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This is our biweekly recap of news and industry happenings curated for our paid subscribers. Our goal is to bring you the headline news and the stories, research, and insights that might be harder to find.

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Here are some key items from the past couple of weeks.

💊 = Pharma, biologic, and biotech.
💉 = Medical device, medtech, diagnostics, and digital health.

FDA Leadership and Administration

• Senior leadership overhaul follows Makary’s exit: The FDA cleared out much of its senior team in a shake-up. Tracy Beth Høeg, acting director of the Center for Drug Evaluation and Research, said she was given the choice to resign or be terminated and chose to be fired. Mike Davis, a former acting director, now leads CDER. Katherine Szarama was moved into an advisor role and replaced as acting CBER director by Karim Mikhail, the former CEO of Amarin who most recently advised Makary. Chief of Staff Jim Traficant was reassigned, with Lowell Zeta taking over his duties. Jeremy Walsh, the FDA’s first chief artificial intelligence officer, resigned, and no successor has been named.

• Eight senior roles are now filled on an acting basis: The FDA’s leadership roster includes acting officials in the commissioner, CBER director, CDER director, chief information officer, chief of staff, deputy commissioner for food, associate commissioner for external affairs, and director of the Center for Tobacco Products positions. The breadth of the turnover suggests the agency will stay relatively quiet until a permanent commissioner is confirmed.

• The shake-up reads as a clean break from Makary: The removal of Makary’s close advisors appears deliberate, a signal that leadership decisions had been made by multiple people rather than one. Acting Commissioner Kyle Diamantas has reportedly so far kept a low profile, sticking to traditional announcement channels rather than the frequent podcast and conference appearances his predecessor favored.

• Commissioner search narrows as candidates rule themselves out: Brett Giroir, a former acting commissioner, wrote that he asked not to be advanced for the role, citing family and work obligations. Former Commissioner Stephen Hahn joined Turn Therapeutics as its executive clinical and regulatory lead, which all but ends speculation about his return. Former Oncology Center of Excellence Director Rick Pazdur spoke at a healthcare conference but stopped short of putting his name forward. Houman Hemmati, an ophthalmologist and biotech executive, posted a photo from the office of Sen. Tommy Tuberville (R-Ala.), a member of the committee that will vote on the next commissioner.

• Oncology staff departures continue: Paz Vellanki, most recently associate director of the Division of Oncology 2, which oversees lung, head, and neck cancers, left to join Precision for Medicine as vice president of clinical development for oncology. The exit adds to a steady run of oncology departures over recent months.

FDA General

• PDUFA technical negotiations have wrapped up: 💊 The FDA concluded technical negotiations on the Prescription Drug User Fee Act commitment letter, the document that sets out what the agency will do over a five-year period in exchange for industry user fees. Several steps remain before the letter is finalized, including FDA and industry ratification, HHS and OMB clearance, public comment, re-clearance, and transmittal to Congress. Those steps have historically taken several months, with the text usually available in late summer or fall.

• CNPV program will be reassessed, and its council role is shrinking: 💊 The Commissioner’s National Priority Voucher program will continue despite Makary’s departure, but the FDA plans to reassess it after a June 4 input meeting. The agency is also making one notable change: the council of senior FDA leaders that initially weighed in on approval decisions will no longer be routinely required for applications. That council’s early prominence had raised concerns about political interference in drug reviews. The change could shift the program to function more like Real-Time Oncology Review.

• Real-time trials pilot gets a longer comment window: 💊 The FDA extended the comment period for its early-phase real-time clinical trials pilot by 30 days, to June 29, after the Alliance for Regenerative Medicine asked for more time. The agency had wanted to set selection criteria by July and complete selections by August. The future of the effort is uncertain: Jeremy Walsh, who led the pilot and coordinated the broader real-time trials work, resigned within hours of leading a May 15 industry session, and the broader project no longer has a clear internal champion.

• Final human factors guidance published: 💉 The FDA released its final guidance on the content of human factors information in medical device marketing submissions, a document it had worked on for a decade with drafts in 2016 and 2022. Human factors covers how a device will be used and the testing needed to confirm that intended and actual use don’t cause errors or safety problems. CDRH described the guidance as deregulatory, intended to reduce the amount of human factors information manufacturers must submit based on risk. The document carries a minimum 60-day implementation timeline and runs 20 pages longer than the 2022 draft, mostly because of three new appendices.

• Draft guidance streamlines nonclinical safety studies for oncology drugs: 💊 A new draft guidance supports streamlined approaches that avoid unnecessary animal use for oncology biologics and conjugated products. Sponsors can propose alternatives to the standard three-month general toxicology studies, including non-sacrificial study designs, designs that reduce animal numbers, or a weight-of-evidence risk assessment for products with well-understood targets. Sponsors can supplement these with data from new approach methodologies given appropriate scientific justification. The FDA said the guidance could also shorten oncology development timelines.

• Final M11 guidance on electronic structured protocols: 💊 The FDA published the final M11 guidance, finalized last year by the International Council for Harmonisation. It provides a template for the ICH’s Clinical Electronic Structured Harmonised Protocol (CeSHarP) and defines key terms, page elements, and formatting.

• 71 new and revised product-specific generic guidances: 💊 The FDA released 71 product-specific guidances that help generic developers design acceptable bioequivalence studies. The batch includes guidances tied to drugs such as Otezla, Procysbi, Qfitlia, Rytelo, Gomekli, and Brukinsa.

• Two final generic bioequivalence guidances: 💊 The FDA finalized two guidances on generic drug bioequivalence. One is a practical how-to for designing studies using pharmacokinetic endpoints. The second covers statistical approaches to establishing bioequivalence.

• Food-effect guidance updated: 💊 The FDA made minor updates to its 2022 guidance on assessing how food affects investigational drugs, including grammatical changes and the removal of an appendix of labeling examples. The agency did not explain why the appendix was removed.

• BSUFA negotiations continue: 💊 The FDA and the biosimilars industry are still working through proposals for the next Biosimilar User Fee Act agreement. At an April 16 meeting, the agency responded to an industry proposal on supplement classifications for chemistry, manufacturing, and control issues, shared a counterproposal on the Pediatric Research Equity Act, and heard a new industry plan on Investigational New Drug protocols.

• Outlook wins dispute resolution appeal on eye drug: 💊 After three rejections, Outlook Therapeutics won an appeal through the FDA’s formal dispute resolution process for its ophthalmic formulation of bevacizumab, which treats neovascular age-related macular degeneration. The FDA determined the company had established substantial evidence of effectiveness and directed its review offices to work with Outlook on final labeling. Outlook plans to resubmit in June and expects a Class 1 classification with a decision about 60 days later.

• Camizestrant decision date pushed: 💊 AstraZeneca said the FDA extended the user fee goal date for camizestrant in combination with a CDK4/6 inhibitor for first-line treatment of certain advanced breast cancers with an emergent ESR1 mutation. The extension gives the agency time to review additional requested data, including ctDNA clearance data linked to longer-term efficacy. An advisory committee voted 6-3 against the drug’s demonstrated benefit in late April, finding the circulating tumor DNA switching paradigm in the pivotal trial unsupported by the data.

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We recently shared some observations on how a new eQMS can be underbuilt for the stage a company is entering. Today, we have an actual case study that shows what that risk looks like in a real operation.

A clinical-stage biotech approached us after it ran an internal quality review and found a documentation issue. The eQMS it had been using since its early days wasn’t producing audit trails that met 21 CFR Part 11. The out-of-the-box system also didn’t have genuine access controls. Users could change fields in a document's metadata, and those permissions had been open for a while.

The company’s initial assessment left it unable to determine whether the documentation it had generated remained trustworthy under regulatory requirements. In the worst-case scenario, the issue could call its clinical programs into question. The team recognized that it needed an outside perspective from someone who had scoped similar problems before, and it needed that support quickly.

We placed a seasoned QA consultant inside the organization within days. Just a few weeks later, he had:

• Isolated the system vulnerabilities.

• Confirmed through statistical sampling that the document library was intact.

• Built a remediation plan to ensure data integrity and system configuration requirements.

The damage was more contained than the company had feared, but the platform underneath it still wasn’t fit for purpose at the company’s current stage.

By the end, the company had interim controls in place, a Part 11 compliance assessment on the record, and clear recommendations to migrate to a more capable platform. They moved forward with the migration.

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Separating a system vulnerability from a data integrity failure

This pattern repeats across the industry more often than most companies like to admit: A small biotech in its early stages needs a quick QMS, but budget is tight, and there’s no eQMS specialist on staff. Typically, the high-level team reviews a handful of options, picks one that demos well, implements it with minimal configuration, and drives ahead with a focus on drug discovery and development (and not an eQMS).

For the first year or two, this works well enough. Then the company grows and its clinical programs (hopefully) advance. The compliance footprint widens, and regulatory expectations get more specific. The system that was fine in the early days starts showing gaps. By the time anyone looks closely, there’s a panicked realization that those gaps have been open for a long time.

That’s where this engagement started. The eQMS had been deployed out of the box with almost no customization or user requirements. As the company grew, several issues came into focus:

• The platform’s audit trail didn’t meet Part 11. The company believed it had audit trail coverage, but its internal definition didn’t match what regulators expect: a tracked record of who changed what, when, and why.

• Access controls were effectively absent. The system was wide open to all users at the same level. Anyone could modify document metadata, form field labels, or file names without restriction. No read-only tier, role-based access, or training gate before a user could make changes.

• Because changes weren’t controlled or tracked, the company couldn’t confirm that the original versions of documents across the system were still intact.

That last point is what created the urgency in this case. The company had an active clinical program. If the document library had been compromised at scale, the implications would extend well beyond the quality system.

Containing the risk, documenting the evidence, and defining the path forward

Our consultant came in with a background in clinical auditing and QMS systems and moved quickly to scope the actual risk rather than the assumed worst-case scenario.

The first priority was to answer a question the company could not resolve on its own: whether it had a data integrity issue or an unexploited system vulnerability. He conducted a statistical sampling exercise across the document library, comparing current versions with original records across quality, regulatory, and CMC functions. The sampling results were clean, indicating that the library had not been compromised at scale. But the review did identify system vulnerabilities.

Our consultant worked with the QMS supplier to document the quality event, root cause, and interim controls implemented by the supplier. Together, the client and QMS supplier reviewed the system’s configuration, installation, and ongoing management. This review provided objective evidence and established a clear understanding of the situation.

With that question resolved through the investigational work, the effort was split into two workstreams:

1. Putting interim controls in place so the system was no longer wide open. The consultant established role-based access tiers (read-only, workflow execution, administrative), required training before access was granted and required demonstrated competency before any user could operate at higher permission levels. The vulnerability that had allowed unrestricted changes was closed.

2. Second, a full Part 11 compliance assessment of the eQMS itself. The assessment concluded that the platform, even with new controls, wasn’t adequate for the company’s current regulatory posture. The out-of-the-box system had been workable at an earlier stage of regulatory expectations. But it wasn’t workable now, going into clinical trials. The recommendation was either a full revalidation with significant modifications and testing or migration to a system better suited to where the company actually was.

In this case, the company chose to migrate to another system. Throughout the engagement, the consultant documented findings and remediation actions in a format suitable for a health authority, should one ever ask. A clean, defensible record of what was found, what was done about it, and what came next. If a regulator brought the issue up in an inspection, the company wouldn’t be caught flat-footed.

What the company had in place by the end of the engagement

The engagement ran for several months. By the end, the company had:

The internal team came out with a clearer view of what Part 11 actually requires and what to look for in their next platform. Our consultant’s read: the worst part of the situation had been the uncertainty. Once the scope was defined and the document integrity sampling came back clean, the path forward was workable.

The broader lesson here

This case is less about one company’s eQMS than about a pattern we see repeating across growing biotechs.

Out-of-the-box eQMS platforms are sold aggressively to early-stage companies with small budgets. The demos look polished, and sales teams run an effective playbook. For a company in its earliest stages, the platform may provide a complaint system for a while. The problem arises later, when nobody goes back to reassess the system's validation as the company’s compliance needs change. What worked at proof of concept doesn’t work in clinical operations. By the time someone notices, the gap has been open for months or years.

Our consultant’s advice to any company in a similar position: build your processes first, then make the system fit them. Not the other way around! And if you implemented a QMS early without doing the fit-for-purpose work to back it up, have someone with systems and compliance experience review it before a regulator does.

Need eQMS support? Let’s talk!

If your company implemented a quality management system early and hasn’t revisited whether it still meets regulatory requirements, you may be carrying compliance gaps you don’t know about.

We can place a consultant with eQMS assessment and Part 11 compliance experience inside your organization to evaluate the system, surface vulnerabilities, and build a remediation or migration plan before a regulator asks the same questions.

We also help firms with their very first QMS builds. To talk through your current situation, drop us a line.

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The FDA Group helps life science organizations rapidly access the industry's best consultants, contractors, and candidates. Our resources assist in every stage of the product lifecycle, from clinical development to commercialization, with a focus on Quality Assurance, Regulatory Affairs, and Clinical Operations.

With thousands of resources worldwide, hundreds of whom are former FDA, we meet your precise resourcing needs through a fast, convenient talent selection process supported by a Total Quality Guarantee. Learn more and schedule a call with us to see if we’re a fit to help you access specialized professionals and execute your projects on time and on budget.

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With so many new subscribers now coming to the newsletter each week, we’re resharing one of our favorite conversations from a few years back.

We’re bringing it back because it’s just as relevant today as it was when it was recorded, and Chris offers a wealth of knowledge on pre-approval inspections, 483 responses, and what FDA investigators are actually looking for. We’ve also been deploying quite a few auditors for PAI readiness recently, and the topic is always important.

Chris is a former FDA investigator who spent over a decade at the agency before moving into industry and consulting. The conversation covers what most companies misunderstand about pre-approval inspections, and the practical things that separate a smooth inspection from a painful one.

Chris began his career as an FDA investigator in the Detroit district, conducting GxP inspections across foods, drugs, biologics, and devices. He was one of seven people selected for the FDA’s Executive Development Program and advanced through headquarters roles in public affairs, congressional affairs, and the commissioner’s office, ultimately serving as Deputy Associate Commissioner for Public Affairs.

