CBER official stresses importance of preapproval inspection readiness

WASHINGTON – The top compliance official at the US Food and Drug Administration’s (FDA) biologics center said it is imperative for sponsors to schedule preapproval inspections (PAIs) at the midpoint of the review cycle, rather than waiting till later on in the process. Waiting till late in the review process could jeopardize an application, as sponsors will have less time to address any inspection issues.

Melissa Mendoza, director of the Office of Compliance and Biologics Quality (OCBQ), shared insights on inspection readiness, the do's and don'ts for responding to inspections, collaborating with contract manufacturers, and recent Center for Biologics Evaluation and Research (CBER) enforcement actions at the Food and Drug Law Institute’s 2025 Enforcement, Litigation, and Compliance Conference on 4 December.

She emphasized the importance of being prepared for an inspection once the inspection readiness box is checked on the Form 356h, which is the application for marketing a new drug or biologic. “One of the questions on the form is whether the site is ready for an inspection. If the box is checked, we expect the facility to be ready for an inspection,” she said.

Yet there are instances when the box is checked, but the sponsors is not ready for a PAI. “We’re told the facility needs a bit more time or wants to be inspected closer to the decision date, sometimes a month before the decision date. Not only is this difficult for inspectors and reviewers, it seriously disadvantages the applicant and sets them up for failure,” Mendoza said.

“We want to inspect facilities no later than mid cycle, not late cycle, this gives the applicants enough time to respond to the observations well before the decision date and it gives FDA preapproval inspections staff time to prepare and time to resolve any inspection deficiencies,” she added.

This challenge is even greater for supplemental applications, Mendoza noted; if a facility is not ready for an inspection, it complicates the process significantly.

Mendoza recommended sponsors take advantage of available meetings with the review team, ensure they have a robust quality control unit, and to carefully consider audits from foreign authorities.

Although the legal authorities in foreign inspections differ, they often identify the same issues as an FDA inspection would and noted that her office may review a foreign inspection report before conducting its own inspections when a mutual recognition agreement with the a specific foreign authority exists.

She also pointed out that just because a facility has an “extensive manufacturing history” does not mean it is ready for an inspection. Mendoza also advised sponsors to “not dispute reality.” She said that if something is observed by an inspector first-hand, disputing observations “escalates the situation and will not help.”

Her overall take home message was that sponsors should “not rush to market if your facility is not ready.”

Another bit of advice offered by Mendoza was that manufacturers should choose their contract manufacturing partners with care.

“We often see sponsors caught off guard when their contract manufacturers are not ready to take on the manufacturing of their products. Does the contract manufacturer have trained operators or are they still bringing operators on board? If that is the case, that’s not a good sign. It’s not a good sign that the operators will have a handle on the manufacturing process, which could lead to manufacturing deviations. We often see the two go hand-in-hand,” she said.

Mendoza also stressed the importance for sponsors to maintain effective communication with contract manufacturers, and vice versa. This “can significantly impact the quality of a product,” she said.

This year, Mendoza said a key priority for FDA has been targeting manufacturers of unapproved HIV tests and collection kits. Another focus is on sponsors responsible for false and misleading advertising.

Additionally, CBER compliance efforts have focused on producers of unapproved regenerative medicine products, which include items derived from amniotic membrane, placenta, umbilical cords, or adipose tissue. In FY 2025, CBER issued 25 warning letters, with approximately 60% of these letters directed at unapproved regenerative medicines.

In other enforcement areas, Mendoza provided an update on the lawsuit United States v. California Stem Cell Treatment Center which challenged FDA’s authority to regulate certain stem cell procedures as drugs under the federal Food, Drug, and Cosmetic Act (FDCA).

In October 2025, the Supreme Court decided not to hear an appeal from two stem cell clinics in California that were challenging the FDA's authority to regulate certain stem cell procedures as drugs under the federal Food, Drug, and Cosmetic Act (FDCA). By opting not to hear the appeal, the Court upheld a September 2024 ruling from the Ninth Circuit Court of Appeals, which affirmed the FDA's regulatory oversight of these therapies.

CBER official stresses importance of preapproval inspection readiness

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