I have a few concerns about George Tidmarsh’s recent appointment as director of the FDA’s Center for Drug Evaluation and Research (CDER) which fits into wider concerns about the current administration. As usual in this adminstration, this boils down to a tendency to fringe medicine and vaccine denial adjacent thinking.
Association with “fringe” medical publishing: Tidmarsh contributed to the Journal of the Academy of Public Health, which Bloomberg and other outlets have described as a “fringe medical journal” connected to a conservative nonprofit.
Criticism of COVID-19 public health policy: Tidmarsh has openly criticized the government’s handling of the COVID-19 pandemic. On the “Derate the Hate” podcast, he lamented what he saw as political polarization and lack of “academic freedom” in pandemic-era policy discussions, and suggested openness to the theory of a lab origin for the coronavirus.
I also find a degree of irony in Tidmarsh’s leadership roles in several biotech and pharmaceutical companies—including as founder and CEO of Horizon Therapeutics and Threshold Pharmaceuticals. RFKJr, and others have spent a lot of time criticizing the revolving door between industry and government regulation. And here we have a great example of that revolving door.
In any other administration, Tidmarsh would be concerning due to his connections to fringe science. In this administration he is another worrisome personnel decision given authority.
Four weeks may not seem a lot to outsides (though every day of delay counts when you are talking launch plans) but I am thinking this is not the last, or the greatest, of delays ahead.
The first 100 days of President Trump’s second term have been nothing short of seismic for the Food and Drug Administration (FDA). Sweeping layoffs, high-profile firings, and a mass exodus of experienced staff have left the agency reeling, raising urgent questions about the safety of drugs, devices, and food in the United States.
Unprecedented Layoffs and Firings
Mass Layoffs and Restructuring
On April 1, 2025, the Department of Health and Human Services (HHS) executed a reduction in force that eliminated 3,500 FDA employees. This was part of a larger federal downsizing that saw at least 121,000 federal workers dismissed across 30 agencies in Trump’s first 100 days, with health agencies like the FDA, CDC, and NIH particularly hard hit. Security guards barred entry to some FDA staff just hours after they received termination notices, underscoring the abruptness and scale of the cuts.
The layoffs were not limited to support staff. Policy experts, project managers, regulatory scientists, and communications professionals were let go, gutting the agency’s capacity to write guidance documents, manage application reviews, test product safety, and communicate risks to the public. Even before the April layoffs, industry had noticed a sharp decline in FDA responsiveness to routine and nonessential queries-a problem now set to worsen.
High-Profile Departures and Forced Resignations
The leadership vacuum is equally alarming. Key figures forced out or resigning under pressure include:
Dr. Peter Marks, CBER Director and the nation’s top vaccine official, dismissed after opposing the administration’s vaccine safety stance.
Dr. Robert Temple, a 52-year FDA veteran and regulatory pioneer, retired amidst the turmoil.
Dr. Namandjé N. Bumpus, Deputy Commissioner; Dr. Doug Throckmorton, Deputy Director for regulatory programs; Celia Witten, CBER Deputy Director; Peter Stein, Director of the Office of Drugs; and Brian King, head of the Center for Tobacco Products, all departed-some resigning when faced with termination.
Communications, compliance, and policy offices were decimated, with all FDA communications now centralized under HHS, ending decades of agency independence.
The new FDA Commissioner, Martin “Marty” Makary, inherits an agency stripped of much of its institutional memory and scientific expertise. Add to this very real questions about about Makary’s capabilities and approach:
1. Lack of FDA Institutional Memory and Support: Makary steps into the role just as the FDA’s deep bench of experienced scientists, regulators, and administrators has been depleted. The departure of key leaders and thousands of staff means Makary cannot rely on the usual institutional memory or internal expertise that historically guided complex regulatory decisions. The agency’s diminished capacity raises concerns about whether Makary can maintain the rigorous review standards and enforcement practices needed to protect public health.
2. Unconventional Background and Public Persona: While Makary is an accomplished surgeon and health policy researcher, his career has been marked by a willingness to challenge medical orthodoxy and criticize federal health agencies, including the FDA itself. His public rhetoric-often sharply critical and sometimes inflammatory-contrasts with the FDA’s traditionally cautious, evidence-based communication style. For example, Makary has accused government agencies of “lying” about COVID-19 boosters and has called the U.S. food supply “poison,” positions that have worried many in the scientific and public health communities.
