The New FDA Era Of Radical Transparency And Pervasive Oversight

By David Grote, principal consultant, Curadian Group

The first half of 2025 has been transformative for biopharmaceutical quality and regulatory affairs, with the FDA leading the charge with four significant changes. The FDA is rapidly moving from an event-driven compliance model to a system of continuous, global, data-driven oversight. To succeed, companies that study or market biopharmaceutical products in the U.S. need to take immediate action.

Key FDA Initiatives And Recent Milestones

This table provides a concise overview of the most impactful changes to the FDA's regulatory approach as of mid-2025.

Initiative	Milestone Date	Key Development
Unannounced Foreign Inspections	May 6, 2025	The FDA announced the expansion of unannounced foreign inspections, spurred by a Presidential Executive Order to address the historical "double standard."
Remote Regulatory Assessments (RRAs)	June 26, 2025	Final guidance, Conducting Remote Regulatory Assessments: Questions and Answers, was published, making RRAs a permanent part of the FDA's toolkit.
Public CRL Database	July 10, 2025	FDA launched a centralized database of over 200 redacted CRLs on open FDA, part of its "radical transparency" push.
Elsa Generative AI Tool	Mid-2025	FDA officially launched Elsa, a generative AI tool designed to assist employees with tasks, such as identifying high-priority inspection targets.

Three key pillars of these changes are: a formalized "anytime, anywhere" inspection paradigm, the emergence of a predictive "regulatory intelligence engine" powered by AI and public data, and an intensified focus on data integrity.

For biopharmaceutical leaders, success in this environment requires a cultural shift. The imperative is to move beyond a defensive, reactive compliance posture and proactively build a strategic, data-centric culture of quality. Organizations that embrace this transformation will gain a significant competitive advantage, while those who fail to adapt will face increasing exposure to regulatory delays, financial penalties, and reputational damage.

FDA Oversight: Beyond Episodic Compliance

Much like students who cram for a big test, many organizations have, for years, delayed ensuring readiness for regulatory scrutiny until after submission, confident they could prepare facilities and staff for inspection success when the time comes. Ex-U.S. sites also often believed they could control the narrative during inspections, as these were always scheduled in advance, allowing ample time for staff and facilities to be trained and ready.

However, the recent shifts from the FDA indicate that this mindset of episodic compliance, where organizations could rely on preparing for a preannounced inspection, is now obsolete. The new paradigm demands a continuous state of verifiable compliance, and companies must adapt to succeed.

The Unforgiving Baseline: A Quantitative View Of Past Failures

To effectively navigate this new regulatory environment, it's crucial to understand the data driving the FDA’s new enforcement posture. The launch of the FDA’s “radical transparency” initiative began with the release of an easily accessible file containing over 200 recent redacted complete response letters (CRLs). This file serves as a map of the industry's most common vulnerabilities and the agency's current areas of focus.

It's important to note that the released CRLs were for products that were eventually approved. However, the data shows that the path to approval is most often blocked by failures in execution, rather than a lack of scientific innovation or clinical data.  An analysis of the public CRL data base shows the following:

With an incidence rate of 74%, CMC failures were the most significant hurdle to drug approval. A breakdown of these deficiencies reveals a clear hierarchy of risk. The single largest failure point, cited in 58% of CRLs, is unresolved facility inspection issues, where the CRL was a direct consequence of "objectionable conditions" found during a pre-approval inspection (PAI). This statistic serves as a direct justification for the FDA's new, more agile inspection model. Another cluster of deficiencies relates to an incomplete understanding of the drug product itself. Impurity and degradant qualification issues appeared in 28% of CRLs, while inadequate leachable and extractables data were cited in 15%.  

While less frequent than CMC issues, clinical deficiencies, such as failure to demonstrate significant superiority or PK comparability (35% incidence), and device-related deficiencies, such as failure to demonstrate device performance and reliability (18% incidence), represent fundamental strategic errors. For combination products, human factors (HF) validation failure, such as failing to demonstrate the user interface supports safe and effective use, is the dominant issue, cited in 14% of all CRLs and accounting for an overwhelming 78% of all device-related CRLs, according to my own research.

The New Regulatory Toolkit In Practice

The FDA's modernization of its oversight capabilities has endowed the agency with unprecedented flexibility, reach, and unpredictability. By integrating RRAs, unannounced foreign inspections, and an AI-powered data engine, the FDA has created a powerful new system of continuous global regulatory scrutiny.

Anytime, Anywhere Oversight: The End Of Hiding

The FDA's formalization of RRAs and the expansion of unannounced foreign inspections represent a significant shift toward real-time scrutiny. The final guidance for RRAs, published on June 26, 2025, solidifies their role as a permanent distinct oversight mechanism, separate from traditional inspections. RRAs are not just a pandemic-era tool; they are here to stay, and they apply not only to GMP but also to GCP clinical trial conduct and all other GxP activities.

