Navigating FDA Oversight in an Era of Advanced Digital Tools
By Michael Bronfman, July 14, 2025
The pharmaceutical industry is undergoing a transformation. Across the drug development lifecycle, from early discovery through clinical trials and into postmarket monitoring, companies increasingly rely on sophisticated digital tools. These tools analyze complex data, personalize treatments, and speed up development. However, as these digital systems begin to inform decisions traditionally in the hands of clinicians or regulators, the U.S. Food and Drug Administration (FDA) is adapting its regulatory framework accordingly.
For biotech professionals, this means that digital tools are no longer optional supports, they are deeply intertwined with product strategy and regulatory planning. This post explores how digital technologies are reshaping the regulatory landscape, what it means for pharma companies, and the practical steps organizations must take to thrive.
1. Digital Innovation in Pharma: Opportunity and Responsibility
The industry is leveraging digital capabilities in areas such as:
Target identification and compound screening: using pattern recognition systems to highlight promising molecule targets.
Clinical trial efficiency: tools that help select study sites, recruit patients, or monitor data in real time.
Image analysis in diagnostics: supporting clinical insights through automated interpretation of scans or pathology slides.
Postmarket surveillance: identifying safety signals and performance trends from real-world data.
Patient engagement platforms: improving compliance, remote monitoring, and decentralized trial models.
These tools can significantly reduce time and cost, improve decision-making, support personalized approaches, and with increased impact comes increased scrutiny.
Regulators now expect the same rigor, transparency, and oversight for digital tools as for manual tools.
2. The FDA’s Strategic Response
The FDA has long recognized the growing role of technology in clinical care and has been refining its regulatory oversight:
SaMD Framework (Software as a Medical Device): Software that diagnoses, treats, or manages patient care falls under medical device regulations. The FDA applies standards for safety, effectiveness, and Quality.
Proposal for Iterative Updates (2019): The agency introduced methods for handling software that adapts post-approval, suggesting that plans be in place to anticipate upgrades.
Action Plan (2021):
This plan emphasized:
1. Clear documentation of tool design and data use
2. Risk and bias evaluation
3. Transparency and explainability
4. Postmarket monitoring
5. Collaboration with global regulators and external experts
Digital Health Advisory Committee (established 2023): Brings together external leaders to advise the FDA on emerging digital health trends, including data platforms and analysis tools.
Taken together, these efforts show the FDA is no longer reactive—it’s taking steps to guide the shift toward intelligent, data-driven healthcare responsibly.
3. Why This Matters to Pharma Companies
When digital tools are used to inform diagnosis, treatment, or clinical decisions, they are treated as regulated medical products, not simple IT solutions. This has several consequences:
Raised Standards for Evidence and Validation:
Digital tools must now deliver clear, reproducible performance:
Auditable data lineage: where data comes from, how it was processed
Testing in real-world settings and across diverse patient groups
Bias assessments to ensure performance isn’t limited to specific subpopulations
Explainable outputs so clinicians and patients trust the insights
These developing supportive tools in trials must meet these requirements.
Managing Tools that Evolve Over Time
Unlike a tablet with a fixed formula, software can be updated. The FDA expects companies planning to:
Define what changes are permissible
Assess the impact and validate updates
Communicate effectively with regulators and end users
This is often captured in a Predetermined Change Control Plan (PCCP). Whether it’s a predictive model or diagnostic classifier, understanding the change process and its controls becomes essential.
Implications for Clinical Trials
When digital tools:
Support trial operations (by speeding recruitment or monitoring risk) they must be shown not to skew results or introduce bias.
Serve as the trial’s intervention (e.g., diagnostics or decision support systems) they need their own efficacy and safety data, potentially requiring standalone validation or randomized comparisons.
This dual role calls for early regulatory planning and deep engagement with trial design teams.
Increased Focus on Post-Market Oversight
The FDA now expects:
Ongoing monitoring after product launch
Collection of real-world performance data
Alert systems for declining tool performance or unexpected failures
Protocols for updating the tool and notifying regulators or users.
This mirrors pharmacovigilance demands and supports long-term patient safety.
4. What Pharma Executives Should Watch
In the coming months and years, several developments will shape digital tool regulation:
Final Edited Guidance on Adaptive Tools
We can expect finalized positions covering:
Permissible software updates
Required audit trails
Performance metrics and thresholds
Monitoring and reporting protocols
Aligning technology roadmaps to these expected updates will smooth regulatory
Reviews.