3. Alignment with Political Leadership and Potential Conflicts: Makary’s views align closely with those of HHS Secretary Robert F. Kennedy Jr., particularly in their skepticism of certain mainstream public health measures and their focus on food additives, pesticides, and environmental contributors to chronic disease. This alignment raises questions about the degree to which Makary will prioritize political directives over established scientific consensus, especially in controversial areas like vaccine policy, food safety, and chemical regulation.
4. Contrarianism and a Tendency Towards Conspiracy: Makary’s recent writings, such as his book Blind Spots, emphasize his distrust of medical consensus and advocacy for challenging “groupthink” in health policy. Critics worry this may lead to the dismissal of well-established scientific standards in favor of less-tested or more ideologically driven policies. As Harvard’s Dr. Aaron Kesselheim notes, Makary will need to make decisions based on evolving evidence, even if that means occasionally being wrong-a process that requires humility and openness to expert input, both of which could be hampered by the loss of institutional expertise.
5. Immediate Regulatory and Ethical Challenges: Makary inherits unresolved, high-stakes regulatory issues, such as the controversy over compounded GLP-1 drugs and the agency’s approach to ultra-processed foods and food additives. His prior involvement with telehealth companies and outspoken positions on food chemicals could present conflicts of interest or at least the appearance of bias, further complicating his ability to act as an impartial regulator.
Impact on Patient Health and Safety
Reduced Oversight and Enforcement
The loss of thousands of staff-including scientists and specialists-means fewer eyes on the safety of drugs, devices, and food. Despite HHS assurances that product reviewers and inspectors were spared, the reality is that critical support staff who enable and assist reviews and inspections were let go. This has already resulted in:
Delays and unpredictability in drug and device approvals, as fewer project managers are available to coordinate and communicate with industry.
A likely reduction in inspections, as administrative staff who book travel and provide translation for inspectors are gone, forcing inspectors to take on additional tasks and leading to bottlenecks.
The pausing of FDA’s unannounced foreign inspection pilot program, raising the risk of substandard or adulterated imported products entering the U.S. market.
Diminished Public Communication
With the elimination of FDA’s communications staff and the centralization of messaging under HHS, the agency’s ability to quickly inform the public about recalls, safety alerts, and emerging health threats is severely compromised. This loss of transparency and direct communication could delay critical warnings about unsafe products or outbreaks.
Loss of Scientific Capacity
The departure of regulatory scientists and the decimation of the National Center for Toxicological Research threaten the FDA’s ability to conduct the regulatory science that underpins product safety and efficacy standards. As former Commissioner Robert Califf warned, “The FDA as we’ve known it is over, with most leaders who possess knowledge and deep understanding product development safety no longer in their positions… I believe that history will regard this as a grave error”.
Impact on Clinical Studies
Oversight and Ethical Safeguards Eroded
FDA oversight of clinical trials has plummeted. During Trump’s previous term, the agency sent far fewer warning letters for clinical trial violations than under Obama (just 12 in Trump’s first three years, compared to 99 in Obama’s first three), a trend likely to worsen with the latest staff cuts. The loss of experienced reviewers and compliance staff means less scrutiny of trial protocols, informed consent, and data integrity, potentially exposing participants to greater risk and undermining the credibility of U.S. clinical research.
Delays and Uncertainty for Sponsors
With fewer staff to provide guidance, answer questions, and manage applications, sponsors of clinical trials and new product applications face longer wait times and less predictable review timelines. The loss of informal dispute resolution mechanisms and scientific advisory capacity further complicates the regulatory landscape, making the U.S. a less attractive environment for innovation.
Impact on Good Manufacturing Practices (GMPs)
Inspections and Compliance at Risk
While HHS claims inspectors were not cut, the loss of support staff and administrative personnel is already affecting the FDA’s inspection regime. Inspectors now must handle both investigative and administrative tasks, increasing the risk of missed deficiencies and delayed responses to manufacturing problems. The FDA may increasingly rely on remote, paper-based inspections, which proved less effective during the COVID-19 pandemic and could allow GMP violations to go undetected.
