History and Why FDA’s Reversion to “Generalist” Investigators May Finally Solve the Combination Product Problem

Having read several articles on LinkedIn and held many spirited conversations with ex-FDA colleagues, I want to offer a different perspective on the move from specialized investigative staff back to a more generalist approach.

The History of FDA Investigators

Most are familiar with the history. The FDA's Office of Regulatory Affairs (ORA) traditionally operated with investigators starting as generalists, honing their skills in food programs—particularly general sanitation inspections—before advancing to more specialized areas like complex food manufacturing, pharmaceuticals, medical devices, or biologics.

This progression made sense. Even engineers or Pharm.D.s needed to learn the fundamentals of being an investigator: conducting inspections effectively and legally, documenting observations, and writing evidence-based reports. General sanitation served as an ideal starting point. Investigators had to wait six months to qualify for a three-week course in FDA Law and Evidence Development. Only after passing that could they pursue specialized training, which often spanned two to three years.

The FDA today differs markedly from its past in terms of employee and investigator longevity. When I joined in 2000, many colleagues had started in the 1970s as "Project Hire" civil servants and built long careers in the field. By the time I left in 2016, many investigators under my leadership had stayed only 2 or 3 years before leaving to become "seasoned FDA investigators" turned consultants. As the 1970s cohort retired, institutional experience waned. Given the training timeline, a two- to three-year investigator was only beginning to develop expertise.

The Shift to Program Alignment (PAG)

Around 2013 (approximately, lest my FDA friends correct me), ORA began seriously discussing a shift to Program Alignment, or PAG. As my friend Michael Rogers of Canal Row recently noted in his article “FDA’s Evolving Inspection Strategy: Two Shifts That Will Shape the Future of Regulatory Oversight,” PAG introduced its own challenges. It eliminated district flexibility in managing work plans by realigning them into product-oriented "regions." Culturally, it was a poor fit from the start, with full implementation kicking off in May 2017.

Younger FDA investigators resisted the constant travel, as regional territories expanded, increasing domestic trips. It wasn't unusual for an East Coast investigator to inspect a Midwest site. Those unwilling to relocate to a designated region for their commodity had to shift focus or work remotely under their program supervisor and compliance officer. For example, I knew an excellent medical device investigator in the Chicago District who, post-PAG, was reassigned to food inspections because Chicago fell under the Food Region. This made little sense and further frustrated already underpaid and under-resourced investigators. ORA's reluctance to support office changes or relocations exacerbated the shrinking tenure across the investigations staff.

My view—unpopular at the time—was that PAG would accelerate turnover, hinder responses to emergencies like widespread foodborne outbreaks, and, most critically for me, provide inadequate coverage for mixed-commodity or combination products. This could lead to redundant inspections and resource drains.

You might not realize how common it is for firms to manufacture and distribute multiple commodities from a single facility, but it's common. I've worked with companies producing dietary supplements (under FSMA and Part 111), traditional foods (Part 110), over-the-counter monograph drugs, and prescription drugs (Parts 210/211)—and one that included devices. Pre-PAG, districts assigned investigators capable of covering multiple program codes in a single inspection, requiring cross-training.

I know what you're thinking: cross-trained equals generalist. But that's not quite right. Many medical device, pharma, and BIMO specialists (GS-13/GS-14) who joined pre-PAG learned multiple programs while specializing, making them rare today.

The Combination Product Problem

The combination product market grew from approximately $80 billion in 2015 to over $165 billion in 2025. The market is projected to expand at 7%-10% annually through 2030, driven by innovations in drug delivery and patient-centric care. By 2016, it was clear combination products represented the future of medicine.

Overlay PAG on this: From hiring through career progression, investigators specialized in drugs, medical devices, or biologics. Few remained proficient in multiple areas, especially across drugs/biologics and devices.

Despite questions about combination product-trained investigators yielding promises of "developing training," reality fell short. Over 9.5 years serving hundreds of clients in this space, I've seen inspectors represent only the lead Center. Not once has a dual drug-and-device expert appeared for a routine inspection. Invariably, they focused on the primary technology, ignoring the secondary.

Why does this matter? It's crucial, especially for drug- or biologic-led combination products. Several NDAs or ANDAs passed pre-approval inspections with minimal device review, only for products to fail due to poor device design.

As recently as two months ago, executive leadership at one firm dismissed device concerns, citing past FDA approvals where "the FDA has never looked at the device."  Industry has learned that in drug/biologic lead combination products, it is a rare occurrence when the device is questioned with any rigor.

This inconsistency extends to Center reviews. One client submitted three ANDAs for pre-filled syringes: one reviewer had no comments, another posed minor questions, and the third requested extensive design control details, resulting in a Complete Response Letter.  This leaves industry confused and often rolling the dice that no serious questions will be posed, particularly with the more common device constituents, such as syringes.

Medical device investigators typically arrive only post-failure, for cause. Compounding this: the 510(k) program for device constituents not designed initially as primary containers/closures—a brewing disaster already unfolding.

Why the Reversion to Generalists Offers Hope

With PAG's mixed results—some successes but clear failures in combination products—what can we expect from the 2025 reversion under the "Simple Reform" initiative? This shift merges specialist corps back into a generalist framework to boost flexibility, address staffing shortages, and enhance oversight. We can hope the FDA will:

- Foster environments where proper cross-training and specialization coexist.

- Acknowledge market growth and technological advances, committing to improvements.

- Train investigators for rigorous work; for instance, the QSIT program often skipped design controls in abbreviated inspections—that must change, with real emphasis on design controls and risk management.

- Collaborate more with Centers to ensure thorough application reviews for both constituents and target pre-approval inspections, highlighting device risks.

- Signal to industry that separate drug and device inspections won't occur, then deliver inspections aligned with Part 4 Combination Product regulations.

Change isn't all good or bad. I commend the FDA for recognizing the need to adapt, even if it means revisiting proven methods.

To industry colleagues worried that generalists lack expertise: It's always been your duty to explain your product and technology. Investigators assess compliance with regulations—demonstrate it. Treat inspections as partnerships, not battles, for mutual success.