He was one of the key authors of the FDA’s major rewrite of the IND and NDA regulations in the 1980s, and he managed the tamper-resistant packaging regulations that followed the 1982 Tylenol cyanide poisonings. After the agency, he held senior regulatory and quality roles at Abbott Laboratories, AAIPharma, and Endeavor Pharmaceuticals before founding Coastal Pharmaceutical Consultants, which he ran for 12 years.

He’s now retired on his farm in North Carolina.

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Chris's key insights and practical takeaways

If you're short on time, here are the most important lessons from the discussion.

• There are no secrets about pre-approval inspections, and the FDA wants you to know that. The agency publishes compliance program guides on its website that tell its own field and headquarters staff exactly what investigators should cover, what they write up, where reports go, and what recommendations compliance officers should make. There’s a specific guide for pre-approval inspections. Chris’s point: this material exists to educate the FDA’s own people, and industry can read the same thing to prepare. The information is public. Most companies just don’t go looking for it!

• The PAI program exists because the field and headquarters used to operate in (sort of) isolation. Chris described an inspection of a new Parke-Davis sterile facility in Detroit early in his FDA career. The team found problems and issued a substantial 483. Two days after the report reached headquarters, the drug was approved and announced in the press. The field and the headquarters reviewers weren’t talking to each other. Around 1999, the FDA moved to fix that, partly by creating the pre-approval inspection program and sending headquarters reviewers into the field.

• A PAI checks three specific things. First, whether what you said in your application matches what you actually have. Investigators look at the raw data behind your claims. If you said you have stability data supporting a two-year expiration date, they’ll want to see the raw stability data. Second, commercial readiness. If the FDA approves you tomorrow, is the plant truly ready to make a commercial product? Third, data integrity, which has only grown in importance since the program started.

• A PAI is focused, but it can expand. Unlike a general inspection where the investigator can wander in and decide to look at the water system or the labs or manufacturing on a whim, a pre-approval inspection has a stated purpose tied to your pending application. You know what they’re there to look at. That said, if they find a problem, they can widen the scope.

• FDA’s public dashboard is a genuinely useful preparation tool. The agency posts inspection data, recall data, top citations, and trends. Nick walked through it during the conversation. The broader theme connects back to the start: this isn’t secret information! The FDA has gotten much better at putting data on its website, even if the search function makes it hard to find. The top citations alone tell you where inspectors are finding problems.

• ICH guidances aren’t law, and the FDA can’t write you up for ignoring one directly. An FDA investigator inspects you against your application, against good manufacturing practices, and against good clinical practices, not against ICH guidance documents or even the FDA’s own guidance documents, which don’t carry the force of regulation. The nuance is that when the FDA has adopted an ICH guidance as its own, it usually links it to an underlying regulatory requirement, and that requirement is what they cite. It’s worth watching what EMA, Health Canada, ANVISA, and PMDA are doing, along with technical reports from groups like PDA, to understand what inspectors broadly are focused on.

• The biggest misconception: forgetting that the FDA’s job is to be the cop, not the consultant. When an investigator finds something they consider out of compliance, the natural question is “what should I do to fix it?” Investigators are trained not to answer that. It isn’t the agency’s job, the advice could backfire, and a different investigator might recommend something different and create a mess. Chris’s analogy runs throughout the conversation: the investigator is a cop on the beat, and the 483 is the ticket. You can argue your case before they write it, but once it’s written, your recourse is your day in court.

• You’re allowed to disagree with the agency. A misconception Chris sees often is that companies feel they can’t push back. If you have good science and you’ve made a sound decision, an investigator disagreeing doesn’t automatically make them right. Before they write an observation into a 483, you have the chance to explain your reasoning and potentially avoid it entirely. The conversation matters.

• New or out-of-area investigators can produce surprises, and that’s worth understanding. Companies sometimes call Chris saying they’ve operated for 25 years without an issue and suddenly received a 483 full of observations. His first question: was it a new investigator? Often the answer is yes. There’s pressure on younger investigators to demonstrate they can find problems, to earn their stripes. The FDA also moves people around more now, sending someone from California to inspect a plant in Connecticut where they know no one. None of that makes the observation wrong, but it explains the pattern. As Chris puts it, telling the cop you always drive 90 down this street doesn’t make it right. This time you got caught.

• The biggest weakness Chris sees in industry: investigations that are written for insiders. Deviations happen. Machines break, people make mistakes, experiments go wrong. FDA expects that. What matters is that you document what happened, follow your procedures, investigate, and put a corrective action in place. The failure is in the writing. Companies write investigations using their own acronyms, referencing their own procedures, assuming familiarity with equipment the reader has never seen. But the investigator doesn’t work at your company. An investigator should be able to read your investigation, whether it’s one page or twenty-five, and reach the end thinking “I know exactly what happened and you handled it right,” rather than walking away with fifty questions. Write for a layperson who doesn’t know your systems.

• Apply the same logic to your 483 response. Don’t write the response as if you’re still talking to the investigator who was in the room. That person already understands what they wrote up. Your response gets read by people at the district office who weren’t at your plant, and possibly by headquarters reviewers who know nothing about your firm or its reputation. That’s your opportunity to lay out your argument clearly, to explain where the inspector missed a point or where there’s more to the story, so that someone with no context gets a clear picture.

• The 15-day warning letter response window is short, and Chris agrees it’s unfair. Both Chris and Nick see the irony. The FDA can take months to issue a warning letter and sometimes a year to provide an establishment inspection report, even for inspections with no findings, yet companies get 15 days to respond. You can file for an extension, and you can make commitments about when you’ll deliver a fuller response. But the asymmetry is real. Part of the reason nobody fights it: when you’ve received a warning letter, you want the spotlight off you as fast as possible, so the unreasonableness of the timeline becomes a secondary concern.

• Warning letters now often recommend hiring an outside firm, and that benefits everyone. Chris, as a former FDA investigator, was struck that the agency now sometimes recommends bringing in a consultant to help remediate. Nick has reviewed many warning letters that include exactly that. The shared point: FDA isn’t trying to shut companies down or prove the company is bad. The agency wants businesses running, people employed, and safe products reaching patients. Getting expert help moves a company back toward a compliant state faster and ends the costly cycle of reinspections.

• Some of the hardest cases are small, family-owned firms that never built a culture of quality. Chris and Nick both see a recurring pattern: a business started by a parent or grandparent, now run by the next generation, making a few products, with the FDA having visited a few times as a low priority. Then a new investigator or a team arrives, finds practices that wouldn’t pass scrutiny, and the owners are genuinely shocked. A related problem Nick raises: reviewing the CV of the person responsible for quality and finding they aren’t qualified for the role. Startups founded by academics or clinicians can fall into a version of this, too, focused on the cure they believe in while treating manufacturing as an afterthought, when the FDA considers manufacturing just as important. A drug that isn’t made correctly won’t help the patient even if the science is sound.

• Don’t be afraid! If you are, that fear is telling you something. Chris’s closing advice: if you’re afraid of the FDA walking in the door, ask why. If you’re worried about what your people will say, train them. If you’re worried about what they’ll find in the lab or in manufacturing, fix it first. Educate yourself on what the FDA looks at. Understand the team approach, where a sterile manufacturer might see a microbiologist examining the micro lab, an engineer reviewing water and air systems, and a reviewing chemist from headquarters asking questions based on your application. Be honest, be cooperative, and be willing to manage the logistics, asking whether something can happen tomorrow morning or whether the right person can lead a particular tour. Most good investigators will work with you to make the inspection successful.

One thing to bring back to your team

Pull one of your recent deviation investigations and hand it to someone who doesn’t work in your department. Then ask:

• Can they reach the end and explain what happened, why it happened, and what you did about it, without asking you a single question?

• Did you spell out the acronyms, explain the equipment, and walk through the procedure references, or did you assume knowledge a stranger wouldn’t have?

• If an FDA investigator pulled this document tomorrow, would it build their confidence in your systems or generate fifty questions?

• Now do the same thing with your most recent 483 response, if you have one. Was it written for the inspector who was in the room, or for the headquarters reviewer who has never set foot in your facility and doesn’t know your reputation?

The companies that handle inspections well aren’t the ones with no deviations. They’re the ones whose documentation tells a clear story to someone who wasn’t there.

Christopher Smith spent his career across the FDA, large and small pharmaceutical companies, and contract research organizations, with 47 years of experience in the industry. He began as an FDA investigator in the Detroit district, conducting GXP inspections, and spent 12 years at the agency in roles of increasing responsibility, including Assistant Director of Congressional Operations, Associate Director of Program Management, and Deputy Associate Commissioner for Public Affairs. He was one of the key authors of the FDA's last major rewrite of the IND and NDA regulations in the 1980s and managed several other FDA initiatives, including the tamper-resistant packaging regulations that followed the 1982 Tylenol cyanide poisonings. After the FDA, he served as Associate Director of Regulatory Affairs at Abbott Laboratories, held senior regulatory and quality leadership roles at AAIPharma, and was Vice President of Regulatory Affairs and Quality Assurance at Endeavor Pharmaceuticals, a women's health startup later sold to Barr Laboratories. He founded Coastal Pharmaceutical Consultants in 2011 and ran it for 12 years, conducting GMP and GCP audits, supporting firms through FDA inspections worldwide, and helping clients respond to 483s and warning letters. He’s now retired.

Connect with Chris on LinkedIn here.

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The FDA Group helps life science organizations rapidly access the industry's best consultants, contractors, and candidates. Our resources assist in every stage of the product lifecycle, from clinical development to commercialization, with a focus on staff augmentation, auditing, remediation, QMS, and other specialized project work in Quality Assurance, Regulatory Affairs, and Clinical Operations.

With over 3,750 resources worldwide, over 325 of whom are former FDA, we meet your precise resourcing needs through a fast, convenient talent selection process supported by a Total Quality Guarantee.

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Check out our newly launched AI-powered QMS audit tool, AICA (the Audit Intelligence Compliance Assistant).

Welcome to Insider issue #49.

Also, hello to the 522 life science professionals who joined us last month. If you haven’t already upgraded to a paid subscription to unlock our in-depth analysis issues like this one, you can do so here. Read our past deep dives here.

This month, Jesse Hart breaks down CDER's draft guidance for new approach methodologies in drug development: the four-pillar framework, the validation-versus-qualification distinction, and where programs typically fall short. Jonathan Wacks explains the finalized Patient Preference Information guidance and how to structure a PPI initiative. And Judson Russell dissects the warning letter to PhysiTemp Instruments and what it teaches about 510(k) exemption claims, process validation, and complaint handling.

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It’s been hard to keep up with all the personnel changes at the FDA recently. In the last few weeks alone, the agency has lost its commissioner, the heads of both its drug and biologics review centers, and its chief of staff.

Here’s what happened and who’s sitting in which chair right now in case you’ve been too busy to be following the news.

Makary resigns as commissioner

On May 12, FDA Commissioner Marty Makary resigned after a little over a year in the role. The sort of “proximate” cause was an acute clash over the agency’s first-ever authorization of flavored e-cigarettes. Multiple outlets reported that President Trump pressured Makary to approve fruit-flavored vapes from Glas Inc., which Makary opposed. Rather than testify before Congress the next day defending a decision he didn’t support, he stepped down.

Makary’s tenure has been pretty bumpy from the start. Mass layoffs hit the agency under DOGE, senior career officials left or were reportedly pressured out, and the agency drew criticism from both industry and public health groups over inconsistent drug review decisions. Career FDA staff told CBS News there was widespread relief inside the building when he resigned.

Kyle Diamantas, the FDA’s deputy commissioner for food, stepped in as acting commissioner. Diamantas is a lawyer, not a physician or scientist, which is unusual for the role. According to CNN, the White House hopes to nominate a permanent replacement by early June. No candidate has been publicly named.

Høeg leaves CDER

Three days after Makary’s exit, Tracy Beth Høeg was, in her own words, fired as acting director of CDER, the center responsible for reviewing prescription and OTC drugs, generics, and biological therapeutics.

Høeg had held the role since December 2025 and was the fifth person to occupy it during the Trump administration.

Here’s the full CDER leadership chain since January 2025:

Davis is a longtime FDA career official and psychiatrist who served as CDER’s deputy center director. He has an MD/PhD from Case Western Reserve and spent years in CDER’s Office of New Drugs reviewing psychiatric drugs before moving into senior leadership. He is the new acting CDER director.

Høeg was known for her skepticism toward vaccines and some antidepressants, positions aligned with HHS Secretary Robert F. Kennedy Jr. During her time at FDA, she led an overhaul of the childhood immunization schedule that reduced the number of recommended vaccines for children. That drew strong criticism from mainstream public health organizations.

Szarama replaced at CBER (after 10 days)

Over at CBER, which oversees vaccines, gene therapies, blood products, and biologics, Katherine Szarama was replaced as acting director after roughly 10 days on the job. Szarama had stepped in when Vinay Prasad left at the end of April.

Prasad’s own CBER tenure was a saga. He was first appointed in May 2025 after Peter Marks resigned over vaccine policy disagreements with RFK Jr. Prasad left in July 2025, then came back two weeks later, then departed again in April 2026, officially to return to his faculty position at UCSF.

Szarama’s replacement is Karim Mikhail, a former biopharma executive who spent 20+ years at Merck and later served as CEO of Amarin Corporation. He joined the FDA last year as a senior advisor in the Office of the Commissioner and is now CBER’s fourth acting director and sixth leader since January 2025.

Other changes

The agency’s chief of staff, Jim Traficant, was also removed. Lowell Zeta is now acting chief of staff. Rich Danker, a top HHS spokesman who had worked with Makary on communications strategy, resigned over the flavored e-cigarette decision. HHS Director of Public Strategy Mitchell Hailstone also departed recently.

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We’ve been seeing a specific situation pretty regularly: a growing clinical-stage firm discovers that the eQMS it bought maybe two years ago doesn’t actually meet Part 11 requirements. The vendor oversold an underbuilt system, and there wasn’t anyone around to realize it.

But eventually, someone with systems and compliance experience finally takes a close look and the gaps are obvious. And even more worrying, they’ve been open the whole time.