While a company or site can technically decline a "voluntary" RRA without committing a direct violation, the guidance clarifies that a refusal may "delay FDA's ability to make regulatory decisions," including those tied to a pending application, or it may "prompt the FDA to initiate a traditional on-site inspection instead." This integrated system allows the FDA to begin low-cost, rapid triage via a remote review of electronic records. If a facility declines the RRA or provides incomplete data, this can justify an unannounced for-cause inspection.

Another part of the anytime, anywhere inspection framework is the FDA's expansion of unannounced inspections for foreign manufacturing facilities. On May 6, the FDA announced it would increase unannounced inspections abroad. The rationale is to hold foreign manufacturers to the same standards as their domestic counterparts and to more effectively expose bad actors who might otherwise falsify records or conceal violations with advance notice of inspections.

The AI-Powered Regulatory Intelligence Engine

FDA's strategic pivot is further amplified by its adoption of advanced technology. FDA launched its generative AI tool, Elsa, in mid-2025. A key function of Elsa is to "identify high-priority inspection targets" by sifting through vast data sets of adverse event reports and manufacturing data. AI’s ability to detect patterns from vast data sets and to identify areas for human scrutiny dramatically increases the capabilities for inspectors, both in selecting companies, sites, and products for inspection, as well as sifting through vast data sets to find issues during inspections.  

As part of traditional inspections, FDA investigators would review a few batch records, examine several of the most recent significant deviations with corrective and preventive action (CAPA) records, evaluate the quality management system as a whole, and review a small subset of SOPs. With an AI tool, the entire electronic footprint of a company’s data can be evaluated in minutes, highlighting weaknesses, inconsistencies, or problems that traditional inspections might take a team of investigators weeks to find.

Rapid modernization is not without challenges. AI systems are rapidly developing, and sources have raised concerns about Elsa’s reliability in a high-stakes environment. There is also concern that the FDA is attempting to modernize faster than its internal capacity allows due to recent downsizing, creating a complex and uncertain landscape for the industry.

Data Integrity And A Modern Supply Chain

This oversight paradigm, built on remote assessments, unannounced inspections, and AI-driven analytics, rests on the reliability of underlying data. The principle of data integrity — ensuring data is attributable, legible, contemporaneous, original, and accurate (ALCOA++) — is no longer just a cornerstone of good manufacturing practice but a prerequisite for operating effectively. The FDA’s enforcement actions continue to show that the most common data integrity failures are foundational gaps in quality systems, such as inadequate software validation, failure to review audit trails, and the use of shared user accounts.  

A Strategic Framework For Adaptation

Quality can no longer be a siloed department focused on historical compliance; it must become a proactive and data-driven enterprise capability. Another concern raised by the transparency from the FDA is new and significant legal and financial risks. For instance, the new CRL database is a potential goldmine for shareholder plaintiffs to search for inconsistencies between a company's public statements and regulatory deficiencies detailed in a CRL. This creates an environment where market risk (financial and reputational) directly reinforces the need for regulatory compliance. Compliance becomes a prerequisite for maintaining investor trust and avoiding costly litigation.  

Considering these developments, what should leaders do? These shifts demand immediate action. Key actions are summarized in the table below. It's crucial to stay informed about new developments from the FDA. The agency's reinvention is ongoing, and one thing is certain: more changes are on the horizon.

Biopharma Quality Readiness Framework

This table summarizes actionable advice for navigating the new regulatory environment as a road map for senior leaders.

Pillar	Key Action
Continual Inspection Readiness	Conduct unannounced internal audits that mirror the new FDA reality.  Leverage AI tools to evaluate and continuously monitor quality management systems for gaps and issues.
Proactive CRL Risk Mitigation	Systematically use the new public CRL database to de-risk submissions. Assume public disclosure of any future CRL. Prior to any submission, perform a joint legal, regulatory, and investor relations assessment to ensure alignment between internal risks and public communications.
Robust Data Governance	Break down data silos by creating a formal, centralized data governance committee with executive sponsorship, ensuring consistent standards across GxP and supply chain data.

Conclusion

In 2025, the FDA did not merely modernize its tools; it fundamentally altered the rules of engagement. Operational excellence and data integrity are no longer just elements of good practice; they are now transparent, measurable, and continuously scrutinized. The FDA is creating a new ecosystem where past failures are used to predict future risks and market risk directly reinforces regulatory compliance.

Companies that embrace this shift and move beyond a reactive, compliance-oriented mindset to a proactive, data-driven culture of quality will thrive. By adopting a forward-thinking, strategic framework, biopharmaceutical organizations can build the robust foundations necessary to succeed in this new reality, securing a significant and lasting competitive advantage.

About The Author:

For over 25 years, David Grote has turned biopharma's most complex crises into commercial triumphs. As a strategic advisor, he transforms quality from a cost center into a business accelerator, a skill honed through leadership roles at Amgen, Teva, and Immunocore,  where he helped enable rapid product commercialization. He has built global quality systems that secure multinational FDA/EMA approvals for blockbuster drugs. Today, David brings this expertise to his clients, leveraging AI and predictive analytics to de-risk supply chains, speed up approvals, and build elite, data-driven quality operations.