GLP and GCP: How the FDA and EPA Watch Over Science

This week in the Guardrail…

We explore how federal oversight is shifting standards in 2026, making rigorous data integrity the new baseline for every laboratory and clinic.

By Michael Bronfman

The world of making new medicines and chemicals is a very busy place. Every day, scientists are working in labs and clinics to find the next big cure or a safer way to clean our homes. Because these products can affect our health and the planet, the government has very strict rules to ensure everything is done correctly. Two of the most important sets of rules are called GLP and GCP. In 2026, the two main government agencies responsible for these rules, the Food and Drug Administration (FDA) and the Environmental Protection Agency (EPA), are working together more than ever before. This “shaking out” of the rules is changing how companies operate.

What Do These Letters Mean

To understand the future of science, you first have to know what these abbreviations stand for. They are like a specialized language for safety and honesty.

• GLP stands for Good Laboratory Practice. These rules are for the early stages of research. This is the work that happens in a lab with test tubes, plants, or animals before a human ever touches the product. The Environmental Protection Agency uses these rules to ensure that a new pesticide or powerful cleaner will not harm the environment or the people using it.

• GCP stands for Good Clinical Practice. These rules start when the research moves into a clinic and involves human volunteers. The Food and Drug Administration uses GCP to ensure that participants in medical studies are safe and that the results are truthful.

The FDA and the EPA Joining Forces

In the past, these two agencies mostly stayed in their own separate worlds. If a company were making a heart medicine, they would talk to the FDA. If they were making a new bug spray, they would talk to the EPA. But today, many new products fall into both categories. For example, a special soap that kills germs on your skin might be considered both a medicine and a chemical.

Because of this, the FDA and EPA are now sharing their notes. If an EPA inspector finds that a lab is messy or that the scientists are not recording their results correctly, they report it to the FDA. This means companies can no longer be “half good.” They have to follow the rules perfectly for both agencies. This coordination ensures that, no matter what kind of product is being made, the public is protected by the highest standards.Official Federal Register : How these agencies work together

Why Honesty Is the Only Policy

The main goal of both GLP and GCP is to ensure data integrity. Data is just a fancy word for the information and results gathered during an experiment. If a scientist says that a drug worked on ten people, the government wants to see the actual signatures and blood test results to prove it.

If a company is caught lying about its data, it can be fined millions of dollars. They might even be banned from ever making products again. This is why risk management is so important during the middle stages of a study. If a company finds a minor mistake in its lab records, it needs to fix it immediately. Waiting until later to “clean up” the paperwork is a huge risk that can lead to a total failure when the FDA or EPA comes to visit.

Protecting the People in the Studies

While GLP protects the science in the lab, GCP protects the people in the clinics. Every person who joins a clinical trial is a volunteer. They are doing something brave to help others. GCP rules ensure that these volunteers are treated with respect.

Under these rules, every volunteer must sign a form acknowledging the risks. This is called informed consent. The doctors must also closely monitor the volunteers for any side effects. If a patient experiences a headache or dizziness, it must be recorded in the official files. TheNational Institutes of Health provides extensive information on how these rules help keep people safe in medical research.

The Quality Control Revolution

In 2026, many companies are hiring specialized teams just to ensure quality. These teams are like the “referees” of science. They do not do the experiments themselves. Instead, they monitor the other scientists to ensure they follow all GLP and GCP rules.

They check that lab machines are properly calibrated. They check to ensure that every signature on a form is genuine and dated correctly. This might sound like a lot of extra work, but it saves the company from failing an inspection. When a company has a high “quality score,” the FDA and EPA can trust their results much more easily. Organizations like theSociety of Quality Assurance help train these specialized workers to stay up to date on the latest rules.

Using Technology to Stay Safe

Technology is making it easier for the FDA and EPA to do their jobs. In the old days, inspectors had to look through thousands of paper files. Now, most of the data is digital. This allows the government to look at the data in real time.

If a lab in California runs a test, an official in Washington, D.C., can see the results almost instantly. This helps catch mistakes before they become big problems. It also makes it harder for anyone to change their results later to make a drug look better than it really is. This transparency is a big part of why the “shake out” between the two agencies is happening so fast. Digital tools make it impossible to hide in the shadows.