Global Supply Chain Vulnerabilities
The rollback of foreign inspection programs and diminished regulatory science capacity further expose the U.S. to risks from overseas manufacturers, particularly in countries with less robust regulatory oversight. This could lead to more recalls, shortages, and public health emergencies.
A Historic Setback for Public Health
The Trump administration’s first 100 days have left the FDA a shell of its former self. The mass layoffs, firings, and resignations have gutted the agency’s scientific, regulatory, and communications capacity, with immediate and long-term consequences for patient safety, clinical research, and the integrity of the U.S. medical supply. The loss of institutional knowledge, the erosion of oversight, and the retreat from global leadership represent a profound setback for public health-one that will take years, if not decades, to repair.
As former FDA Commissioner Califf put it, “No segment of FDA is untouched. No one knows what the plan is”. The nation-and the world-are watching to see if the agency can recover from this unprecedented upheaval.
As an American Pharmaceutical Quality professional who has worked in and with European colleagues for decades, I am used to hearing, “But the requirements in country X are different,” to which my response is always, “Prove it.”
EudraLex represents the cornerstone of Good Manufacturing Practice (GMP) regulations within the European Union, providing a comprehensive framework that ensures medicinal products meet stringent quality, safety, and efficacy standards. You will understand the fundamentals if you know and understand Eudralex volume 4. However, despite this unified approach, a few specific national differences exist in how a select few of these regulations are interpreted and implemented – mostly around Qualified Persons, GMP certifications, registrations and inspection types.
EudraLex: The European Union Pharmaceutical Regulatory Framework
EudraLex serves as the cornerstone of pharmaceutical regulation in the European Union, providing a structured approach to ensuring medicinal product quality, safety, and efficacy. The framework is divided into several volumes, with Volume 4 specifically addressing Good Manufacturing Practice (GMP) for both human and veterinary medicinal products. The legal foundation for these guidelines stems from Directive 2001/83/EC, which establishes the Community code for medicinal products for human use, and Directive 2001/82/EC for veterinary medicinal products.
Within this framework, manufacturing authorization is mandatory for all pharmaceutical manufacturers in the EU, whether their products are sold within or outside the Union. Two key directives establish the principles and guidelines for GMP: Directive 2003/94/EC for human medicinal products and Directive 91/412/EEC for veterinary products. These directives are interpreted and implemented through the detailed guidelines in the Guide to Good Manufacturing Practice.
Structure and Implementation of EU Pharmaceutical Regulation
The EU pharmaceutical regulatory framework operates on multiple levels. At the highest level, EU institutions establish the legal framework through regulations and directives. EU Law includes both Regulations, which have binding legal force in every Member State, and Directives, which lay down outcomes that must be achieved while allowing each Member State some flexibility in transposing them into national laws.
The European Medicines Agency (EMA) coordinates and harmonizes at the EU level, while national regulatory authorities inspect, license, and enforce compliance locally. This multilayered approach ensures consistent quality standards while accommodating certain national considerations.
For marketing authorization, medicinal products may follow several pathways:
Authorizing body
Procedure
Scientific Assessment
Territorial scope
European Commission
Centralized
European Medicines Agency (EMA)
EU
National authorities
Mutual Recognition, Decentralized, National
National competent authorities (with possible additional assessment by EMA in case of disagreement)
EU countries concerned
This structure reflects the balance between EU-wide harmonization and national regulatory oversight in pharmaceutical manufacturing and authorization.
National Variations in Pharmaceutical Manufacturing Requirements
Austria
Austria maintains one of the more stringent interpretations of EU directives regarding Qualified Person requirements. While the EU directive 2001/83/EC establishes general qualifications for QPs, individual member states have some flexibility in implementing these requirements, and Austria has taken a particularly literal approach.
Austria also maintains a national “QP” or “eligible QP” registry, which is not a universal practice across all EU member states. This registry provides an additional layer of regulatory oversight and transparency regarding individuals qualified to certify pharmaceutical batches for release.
Denmark
Denmark has really flexible GMP certification recognition, but beyond that no real differences from Eudralex volume 4.