The eQMS platforms themselves aren’t the whole problem here. Many of them work well enough. The problem is what happens during implementation. A small, early-stage team buys a system, installs whatever comes in the default configuration, and starts using it without doing any fit-for-purpose work. The salesperson's demo looked great, but it was in a developed environment. What you get out of the box is something different.

Here’s where most companies that are getting started with their first eQMS need to do work they haven’t done yet based on what we’re seeing in the field.

Audit trails

This is the one that in our exeerience creates the most regulatory exposure.

Part 11 requires that electronic records maintain a complete audit trail: who made a change, what was changed, when it happened, and why. Most eQMS platforms will tell you they support audit trails. Technically, some of them do. But “supports audit trails” and “produces Part 11-compliant audit trails in the default configuration” are different claims.

In practice, companies assume they have coverage because, again, the vendor said so during the sales process. When someone reviews what the system is actually tracking, the trail is either incomplete, logging the wrong events, or using a definition of “audit trail” that doesn’t match what a regulator expects.

We’ve seen companies go through quality reviews and find that their internal understanding of what counted as an audit trail had little relationship to the industry standard. If an investigator pulls a document and asks for the change history, you need to be able to produce a record that shows every modification, the user who made it, the timestamp, and the justification. If the system doesn’t generate that automatically, you don’t have what the regulation asks for.

Access controls

Most out-of-the-box configurations are too permissive. In practice, that usually looks like all (or at least too many) users in the system having the same level of access to modify a document title, change a form field label, rename a file, or overwrite metadata, etc.

We’ve seen eQMS implementations where a user could change “Due Date” to “Date Due” on a controlled form, and the system wouldn’t flag it, block it, or log it. Over time, small changes like that accumulate across hundreds of documents, and nobody notices until someone does a QC review and the records don’t match what the team remembers approving.

After configuration, the system should have tiered access.

• Read-only users who can view documents but not change them.

• Workflow-level users who can execute within defined processes.

• Administrative users who can make structural changes.

Each tier should require training before access is granted. Higher tiers should require demonstrated competency within the system before permissions are upgraded.

If your eQMS has one access level for all users right now, fix that first. It’s the fastest path to a data integrity exposure you didn’t intend to create.

Document lifecycle workflows

The default document lifecycle in most eQMS platforms (especially “smaller” ones) is generic. It covers the basics (draft, review, approve, release), but usually doesn’t reflect how your organization actually manages documents.

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Let’s talk about AI for a moment and its use in our newsletter. We’ll be brief!

Every article, analysis, and opinion in this newsletter comes from people who do regulatory, quality, or clinical work for a living. Our contributors are consultants, former FDA personnel, quality system specialists, and other industry practitioners who have spent years inside the environments they write about.

When we break down a warning letter and pull lessons from it, that insight has come from one of our senior consultants on our contributor team.

We don’t accept AI-generated anything from our contributors. That’s a firm policy that, in full transparency, we’ve had to start enforcing, given how “good” LLMs are getting at generating content. We want this newsletter to be a refreshingly human source of information.

So let’s talk about it.

Where AI shows up in our process

We’re fully committed to keeping our content human and experience-sourced because we know it’s what you’re here for. But we’re not going to be digital Luddites and deny ourselves tools that support that commitment.

Some of the datasets we work with, things like warning letter trends, inspection citation patterns, and adverse event signals, are large enough that manual analysis would take days or weeks or wouldn’t happen at all. We use the most advanced models to let us ingest that data and identify patterns. But the interpretation, context, and the editorial judgment about what those patterns actually mean still come from our team.

Also, much of what we publish here starts with interviews with subject matter experts in our consulting network. We meet on Zoom and have conversations to extract insights firsthand. These conversations are often dense; they jump around, and the best stuff is often buried in an aside fifteen minutes in. We use AI to extract raw insights from those transcripts and organize them so we can write from them more efficiently and make sure nothing gets lost. The thinking and the opinions are the SME’s, but AI helps us make sure we capture all of it before we start writing. It would take hours to sift through transcripts manually, and honestly, a human misses more than a machine does at this point.

We also use AI to catch typos, flag inconsistencies and inaccuracies, and check whether a paragraph reads clearly before publication. Neither we nor any tool is perfect, so we do ask for an ounce of grace when things are missed. We’re a very small team with ambitious publishing goals. The ideas, arguments, and conclusions are already on the page before any AI tool touches them.

That’s about it when it comes to where AI and LLMs show up in our workflow. To be clear, we don’t use AI to generate insights or analysis from scratch, and we don’t feed it a topic and publish what comes back. Anyone with an internet connection can do that at this point.

What we don’t do

Just to put a finer point on this, we don’t generate insights from whole cloth, and we don’t allow AI models to train on confidential or sensitive client information. Our contributors work with regulated companies, and the trust those relationships require extends to every tool we use.

We also don’t use AI to manufacture perspectives we don’t hold, to pad word counts, or to produce content faster than our contributors can think through it. Speed isn’t the point here.

This matters more here than it might elsewhere

There’s a practical reason this distinction matters here and why we want to be super clear about it.

In any business content, a wrong detail is embarrassing. In the life sciences, a wrong detail about a regulatory pathway, a misread of a guidance document, or a sloppy characterization of an enforcement trend can lead someone to make a bad decision about a product that affects patient safety. The cost of getting it wrong in our space is actually operational and sometimes clinical.

This is also a field where experience-based judgment counts for a lot. Knowing what regulators are likely to focus on during an inspection, or how the FDA tends to interpret a given question, isn't knowledge that tends to live in LLM datasets you can conjure with a prompt. It lives in the brains of the people who’ve actually been in those rooms.

That’s what we’re trying to preserve in this newsletter. Not because AI is “bad,” but because the content that actually helps our readers requires something AI can’t provide on its own in the same fidelity or depth.

Why we care about this enough to write about it

We started this newsletter because we noticed the same thing many of you have: the amount of life sciences “content” online keeps growing, and most of it is “thin” to put it nicely. There’s a lot of generic advice that applies to everything and helps with nothing.

So when someone asks whether we use AI, we take it as a reasonable question from a reader trying to figure out what they can trust. We hope this answers it. If you have specific questions about this or anything in general, just email us:

thefdagroup@substack.com

Who is The FDA Group?

The FDA Group helps life science organizations rapidly access the industry's best consultants, contractors, and candidates. Our resources assist in every stage of the product lifecycle, from clinical development to commercialization, with a focus on Quality Assurance, Regulatory Affairs, and Clinical Operations.

With thousands of resources worldwide, hundreds of whom are former FDA, we meet your precise resourcing needs through a fast, convenient talent selection process supported by a Total Quality Guarantee. Learn more and schedule a call with us to see if we’re a fit to help you access specialized professionals and execute your projects on time and on budget.

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These RA/QA news rolls are available in full only to paid subscribers. Upgrade here.

This is our biweekly recap of news and industry happenings curated for our paid subscribers. Our goal is to bring you the headline news and the stories, research, and insights that might be harder to find.

If you haven’t upgraded to a paid subscription yet, you can do so here. Also, make sure to follow us on LinkedIn and catch the latest episodes of our podcast, The Life Science Rundown.

Here are some key items from the past couple of weeks.

💊 = Pharma, biologic, and biotech.
💉 = Medical device, medtech, diagnostics, and digital health.

FDA Leadership and Administration

• Makary resigns; Diamantas takes over as acting commissioner — FDA Commissioner Martin Makary resigned on May 12 after weeks of pressure from HHS leadership. HHS Secretary Kennedy, not the White House, ultimately made the call. Kyle Diamantas, the agency’s deputy commissioner for food and an HHS senior counselor, is now acting commissioner. Diamantas is a former Jones Day partner who focused on FDA regulatory matters, is reported to be close to the Trump family, and has generally been well-regarded by FDA staff. Among his first meetings as acting commissioner was one with the president of March for Life, a signal that he’s working to repair relationships with antiabortion groups that had called for Makary’s removal.

• White House targets early June for new FDA commissioner pick — Senior health officials in the Trump administration are aiming to select Makary’s permanent successor within weeks. The search is in early stages but officials plan to narrow the list quickly. Several names have been discussed publicly, including former acting commissioner Sara Brenner, ophthalmologist Houman Hemmati, and former commissioners Stephen Hahn and Brett Giroir, though each faces confirmation challenges. The position requires Senate confirmation, and HELP Committee Chair Bill Cassidy (R-La.) has indicated the next nominee must have an M.D. or Ph.D. and demonstrate commitment to antiabortion priorities. Sen. Josh Hawley (R-Mo.) has also signaled that mifepristone will be a litmus test. With midterm elections approaching, the acting commissioner is likely to remain in place through the end of the year.

• More FDA leaders expected to exit — Reuters reported that CDER Acting Director Tracy Beth Høeg is likely to leave soon, with Bloomberg later reporting her departure was expected immediately. Chief of Staff Jim Traficant, Deputy Chief of Staff Samuel Doran, and Associate Director of Policy and Research Strategy Sanjula Jain-Nagpal are also expected to depart.

• Multiple acting leaders across the FDA — Several of the agency’s most important positions are filled on a temporary basis. Katherine Szarama is acting CBER director following Vinay Prasad’s departure. CDER continues under Tracy Beth Høeg on an acting basis (though her departure is expected). Mallika Mundkur is acting chief medical and scientific officer. R. Angelo de Claro became the permanent director of the Oncology Center of Excellence, the only major center to name a permanent leader in recent weeks.

• CBER director search continues 💊 — The FDA is looking at three or four finalists for the CBER director position, with Houman Hemmati among them. Szarama, the current acting director, is not in the running. The Wall Street Journal reported that Makary’s preference for hiring Hemmati had been blocked by the White House and senior health officials in recent weeks. BIO CEO John Crowley said the FDA had reached out to industry groups and patient organizations for input on the search.

• HHS investigating vaccine-chronic disease links 💊 — The New York Times separately reported that HHS Secretary Kennedy is pushing government scientists and federal data contractors to examine his long-held theory that vaccines help fuel chronic disease, with assistance from FDA and CDC career officials and contractors with access to millions of patient records. Former FDA Principal Deputy Commissioner Sara Brenner is expected to help lead the effort in her new HHS role.

• FDA’s hiring numbers keep climbing — At the Milken Institute Global Conference, Makary said the agency is now hiring 3,000 new scientists, up from the 2,000 figure he cited just weeks earlier and the original 1,000. Whether this hiring effort continues without his active support is an open question.

• HHS considering ban on some antidepressants 💊 — Reuters reported that HHS officials are actively exploring whether they can ban certain selective serotonin reuptake inhibitors (SSRIs). HHS disputed the reporting, though the department recently announced a MAHA Action Plan to Curb Psychiatric Overprescribing, which calls for agencies to evaluate prescription patterns for psychiatric medications and elevate nonmedication treatments.

• SSRI labeling petitions under FDA review 💊 — CDER’s deputy center director for substance use and behavioral health, Marta Sokolowska, said at the MAHA overmedication summit that the FDA is currently evaluating about five citizen petitions requesting revision of SSRI labeling related to adverse effects, along with additional information from literature and other databases.

• Trump pushing for approval of natural kratom 💊 — President Trump told reporters he is “looking very seriously at natural 7-OH and getting that approved.” This would be a significant departure from the FDA’s prior statements and warnings about 7-OH, an alkaloid compound the agency has said has potential for abuse because of its ability to bind to opioid receptors.

FDA General

• Single-day, AI-prioritized inspection pilot launched 💊 💉 — At the FDLI Annual Conference, Commissioner Makary (before his resignation) announced a pilot program for one-day screening inspections at manufacturing facilities identified as low-risk by AI. Full inspections typically take several days. The new screening assessments are intended to complement full inspections as part of a risk-based approach. If safety issues surface during a one-day screening, inspectors can extend the visit. The pilot is expected to continue throughout 2026.

• IND reform plans detailed 💊 — Makary outlined plans for large-scale reform of IND and Phase 1 clinical trial processes at FDLI. The FDA is interested in piloting a three-to-six-month timeline from pre-IND counseling request to IND submission. The agency plans to publish a list of information it does not require in IND submissions and is looking at cutting or deferring requirements unrelated to safety. Makary also reiterated interest in reforming the institutional review board process.

• Real-time clinical trials pilot draws interest 💊 — Fifteen companies have signaled interest in participating in the real-time clinical trial reporting pilot. The FDA held a Q&A session on May 15 where Chief AI Officer Jeremy Walsh clarified that the pilot is not interested in patient-level data but rather prespecified signals about what’s happening in a trial. The agency plans to share selection criteria in July and complete selections in August.

• Digital health technology submissions guidance 💉 — The FDA issued a technical specification on how drug sponsors should present continuous glucose monitor data in submissions, including guidance on CDISC standards, time horizons, and traceability expectations.

• Plausible mechanism pathway draws tons of comments 💊 — The FDA received over 150 comments on its draft plausible mechanism pathway guidance. Multiple stakeholders expressed confusion about which diseases and drugs would be eligible. The American Society of Gene and Cell Therapy noted the guidance at times appears focused on ultra-rare diseases while other language suggests broader applicability. PhRMA recommended broadening the eligible diseases and products.

• Patient Listening Session summaries coming — The FDA updated its Patient Listening Session webpage, noting that summaries are coming soon for four 2026 meetings on CACNA1A, SCN8A-related disorders, idiopathic pulmonary fibrosis, and primary sclerosing cholangitis.

• Cell and gene therapy CMC guidance finalized 💊 — The FDA quietly published a final guidance on chemistry, manufacturing, and controls flexibilities for developing human cellular and gene therapy products. The 10-page document is a direct-to-final guidance that formalizes the agency’s January 2026 announcement on flexible requirements for cell and gene therapies.

• New draft genome editing safety guidance 💊 — The FDA released a draft guidance on using next-generation sequencing to assess the safety of genome editing therapies, broadening the definition of genome editing products to include those modifying the epigenome or transcriptome.