Global Harmonization Efforts
Agencies such as EMA (Europe) and IMDRF (international) are converging on:
Data governance
Model transparency
Security and privacy safeguards
Pharma firms operating cross-border must design systems that comply across jurisdictions.
Evolving Quality Standards
Expect new additions to quality standards, including Good Machine Learning Practices
(GMLP) and guidance on digital quality systems, covering:
Metadata and dataset versioning
Traceability of analysis and results
Risk management for software failure
Early adoption helps avoid later compliance issues.
Liability and Responsibility Issues
As intelligent tools play bigger roles, questions arise:
Who is responsible if a tool provides flawed guidance?
What disclaimers or training must accompany tools?
How are clinicians involved in oversight?
Proactive definition of roles, responsibilities, and risk management processes now can help minimize legal exposure.
Prioritizing Trust and Interpretability
Stakeholders increasingly demand:
Intuitive, explainable interfaces
Clear output and user instructions
Evidence that supports clinical decision-making
Transparent tools are more trusted—and more likely to sail through regulatory evaluation.
5. Action Plan for Pharma Leaders
To stay ahead, companies should take these definitive steps:
Form a Cross-Functional Digital Oversight Committee
Include regulatory, clinical, IT, data science, legal, and quality assurance leaders from the start.
Classify All Digital Initiatives Early
Identify which tools may require regulatory filings, versus those that support internal operations.
Create Clear Documentation Standards
Maintain logs of:
Data sources and preprocessing steps
Model tests and performance evaluations
Change histories and validation results
Incident logs and monitoring updates
Engage Regulators Early
Use the FDA’s QSubmission (presubmission) process to preview plans, especially for trailblazing tools.
Build Post-Deployment Infrastructure
Plan upfront for:
Routine performance audits
Data pipelines for real-world monitoring
Reporting processes for updates or safety concerns
Train Users and Maintain Accountability
Educate clinicians and trial sites on:
The tool’s purpose and scope
How outputs should and shouldn’t be used
When to escalate concerns or deviations
Include user accountability protocols to reinforce oversight.
6. Case Examples: Learning from the Field
While specific details vary, high-level examples illustrate these principles:
Digital diagnostics used in trial site selection:
Validated on diverse patient data, with ongoing monitoring to ensure fair representation.
Automated image analysis used for tumor response:
Incorporated early feedback from the FDA but included plans for updates, accuracy validations, and clarity documentation.
Remote patient monitoring device:
Treated as a regulated device—complete with device history record, software verification benchmarks, and firmware update protocols.
These mature implementations underscore the necessity of structured design, planning, and oversight through the entire tool lifecycle.
Aligning Digital Ambition with Regulatory Expectations
Pharmaceutical companies today are stepping up digital innovation, fueled by data advances and software capabilities, and the balance of opportunity and risk now includes a regulatory dimension: advanced tools are no longer optional, they are regulated.
To lead responsibly:
Treat digital tools as core products
Build in line with regulatory principles
Document everything comprehensively
Continue oversight through deployment and updates
Embracing this approach protects compliance and fosters market adoption and trust.
The Path Forward
Pharma’s digital transformation is accelerating. When executed with foresight and regulatory alignment, digital tools can enhance safety, speed, and efficacy. They must be built with process, governance, and accountability at their core. By mapping development to regulatory frameworks, designing for continuous oversight, and integrating quality systems from the start, companies can harness innovation while meeting the expectations of regulators, clinicians, and patients.
The coming years will not be about whether your organization uses digital tools, but rather how responsibly, transparently, and effectively those tools are designed and managed. Those who plan accordingly will set the standard, and those who hesitate risk falling behind.
If you are looking for guidance and advice on how to take your organization to the forefront of this technology, and how to embrace it. Email us at Hello@metisconsultingservices.com or check out our website www.metisconsultingservices.com
Our experts will help you navigate the future of Pharmaceutical and Medical Device manufacturing.
Matlock’s Misguided Take on the Opioid Crisis
The opioid crisis is a multifaceted public health crisis that has devastated communities around the world. This crisis is a result of a confluence of factors, including addiction, overprescribing, inadequate pain management education, and the illicit manufacturing and distribution of synthetic opioids. While opioids are a valuable tool for managing pain when used appropriately and under medical supervision, their misuse and abuse have led to widespread addiction, societal harm, and death by overdose.