France
The Exploitant Status
The most distinctive feature of the French pharmaceutical regulatory framework is the “Exploitant” status, which has no equivalent in EU regulations. This status represents a significant departure from the standard European model and creates additional requirements for companies wishing to market medicinal products in France.
Under the French Public Health Code, the Exploitant is defined as “the company or organization providing the exploitation of medicinal products”. Exploitation encompasses a broad range of activities including “wholesaling or free distribution, advertising, information, pharmacovigilance, batch tracking and, where necessary, batch recall as well as any corresponding storage operations”. This status is uniquely French, as the European legal framework only recognizes three distinct positions: the Marketing Authorization Holder (MAH), the manufacturer, and the distributor.
The Exploitant status is mandatory for all companies that intend to market medicinal products in France. This requirement applies regardless of whether the product has received a standard marketing authorization or an early access authorization (previously known as Temporary Use Authorization or ATU).
To obtain and maintain Exploitant status, a company must fulfill several requirements that go beyond standard EU regulations:
The company must obtain a pharmaceutical establishment license authorized by the French National Agency for the Safety of Medicines and Health Products (ANSM).
It must employ a qualified person called a Chief Pharmaceutical Officer (Pharmacien Responsable).
It must designate a local qualified person for Pharmacovigilance.
The Pharmacien Responsable: A Unique French Pharmaceutical Role
Another distinctive feature of the French health code is the requirement for a Pharmacien Responsable (Chief Pharmaceutical Officer or CPO), a role with broader responsibilities than the “Qualified Person” defined at the European level.
According to Article L.5124-2 of the French Public Health Code, “any company operating a pharmaceutical establishment engaged in activities such as purchasing, manufacturing, marketing, importing or exporting, and wholesale distribution of pharmaceutical products must be owned by a pharmacist or managed by a company which management or general direction includes a Pharmacien Responsable”. This appointment is mandatory and serves as a prerequisite for any administrative authorization request to operate a pharmaceutical establishment in France.
The Pharmacien Responsable holds significant responsibilities and personal liability, serving as “a guarantor of the quality of the medication and the safety of the patients”. The role is deeply rooted in French pharmaceutical tradition, deriving “directly from the pharmaceutical monopoly” and applying to all pharmaceutical companies in France regardless of their activities.
The Pharmacien Responsable “primarily organizes and oversees all pharmaceutical operations (manufacturing, advertising, information dissemination, batch monitoring and recalls) and ensures that transportation conditions guarantee the proper preservation, integrity, and safety of products”. They have authority over delegated pharmacists, approve their appointments, and must be consulted regarding their departure.
The corporate mandate of the Pharmacien Responsable varies depending on the legal structure of the company, but their placement within the organizational hierarchy must clearly demonstrate their authority and responsibility. This requirement for clear placement in the company’s organization chart, with explicit mention of hierarchical links and delegations, has no direct equivalent in standard EU pharmaceutical regulations.
Germany
While Germany has many distinctive elements—including the PZN identification system, the securPharm verification approach, specialized distribution regulations, and nuanced clinical trial oversight—the GMPs from Eudralex Volume 4 are the same.
Italy
Italy has implemented a highly structured inspection system with clearly defined categories that create a distinctive national approach to GMP oversight.
National Preventive Inspections
Activating new manufacturing plants for active substances
Activating new manufacturing departments or lines
Reactivating departments that have been suspended
Authorizing manufacturing or import of new active substances (particularly sterile or biological products)
National Follow-up Inspections to verify the GMP compliance of the corrective actions declared as implemented by the manufacturing plant in the follow-up phase of a previous inspection. This structured approach to verification creates a continuous improvement cycle within the Italian regulatory system.
Extraordinary or Control Inspections: These are conducted outside normal inspection programs when necessary for public health protection.
Spain
The differences in Spain are mostly on the way an organization is registered and has no impacts on GMP operations.
Regulatory Recognition and Mutual Agreements
EU member states have received specific recognition for their GMP inspection capabilities from international partners individually.
The Establishment Inspection Report (EIR) is a comprehensive document generated after FDA investigators inspect facilities involved in manufacturing, processing, or distributing FDA-regulated goods. This report not only details compliance with regulatory standards but also serves as a vital tool for both the FDA and inspected entities to address potential risks and improve operational practices.