The Global Impact of These Rules

Australia, Europe, and the United States all have their own versions of these rules. However, they are all starting to look very similar. This is good news for the public. It means that a drug tested in Australia can be sold in America as long as it follows the same high standards of GLP and GCP.

When countries agree on the rules, medicines can travel around the world much faster. This helps people in every country get the help they need without waiting years for additional testing. TheWorld Health Organization works to help all countries follow these same high standards for health and safety.

Education Is the Key

For these rules to work, every person in the pharmaceutical industry needs to be educated. It is not just the boss's job. Even the person cleaning the lab or the nurse at the clinic needs to understand why the rules matter.

Education helps people understand that following the rules is about more than just avoiding a fine. It is about making sure that the medicine your grandmother takes, or the soap you use on your children, is 100 percent safe. When everyone knows the “why” behind the rules, they are much more likely to follow them correctly every single day.

Risk Management and Quality Systems

Modern pharmaceutical companies use a Quality Management System (QMS) to track everything. A QMS is like a giant digital brain that stores all the company's rules and records. It helps with risk handling by flagging errors the moment they happen.

In 2026, risk management strategies are no longer just about fixing problems. They are about predicting them. By using clinical data management tools, a biotech firm can detect whether a machine is starting to wear out or whether a lab is experiencing too many small errors. This type of risk management planning helps prevent major disasters that lead to FDA warning letters.

The Role of REMS in Safety

Another way the FDA keeps people safe is through REMS, which stands for Risk Evaluation and Mitigation Strategies. These are extra safety programs for drugs that might be dangerous if not used exactly right. For example, some medicines require a patient to get a blood test every month. TheFDA REMS website tracks these programs to ensure drug companies are doing their part to manage risk.

Final Thoughts on the Future of Quality

The “shaking out” of rules between the FDA and the EPA is a positive step for everyone. It means that science is becoming more open and more honest. Companies are learning that they cannot take shortcuts during any stage of research.

By following the rules of GLP and GCP, we ensure that the future of medicine is bright. We can trust the products we buy because we know the government is watching and the scientists are being careful. Quality is not just a set of letters; it is a promise to the public that their safety is the most important thing of all. Don’t wait for a problem to appear before you start being careful. Start with quality on day one and the rest of the journey will be much smoother for everyone.

Frequently Asked Questions: GLP, GCP, and Regulatory Compliance

• What is the main difference between GLP and GCP?The biggest difference is when they are used. GLP is for the preclinical stage, which is work done in a lab on animals or cells. GCP is for the clinical stage involving human volunteers.

• Why does the EPA care about laboratory rules?The EPA ensures that chemicals like weed killers do not pollute our water. They use GLP to ensure companies are honest about chemical safety. You can find guidelines on theEPA Compliance Monitoring page.

• Can a company fail a trial if they follow the science but miss the paperwork?Yes. In the eyes of the FDA, if a test was not documented correctly, it never happened. “Clean data” is just as important as the medicine itself.

• What happens during an FDA or EPA inspection?Inspectors check original notebooks, computer logs, and even equipment logs. They want to see a clear trail from the study's start to the final report.

• How does Risk Mitigation help with these rules?It means finding small mistakes before the government does. Fixing a mistake early in a study costs much less than fixing it later, when thousands of people are involved.

• Where can I stay updated on these changing rules in 2026?The best place to watch for updates is theFDA Voice blog. This site tracks how the agencies are joining their rules for digital data. https://www.fda.gov/news-events/fda-newsroom/fda-voices. 

The Pre-Inspection Compliance Checklist

When an inspector arrives, they look for a “culture of quality.” If you are preparing for an audit in 2026, here are the top ten things you must have ready.

Item

Description

1. The Master Schedule

A list of every study that has happened in your lab.

2. Current SOPs

Proof that your team is using the newest versions of your rulebooks.

3. Training Logs

Proof that every person was taught how to do their job before starting.

4. Equipment Records

Logs showing that every scale and fridge is checked regularly.

5. Chain of Custody

A record of who touched a sample at every single minute.

6. Raw Data

Original handwritten notes or machine printouts.

7. QA Reports

Reports from your own internal “referees.”

8. CAPA Plans

Records showing how you found and fixed past mistakes.

9. Computer Validation

Proof that your digital data is secure and cannot be changed.