Written by Dr. Olivia Fletcher
Kathy Bates' revival of the iconic Matlock series has brought back the legal drama we all know and love. As much as we love the reboot, the portrayal of the opioid crisis is deeply flawed and misleading. In the pilot episode, Madeline “Maddy” Matlock suggests the attorneys she works with had confidential client information that would have motivated the FDA to take opioids off the market ten years earlier. This claim is both inaccurate and harmful, as it misrepresents the complexities of the opioid crisis and disregards the ethical obligations of attorneys.
The Opioid Crisis: A Complex Issue
The opioid crisis is a multifaceted public health crisis that has devastated communities around the world. This crisis is a result of a confluence of factors, including addiction, overprescribing, inadequate pain management education, and the illicit manufacturing and distribution of synthetic opioids. While opioids are a valuable tool for managing pain when used appropriately and under medical supervision, their misuse and abuse have led to widespread addiction, societal harm, and death by overdose.
Attorney-Client Privilege: A Cornerstone of the Legal System
The principle of attorney-client privilege is fundamental in our legal system. It protects confidential communications, ensuring that individuals can seek legal advice without fear of disclosure. This privilege is essential for the establishment and maintenance of trust in the legal system to facilitate open and honest communication between attorneys and their clients. Attorney-client privilege only allows the attorneys to divulge communications in the case the client intends to use advice from the attorney to commit further crimes.
As a therapist myself, confidentiality and morality don’t always play nicely together. Confidentiality is the province of ethics, not morality. What may seem Right or Wrong in the micro may not align neatly with what is necessary in the macro. Our legal system requires clients to be able to confide fully in their attorneys in order to assist in their own representation. So while a client cannot ask an attorney for advice on how to hide the body of the next person they murder, they absolutely can tell the attorney they plan to murder someone else and the attorney’s hands are tied. This is the strictest confidentiality in our legal system. No other communication is given such broad protections by our courts. Therapists, physicians, clergy, and even spouses have more exceptions.
The Role of the FDA in Opioid Regulation
The Food and Drug Administration (FDA) plays a crucial role in regulating the safety and efficacy of prescription drugs, including opioids. The FDA approves drugs for use based on rigorous scientific evidence and requires manufacturers to submit post-market surveillance data to monitor the safety of approved products. If the FDA becomes aware of serious safety concerns, it may take action to restrict or withdraw the approval of a drug. As explained in the book, Empire of Pain by Patrick Radden Keefe, the Food and Drug Agents involved in monitoring Purdue Pharma, the company responsible for initially bringing oxycontin to the market, were deeply entwined with the company.
The REMS Program: A Critical Tool for Opioid Risk Management
The Risk Evaluation and Mitigation Strategy (REMS) program is a regulatory tool used by the FDA to manage risks associated with certain drugs. REMS programs can include requirements for prescribers, pharmacies, and patients, such as education and training, monitoring, and restrictions on distribution. Opioids are subject to REMS programs that aim to reduce the risk of abuse and diversion.
The Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS) is a program implemented by the FDA to address the risks associated with opioid analgesics. It requires certain actions from healthcare providers and patients to ensure the safe use of these medications.
The requirements of these programs include:
For Prescribers:
Education: All healthcare providers involved in the management of patients with pain, including prescribers, nurses, and pharmacists, must complete accredited continuing education (CE) courses on the safe use of opioids. These courses must be based on the FDA's Opioid Analgesic REMS Education Blueprint.
Patient assessment: Healthcare providers must assess a patient's risk factors for opioid misuse, addiction, and overdose before prescribing opioids. This assessment should include a thorough medical history, physical examination, and consideration of the patient's social and psychological factors.
Treatment plan: If opioids are prescribed, healthcare providers must develop a comprehensive treatment plan that includes:
Clear goals for pain management
A risk assessment and mitigation strategy
A plan for monitoring the patient's response to treatment
A plan for tapering or discontinuing opioids as appropriate
Documentation: Healthcare providers must document their assessment, treatment plan, and monitoring of the patient's response to treatment in the patient's medical record.
For patients:
Education: Patients who are prescribed opioids must receive information about the risks and benefits of these medications, as well as instructions on how to use them safely.
Agreement: Patients must sign a written agreement that outlines their understanding of the risks and benefits of opioids and their commitment to follow the prescribed treatment plan.
Monitoring: Patients must be monitored regularly for signs of opioid misuse, addiction, and overdose. This may include regular follow-up appointments, urine drug testing, and other assessments as appropriate.
Manufacturer requirements:
Manufacturer reporting: Opioid manufacturers must report any adverse events associated with their products to the FDA.