• RAPID coverage pathway details emerge 💉 — At the Medical Device Innovation Consortium’s Innovations in Evidence Summit, CDRH Director Michelle Tarver and CMS Chief Medical Officer Dora Hughes provided more detail on the joint FDA/CMS RAPID pilot for breakthrough device coverage. Tarver confirmed that companies will receive written feedback from both agencies that they can share with investors and consultants. Hughes said CMS is working to publish more resources on the coverage process. Expert analysis from outside law firms found the program valuable for qualifying sponsors but noted that key implementation details remain pending.

• Interoperability roadmap coming from CDRH 💉 — CDRH Director Tarver said at FDLI that the center is working on a discussion paper covering interoperability standards across the medical device, electronic health record, and consumer tech sectors.

• CDRH joins Rare Disease Innovation Hub 💉 — CDRH is now officially part of the FDA’s Rare Disease Innovation Hub, making it a three-center co-chaired effort alongside CDER and CBER. Hub Director Amy Comstock Rick noted that CDRH participation could help sponsors evaluate disease measurements in pediatric R&D.

• Drug repurposing push 💊 — The FDA published a call for input on disease areas with significant unmet need where existing evidence may support a new use for an approved drug, as well as cases with promising preliminary data. The agency is also looking to facilitate repurposing opportunities alongside the NIH and CMS.

• Kidney safety biomarker incubator 💊 — The FDA announced a new regulatory science initiative focused on advancing biomarkers for drug-induced kidney injury. The Biomarker Incubator will aggregate data from multiple sources to validate biomarkers, and the agency is requesting voluntary submission of human data for the pilot phase.

• CDRH promotes Experiential Learning Program 💉 — CDRH opened its 2026 proposal submission cycle for the Experiential Learning Program, which allows industry to invite center staff for tours of duty in their companies. Priorities this year include the Home as a Health Care Hub initiative, designing devices for home environments, and medical device interoperability.

• Obesity and drug dosing: FDA seeks input 💊 — The FDA is requesting comments on how obesity affects the pharmacokinetics and pharmacodynamics of experimental medicines, citing low enrollment of obese patients in clinical trials. Comments are open through June.

• FDA updates surrogate endpoints table 💊 — The FDA quietly updated its table of surrogate endpoints used as the basis for drug or biologic approval, a required resource that helps stakeholders evaluate which surrogates the agency has historically accepted.

• eSTAR FAQ updates 💉 — CDRH updated the eSTAR webpage with new FAQs covering submission requirements, version updates, and attachments. The templates themselves have not yet been updated.

• READI-Home webinar scheduled 💉 — The FDA announced a June 24 webinar on its READI-Home Innovation Challenge for medical devices intended to reduce hospital readmissions.

• PreCheck program deadline passed 💊 — May 1 was the deadline for finalists in the Commissioner’s FDA PreCheck Program to submit follow-up information. The FDA will review packages and make selections by June 30, with a July 1 start for pre-operational engagement.

• GLP-1 generics workshop scheduled 💊 — The FDA and the Center for Research on Complex Generics will cohost a September 23-24 workshop on the GLP-1 generic drug pathway, covering product-specific guidance, bioequivalence studies, and manufacturing considerations for drug-device combination products.

• Record month for generic approvals 💊 — The Office of Generic Drugs approved 85 generics in April, the most in a single month since August 2023 and the second-best month in the last five years. Forty-one were first-time generics.

Read more

Many life science companies treat inspections more or less like exams. There’s a date on the calendar (or there might be, or there might not be), and at some point before it arrives, a quiet scramble begins. “Pull the documents.” “Prep the SMEs.” “Start cleaning up the backlog.”

The problem with that approach isn’t that it can fail spectacularly. It’s that it works just well enough to reinforce the habit. Until one day, of course, it doesn’t.

Nick Capman recently sat down with Yeime Martich, Vice President of Quality Assurance at TerSera Therapeutics, to talk about what it looks like when inspection readiness stops being a periodic exercise and becomes the way a company actually operates.

Yeime has spent 25 years in pharma and medical device quality systems. She’s a computer system engineer by training who has dedicated her entire career to compliance, quality system design, and inspection readiness. Before TerSera, she spent over 11 years at Hospira in global compliance roles (building internal audit programs across manufacturing sites in the US, Canada, Europe, India, and Australia) and held quality systems leadership positions at Melinta Therapeutics and Abbott.

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Yeime's key insights and practical takeaways

If you're short on time, here are the most important lessons from the discussion.

• Companies treat inspections as events when they should treat them as the natural output of a healthy quality system. The instinct to prepare for an inspection weeks in advance is a symptom. If your processes, systems, and procedures are functioning the way they should, and if the people who present during inspections understand what they do and why, readiness isn’t something you “build.” It’s something you should already have. When organizations treat readiness strategically, they design systems that are always in a state of control.

• Inspection readiness as a competitive advantage looks like confidence and speed, not perfection. You don’t need to have everything at 100%. You need to be able to confidently present the activities you do every day. Yeime uses the phrase “minimally compliant” not as a shortcut, but as a discipline. Understand the requirement and the intention behind it. Then meet it. Add the bells and whistles later. The danger is building procedures that look impressive on paper but are impossible to follow in practice. That’s where companies get dinged: not for lacking procedures, but for not following the ones they wrote.

• Overcommitting in your procedures creates risk that doesn’t need to exist. If your deviation procedure says you can’t release a product until every associated CAPA is closed, you’ve built a bottleneck into your system that the regulation doesn’t require. You could define that CAPAs unrelated to product disposition don’t block release. But if your procedure says otherwise, an auditor will hold you to what you wrote. Yeime has seen this across organizations. Companies are adding requirements beyond what the regulation asks for, then being judged against their own inflated standard.

• A well-designed QMS doesn’t slow the business. It gives the business the tools to move. Quality should be at the table with options, not blocking the door saying no to everything. When the quality organization functions as an enabler, business integrations accelerate: vendor selection moves faster, geographic expansion becomes manageable because you can handle multiple regulatory frameworks, and risk-based decisions happen in real time rather than in committee after committee. That only works when the QMS is flexible enough to accommodate new products, new regulations, and new requirements without major disruption.

• Leadership shapes quality culture through three things: what they ask about, what they fund, and what they tolerate. If leadership asks for metrics on how quickly deviations close rather than whether investigations are thorough and CAPAs prevent recurrence, that tells the organization what matters. If they restrict resources for quality because they’re allocating to sales, that tells the organization what matters. And if quality keeps raising risks and leadership ignores them, that tells the organization what matters. Senior leadership has a responsibility to signal that quality is not just a compliance function but an enabler of sales and operations. But Yeime is clear that the responsibility runs both ways: the quality organization needs to present the facts, explain the impact, and make the case for why their decisions matter. If you can’t release a product, you can’t have sales. That’s the argument.

• The “quality as police” perception is quality’s problem to solve. Yeime doesn’t put this on the business. She puts it on the quality organization to do better at explaining the why. Why something can or can’t be done. What the risk is. What the mitigations are. What happens if you skip them. And then offering options — not just a no. “I can release a product on risk to the warehouse so we don’t lose the manufacturing window. But I’m not releasing it to market until the investigation is closed.” That’s the difference between policing and partnering.

• The strongest signal of a healthy quality culture is when people come to quality voluntarily to say they messed up. When employees feel safe enough to surface issues without fear of blame, the system is working. When they hide problems because last time someone made a big deal out of it, or because they’ve raised issues before and nobody cared, the system is failing, and you probably won’t find out until an investigator does.

• Yeime has seen both failure modes firsthand. After inspections, she’s had SMEs say “I knew about that,” either because they were afraid to escalate or because they’d raised it and been ignored. Both are organizational failures. Her response: don’t wait for employees to come to you. Have the conversations proactively. Ask what would worry them if an inspector showed up tomorrow. Then address those things. Nobody should be in a position where known issues surface for the first time during an inspection.

• Preparing people for inspections is about competence, not scripts. Employees should be able to explain what they do, how they do it, and how it connects to the procedure and to patient safety. That ability comes from practice via internal audits, self-assessments, and cross-functional meetings where people explain their work and its impact on other departments. It doesn’t come from handing someone a printed SOP to read in front of an investigator. If the SME can’t present their own work and the QA administrator has to do it instead, that’s a problem to fix before the inspection, not during it.

• AI is useful. Accountability is still yours. Yeime uses AI daily and sees real value in how it processes data, analyzes metrics, and accelerates review. But she referenced a recent FDA warning letter involving a facility in India where the company’s response to a question about process validation was essentially that AI didn’t tell them it was needed. That made it into the warning letter. The FDA has implemented ELSA to review INDs and NDAs, and the agency can process data faster because of it. But the final decision — the quality judgment — sits with people. AI can hallucinate. It can pull bad data. It learns from what you give it. In Yeime’s view, AI will not replace the judgment that comes from historical experience, pattern recognition, and the gut instinct that tells you to take a closer look.

• Human in the loop is not a buzzword. It’s the operating principle. Both Yeime and Nick agreed on this. Even as AI matures, someone will still be signing off. The question is whether that person is actually reviewing what they’re approving or treating it like mortgage documents: signing without reading. In a GxP environment, that distinction is the difference between compliance and a warning letter.

• Three moves to embed inspection readiness into your culture for the long term. First, design your QMS around lifestyle thinking, not compliance checklists. Don’t focus on check, check, check. Make sure everyone understands the process, understands the why, and understands the impact of their work on patients and product quality. Second, make integrity and decision transparency non-negotiable. You cannot compromise patient safety. You cannot compromise integrity. Make that clear and unambiguous across the organization. Third, build two things simultaneously: a strong relationship between quality and senior leadership (so they understand the value and spread it top-down) and a psychologically safe environment where employees surface issues without fear of blame.

One thing to bring back to your team

Ask yourself whether your quality system is designed for the organization you actually are, or for the organization you wish you were. Then ask:

• Are there requirements in your procedures that go beyond the regulation, and is your team actually following them, or are you creating audit risk by writing aspirational SOPs?

• If quality raises a risk to leadership, what happens? Does it get addressed, or does it get ignored?

• If an operator made an error tomorrow, would they come to quality on their own, or would you find out during an inspection?

• Can your SMEs explain what they do, how it connects to the procedure, and why it matters for patients without reading from a script?

Yeime Martich is Vice President of Quality Assurance at TerSera Therapeutics, where she has led the quality organization for over three years. She has 25 years of experience in pharmaceutical and medical device quality systems, with a career dedicated to compliance, quality system design, and inspection readiness. Before TerSera, Yeime spent over seven years at Melinta Therapeutics in quality systems leadership and over 11 years at Hospira in global compliance roles, where she built and oversaw internal audit programs across manufacturing sites in the US, Canada, Europe, India, and Australia. She also held a quality engineering role at Abbott.

Connect with Yeime on LinkedIn here.

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The FDA Group helps life science organizations rapidly access the industry's best consultants, contractors, and candidates. Our resources assist in every stage of the product lifecycle, from clinical development to commercialization, with a focus on staff augmentation, auditing, remediation, QMS, and other specialized project work in Quality Assurance, Regulatory Affairs, and Clinical Operations.

With over 3,750 resources worldwide, over 325 of whom are former FDA, we meet your precise resourcing needs through a fast, convenient talent selection process supported by a Total Quality Guarantee.

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Check out our newly launched AI-powered QMS audit tool, AICA (the Audit Intelligence Compliance Assistant).

Most small pre-commercial sponsors don’t have the luxury of spending much time thinking about what happens if their drug actually makes it out of Phase 1 and 2 trials.

Most of the time, these teams are small, the budgets are tight, and the procedures that exist are good enough to keep things moving. But it’s rare to see anyone writing inspection-readiness checklists when the question is still whether the molecule does what they think it might.

For the fortunate, Phase 2 data comes back strong and the timeline to Phase 3 stops being theoretical. And that’s usually when a sort of panic sets in: the FDA is going to show up at some point, and what’s been good enough for early-phase work isn’t going to hold up under a Phase 3 inspection.

That’s exactly where one of our recent clinical staff augmentation projects started. We placed one of our clinical QA consultants, Ranee Moor, with a small biotech sponsor that found itself in exactly this position. They had promising results, a Phase 3 trial to plan, and a quality system that wasn’t built for what was coming next.

Here’s how the next six months played out to give you an idea of how the right embedded outsider can make an enormous difference across clinical operations on a short timeline.

Learn more about our staff augmentation services »

What the gap analysis turned up

Ranee’s first task was a gap analysis in June of last year. The goal was to identify everything that would be a problem if the FDA came in for a Phase 3 inspection.

The list turned out to be pretty long:

• The sponsor had SOPs, but they were hard to follow and didn’t give people enough detail to know what to actually do in many cases.

• There were no work instructions, no forms, no templates backing up the procedures.

• Entire categories were missing: no SOP for sponsor oversight, no process for internal monitoring, no inspection readiness training or checklists. No learning management system. No document management system. And the budget to license one wasn’t there.

A prior CRO qualification was on file, but it didn’t hold up when you looked at it closely. The internal QA function was just two people, one of whom was still getting oriented in clinical quality.

None of this is unusual for a company at this stage, of course. Small sponsors regularly get through early-phase work on momentum. The problem only becomes urgent when Phase 3 forces the question of whether you can defend your processes to a regulator.

Establishing a weekly work cadence

The substantive work started in September. Ranee partnered with an SOP author from our team, and they set up a production cadence that the sponsor’s reviewers could keep up with without drowning.

Here’s what that looked like:

Running ClinOps work in parallel

While the QMS was getting written, Ranee was handling the clinical side of Phase 3 startup:

• Protocol review

• Master informed consent

• CRO selection and qualification

• Quality agreements

• Vendor management plans

• Communication plans

As each new SOP was approved, she put it to use immediately.

The philosophy was three tiers of work happening at once. First, build the process. Second, produce the deliverables the process calls for. Third, generate the evidence that the process is actually being followed.

That third tier is where we see a lot of sponsors fall short. It’s one thing to have an SOP that requires meetings to have an agenda and minutes. It’s another to actually put meetings on the calendar, send the agendas, store the minutes, and be able to point to all of it during an inspection.

Ranee spent quite a bit of her time on that gap between having a procedure and living by it. If the SOP said an agenda was required, where was the agenda? If it said minutes had to be stored, where were they going? The SOP had to reflect the way people actually worked now.

