CBER, CDER Compliance Leaders Outline 2026 Guidance Shifts and Rising GMP Violations

At the 2026 PDA/FDA Joint Regulatory Conference, a "Compliance Office Updates" session saw Vincent Amatrudo, JD, acting director of the Office of Compliance and Biologics Quality (OCBQ) at FDA's Center for Biologics Evaluation and Research (CBER), and Jill Furman, JD, director of the Office of Compliance at FDA's Center for Drug Evaluation and Research (CDER), review recent guidance, enforcement priorities, and warning letter trends spanning both centers.¹

What new guidance is FDA's biologics compliance office advancing?

Amatrudo highlighted several guidance and rulemaking efforts moving through CBER's OCBQ. A March 2026 revision to FDA's pyrogen and endotoxins testing guidance² removed references to the limulus amebocyte lysate (LAL) assay to make clear that alternative methods, including recombinant technologies, may be used, provided sponsors verify the chosen method's suitability for its intended use. Amatrudo tied this shift to agency priorities for reducing and replacing animal testing.

A companion draft guidance on 483 observation responses, also issued in March 2026, spells out recommended content and format for responses and reiterates that firms may dispute individual observations. Amatrudo also pointed to finalized chemistry, manufacturing, and controls (CMC) flexibility guidance for human cellular and gene therapy products,³ which lets sponsors scientifically justify the number of process performance qualification (PPQ) lots submitted rather than defaulting to 3, particularly for products with small patient populations or batch sizes. He said rulemaking on Code of Federal Regulations Title 21 Part 610.13(b),⁴ which governs pyrogen testing requirements for biological products, remains listed on the federal Unified Agenda, alongside a still-in-development draft guidance on alternative microbiological methods.

How is FDA targeting illegal online drug sales?

Furman said at least 40% of FDA's warning letters this year have gone to telehealth companies or unsafe online pharmacies, part of a broader effort against unapproved drugs and unsafe websites that has included outreach to state and medical boards on regulatory issues tied to glucagon-like peptide-1 medications. The agency has also taken action against online sellers of unapproved controlled substances, including opioids and benzodiazepines, and issued warnings over unapproved Botox and ketamine products sold online.

Furman emphasized that FDA's message is the same whether a violation involves a website or a traditional manufacturer. The agency’s rules apply to all. She also flagged ongoing public health priorities, including sustained oversight of ophthalmic products, where sterility failures can have severe consequences, attention to potential drug shortages, and a recent action to preserve newborn access to the lifesaving drug alprostadil.¹

What recurring GMP failures is FDA's drug compliance office seeing?

Furman further described 3 recurring problem areas in CDER warning letters. Sterility and aseptic processing failures remain common, including a jump in facility design violations at sites that don't meet contemporary design standards. In 1 case, a sterile injectable manufacturer released a lot after finding insect larvae in an aseptic filling area and characterized the contamination risk as low.

Falsification of records and data integrity issues, a concern Amatrudo also raised, included a microbiology team leader cutting pages from a laboratory logbook with a knife, original current good manufacturing practice (CGMP) records discovered in a garbage bag, and contaminated lab plates quietly swapped overnight. These findings from 2022-2023 can prompt firms to suspend operations and recall products, Furman said.

Inadequate supplier oversight, including accepting certificates of analysis without verifying their reliability or skipping incoming testing, has also drawn warning letters to finished-product manufacturers as well as their ingredient suppliers and contract testing labs. Furman also said sustained, not transient, compliance requires senior leadership to fund infrastructure upgrades and ensure staff are trained to speak up about problems.

Why did FDA cite a manufacturer over its use of AI?

Furman described the first-ever FDA warning letter for artificial intelligence (AI) use, issued after FDA investigators found the firm had deployed AI agents to generate quality documents, including drug specifications and master production records, without adequate human review, in violation of CGMP recordkeeping and process-validation requirements.⁵ When asked about the absence of process validation, the manufacturer said its AI agent had never indicated the step was required, Furman stated.^1,5

“A key takeaway here is that an AI tool is not a regulatory authority,” Furman stressed at the conference, adding that no amount of training gives such a tool the accountability to substitute for a qualified quality professional. The AI issue accompanied a broader set of violations at the firm, including sanitation deficiencies and inadequate component and finished-product testing.⁵

Looking to 2027, both FDA officials said the agency will lean on risk-based prioritization, proactive outreach such as webinars and guidance documents, and rapid response to emerging public health threats.

The PDA/FDA Joint Regulatory Conference 2026 ran September 14-16, 2026, in Washington, DC. Explore more conference coverage here.

References

1. Parenteral Drug Association. PDA/FDA Joint Regulatory Conference 2026. Accessed September 14-16, 2026. https://www.pda.org/global-event-calendar/event-detail/pda-fda-joint-regulatory-conference-2026#agenda
2. FDA. Guidance for industry, pyrogen and endotoxins testing: questions and answers (CBER, CDER, March 2026). Accessed September 17, 2026. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/pyrogen-and-endotoxins-testing-questions-and-answers
3. FDA. Guidance for industry, chemistry, manufacturing, and controls flexibilities for developing human cellular and gene therapy products for a biologics license application (CBER, May 2026). Accessed September 17, 2026. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/chemistry-manufacturing-and-controls-flexibilities-developing-human-cellular-and-gene-therapy
4. Code of Federal Regulations. Current good manufacturing practice for finished pharmaceuticals. 21 CFR §610.13(b) Accessed September 17, 2026. https://www.ecfr.gov/current/title-21/chapter-I/subchapter-F/part-610/subpart-B/section-610.13
5. FDA. Warning letter: Purolea Cosmetics Lab MARCS-CMS 722591. April 2, 2026. Accessed September 17, 2026. https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/purolea-cosmetics-lab-722591-04022026