On April 14, 2026, the Food and Drug Administration (FDA) issued Compliance Program 7346.832M, Prelicense and Preapproval Inspections of CDER-Regulated Biological Product Manufacturers, effective May 14, 2026. The compliance program governs Center for Drug Evaluation and Research (CDER) pre-license inspections (PLIs) and preapproval inspections (PAIs) of manufacturing facilities to support approval of original and supplemental biologics license applications (BLAs).
The compliance program fills a gap in the FDA’s inspection framework. While both the Center for Biologics Evaluation and Research (CBER) and CDER regulate biological products (see our earlier advisory), the FDA assigns responsibility based on product category, mechanism of action, and center expertise. Vaccines, cell and gene therapies, and blood- or plasma-derived products fall under CBER, which already has a standard operating procedure (SOPP 8410). Therapeutic proteins, monoclonal antibodies, and enzymes are regulated by CDER, which until now lacked a comparable inspection program.
Scope of the New Compliance Program
The compliance program applies to CDER-regulated biological products licensed under Section 351 of the Public Health Service Act, including both stand-alone 351(a) BLAs and abbreviated 351(k) BLAs for biosimilar and interchangeable biosimilar products. For a fuller discussion of these two pathways, see our advisory.
The FDA does not distinguish between the inspectional approaches used to support approval of original or supplemental 351(a) and 351(k) BLAs. Whether the CDER-regulated biological product is a stand-alone biologic or a biosimilar, the FDA will use the same compliance program to determine the need for a PLI or PAI and guide the scope of any inspection.
Compliance Program 7346.832M differs from Compliance Program 7346.832, Preapproval Inspections, which applies to PAIs of manufacturing facilities in support of pending new drug applications (NDAs) and abbreviated new drug applications (ANDAs). Although both programs address preapproval inspections, the term “PAI” differs in meaning. Under Compliance Program 7346.832, PAI generally refers to an inspection supporting approval of a pending NDA or ANDA. Under Compliance Program 7346.832M, the FDA distinguishes between PLIs and PAIs for BLAs:
- A PLI is an inspection of a facility that manufactures a new biological product subject to an original BLA.
- A PAI is an inspection of a facility that manufactures a licensed biological product for which the applicant has submitted a supplement for a significant manufacturing change, such as a prior approval supplement, that requires on-site review.
In short, inspections supporting an original BLA are generally PLIs, while inspections supporting post-approval manufacturing changes of an already licensed biologic are PAIs.
The Role of the Office of Pharmaceutical Quality
A key feature of the compliance program is the central role of the FDA’s Office of Pharmaceutical Quality (OPQ), particularly the Office of Pharmaceutical Manufacturing Assessment (OPMA). Unlike routine surveillance inspections conducted by the Office of Inspections and Investigations, PLIs and PAIs for CDER-regulated biological products are closely integrated with BLA reviews. OPMA determines whether a PLI or PAI is needed and makes the final recommendation to approve or withhold when the inspection review is complete.
Historically, OPMA was known as the Office of Process and Facilities, reflecting its role in evaluating both manufacturing facilities and process elements such as process development, scale-up, process control, and facility readiness. OPMA facility reviewers bring scientific, facility, process, and inspection expertise to the inspection. Because OPMA is directly involved in application assessment, the inspection teams have product-specific knowledge from the BLA, including the proposed manufacturing process, control strategy, validation package, facility information, and application commitments. For BLA applicants, this means a PLI or a PAI is an application-integrated inspection led by a team with detailed knowledge of the BLA.
Although PLIs and PAIs are intended to support a regulatory decision on a specific biological product, the findings can have broader implications if the FDA identifies broader facility or quality system concerns that affect other products. Significant findings may also affect other pending applications that rely on the same facility.
When the inspection uncovers critical or systemic current good manufacturing practice (CGMP) deficiencies, including data integrity deficiencies, OPQ will communicate those deficiencies in the complete response letter (CRL), as well as with CDER’s Office of Compliance, and discuss next steps, including a potential official action indicated (OAI) alert or a follow-up inspection. For this reason, BLA applicants should be diligent in conducting inspection readiness activities.
How the FDA Determines Whether a PLI or PAI Is Needed
The new program describes a risk-based approach in determining whether a PLI or PAI is necessary. The integrated quality assessment team considers:
- The manufacturing operations described in the application.
- Prior inspection history.
- Prior assessment of the same or similar operations.
- Product and process complexity.
- Quality signals.
The FDA may also use alternative tools in lieu of, or before, an inspection. For example, the compliance program identifies inspection reports and information from foreign regulatory partners, records requests under Section 704(a)(4) of the Federal Food, Drug, and Cosmetic Act, and remote interactive evaluations. The FDA’s Staff Manual Guide 6001.1 states that a records request under Section 704(a)(4) can be used in lieu of, or before, a PLI or PAI to support assessment of an application.
Two Inspection Objectives
The FDA identifies two primary objectives for PLIs and PAIs.
The first objective is to evaluate and verify application commitments and compliance with applicable CGMP requirement. This objective is product-specific and maps to six CGMP system elements, including quality systems, facilities and equipment, materials management, production and process controls, laboratory controls, and packaging, labeling, storage, and shipping.
The second objective is to evaluate the integrity of the data associated with the application. To do so, inspection teams select a subset of application data to audit on-site for accuracy and completeness. The FDA notes that the teams should audit data with issues or risks identified during the application assessment. BLA applicants should be aware that inspection teams will know where to look because they are integrated with the application assessment. The team will understand what data were submitted, how those data support the proposed control strategy, and where the key product and process risks may be.
Practical Tips for BLA Applicants
Submit a manufacturing schedule with the BLA
Applicants should provide a preliminary manufacturing schedule with the BLA submission. As we have discussed, 21 C.F.R. § 601.20 requires facilities to be in operation and to manufacture the product under review during the prelicense inspection.
Ensure consistency in inspection responses
Form 483 response strategies for PLIs differ from those for typical surveillance inspections. In routine surveillance inspections, an OII investigator conducts the inspection and prepares the establishment inspection report (EIR), while a compliance officer from Office of Compliance separately evaluates the findings.
For PLIs, by contrast, the same OPQ team will review the BLA, conduct the PLI, and review the response. Accordingly, consistency is critical across written responses, information submitted in the BLA, and on-site communications.
For an overview of the FDA’s recent guidance on Form 483 responses, see our advisory.
Conclusion
Compliance Program 7346.832M provides a long-awaited framework for pre-license and preapproval inspections of CDER-regulated biological products. The program clarifies how the FDA will evaluate commercial readiness, application commitments, CGMP compliance, and data integrity for both 351(a) and 351(k) BLAs. BLA applicants should prepare for an application-integrated inspection led by OPQ reviewers with specialized product, process, facility, and inspection expertise.
If you have questions about preparing for, or responding to findings in, a prelicense inspection or need assistance with compliance strategies, please contact us.
If you have any questions, or would like additional information, please contact one of the attorneys on our FDA: Compliance & Enforcement team.
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