A CRO timeline problem

The CRO selected for the Phase 3 trial had committed to a set of deliverables on a timeline that started in October: A comms plan, monitoring plan, safety management plan, data management plan, and risk plan. October passed, then November. Then December. Then January!

Status updates kept reading “drafting” with no dates attached.

In January, Ranee started running separate meetings and pushing for firm delivery dates instead of status labels. Everything showed up at once in February. The sponsor’s team had days, not weeks, to review plans that had originally been promised months earlier. They divided the work and got everything signed off before the first patient enrolled.

This kind of “CRO slippage” is common, and it’s one of the reasons Ranee’s role extended well beyond QMS authoring. Someone had to own the tracking and the follow-up, and neither the CRO’s internal processes nor the sponsor’s small team was positioned to catch the delays on their own. That accountability function turned out to be just as important as the documents themselves. We often embed consultants simply to serve as a strong manager between the sponsor and CRO, given the sensitive politics that get in the way when there isn’t an outside party.

Training built into every conversation

One thing that set this project apart from a pure document build was that Ranee treated every interaction as a training exercise. She walked people through why each decision mattered and how to defend it if a regulator asked. When prior work needed to be upgraded, she framed it as an improvement, not criticism.

“You did a great job with the information you had. Here’s what we want to improve on and why.”

By the end of the engagement, the sponsor’s internal QA contact had grown from someone who was still learning the function into a confident operator who understood the system and could run it independently. That growth happened because they were explained the reasoning behind every decision, not just the output. Six months of that adds up.

Wrapping in a ready state

The first Phase 3 patient was enrolled in March, ahead of the original date. The sponsor had a working quality management system, qualified vendors, executed agreements, and two inspection-readiness checklists (one for pre-first-patient, one for trial close) that the team was actively tracking against.

At that point, the sponsor hired a full-time QA lead — Ranee essentially worked herself out of the job. Still, she spent two weeks onboarding him, walking through what had been built, where things stood, and what needed ongoing attention.

And then the engagement was over. The sponsor didn’t need outside help anymore. As Ranee put it, she had to build the room before the furniture could come in. By March, the room was built, the furniture was in place, and the people inside it knew how to keep it organized.

What made it work

We asked Ranee for her take on why this project succeeded given how much was working against that outcome. She said it came down to the people:

• The sponsor acknowledged their weaknesses without taking it personally.

• They welcomed direction instead of resisting it.

• When someone’s prior work needed to be redone, the team took the feedback and improved.

• Both sides matched each other’s energy and hours. Trust built quickly because the working relationship worked.

The same consultant placed with a less receptive team might have delivered the same documents, but not the same outcome. The quality system works today because the people who now own it understand it and believe in it. That’s the part that can’t be copied from a template.

What she’d tell the next small sponsor

When asked what advice she’d give to other sponsors heading into a similar situation, Ranee’s answer had less to do with the mechanics of documentation strategy and more to do with being in the right mindset to accept the help:

None of that is specific to this sponsor or this drug. Any small company approaching a Phase 3 transition is going to face some version of this problem. The ones that come out of it ready for inspection tend to share two things: they accept that their early-phase systems won’t scale, and they’re willing to let someone come in and help them build what’s next.

Ranee Moor is a Clinical QA Consultant with The FDA Group. She has more than 25 years of experience in pharmaceutical quality across GCP, GMP, GLP, and computer systems validation. She runs Quality Systems & Technology, Inc., an independent QA consulting firm, and has held senior QA, validation, and IT compliance roles at Charles River Laboratories, ICON plc, and META Solutions. She’s represented sponsor organizations during regulatory inspections and led validation and quality system efforts for both small biotechs and large CROs.

Need expert clinical support?

If you’re approaching a Phase 3 transition, a planned inspection, or any milestone where your quality system needs to be ready faster than internal capacity allows, this is the kind of work we do every week.

We place clinical QA consultants inside sponsor organizations on short notice, sometimes within days, to build out or take over quality systems alongside your internal team. They come in ready to work, without the ramp time of a new hire or the cost of a permanent headcount.

To talk through your situation or request a consultant, reach out to us.

Who is The FDA Group?

The FDA Group helps life science organizations rapidly access the industry's best consultants, contractors, and candidates. Our resources assist in every stage of the product lifecycle, from clinical development to commercialization, with a focus on Quality Assurance, Regulatory Affairs, and Clinical Operations.

With thousands of resources worldwide, hundreds of whom are former FDA, we meet your precise resourcing needs through a fast, convenient talent selection process supported by a Total Quality Guarantee. Learn more and schedule a call with us to see if we’re a fit to help you access specialized professionals and execute your projects on time and on budget.

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We’ve run SOP gap analyses across a wide range of organizations: device manufacturers, pharma sponsors, CROs, and clinical sites.

Each engagement starts with a different set of procedures and standards to assess against. Sometimes we’re evaluating clinical investigation SOPs against ISO 14155. Sometimes it’s GMP documentation, quality system controls, supplier qualification processes, or CAPA. The organization, regulatory context and procedures are different. But what isn’t different, or not nearly as different as you’d expect, is the pattern of what’s wrong when we put procedures under the microscope.

We always tell teams that a gap analysis isn’t a pass/fail audit; it’s a diagnostic. The goal is to identify where your documented procedures fall short of the applicable requirements before an inspector or notified body does the same review. In our experience, that review tends to surface the same categories of problems regardless of what type of SOP is on the table.

Below are five findings we see consistently enough that we go looking for them at the start of every engagement. These trends are pulled directly from the last ~18 months of gap analyses.

1. The SOP was written against a standard that has since been revised

This happens a lot with companies that have been operating for a while. The SOPs get written when the standard is current, the standard gets revised, and nobody updates the procedure.

• The language still maps to the old version.

• Requirements added or changed in the revision aren’t addressed.

• In some cases, the SOP explicitly references the superseded document by name and number.

This has recently come up a lot with device firms that haven’t reconciled their quality procedures to the QMSR, which amended 21 CFR Part 820.

The fix isn’t always a full rewrite. Sometimes it’s a targeted amendment that addresses only the delta between versions. But you can’t know what you’re dealing with until you do a section-by-section comparison against the current version. That comparison is usually the first thing we do.

2. The scope statement and the procedure cover different things

The purpose and scope section is supposed to tell you what the procedure governs and who it applies to. In practice, it’s often the part that was pulled from a template early on and never really touched again.

We tend to see two versions of this:

Both versions create the same audit risk. A reviewer who reads the scope statement and then reads the procedure is going to notice when they don’t describe the same thing.

Here’s a quick test: read the scope, then read the procedure, and ask whether someone who had never seen this process before could execute everything described in the scope using only what’s in the procedure. If not, you’ve found a gap.

3. Responsibilities are assigned to roles that are poorly defined, vacant, or gone

This is easy to miss in a document review because it looks fine on paper and doesn’t call attention to itself as much as other problems.

The SOP assigns ownership to a named role (QA Manager, Study Coordinator, Regulatory Specialist) and if that role exists somewhere in the org chart, the procedure gets approved. Whether the person in that role knows they own the step, and whether their qualifications match what the SOP actually requires, are separate questions.

We’ve reviewed SOPs that point to roles from a previous organizational structure eliminated years earlier. We’ve also seen responsibilities handed to an unspecified “Designee” with no guidance on who designates, what qualifications apply, or how the designation gets documented. We’ve seen tasks split between two roles in a way that creates a handoff gap neither party noticed because each assumed the other was handling it.

Updating role names gets you partway there. The more useful step is confirming that the people filling those roles know about the responsibility and have the training to execute it. If your SOP assigns a critical review step to the QA Manager and your QA Manager doesn’t know that’s their job, you have a gap in your training records as much as in your procedure.

Read more

FDA Commissioner Marty Makary announced a new inspection pilot yesterday morning at the Food and Drug Law Institute Annual Conference in Washington. The FDA also made an official announcement on its website.

The agency has been conducting one-day “screening assessments” at select facilities across human and animal foods, biologics, medical products, and clinical research programs since April.

As of late April, the FDA has completed roughly 46 of these assessments. Most resulted in No Action Indicated outcomes. A few extended past one day when investigators found something worth looking at more closely. This is an additional tool, not a replacement for standard inspections. Investigators retain full authority to extend scope and duration if warranted.

Here’s what we know.

Before we jump in, if your site was among these first ~46 assessments, we’d love to hear from you. Send us a message at thefdagroup@substack.com.

How sites get selected

According to what’s known about this program, facilities are chosen based on product type, prior inspection history, and “operational characteristics.” The announcement also specifically called out discrepancies between what a facility has registered and what’s actually happening on the floor as a risk signal feeding into site selection.

The FDA says it plans to use data from these assessments — compliance patterns, facility-specific risk scores, operational gaps — to sharpen its broader risk models going forward.

What the FDA hasn’t published yet are the specific criteria that would classify a facility as low-, moderate-, or high-risk. That’s worth watching as the pilot continues through the rest of the year.

What investigators are probably looking at

We’re speculating here! They can only do so much in one day. Based on the FDA's description of the program’s purpose, a few items are likely to be on the list.

Beyond that, the specific focus areas will most likely vary by program. We’d guess that investigators will prioritize the highest-consequence failure points for the product type.

To be very clear, the FDA hasn’t released detailed protocols, and until more facilities go through the process and outcomes get published, the exact scope of these assessments isn’t fully known. The safest assumption remains that anything a standard inspection could catch is technically in play. The one-day format just limits how far they can go before they’d need to extend.

A few things to think about

Treat current inspection readiness as a baseline. A screening assessment that surfaces issues will likely become a full inspection. That's built into the program design. A few suggestions in light of this, none of which should be novel or earth-shattering:

The FDA is building evaluation metrics — escalation rates, outcome trends, investigator feedback — to determine how the program evolves beyond 2026. We’ll report on those findings as they become available.

Who is The FDA Group?

The FDA Group helps life science organizations rapidly access the industry's best consultants, contractors, and candidates. Our resources assist in every stage of the product lifecycle, from clinical development to commercialization, with a focus on Quality Assurance, Regulatory Affairs, and Clinical Operations.

With thousands of resources worldwide, hundreds of whom are former FDA, we meet your precise resourcing needs through a fast, convenient talent selection process supported by a Total Quality Guarantee. Learn more and schedule a call with us to see if we’re a fit to help you access specialized professionals and execute your projects on time and on budget.

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This one’s important for our CGT professionals out there.

The FDA’s CBER just issued a final guidance titled Chemistry, Manufacturing, and Controls Flexibilities for Developing Human Cellular and Gene Therapy Products for a Biologics License Application. It was issued for immediate implementation under 21 CFR 10.115(g)(4)(i), so sponsors should treat it as the FDA’s current final thinking now, not as a draft awaiting finalization.

The FDA put into writing what CBER has been doing in practice for some time: applying flexible CMC expectations to CGT products because their manufacturing challenges don’t fit neatly into frameworks designed for conventional biologics.

“Limited” patient populations, patient-specific manufacturing, short shelf lives, limited batch quantities, and complex processes all create situations where traditional CMC development timelines and data packages just don’t work the same way.

If you’re a CGT sponsor preparing for a BLA, this document tells you where the flexibility exists and how CBER expects you to justify using it.

Scope and applicability

This guidance applies only to human CGT products regulated by CBER and developed for a BLA under 21 CFR Part 601.

It does not apply to animal CGT products regulated by the Center for Veterinary Medicine, and it does not apply to other biological products.

CBER also notes that some of these flexibilities may extend to manufacturing supplements submitted after licensure, though the guidance doesn’t commit to that.

One thing the guidance says repeatedly: talk to CBER early and often! Sponsors should discuss their CMC development approach with the relevant review division before implementing any of these strategies. That’s a recurring theme throughout the document.

Flexibilities during clinical development

CBER outlines five flexible approaches sponsors should consider during clinical development.

Process validation flexibilities

There are two flexibilities here, both addressing a practical reality: CGT sponsors often can’t produce large numbers of PPQ batches.

Let’s take them both:

Flexible PPQ batch numbers

CBER does not specify a minimum number of process performance qualification (PPQ) batches in either the biologics licensing requirements or CGMP regulations. Sponsors should justify the number based on their level of process understanding, manufacturing complexity, and controls in place.

The guidance asks sponsors to document the studies performed during process design, the control strategy, and any relevant manufacturing experience from similar products.

(The FDA still says PPQ is a critical step in validating the commercial manufacturing process and that sponsors are expected to include PPQ data in the BLA, but it does not specify a minimum number of PPQ batches.)

Concurrent release of PPQ batches

When production limitations exist, CBER may allow sponsors to complete PPQ studies after licensure. The FDA says a PPQ protocol can be designed to allow release of a PPQ batch for distribution before all protocol steps and activities are completed, when PPQ production limitations exist.

The FDA may consider allowing concurrent release of PPQ batches for commercial use after BLA approval if the batches meet the commercial release specification and are within the commercial shelf life. Batches meeting phase-appropriate IND release criteria can be used for clinical investigations.

Commercial spec flexibilities

Three approaches for sponsors dealing with the common CGT problem of having very few lots available at the time of BLA submission:

More flexibilities

The guidance discusses a few more areas, covering stability, reserve samples, and analytical methods:

Read more

Many sponsors we talk to still think about resourcing their ClinOps functions in one of two ways: Either open a full-time req and wait, or outsource the work. But we've seen more teams moving away from that binary, and the companies getting it right are the ones using some form of a third option: embedding full-time clinical professionals on contract. “Insourcing,” as some call it (although that term means different things to different people).

To us in this context, it means bringing someone into your org chart, reporting to your ClinOps lead, and doing the same work a permanent hire would do. The difference is speed (filling the seat in weeks instead of months) and flexibility (you define the scope and duration).

With the old binary “broken,” the question we field from sponsors is: what’s the right blend of insourcing and outsourcing for our situation?

Based on how we’ve placed consultants at sponsors ranging from pre-IND biotechs to mid-size pharma companies with active Phase III programs, here are six distinct ways the embedded model works in practice.

