Contract development and manufacturing organizations (CDMOs) are expressing interest in the U.S. Food and Drug Administration’s PreCheck program, viewing it as a potential solution to challenges faced when opening new production sites in the United States. Currently, these organizations cannot have their facilities inspected by the FDA before a client submits a drug approval application, making it difficult to attract initial customers.
The issue of decoupling facility inspections from drug approval applications was first raised by major pharmaceutical companies during an FDA request for feedback on the PreCheck initiative last year. While large pharmaceutical firms cited concerns about late-stage rejections based on manufacturing issues, CDMOs say the matter is especially significant for them due to PreCheck’s emphasis on supporting new domestic sites.
Under current regulations, the FDA only inspects manufacturing plants once they are named in drug approval filings. Kindeva Drug Delivery provided written feedback to the agency, stating that this lack of prior regulatory validation “has made it difficult to achieve manufacturing contracts with clients.”
This situation results in what industry observers call a first-mover disadvantage: biopharma companies that choose to work with newly built CDMO facilities face the risk that those sites may not meet FDA standards, potentially leading to rejection of their drug applications.
Christopher Shilling, chief regulatory officer at Forge Biologics, told BioSpace that FDA inspectors typically do not visit new CDMO facilities until years after their design phase. The first inspection usually occurs close to deadlines for approval decisions. According to draft plans for PreCheck, the FDA intends to provide guidance early in a facility’s launch process to help avoid costly design mistakes and build confidence that sites will comply with regulations.
One proposed element of PreCheck involves using Type V Drug Master Files (DMFs), which would allow CDMOs to submit detailed information about a facility’s layout and quality management systems. Drugmakers could then reference these DMFs in their product filings, focusing more on product-specific data rather than general site details.
Kindeva said the DMFs “will facilitate the procurement of new clients in the U.S. by quickly establishing domestic manufacturing facilities as cGMP compliant.” Jubilant HollisterStier called this pathway “the most valuable element of the PreCheck proposal because it offers the greatest potential to accelerate domestic facility establishment.”
However, some concerns remain regarding Type V DMFs. Lonza noted caution about “the type and amount of [good manufacturing practice] information that would be required in a Type V DMF as part of the PreCheck program, compared to what is typically reviewed during an on-site inspection.” The company added that “it is important that the scope of information requested for a Type V DMF is clearly delineated and does not duplicate or exceed what is necessary for effective regulatory oversight.” Lonza also emphasized confidentiality and warned against creating extra or redundant regulatory obligations.
Lisa Wright, director of regulatory policy at Novo Nordisk, asked during an FDA meeting how biopharma companies should reference Type V DMFs owned by contract manufacturers when filing for drug approvals: “If the DMF is owned by a CMO, how are we to utilize that DMF in the most efficient manner? Since [the DMF is] not owned by the sponsor submitting the application, that is a big hurdle that I see from a practical perspective.”
To date, neither CDMOs nor biopharma companies have received public answers from the FDA regarding their questions or whether CDMO-run facilities can participate in PreCheck. In its comments submitted to regulators, Lonza argued: “Given the critical role that CDMOs play in the domestic production of pharmaceuticals and APIs, it is essential that the PreCheck program explicitly includes CDMOs,” adding: “Excluding CDMOs from the PreCheck program could inadvertently create gaps in oversight and preparedness, particularly in scenarios where these entities are responsible for high-risk or high-volume products.”