Public education: Opioid manufacturers must also conduct public education campaigns to raise awareness about the risks of opioid abuse and addiction.
Risk vs Benefit
All medications come with risk and side effects. Even the most thorough clinical trials may not make all of these clear in the limited time and population available. One of the key points the FDA focuses on is whether the benefits of the medication outweigh the risks. Midrin, a migraine abortant, was widely prescribed for decades before studies indicated that the Schedule IV substance, dichloralphenazone, which was one of three substances in midrin, was too prone to abuse. That combined with the concerns over liver damage from overuse of acetaminophen led the FDA to remove it from the market. Opioids do provide significant pain relief to patients for whom they are prescribed. It is important not to throw the baby out with the bath water. As we continue to advance pharmaceutical science, we may, hopefully, find a way to relieve pain without the dangers associated with narcotics. Knowing everything we know about the dangers of opioids, they are still considered worth the risk.
Conclusion
While Matlock is an entertaining show, the portrayal of the opioid crisis is deeply flawed and highly misleading. The show's suggestion that attorneys could have prevented the crisis by divulging confidential client information is inaccurate and disregards the ethical obligations of attorneys. The opioid crisis is a complex issue that requires a multifaceted approach, including improved pain management education, increased access to treatment, and stricter regulations on the prescription and distribution of opioids. We have enough misinformation circulating without adding to the detritus, perhaps some accountability is due here.
RIC, REMS, and the REMarkable Dr. Frances Oldham Kelsey
Frances Oldham Kelsey was a Canadian-born physician who fought big pharma companies and a tremendous amount of pressure to do her job. In the process, she saved lives and heartbreak for thousands of Americans.
Dr Francis Oldham Kelsey - image from Library of Congress
Written by Li-Anne Rowsell Mufson
METIS' CEO and Founder Michelleanne is finishing up with the SQA Conference and is headed to the REMSIndustry Consortium (RIC) to Convene on March 22nd and 23rd.
The promised second half of our blog on REMS and The history of Thalidomide is below. I wound up becoming even more fascinated with Dr. Frances Oldham Kelsey and her heroism, and it is particularly appropriate to celebrate her during Women's History Month. If you want to hear more about REMS, listen to Ep. 6 Of the "Queens of Quality Podcast."
if you'd like to know more about how our consultants can help your company with REMS programs, drop us a line at Hello@metisconsultingservices.com
Frances Kelsey: A Woman Who Made a REMarkable Difference in the World of Medicine
Who is Dr. Frances Oldham Kelsey?
Frances Oldham Kelsey was a Canadian-born physician who fought big pharma companies and a tremendous amount of pressure to do her job. In the process, she saved lives and heartbreak for thousands of Americans. She was born in 1914 and received her bachelor of science and master of science degrees from McGill University, Montreal, in 1934 and 1935. In 1938 she earned her Ph.D. from the University of Chicago and married and had two children while teaching and earning her medical degree there. She began her career at the Food and Drug Administration (FDA) in 1960 at the age of 46. At the FDA, Kelsey worked in the Division of New Drugs and was responsible for reviewing and approving new drugs for the American market. During her time at the FDA, Kelsey became a vocal advocate for rigorous testing and regulation of new drugs. She also believed in ensuring the safety and efficacy of new medicines before they were approved for sale.
What did Frances Kelsey do that was so remarkable?
In 1961, during her first month at the FDA, Kelsey began her very first significant project, reviewing a new drug called Thalidomide. It was a sedative being marketed as a safe and effective treatment for morning sickness in pregnant women, among other sedative uses. As other countries began approving the drug for sale, Kelsey was skeptical about its safety. Dr. Kelsey knew that drugs could cross the placental barrier and harm an unborn baby. So she asked for evidence of trials on pregnant animals and requested that the company submit more data about its safety and efficacy, but they were reluctant to do so. These were never provided.
In fact, that company resubmitted the NDA several times without ever providing the information she sought. Dr. Kelsey's insistence on more testing and regulation saved thousands of lives. When other countries began approving the drug for sale, thousands of babies were born with congenital disabilities. However, the drug was never approved for sale in the United States due to Kelsey's diligence and attention to detail. Despite all her efforts, and even though the drug was not approved in the United States, as many as 20,000 Americans were given Thalidomide in the 1950s and 1960s. These individuals were part of two clinical trials operated by the American drug makers Richardson-Merrell and Smith, Kline & French. The Sales manuals even assured doctors that the new drug had been "shown to be absolutely harmless" in pregnant women and children.