Few we jump in, we sat down with Mark Shapiro a few years back, then a Partner with biopharma consulting firm Pharma Initiatives (now SVP and GM at Tempus AI), to discuss outsourcing and insourcing models in the current clinical R&D environment, and what to consider when selecting the right model or mix of models for a project.

If you haven’t already, catch that conversation first:

📄 Read our companion white paper: A Modern Guide to Clinical Operations Resourcing. We also have a column on the subject in Clinical Leader.

1. Full-time Clinical Operations staff augmentation

We see these situations play out quite a bit: Your Clinical Operations Manager leaves for another company, or you’re scaling from one trial to three, and your existing team can’t absorb the workload. Either way, the work needs to happen now, and recruiting is telling you it’ll be three to five months before someone starts. That’s often just too long a time when you have sites enrolling patients and regulatory milestones on a fixed calendar.

We’ve helped firms in those kinds of binds embed a full-time consultant into the role, whether that’s a Clinical Operations Manager, Senior Manager, or general Clinical Operations Support.

They report to your internal leadership, use your systems and SOPs, and manage the same deliverables a permanent hire would own. That last part matters a lot since using the client’s own processes, systems, and SOPs makes it easy to scale staff augmentation without introducing the coordination burdens that come with outsourced models.

We’ve placed full-time Clinical Operations Managers at sponsors who needed experienced leadership on day one.

• One engagement placed a Clinical Ops Manager at a biotech running active trials, and the placement ran for months longer because the consultant stayed through an extended program phase.

• Another placed a Senior Manager of Clinical Operations at a sponsor scaling its pipeline. That one gave the company immediate senior-level ClinOps capacity while they continued recruiting for a permanent hire.

These usually aren’t short stints. When a consultant is embedded full-time, the engagement often extends because the sponsor realizes the arrangement is working and the program still needs the coverage after the expected end date.

2. Part-time Clinical Operations support

Not every situation calls for a full-time hire. A smaller biotech running a single trial, or a company that needs specific help with submission support, trial planning, or site management oversight for a few months shouldn’t have to choose between overpaying for capacity they don’t fully use and going without.

A part-time consultant picks up a defined scope within your ClinOps function, maybe 15 to 25 hours a week, maybe scoped to a specific deliverable.

We recently placed a part-time consultant for clinical trial support at a smaller sponsor for a comparatively modest rate. That gave the company access to an experienced ClinOps professional without what would have been a six-figure all-in cost of a full-time hire. We’ve done similar placements for part-time clinical project management and investigator-facing planning work.

This part-time model is especially useful for companies between major trial phases, or those that need a specific skill set (eTMF cleanup, for example) for a defined period. You get real Clinical Operations capacity at a cost that matches your current workload, and you can scale up later if the program grows.

It’s a natural scaling path: a company might start with one insourced functional leader in Phase 1, scale up its internal expertise in Phase 2 as needs grow, and shrink the contingent workforce back down in Phase 3.

3. Clinical Project Managers and Clinical Trial Management

Here’s another scenario we’ve seen multiple times: Your trial is running, but nobody is clearly owning the project management layer.

• Timelines are tracked in spreadsheets that three different people update.

• Your eTMF has gaps that keep growing.

• Your Clinical Operations lead is spending half their time on project coordination instead of the strategic work they were actually hired to do. “Working on the work.”

CPM and CTM roles just sort of naturally sit at the intersection of project management and clinical execution, and they’re some of the most natural fits for embedded consultants.

CPMs tend to focus on timelines, milestones, cross-functional coordination, and status reporting. CTMs tend to focus on eTMF oversight, trial documentation, and the operational mechanics of trial management.

We’ve seen a broader strategic advantage here, too. A well-placed contract Clinical Operations Manager or contract Project Manager is function-specific and ingrained as an extension of the company. That’s a different animal than an outsourced project manager working through a CRO, who is also juggling other clients and operating within the CRO’s systems rather than yours.

4. In-house CRAs, site-facing roles, and investigator support

The gap between “we outsource monitoring to a CRO” and “we have a full in-house monitoring team” is usually pretty wide, and a lot of sponsors sit in that gap without a good solution. You want more visibility into what’s happening at your sites, but you don’t have the headcount to support a full internal CRA team.

This is also where the CRO dependency risk becomes real. Many companies, especially those in competitive or niche therapeutic areas, need someone from the sponsor side to participate in relationship activities with investigators and sites. When a CRO owns all of those relationships, the sponsor becomes dangerously reliant on specific CRO personnel who might rotate onto other projects or leave entirely. We see this all the time.

An embedded CRA or site-facing consultant is different from a contract monitor working through a CRO. This person reports to you, uses your systems, and builds relationships with your sites as a representative of the sponsor, not a third party.

We’ve placed in-house CRAs at sponsors who wanted monitoring oversight closer to home, and we’ve placed clinical specialists and consultants in clinical/medical affairs roles, including an Associate Director/Director-level Clinical and Medical Affairs consultant at a company that needed senior clinical leadership but wasn’t ready to commit to a permanent hire at that level.

The consultant knows your protocols, your systems, and your sites. That institutional knowledge actually stays with you, even if the consultant’s engagement eventually ends, because the relationships and documentation are built under your roof, not the CRO’s.

5. Clinical supply coordination and vendor oversight

Clinical supply management is one of those functions that doesn’t get much attention until something goes wrong. Then it gets a lot of attention very fast! When a depot shipment is delayed, a site runs out of IP, or a supplier qualification audit is overdue, your Clinical Operations team suddenly spends a lot of time managing supply chain logistics instead of running the trial.

Vendor oversight has a similar dynamic:

• Your sponsor obligations include qualifying suppliers, auditing clinical services vendors, and maintaining documentation for inspection readiness.

• When nobody owns that work explicitly, it either falls to your QA team (who may not have a clinical trial context) or your ClinOps team (who don’t have the bandwidth).

This is exactly the kind of under-resourcing problem we warn about:

We’ve placed a Clinical Supply Coordinator at a sponsor that needed someone to own the supply chain side of trial operations, everything from depot logistics to site-level tracking.

On the vendor side, we’ve done clinical supply services audits (including one at a European manufacturing site), supplier qualification audits, and clinical site/vendor audit engagements at multiple sponsors.

These are very different scopes, but they share a common thread: somebody at the sponsor realized this work wasn’t getting done well and brought in a consultant to own it.

6. Clinical QA and GCP QA roles alongside Clinical Operations

Clinical QA and GCP QA aren’t part of Clinical Operations on the typical org chart, but in practice, the quality of your trial operations is inseparable from the work these roles do. When they’re absent, ClinOps absorbs the consequences! GCP compliance gaps accumulate, SOPs go stale, and vendor audits fall behind.

And when an FDA inspection happens, it’s your ClinOps people who are the ones pulled into the war room to gather documentation because there’s nobody else to do it.

An embedded Clinical QA or GCP QA consultant owns quality oversight for clinical activities:

• SOP development

• Inspection readiness

• GCP compliance monitoring

• Vendor/site audit programs

• CAPA management for clinical findings

We’ve placed these consultants at a range of sponsors, from staff augmentation at larger companies to full-time Senior Manager of GCP Quality roles at mid-size sponsors. One extended Clinical QA support engagement ran long because the sponsor needed sustained quality coverage across multiple programs.

We’ve also done more targeted engagements: get inspection-ready for an upcoming FDA visit, stand up a vendor audit program, or remediate GCP compliance findings from a previous inspection. The practical value for Clinical Operations is that quality issues get caught upstream. Your ClinOps team stays focused on trial execution instead of getting pulled into compliance fire drills.

The common thread here

All six of these models solve the same basic problem: a sponsor needs Clinical Operations capacity and doesn’t have it internally. The role is unfilled, the workload is temporary, or the required expertise is too specialized to justify a permanent hire.

But there’s a bigger strategic point underneath the tactical one. With more sponsors moving away from pure CRO outsourcing and toward hybrid models, the question isn’t whether to insource or outsource. It’s which functions benefit from having domain expertise sitting inside your organization, operating under your systems and SOPs, retaining institutional knowledge that stays with you rather than walking out the door with a CRO’s personnel changes.

If you don’t have someone who knows enough about the domain on your side of those relationships, it’s very likely you’ll end up spending more and getting less.

If you’re sitting on an open Clinical Operations role that’s been vacant for 60+ days, or if you need capacity you can’t justify as a full-time headcount, it’s worth considering whether one of these models fits your situation.

Learn more and reach out to our team if you want to talk through it.

Who is The FDA Group?

The FDA Group helps life science organizations rapidly access the industry's best consultants, contractors, and candidates. Our resources assist in every stage of the product lifecycle, from clinical development to commercialization, with a focus on Quality Assurance, Regulatory Affairs, and Clinical Operations.

With thousands of resources worldwide, hundreds of whom are former FDA, we meet your precise resourcing needs through a fast, convenient talent selection process supported by a Total Quality Guarantee. Learn more and schedule a call with us to see if we’re a fit to help you access specialized professionals and execute your projects on time and on budget.

Share The FDA Group's Insider Newsletter

We’ve recently heard from a few drug manufacturers that they’re seeing more post-inspection correspondence from CDER's Office of Manufacturing Quality, even after inspections that ended with one or two Form FDA 483 observations.

One VP of Quality at a major pharma company described it plainly: he's been seeing more OMQ letters, even post-EIR, with only a single observation. His theory was that the FDA might be padding activity to justify headcount and budget.

That could certainly be part of it. The (maybe) more likely explanation is that this is the FDA’s existing inspection closeout process running as designed, now executed more consistently and visibly than many firms are used to.

What these letters actually are

The letters these manufacturers are receiving are likely inspection classification decisional letters associated with the FDA’s FMD-145/EIR release process. They’re how the FDA communicates an inspection’s final classification to the facility.

The FDA began issuing 90-day facility classification decisional letters in late 2017 as part of a Concept of Operations (ConOps) agreement between CDER and ORA.

The program was a direct commitment under GDUFA II. The agency agreed to communicate final surveillance inspection classifications to facility owners within 90 days of an inspection. According to the FDA’s ConOps Q&A page, there are separate letter templates depending on whether the inspection is classified as NAI, VAI, or OAI.

How the post-inspection process works

The workflow is spelled out in the FDA’s Drug Manufacturing Inspections Compliance Program (7356.002) and the ConOps agreement.

• For surveillance inspections, ORA completes the Establishment Inspection Report and an initial classification within 45 days of closing the inspection. If the initial classification is potentially OAI, ORA refers the package to OMQ within those same 45 days. OMQ then makes a final classification and issues a decisional letter within 90 days of the inspection's close.

• For VAI or OAI initial classifications, the inspectional package goes to a CDER Compliance Officer for review. For API, OTC, and many small molecule drug products, that review sits in OMQ. For biologics and certain product-specific programs, review responsibilities may sit in other CDER offices, such as the Office of Pharmaceutical Manufacturing Assessment (OPMA). The Compliance Officer has 45 days from receipt of the complete package to determine the final classification.

If no further action is recommended, whether because of an NAI classification, a VAI classification, or a downgraded OAI, ORA issues the FMD-145 decisional letter within the 90-day window.

The NAI letter is pretty simple. It states the inspection classification, notes that the facility is in an acceptable state of CGMP compliance, and includes a copy of the redacted EIR. It also includes a line that this letter does not constitute an endorsement.

Why firms may be seeing more of them now

We’re speculating a bit here, but a few factors are probably working together:

• The FDA is simply doing more inspections, and this is a natural result. In FY2024, the agency conducted 989 drug quality assurance inspections, a 27% increase from FY2023. More than 62% of those were at foreign sites, an all-time high. More inspections mean more classification letters.

• The ConOps program has also matured. When the FDA first began issuing 90-day decisional letters in late 2017, the goal was 90% compliance with the 90-day timeline. Seven years in, the process is likely more well-established, and the letter issuance rate is more consistent. Firms that went years between inspections during COVID may be encountering this for the first time now that the FDA has resumed normal surveillance schedules.

• And the enforcement trend is real. The FDA issued 105 warning letters for drug quality issues in FY2024, the highest number in five years. Inspection-driven warning letters increased 21% from FY2023. The agency is issuing more inspection-driven correspondence alongside increased inspection activity, and classification letters are part of that broader process.

What the letters mean for your facility

A classification letter after an inspection is not by itself enforcement. For NAI and VAI outcomes, it’s the formal record that the FDA has reviewed your inspection and decided not to pursue regulatory or enforcement action.

But VAI means something. The FDA’s Inspection Classification Database defines VAI as a classification indicating that the inspection found objectionable conditions, but the agency expects the facility to correct them voluntarily. The database also states that if a manufacturer fails to implement voluntary corrections, the next inspection may be classified as OAI.

That escalation path is explicit and documented. It’s the compliance signal that matters here.

Read more

EOS Implementer Peter Martino has spent 7 years coaching leadership teams through more than 600 full-day sessions across 60+ companies.

He also spent 15 years helping grow a remodeling company from a startup to a 40-person team, completing over 600 projects per year. Nick Capman brought him on the podcast to tackle a straightforward question: why do capable, hardworking companies get stuck at “good” and never reach “great”?

The answer, as Peter sees it, is less about effort and more about structure and focus, plus a willingness to stop doing the wrong things.

Peter is an Expert EOS Implementer at EOS Worldwide, based in Westborough, Massachusetts. Before joining EOS in 2019, he spent over 14 years at United Home Experts, where he held roles spanning sales, marketing, and operations management. After the company adopted EOS, it doubled revenue and profit in three years. Peter grew up in his family's stained-glass studio, where he first saw both the rewards and the strain of entrepreneurship firsthand.

Peter’s key insights from the discussion

• Vision usually lives in one person’s head. Peter’s observation is that most leadership teams think they share a vision, but it’s often unwritten and belongs to a single person. He works with teams to pull the vision out of each leader, document it in a two-page Vision/Traction Organizer, and get the full team to debate and agree on every word. When people help shape the vision, they’re far more likely to execute against it.

• Busyness is a symptom, not a badge. The “brute force, white knuckle” approach to work is often covering for deeper problems: weak delegation, avoidance of hard conversations, or wrong people in wrong seats. Peter makes a distinction between working hard and working healthy. Nick added his own observation: some of the most productive thinking happens in those quiet moments after work, when your mind is still processing without a screen in front of you. Peter calls this the “clarity break” and recommends scheduling it deliberately rather than waiting for it to happen.

