for contract manufacturing, which applies to the commercial manufacturing of active pharmaceutical ingredients, finished drug products, combination products, and biological drug products. The draft guidance incorporates provisions from ICH guidelines, like ICH Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients, ICH Q9 Quality Risk Management, and ICH Q10 Pharmaceutical Quality Systems.
In particular, it describes how the two parties (owner and contracted facilities) involved in the contract manufacturing of drugs can utilize Quality Agreements to delineate their responsibilities and assure drug quality, safety, and efficacy. The owner is defined as the party that introduces a drug into interstate commerce and the, contracted facilities are the outside entities performing manufacturing operations for the product owner. It is the responsibility of owner to ensure that the drug introduced in the interstate commerce is neither adulterated and nor misbranded. And the contracted facility must ensure that the product is manufactured, tested and support activities are performed by following the current good manufacturing practices (cGMP). The owner must conduct an audit of the contract manufacturing site and must ensure that processes are in place to assure the control of activities outsourced to Contracted Facilities and the quality of purchased materials. Therefore, both owners and contracted facilities must work together to establish and maintain quality oversight of contracted manufacturing operations and the materials produced under contracted manufacturing arrangements
FDA recommends that Owners and Contracted Facilities establish a written Quality Agreement to record their respective responsibilities in contract manufacturing arrangements. Owners are ultimately responsible for approving or rejecting drug products manufactured, processed, packed, or held under contract by another company. Although the Quality Unit of each Contracted Facility is responsible for release of the product of the operations it performs, final product release of finished goods for distribution must be carried out by the Owner and cannot be delegated to a Contracted Facility under the cGMP regulations or any terms of the Quality Agreement (21 CFR 211.22(a)).
Quality agreement describes the roles and responsibilities of the Owner and the Contracted Facility to ensure that the product is manufactured in compliance with cGMP. The most critical elements of a Quality Agreement includes responsibility of quality unit, maintenance of facility and equipments, product-specific terms, lab controls and proper up-to-date documentation. Discussion of change control for any type of material and their suppliers, manufacturing process, testing procedures, shipping methods, container closure system, key personnel and product discontinuation should be notified to the owner by the contracted facility. Quality Unit responsibilities are the most critical element of a Quality Agreement, which should define the cGMP responsibilities of each party in detail, including the quality activities and measures.
One contracted facility can provide services to multiple product Owners simultaneously, therefore special care should be taken how the two parties should communicate information without causing cross-contamination and maintaining traceability. The parties to a Quality Agreement should include a communication plan that explains how manufacturing deviations will be relayed to the Owner by the Contracted Facility, and how such deviations will be investigated, documented, and resolved.