The pharmaceutical industry and the creation of new drugs is expected to continue growing at a steady rate over the next decade. To keep up with this growth, many companies are turning to contract manufacturing organisations (CMOs) to assist with product manufacturing. A key benefit CMOs provide is to maintain a manufacturing footprint, and the skilled talent needed to support product manufacturing. This reduces the need for the product owners to carry these costs or delay progress of their drug development until these resources are directly available. Often CMOs can also assist in bringing products to market more quickly by providing assistance on process and analytical development aspects as well. However, as with most things, the benefits of CMO use also come with some risks.
A CMO can be an important party in the product supply channel. The product sponsor is expected to ensure the CMO is part of a robust supply channel that minimises the risk to patient safety and product supply. To meet this requirement the product sponsor establishes and maintains a diligent quality management strategy for oversight of the CMO. Outsourcing the manufacturing activity does not alleviate the product sponsor from responsibility for the quality and safety of the drug product. This holds true for product manufacturing whenever the product is intended to be consumed by a patient; clinical trials or post-market approval. As outsourcing has become a more common practice, regulatory authorities have evolved their expectations for contract manufacturing oversight.
Regulatory Expectations
Regulatory authorities worldwide understand the need for use of contract manufacturers. This is evident in the guidelines and directives that directly address the expectations for quality oversight of a CMO. For example, the European Commission devotes the entire GMP Chapter 7 to Outsourced Activities and outlines the activities of Contract Giver (Product Sponsor) and Contract Acceptor (CMO). ICH Q10, contains expectations for oversight of outsourced activities. Additionally, the ICH Q9 (R1) updates include the expectation for integrating quality risk management activities into industry operations. That includes the application of QRM to oversight of outsourced activities.
The regulatory authorities have also reiterated that outsourcing does not mean the product sponsor can outsource responsibility for the quality and safety of the drug. Here are two examples of statements the USFDA has made in warning letters related to use of contract manufacturing and responsibilities:
• Responsibilities as a Contractor
FDA is aware that many drug manufacturers use independent contractors such as production facilities,… FDA regards contractors as extensions of the manufacturer. You are responsible for the quality of drugs you produce as a contract facility regardless of agreements in place with product owners.”
• Use of Contract Manufacturers
FDA is aware that many drug manufacturers use independent contractors such as production facilities,… FDA regards contractors as extensions of the manufacturer… You are responsible for the quality of your drugs regardless of agreements in place with your contract facilities.”
