CDMOs Pin Hopes for Accelerating Uptake at New US Sites on FDA’s PreCheck Program

 

The initiative could tackle the first-mover disadvantage some CDMOs believe deters early customers, but leaders at companies including Novo Nordisk see hurdles to implementing the changes.

Contract development and manufacturing organizations have identified the FDA’s PreCheck program as an initiative that can benefit new U.S. production plants. Unable to get new facilities inspected before a client files for approval, some service providers say they struggle to sign up initial customers. PreCheck could help, they say.

Big Pharma led the call to decouple facility inspections from drug approval applications when the FDA asked for feedback on its PreCheck program last year. Companies cited the potential for the agency to reject filings on manufacturing grounds late in the review process. Yet the topic is particularly important to CDMOs too, especially in the context of PreCheck’s focus on supporting construction of new U.S. sites.

CDMOs that build new facilities in the U.S. face the challenge of winning business before having their site verified by the FDA, which only inspects production plants when they are named in drug approval filings. Kindeva Drug Delivery told the FDA in written feedback that the uncertainty created by the lack of prior regulatory validation of new sites “has made it difficult to achieve manufacturing contracts with clients.”

The difficulty reflects the first-mover disadvantage created by the current regulatory framework. Namely, the first biopharma companies to outsource work to a new CDMO facility expose themselves to the risk that the site will fall short of FDA standards, leading to the rejection of clients’ drug approval applications.

Christopher Shilling, chief regulatory officer at gene therapy service provider Forge Biologics, told BioSpace that FDA inspectors don’t visit new CDMO facilities until years after the sites are designed. The first visit takes place as the clock ticks down toward the deadline for a decision on an approval filing. In its draft plans for PreCheck, the FDA said it will provide guidance early in the process of bringing a new facility online to avoid costly design flaws and provide confidence that facilities will meet regulatory expectations.

How DMFs Could Drive Contracts

CDMOs have identified the Type V Drug Master Files (DMFs) proposed in PreCheck as a way to address concerns about the readiness of new facilities. The FDA laid out plans to encourage participants in the program to use Type V DMFs to provide comprehensive information on a site’s layout, quality management system and other details specific to the facility.

Drugmakers would then be able to reference Type V DMFs in drug approval filings, relying on the master file for general facility information and focusing their applications instead on product-specific data. For CDMOs, Type V DMFs could offer a way to show a site is acceptable for drug product manufacture based on the systems, equipment and procedures described in the file.

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, a fill-finish service provider, told the FDA that the Type V DMF pathway is the most valuable element of the PreCheck proposal because it “offers the greatest potential to accelerate domestic facility establishment.”

Yet CDMOs and biopharma companies have concerns about Type V DMFs. Lonza, a CDMO, told the FDA it is “particularly cautious regarding 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, “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 wants reassurance that facility information outside the context of a specific drug application “will be handled with appropriate confidentiality and will not create additional or duplicative regulatory obligations.”

Lisa Wright, director of regulatory policy at Novo Nordisk, used the FDA’s PreCheck meeting to raise a concern about how Type V DMFs owned by contract manufacturing organizations (CMOs) will affect biopharma companies that outsource drug production. Wright requested clarity on the logistics of referencing Type V DMFs in drug approval filings.

“If the DMF is owned by a CMO, how are we to utilize that DMF in the most efficient manner?” Wright asked. “Since [the DMF is] not owned by the sponsor submitting the application, that is a big hurdle that I see from a practical perspective.”

Waiting on the FDA

Biopharma companies and CDMOs have yet to receive a public response to their feedback from the FDA. As it stands, questions as fundamental as whether CDMO-run facilities can participate in PreCheck are unanswered. In its written feedback to the FDA, Lonza strongly recommended that CDMOs be included in the program.

“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,” Lonza said. “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.”

https://www.biospace.com/fda/cdmos-pin-hopes-for-accelerating-uptake-at-new-us-sites-on-fdas-precheck-program