And if not for Dr. Kelsey, that number would have grown exponentially.
She was eventually awarded the President's Award for Distinguished Federal Civilian Service by John F. Kennedy for her efforts to ensure the safety of drugs prescribed to pregnant women.
How did Kelsey's work impact the regulatory landscape?
Kelsey's story has been told in films, books, and documentaries. She is a powerful symbol of achievement through dedication, hard work, and determination. Her story highlights the importance of rigorous testing and regulation in the world of medicine. The FDA strengthened and improved its regulations due to Kelsey's work. The 1962 Kefauver-Harris Amendment required more data to be collected about the safety and efficacy of new drugs before they were approved for sale. The amendment also allowed the FDA to issue sanctions against pharmaceutical companies that did not comply with the regulations.
Kelsey's work also had a global impact. Organizations like the World Health Organization (WHO) and the International Conference on Harmonization of Technical Requirements for the Registration of Pharmaceuticals for Human Use were formed to coordinate and facilitate the regulation and testing of drugs among different countries. And the FDA would never have created the REMS program.
What’s REMS again?
As we have mentioned, REMS (Risk Evaluation and Mitigation Strategy) is a drug safety program that the U.S. Food and Drug Administration (FDA) has implemented for medications to help ensure the benefits of the medication outweigh the risks. The key participants in the Risk Evaluation and Mitigation Strategy (REMS)are patients, healthcare providers, pharmacists, and healthcare settings that dispense or administer the drug. There are four pieces to REMS:
Risk piece-there are serious risks identified
Evaluation- through trials, analysis, etc.
Mitigation piece- what can be done to reduce that risk
Strategy piece - how that mitigation is done
When was REMS started?
Risk Evaluation and Mitigation Strategies (REMS) are programs instituted by the FDA to monitor medications with a high potential for serious adverse effects. REMS applies only to specific prescription drugs but can apply to brand-name or generic drugs. The REMS program was formalized in 2007. REMS programs are designed to reinforce medication use behaviors and actions that support the safe use of that medication. While all medications have labeling that informs healthcare stakeholders about medication risks, only certain medications require a REMS. REMS are not designed to mitigate all the adverse events of a medication; Rather, REMS focus on preventing, monitoring, and/or managing specific serious risks by informing, educating, and reinforcing actions to reduce the frequency and/or severity of the event.
According to the FDA's website, there are three major components to the strategy for each REMS.
Communication to Patients-REMS may require the drug manufacturer to develop materials for patients like medication guides(these would be in addition to the medication guides all drugs must include.) These handouts contain FDA-approved information in patient-friendly language that can help inform patients about the safest way to use the medication.
Communication to Health Care Providers, Pharmacists, and Health Care Settings-
The REMS may include communicating directly to health care providers, pharmacists, nurses, or other participants involved in the delivery of these medications. In some cases, the communications may also target medical professional societies or state licensing boards to inform them of the REMS' particular safety concerns and/or to support conveying this information to their members. They may provide information about a specific risk and steps to take to reduce it.
3. Required Activities or Clinical Intervention-Sometimes these activities are referred to as "elements to assure safe use (ETASU)."
Sometimes, participants are required to conduct activities that support the safe use of the medication. These activities must be undertaken before the drug can be prescribed, dispensed, or received.
The storied history of Thalidomide was one of the critical elements in the regulations that eventually led to the institution of the REMS programs.
Dr. Frances Kelsey's story can be an inspiration to us all. She was a woman who rose to prominence during a time when women were not taken seriously in the world of medicine. Despite this, she was determined to ensure that the drugs on the market were safe and effective. Kelsey's story highlights the importance of Quality assurance and regulatory oversight in the pharmaceutical and medical device world. Dr. Kelsey's story is also a reminder that change is possible. By questioning the status quo and challenging the accepted standard, she brought about positive change in how drugs are regulated and tested.
Her story should remind us all of the importance of insisting on evidence, putting patient health first, doing the work, and, of course, standing up for what is right.
Cited research
The Story of Thalidomide in the U.S., Told Through Documents. https://www.nytimes.com/2020/03/23/health/thalidomide-fda-documents.html
What's in a REMS? | FDA. https://www.fda.gov/drugs/risk-evaluation-and-mitigation-strategies-rems/whats-rems
Risk Evaluation and Mitigation Strategies | REMS | FDA. https://www.fda.gov/drugs/drug-safety-and-availability/risk-evaluation-and-mitigation-strategies-rems