Regulatory Framework Governing EIRs
The EIR is rooted in the Federal Food, Drug, and Cosmetic Act (FD&C Act) and associated regulations under 21 CFR Parts 210–211 (Current Good Manufacturing Practices) and 21 CFR Part 820 (Quality System Regulation for medical devices). These regulations empower the FDA to conduct inspections and enforce compliance through documentation like the EIR. Key policies include:
Field Management Directive (FMD) 145: This directive mandates the release of the EIR’s narrative portion to inspected entities once an inspection is deemed “closed” under 21 CFR § 20.64(d)(3). This policy ensures transparency by providing firms with insights into inspection findings before public disclosure via the Freedom of Information Act (FOIA).
Inspectional Conclusions: EIRs classify inspections into three outcomes:
No Action Indicated (NAI): No significant violations found.
Voluntary Action Indicated (VAI): Violations identified but not severe enough to warrant immediate regulatory action.
Official Action Indicated (OAI): Serious violations requiring FDA enforcement, such as warning letters or product seizures.
Anatomy of an EIR
An EIR is a meticulous record of an inspection’s scope, findings, and contextual details. Key components include:
1. Inspection Scope and Context
The EIR outlines the facilities, processes, and documents reviewed, providing clarity on the FDA’s focus areas. This section often references the Form FDA 483, which lists observed violations disclosed at the inspection’s conclusion.
2. Documents Reviewed or Collected
Investigators catalog documents such as batch records, standard operating procedures (SOPs), and corrective action plans. This inventory helps firms identify gaps in record-keeping and align future practices with FDA expectations.
3. Inspectional Observations
Beyond the Form FDA 483, the EIR elaborates on objectionable conditions, including deviations from GMPs or inadequate validation processes.
4. Samples and Evidence
If product samples or raw materials are collected, the EIR explains their significance. Extensive sampling often signals concerns about product safety, such as microbial contamination in a drug substance.
5. Enforcement Recommendations
The EIR concludes with the FDA’s recommended actions, such as re-inspections, warning letters, or import alerts. These recommendations are reviewed by compliance officers before finalizing regulatory decisions.
How the EIR Informs Regulatory and Corporate Actions For the FDA
Risk Assessment: EIRs guide the FDA in prioritizing enforcement based on the severity of violations. For example, an OAI classification triggers immediate compliance reviews, while VAI findings may lead to routine follow-ups.
Trend Analysis: Aggregated EIR data help identify industry-wide risks, such as recurring issues in sterile manufacturing, informing future inspection strategies.
Global Collaboration: EIR findings are shared with international regulators under confidentiality agreements, fostering alignment in standards.
For Inspected Entities
Compliance Roadmaps: Firms use EIRs to address deficiencies before they escalate.
Inspection Readiness: By analyzing EIRs from peer organizations, companies anticipate FDA focus areas. For example, recent emphasis on data integrity has led firms to bolster electronic record-keeping systems.
Reputational Management: A clean EIR (NAI) enhances stakeholder confidence, while recurrent OAI classifications may deter investors or partners.
Challenges and Evolving Practices
Timeliness: Delays in EIR release hinder firms’ ability to implement timely corrections. The FDA has pledged to streamline review processes but continued workforce issues will exacerbate the problem..
Digital Transformation: The FDA’s adoption of AI-driven analytics aims to accelerate EIR generation and enhance consistency in inspection classification. Hopefully this will increase transparency.
Global Harmonization: Joint FDA-EMA inspections, though rare, highlight efforts to reduce redundant audits and align regulatory expectations.
Conclusion
The FDA Establishment Inspection Report is more than a regulatory artifact—it is a dynamic instrument for continuous improvement in public health protection. By demystifying its structure, regulations, and applications, firms can transform EIRs from compliance checklists into strategic assets. As the FDA evolves its inspectional approaches, staying abreast of EIR trends and best practices will remain pivotal for navigating the complex regulatory compliance landscape.
Proactively engaging with EIR findings for organizations subject to FDA oversight mitigates enforcement risks. It fosters a quality culture that aligns with the FDA’s mandate to protect and promote public health.
Investigations of a Dog 