By Tim Clarot, Industry Consultant
Empty shelves in supermarkets, cars selling at above list price, and a critical shortage of shipping containers are some of the visible effects of a supply chain breaking down because of COVID-19. Consider, then, how much more important supply chain issues are when you manufacture regulated products like pharmaceuticals, where your supply chain not only must work from a manufacturing and distribution standpoint, but must also comply with current good manufacturing practices (CGMP).
This article is the first in a series of four that will outline the responsibilities that each owner of a pharmaceutical product must meet and maintain to ensure that their supply chain is robust and compliant with CGMP. The definition of the supply chain includes all phases or systems that are required to produce a finished pharmaceutical product—quality, facilities/equipment, materials, production, packaging components, and laboratory. Generally, supply chain is used to characterize materials, distribution, and/or ingredients that are required to make a product. This series of articles, however, will use it to describe the manufacturing controls that are necessary to produce a compliant drug. Another term needing definition is “owner.” This is not necessarily a financial term or one that identifies the head of the corporation, but instead is the party that introduces (or causes the introduction of) a drug into interstate commerce. From FDA’s perspective, this distinction is necessary as it allows them to directly interface with the party that will make the decision regarding remediation or recall. It’s important to note that the individual responsible for making the final approval for the release of drugs to the market must have the necessary education and experience and be empowered to make that decision.
For many reasons, it makes sound business sense to outsource some or a majority of the supply chain. It’s not uncommon that warehousing or laboratory services utilize a third-party partner. Well-established, large pharma companies will often use contract manufacturing organizations (CMOs) for project work, to avoid capital expenditures or because of capacity constraints; small virtual companies might depend exclusively on a CMO. Whatever the reason, outsourcing some or all of the supply chain can be efficient and produce a quality finished product. However, there must be controls and oversight by the owner. FDA has clearly identified all elements of the drug supply chain as critical steps in product quality. The agency routinely issues inspection observations (and Warning Letters) for adulterated or misbranded products when a product is not manufactured, processed, packed, or held pursuant to CGMPs.
On the surface, it might seem that the delineation of quality responsibilities is straightforward: the CMO is responsible for CGMP for all operations that are performed in its facility, and the product owner must make the final decision on release. The real answer is that the parties must be aligned, and their collective and individual responsibilities clearly outlined. Each step in the process must be documented and sequenced to ensure product quality and regulatory compliance. FDA expects that these responsibilities are captured in a written Quality Agreement.
The next article in this series will focus on the management of a CMO, starting with vendor selection and auditing; the third article will discuss the elements of a Quality Agreement; and the last will outline the framework for a Master Service Agreement. The concepts discussed in each of the articles is based on operational experience, not legal opinion. Therefore, before implementing any changes to an existing quality program, it is strongly advised that you review your program with a regulatory professional.
Author: Tim Clarot is a consultant for Church & Dwight, where he was formerly Senior Vice President of R&D and Product Quality. With 40 years’ experience working directly with federal, state, and local regulators, Tim specializes in the regulatory framework of food (including dietary supplements), medical devices, and drugs (homeopathic and allopathic), both in the United States and internationally. He has also chaired company-sponsored scientific and medical advisory boards. He has served on AAHP’s Legal and Regulatory Committee since 2015 and on the Board of Directors since 2018. He can be reached at TClarot@gmail.com.