• When everything is important, nothing is. Peter cites a roofing company he works with that strayed from their core focus. They were excellent at restoration roofing but started subcontracting interior work. Within a quarter, half the issues on their quarterly issues list traced back to the extra services. When the team pulled out their vision document and saw “restoration roofing” in black and white, they stopped cold turkey. Business improved almost immediately. Nick confirmed experiencing something similar at The FDA Group: when they cut expanded service offerings, the core business actually grew.

• A great company has three things: vision, traction, and a healthy leadership team. Traction, in EOS terms, means discipline, accountability, and execution. Health means the leadership team is willing to be open and honest, and that they’re focused on the greater good of the company rather than self-protection. Peter leaned on Patrick Lencioni’s trust pyramid: vulnerability leads to productive conflict, which leads to commitment, which leads to accountability, which leads to results. If there are cracks at the leadership level, he said, there are fissures throughout the organization.

• The tortoise wins. Peter’s framing on the “good to great” mindset: it requires a willingness to do the small, sometimes boring things consistently over time. He pushed back on the impulse to chase flashy ideas and instead pointed to what he called “small and mighty companies” that are quietly excelling in their towns by doing the fundamentals well.

• Know whether leadership is actually your thing. Peter’s closing thought was pointed: not everyone who ends up in a leadership role is wired for it, and that’s fine. But if you want to lead, it’s a skill that requires investment. Reading, training, clarity breaks. It’s diminishable if you don’t put in the work.

Recommended reading from the episode

Peter and Nick referenced several books during their conversation:

• Traction by Gino Wickman

• Good to Great by Jim Collins (and the follow-up, How the Mighty Fall)

• Five Dysfunctions of a Team by Patrick Lencioni

• Atomic Habits by James Clear

For leaders looking to take this further, Nick Capman’s book The Passionate Workforce: How to Create and Maintain Maximum Employee Engagement expands on creating high-trust cultures where ideas and people can thrive.

Drawing from practical strategies, real-world examples, and proven methods, Nick provides actionable insights for leaders at every level. Whether you’re refining your leadership style, implementing engagement initiatives, or preparing your team for the future, this Amazon #1 bestseller equips you with the tools to transform your organization from the inside out.

If you haven’t picked up a copy yet, it’s an invaluable resource for any leader serious about maximizing employee engagement and creating a workplace where passion and performance are inextricably linked. Grab your copy on Amazon.

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We review a lot of CQV protocols. Maybe hundreds or more each year across pharma, medical device, biotech, and combination product companies. Some are written in-house, some by consultants. Some are legacy documents that have been copied and pasted forward for a decade, with the equipment name swapped out. (That’s usually the worst case.)

The uncomfortable truth is that many of them would not survive serious regulatory scrutiny. They’d pass a casual internal review because they look right and sort of work well enough: correct section headers, references to manufacturer specs, a signature block at the end. But the substance, the part that actually protects the company during an audit or an investigation, is often thin in ways that aren’t always obvious.

The people writing these protocols are usually experienced and capable. The problem we typically see is more structural. Organizations treat protocol writing as a documentation exercise when it should be treated as an engineering exercise. The distinction matters in practice.

We spoke with a few of our best CQV engineering-focused consultants to see which problems they see most often with protocols and the fixes they prescribe.

The most common problem: acceptance criteria that don’t accept or reject anything

If we had to pick one issue that shows up more than any other, it’s acceptance criteria written so broadly that virtually any result would pass.

Here’s what we mean in practical terms. Consider this IQ acceptance criterion, which we’ve seen in various forms dozens of times:

On its face, this seems reasonable to many people. But as an acceptance criterion, it's actually useless.

• What specifically needs to be verified?

• What measurement confirms compliance?

If an auditor asks, "How did you determine that this criterion was met?" the answer can't be "We followed the instructions!" That's a description of the activity, not evidence of the outcome.

A better version would be:

Again, the difference is that the second version can actually fail. Someone can run the test, record a number, and that number either falls within the range or it doesn’t. The first version can’t fail because it doesn’t define what failure looks like.

This pattern repeats throughout OQ and PQ protocols as well. We regularly see OQ criteria like “equipment operates within normal parameters” without defining what those parameters are. Or PQ criteria like “product meets quality specifications” without referencing which specifications, what the limits are, or how many samples need to pass.

When acceptance criteria are vague, passing them pretty much proves nothing. And when they prove nothing, the entire qualification exercise becomes a paperwork drill rather than an engineering verification. It’s not doing your future self any favors.

The copy-forward problem

This is a related issue. An official term for it might be “protocol inheritance.” Here’s what it looks like:

• Company A writes a reasonable protocol for a specific piece of equipment in 2016.

• Over time, that protocol becomes a template.

• New equipment gets qualified using the same document structure, the same boilerplate language, and often the same acceptance criteria, even when the new equipment has different operating characteristics, different risk profiles, and different user requirements.

We’ve seen cases where a protocol written for a standalone analytical instrument was adapted for a fully integrated manufacturing line with few changes beyond the equipment name and serial number. The OQ section still tested the same ten parameters from the original protocol. No one asked whether those parameters were the right ones for the new equipment.

The fix is straightforward but time-consuming (which is why it’s often skipped): every protocol should start from the user requirements and work forward, not from a previous protocol and work backward. Templates save time on formatting and structure. They should really never dictate a piece of technical content.

OQ protocols that test the middle but skip the edges

This one is specific to Operational Qualification, and it’s common even in organizations with mature quality systems. Let’s walk through it.

Most OQ protocols test equipment at nominal operating conditions.

• The tablet press runs at its standard speed.

• The autoclave cycles at its standard temperature and time.

• The mixing vessel operates at its standard RPM.

Everything passes, the report gets signed, and the equipment moves to PQ.

The problem is that production doesn’t always happen at nominal conditions. Batch sizes vary, operators adjust speeds, and environmental conditions shift with the seasons. If the equipment was only tested at the midpoint of its operating range, nobody actually knows whether it performs acceptably at the edges.

Good OQ protocols test at the extremes of the operating range, not just the center. For a tablet press, that means running at both the lowest and highest speed settings and confirming that tablet weight and hardness remain within specification across the full range. For temperature-controlled equipment, it means testing at the upper and lower bounds of the operating window, not just the setpoint.

In short, if the equipment can’t perform at the boundaries of its approved operating range, the operating range is wrong. It’s always better to find that out during OQ than during a production run.

No failure mode testing

There’s one question we ask during protocol reviews that almost always gets an uncomfortable pause:

“Where in this OQ protocol do you intentionally cause the equipment to fail?”

Many protocols don’t include failure mode testing at all. Everything in the test plan is designed to pass. The equipment runs through its normal operations, each parameter meets its criterion, and the protocol concludes successfully.

But regulators care whether the equipment responds correctly when something goes wrong.

• Does the alarm trigger when the temperature exceeds the upper limit?

• Does the system lock out when an unauthorized user attempts to change a critical parameter?

• Does the error log capture the event accurately?

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Here are some key items from the past couple of weeks.

💊 = Pharma, biologic, and biotech.
💉 = Medical device, medtech, diagnostics, and digital health.

FDA Leadership and Administration

• Brenner leaves FDA for HHS role — Sara Brenner, the FDA’s principal deputy commissioner and its former acting commissioner, is leaving the agency to become senior counselor for public health to HHS Secretary Kennedy. The move was reportedly orchestrated by HHS Chief Counselor Chris Klomp. It’s not yet clear who will replace Brenner, but whoever is selected could be seen as a potential successor to Commissioner Makary if he were to resign.

• Ibogaine executive order signed at White House event 💊 — President Trump, joined by HHS Secretary Kennedy, Commissioner Makary, and podcaster Joe Rogan, signed an executive order to accelerate the development of ibogaine and other psychedelics for treating mental illness. The order instructs the FDA to provide Commissioner’s National Priority Vouchers to psychedelic drugs with Breakthrough Therapy designations, directs the FDA and DEA to establish a pathway for patient access under the Right to Try Act, and calls for rescheduling psychedelic substances that have completed Phase 3 trials. Rogan said he had directly texted Trump information about ibogaine for opioid use disorder and received a positive response.

• Three new CNPVs for psychedelics 💊 — The FDA issued three new Commissioner’s National Priority Vouchers to psychedelic products: psilocybin for treatment-resistant depression (awarded to Compass Pathways for COMP360), psilocybin for major depressive disorder (to Usona Institute), and methylone for PTSD (to Transcend Therapeutics, being acquired by Otsuka Pharmaceutical). Compass also received rolling review status for its NDA. Commissioner Makary told CNBC that decisions on some psychedelic therapies could come as soon as this summer.

• Makary on mRNA vaccine funding and universal flu shot 💊 — On CNN’s “The Source,” Commissioner Makary responded to questions about the cancellation of $500 million in HHS vaccine development projects, framing it as a shift in priorities rather than a cancellation. He argued that taxpayer dollars should fund research that the private sector will not, citing a universal flu shot as an example.

• WSJ editorial board again criticizes Makary and Prasad 💊 — The Wall Street Journal’s editorial board published another editorial criticizing Commissioner Makary and CBER Director Vinay Prasad following the FDA’s second rejection of Replimune’s melanoma immunotherapy. The editorial alleged that Makary and Prasad had arranged a review designed to cover for their initial rejection of the drug and called on Congress to question both officials.

• White House reviewing update to substantial evidence guidance 💊 — The White House Office of Information and Regulatory Affairs received revised draft guidance from the FDA on demonstrating substantial evidence of effectiveness for drugs and biologics. This would update 2019 draft guidance and follows Makary’s recent policy making one pivotal trial the FDA’s default standard for approval. Last year, 59% of new medicines approved by the FDA’s main review office listed just one pivotal study in their original labeling.

• Kennedy launches HHS podcast — HHS Secretary Kennedy is starting The Secretary Kennedy Podcast, intended to feature interviews with guests who challenge medical “taboos.”

FDA General

• First ibogaine IND cleared 💊 — The FDA cleared the first investigational new drug application for noribogaine hydrochloride as a potential treatment for alcohol use disorder, allowing early-phase human trials in the U.S. The IND went to DemeRx NB.

• CNPV meeting rescheduled to June 4 💊 — The FDA confirmed the reschedule of its public meeting on the CNPV pilot program to June 4. The meeting will seek feedback on eligibility criteria, voucher selection processes, sponsor responsibilities, and program implementation.

• FDA proposes enforcement policy for respiratory products 💉 — The FDA published a new draft guidance proposing not to enforce several medical device requirements for face-filtering respirators and reusable respirators already under NIOSH regulatory oversight, citing overlap between the two agencies.

• FDA removes 12 peptides from safety concerns list 💊 — The FDA officially removed 12 peptides from a list of bulk drug substances that “raise significant safety concerns,” including emideltide, epitalon, Semax, and Melanotan II. The agency previously said it had concerns about immunogenicity risks and peptide-related impurities for many of these substances.

• Compounded peptides meeting set for July 💊 — The FDA announced it will hold a meeting on July 23-24 on bulk compounding of certain peptide substances, including emideltide, Semax, and epitalon.

• Overdue generic drug applications drop sharply 💊 — Speaking at the FDA’s annual Generic Drugs Forum, Office of Generic Drugs Deputy Director Darby Kozak disclosed that the number of generic drug applications pending more than 60 days past their goal date fell from nearly 70 in Q2 2025 to just two in Q2 2026. A new transparency pilot program providing more frequent updates to applicants is one factor driving improvement.

• Continuous trial pilot launched 💊 — Commissioner Makary announced a new pilot program for real-time clinical trials at an event on the FDA’s White Oak campus. Two proof-of-concept studies are already underway: one sponsored by AstraZeneca testing a cancer drug combination in mantle-cell lymphoma, and another run by Amgen enrolling patients with small-cell lung cancer. Under the program, FDA reviewers would see clinical data in real time as it is generated. The FDA plans to publish a request for information in the Federal Register seeking industry input on the pilot, with final selection criteria expected in July and selections in August. FDA Chief AI Officer Jeremy Walsh and Deputy Chief Medical Officer Mallika Mundkur are leading the effort.

• Petition challenges FDA’s release of Complete Response Letters 💊 — A citizen petition filed by Covington & Burling’s Krista Hessler Carver calls on the FDA to change its process for releasing CRLs, arguing the agency is acting unlawfully by disclosing commercially confidential information without offering sponsors the opportunity to redact sensitive content. The FDA recently asked Congress for additional legal authority to release CRLs, indicating the agency itself is concerned it may lack defensible authority.

• ICER calls for accelerated approval reforms 💊 — The Institute for Clinical and Economic Review published a white paper calling for extensive changes to the FDA’s accelerated approval pathway, including requiring advisory committees, issuing after-action reports when confirmatory trials fail, creating risk ratings for accelerated approval products, and establishing a more structured process for developing surrogate endpoints.

• Proposal to reduce CAR-T safety monitoring 💊 — A paper by a working group of industry, academic, and patient representatives argued that the FDA’s current 15-year posttreatment monitoring period for CAR-T cell therapy patients is no longer justified and should be shortened to five years, with streamlined data collection.

• New antibiotics impurities guidance 💊 — The FDA published a new draft guidance on impurity specifications for antibiotics made using fermentation or semisynthetic methods, which can introduce a wider variety of impurities than chemical synthesis. Existing guidance documents do not cover these production methods.

• Bioanalytical methods guidance for biomarkers 💊 — The FDA issued final recommendations on validating bioanalytical methods for biomarker assays, restating advice from 2018 guidelines that had been superseded by ICH M10 guidance in 2022 (which explicitly excluded biomarkers).

• Animal testing reduction report card 💊 — The FDA published a press release citing six developments in the past year to reduce animal testing, including guidance on reducing nonhuman primate testing for monoclonal antibodies and transitioning away from horseshoe crab-based endotoxin testing. The agency still has not updated its animal testing regulations despite the 2022 FDA Modernization Act 2.0.

• CDRH warns about nitrosamines in combination products 💉 — CDRH sent a letter to industry warning about potential nitrosamine impurities in device-led combination products, specifically citing detection in certain products containing the drug rifampin. The agency directed manufacturers to existing drug product guidance. No adverse events have been reported.

• Hormonal contraceptive petition filed 💊 — The Contraceptive Study Group filed a citizen petition asking the FDA to add warnings to hormonally active contraceptives regarding potential autoimmune and inflammatory risks. The petition is notable because key figures in the MAHA movement, including Surgeon General nominee Casey Means, have previously said that birth control side effects are under-discussed.

• MIDD mini review published 💊 — CDER’s Office of Clinical Pharmacology Director Issam Zineh published a narrative review on the history and regulatory impact of model-informed drug development. The paper reports that the FDA’s MIDD meeting program has saved approximately $1.6 billion and over a century of clinical development time since its establishment.

• NDC final rule webinar announced 💊 — Following the FDA’s March finalization of a rule to shift from 10-digit to 12-digit National Drug Codes and allow nonlinear barcodes, Leavitt Partners announced a June 17 webinar to showcase a cross-sector implementation guide and 10-year roadmap.

• Postmarketing requirements mostly on track 💊 — The FDA’s latest report on postmarketing requirements and commitments found that most are progressing on schedule, with 83% of open PMRs tied to biologics license applications and about two-thirds of those tied to new drug applications on track as of September 2024.

• Nonprescription drugs meeting details 💊 — The FDA’s April 23 meeting on increasing access to nonprescription drugs, hosted by Duke-Margolis, was led by FDA nonprescription drug regulation lead Karen Murry. A discussion guide has been released covering key regulatory issues related to mass prescription-to-OTC conversion.

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Earlier this month, CDER issued a warning letter to a Michigan-based manufacturer of homeopathic drug products following an inspection conducted October 28–30, 2025, at the firm’s facility in Michigan.

Read the full warning letter

The letter covers a range of CGMP failures (which we’ll touch on), but the section that sets this letter apart from every other warning letter we’ve seen is the one headed “Inappropriate Use of Artificial Intelligence in Pharmaceutical Manufacturing.”

The firm told FDA investigators that it used AI agents to create drug product specifications, procedures, and master production or control records in an effort to comply with FDA requirements. When investigators pointed out that the firm had not conducted process validation before distributing its drug products, the firm responded that it was not aware of the legal requirement because the AI agent it used never told it that validation was required. This is the slippery slope of AI: the temptation to outsource policy production and core decision-making.

The FDA’s response gives us a pretty clear idea of its position here: AI-generated documents must be reviewed by a qualified human to ensure they are accurate and actually compliant with CGMP. Not using them is fine. But using them without human review and clearance violates 21 CFR 211.22(c), which requires the quality unit to review and approve all procedures and specifications.

The agency further stated that “any output or recommendations from an AI agent must be reviewed and cleared by an authorized human representative of your firm’s [quality unit].”

This is the first warning letter we’re aware of where the FDA has directly addressed the use of AI in drug manufacturing operations and articulated a regulatory position on it. That alone makes it worth reading carefully, given the anecdotes we’ve already heard about firms quietly turning to AI to generate documents from more or less whole cloth, and then turning around to have the AI also review its own output and trust its determination.

Let’s start with the other CGMP issues first.

The facility: insects, filth, and a docking bay that opened directly onto the manufacturing area

The FDA found that drug products at the site were prepared, packed, or held under insanitary conditions, rendering them adulterated under Section 501(a)(2)(A) of the FD&C Act.

According to the letter:

For a facility producing drug products of any type, environmental control is of course a baseline expectation. A manufacturing area that can be exposed to outdoor air, debris, and insects whenever the dock door opens does not have the separation required under CGMP.

No microbiological testing of finished products before release

The firm manufactures multiple homeopathic drug products, some of which can be applied in ways that create microbiological risk. According to the letter, the firm released finished drug products without testing for microbiological attributes: no total count testing, no testing for objectionable microorganisms.

Without testing each batch before release, the firm had no scientific basis for concluding that its products were free of harmful microbial contamination. The FDA cited the agency’s guidance on microbiological quality considerations in non-sterile drug manufacturing.

No adequate component testing, and a reliance on supplier COAs without validation

The firm, according to the FDA, also failed to perform adequate testing for purity, strength, quality, and identity of the components used in its drug products. It relied on certificates of analysis from suppliers without establishing the reliability of those suppliers’ test analyses at appropriate intervals.

Two specific gaps stand out here:

Without component testing, the firm couldn’t ensure the quality or safety of its drug products at the input level, and without finished product testing, it could not ensure quality or safety at the output level. The quality system had no analytical verification at either end of the manufacturing process.

A quality unit that was “inadequate”

The FDA found that the firm’s quality control unit failed to exercise its responsibility to ensure drug products were manufactured in compliance with CGMP and met established specifications.

Three specific failures were cited here:

The FDA concluded that the firm’s quality systems are “inadequate” and cited the agency’s guidance on quality systems approaches to CGMP.

When a quality unit isn’t reviewing batch records before release, isn’t ensuring procedures are followed, and isn’t ensuring process controls exist, it isn’t functioning as a quality unit in any operational sense. The CGMP regulatory structure puts the quality unit at the center of everything. If the quality unit is absent or passive, the rest of the system fails more or less by default.

The AI finding: what the FDA actually said and what it means

Here’s what the warning letter documents:

So, to be clear, the firm appears to have outsourced to AI both the production of documents and the decision-making around whether validation was needed.

The FDA’s response contains two distinct positions.

• First, the procedural requirement: if a firm uses AI to aid in document creation, it must review the AI-generated documents to ensure they are accurate and comply with CGMP. Failure to do so violates 21 CFR 211.22(c), which requires the quality unit to approve or reject all procedures or specifications that impact drug product quality.

• Second, the broader principle: any output or recommendations from an AI agent must be reviewed and cleared by an authorized human representative of the firm’s quality unit in accordance with the FD&C Act and 21 CFR 211.22.

The FDA also described the situation as “overreliance on artificial intelligence for drug manufacturing operations.”

So, what does this tell us?

First, the FDA is not saying firms cannot use AI tools. The letter explicitly acknowledges the possibility of resumed production with AI tools in place:

“If you plan to resume drug production, and use AI to help with CGMP activities, such as development of procedures and specifications, any output or recommendations from an AI agent must be reviewed and cleared by an authorized human representative of your firm’s QU.”

In other words, AI output does not substitute for human review and does not relieve a quality unit of its regulatory obligations. If an AI tool generates a set of specifications or procedures, and the quality unit approves and releases products based on those documents without independently verifying that they are accurate and compliant, the quality unit has failed to exercise its responsibilities under 211.22.

The “we didn’t know because the AI didn’t tell us” defense got no traction. The FDA’s position is pretty clear: the legal obligation to know and comply with CGMP requirements sits with the firm and its quality unit, not with the tool.

Ask yourself:

• If your firm uses AI tools to draft SOPs, specifications, batch records, or other GMP documents, can you show documented evidence that a qualified member of your quality unit reviewed each output for accuracy and CGMP compliance before the document entered your quality system? The FDA’s position in this letter is that AI-generated documents require the same review and approval as any other document. If your process is “generate, format, file,” and the review step is missing or informal, this letter tells you exactly how the FDA will characterize that.

• If an FDA investigator asked your quality unit to explain a specific regulatory requirement in one of your SOPs, could the QU representative explain why that requirement exists and confirm it was verified against the regulation, rather than saying it came from a template or a tool? The compliance obligation under 211.22 isn’t to produce documents. It’s to ensure those documents are correct. A quality unit that can’t explain the basis for its own procedures has the same problem documented here, whether it used AI or not.

• For any component you receive with a supplier COA, can you show that you’ve established the reliability of that supplier’s test analyses at appropriate intervals, and that you’re conducting identity testing on incoming lots? Reliance on COAs without supplier qualification is a common 483 observation, and we catch it in audits and mock inspections all the time. This letter adds the layer of components at risk for a specific type of contamination that has caused fatalities. If your component testing program doesn’t include risk-based testing for known contaminants associated with your ingredient classes, that’s an exposure.

• When was the last time you walked your manufacturing area and assessed environmental controls with the assumption that an FDA investigator would be doing the same walk tomorrow? The findings here (insects, filth, leaves, clutter, a dock door that opens onto manufacturing) are observable conditions. They don’t require analytical testing to detect. They require someone in the organization to actually notice and act.

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On April 20, the FDA issued a draft guidance titled Compliance Policy Regarding Premarket and Other Requirements for Certain NIOSH Approved Air-Purifying Respirators. The comment period runs 60 days from the Federal Register notice.

Since we work on so many 510(k)s and have partnered with several firms that have brought products in this category to market, we wanted to quickly break down this draft guidance.

Long story short: the FDA is proposing to deprioritize enforcement of most FDA-specific requirements — registration, listing, 510(k), labeling, MDR, UDI — for NIOSH-approved respirators used in healthcare settings for medical purposes. The rationale is that NIOSH’s own approval and oversight program already covers enough ground that layering the FDA’s full device regulatory framework on top adds burden without a corresponding safety benefit.

Here's what's in it and what it means.

What devices does this cover?

The guidance applies to three categories of NIOSH-approved respirators when used for medical purposes:

What’s excluded?

The guidance does not cover N95 respirators with antimicrobial or antiviral agents (product codes ORW and ONT). It also excludes any product that makes claims about disease-specific efficacy, infection prevention, viral or bacterial filtration, antimicrobial function, hypoallergenicity, or surgical smoke filtration.

Products with antimicrobial coatings, drug delivery systems, nanoscale technologies, combination products, or emerging tech like germicidal UV are also outside scope. Those products would still need both NIOSH approval and an FDA premarket submission.

What FDA requirements would be deprioritized?

Under this compliance policy, the FDA says it would not prioritize enforcement of:

That’s a lot! Basically, everything in the FDA’s device regulatory toolkit other than recordkeeping and complaints.

What’s still required?

Manufacturers within scope are still expected to comply with recordkeeping and complaint handling requirements under 21 CFR 820.35.

The FDA wants to preserve its ability to review complaint records for postmarket surveillance if safety concerns come up. The idea is that manufacturers should still be tracking whether their products meet specifications and responding to complaints, even if most other FDA requirements are on hold.

And of course, NIOSH approval under 42 CFR Part 84 remains fully in effect. (That’s the entire foundation of this compliance policy.)

Why is the FDA doing this?

Two reasons, according to the guidance.

First, NIOSH’s existing oversight is extensive. NIOSH approval requires initial site qualification, product performance testing, quality control plans, respirator label design review, and ongoing conformity assessment. NIOSH issues certificates of approval after examining, inspecting, and testing each respirator. Post-approval, NIOSH conducts product audits and site audits roughly every two years. NIOSH can revoke approvals for cause (for example, if a manufacturer fails to maintain quality control).

Second, the FDA’s own postmarket data doesn’t show a safety problem. The FDA reviewed MDRs for these devices from January 2020 through December 2024 and found no safety signal. During the same period, there were only two voluntary recalls of FFRs, neither of which involved reports of patient harm. (One was a lot-specific filtration efficiency failure on a surgical N95; the other involved 528 PAPRs with potentially mis-assembled headband rivets.)

The guidance also references the “least burdensome” framework — the FDA’s longstanding policy of not imposing regulatory requirements beyond what’s needed to provide reasonable assurance of safety and effectiveness.

The healthcare use question

There’s an important thread running through this document about intended use. The FDA considers respirators used to prevent wearer exposure to pathogenic biological airborne particulates to be devices intended for a medical purpose.

The guidance goes into some detail about why: healthcare settings present distinct respiratory risks from procedures like intubation, aerosolized drug delivery, and work with bone saws, centrifuges, and blenders, plus the baseline risk of caring for patients with respiratory illness.

This isn’t new. The FDA made the same determination in March 2020 when it issued an EUA for NIOSH-approved FFRs in healthcare settings during COVID-19. But the guidance reinforces the point: these are medical devices under the FD&C Act, and the FDA is choosing to exercise enforcement discretion, not saying they’re unregulated.

What about the COVID-era EUAs?

The guidance provides some useful history here. The FDA issued the first respirator EUA on March 2, 2020, authorizing NIOSH-approved FFRs for use by healthcare personnel.

That EUA was amended several times, most recently on July 12, 2021. The COVID public health emergency expired May 11, 2023, but healthcare personnel kept using these respirators. This guidance is essentially the FDA establishing a durable policy framework for a practice that’s been in place for years, and predates COVID, dating back to tuberculosis protocols in the 1990s.

This is a draft guidance. It’s nonbinding. It doesn’t create enforceable obligations. The comment period is the time to weigh in.

And even if finalized, FDA explicitly reserves the right to enforce any FD&C Act requirement at any time. A compliance policy is not an exemption — it’s a statement of current enforcement priorities. FDA can change course for safety reasons or if circumstances shift.

Bottom line

The FDA is proposing to let NIOSH bear most of the regulatory burden for these respirators, rather than duplicating oversight through its own device framework. For manufacturers of NIOSH-approved respirators that are already going through NIOSH’s approval and surveillance process, this would remove a layer of FDA-specific paperwork — registration, listing, 510(k), MDR, UDI, and most QMS requirements — while keeping complaint handling and recordkeeping in place.

If you manufacture or distribute NIOSH-approved respirators for healthcare use, this is worth reading in full and may warrant comment. If you’re on the quality or regulatory side of a healthcare system that uses these products, the practical impact is minimal — you’ll keep sourcing NIOSH-approved respirators the same way you already do. The changes are upstream, at the manufacturer level.

Also, the standard caveats of any draft apply. It’s nonbinding. It doesn’t create enforceable obligations. The comment period is the time to weigh in.

And even if finalized, FDA explicitly reserves the right to enforce any FD&C Act requirement at any time. A compliance policy is not an exemption. It’s a statement of current enforcement priorities. The FDA can change course for safety reasons or if circumstances shift.

Comments go to regulations.gov. Contact PPE@fda.hhs.gov or 1-888-INFO-FDA with questions. Read the full guidance here.

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