10. Signatures and Dates

Every page must be signed with no blank spaces or whiteout used.

Final Tip: The Clean Room Rule

An inspector will also look at your physical space. If a lab is cluttered, they will assume the data is also messy. A clean and organized lab tells the inspector that you take quality management seriously. For more help, you can check the FDA Inspection Guide for the latest standards. 

Secure Your Future in Science with Metis Consulting Services

When "good enough" no longer passes the test, your organization needs to turn regulatory pressure into a competitive advantage. Contact Metis Consulting Services today to ensure your next breakthrough is backed by an unbreakable foundation of compliance.

Understanding the Significance of CRLs Being Released: Beyond the Regulatory Language

Written by Michael Bronfman, July 28, 2025

This week in The Guard Rail, we at Metis are looking at a hot topic for our industry. Michael Bronfman tackles a hidden power in the pharmaceutical and medical device manufacturing world: the FDA's Complete Response Letters (CRLs). These are not just dry documents. The contents have traditionally been kept secret, known only to the receiving company. However, that secrecy might now be coming into the open. Why? Because a CRL can instantly derail a company's future, send stock prices plummeting, and, most critically, determine if a life-saving treatment ever sees the light of day. Join us as we uncover why these once-confidential letters are at the heart of a tidal wave push for transparency.

The FDA's Complete Response Letter (CRL)-- few documents hold as much weight in the complex and often opaque world of pharmaceutical development, as the CRL. For many outside the industry, the term might sound dry, bureaucratic, or even cryptic. But for drug developers, investors, patients, and clinicians, CRLs are pivotal turning points; letters that can reshape company strategy, impact stock prices overnight, and, most importantly, influence when or even if a new therapy reaches patients.

Historically, the contents of CRLs have often remained confidential, known only to the company receiving them and occasionally, selectively disclosed to the public. Yet the idea of CRLs being more broadly released, whether voluntarily by sponsors or systematically through policy change has gained traction. Why? Let us explore why these letters matter, what they contain, and why making them public can be a significant step forward for science, business, and patient trust.

What exactly is a CRL?

A Complete Response Letter is issued by the U.S. Food and Drug Administration (FDA) when it completes its review of a New Drug Application (NDA) or Biologics License Application (BLA) but decides not to approve it in its current form. Importantly, a CRL does not mean the drug is permanently rejected. Instead, it outlines the deficiencies that prevent approval and often provides guidance on what the sponsor could do to address them.

Deficiencies can include:

• Issues with clinical efficacy or safety data (e.g., not enough evidence that the drug works, or safety concerns in certain patient populations)

• Manufacturing or quality control shortcomings

• Problems with labeling or risk management strategies

• Statistical or methodological issues in trial design

For sponsors, receiving a CRL is both a setback and a roadmap. It’s an official document telling them: “Here is what is missing; come back when you have fixed it.”

The FDA's Complete Response Letter (CRL) few documents hold as much weight, in the complex and often opaque world of pharmaceutical development, as the CRL. For many outside the industry, the term might sound dry, bureaucratic, or even cryptic. But for drug developers, investors, patients, and clinicians, CRLs are pivotal turning points; letters that can reshape company strategy, impact stock prices overnight, and, most importantly, influence when or even if a new therapy reaches patients.

Historically, the contents of CRLs have often remained confidential, known only to the company receiving them and occasionally, selectively disclosed to the public. Yet the idea of CRLs being more broadly released — whether voluntarily by sponsors or systematically through policy change — has gained traction. Why? Let's explore why these letters matter, what they contain, and why making them public can be a significant step forward for science, business, and patient trust.

What exactly is a CRL?

A Complete Response Letter is issued by the U.S. Food and Drug Administration (FDA) when it completes its review of a New Drug Application (NDA) or Biologics License Application (BLA) but decides not to approve it in its current form. Note, a CRL does not mean the drug is permanently rejected. Instead, it outlines the deficiencies that prevent approval. Often, the letter will provide guidance on what the sponsor can do to address the issue.

Deficiencies can include:

• Issues with clinical efficacy or safety data (e.g., not enough evidence that the drug works, or safety concerns in certain patient populations)

• Manufacturing or quality control shortcomings

• Problems with labeling or risk management strategies

• Statistical or methodological issues in trial design

For sponsors, receiving a CRL can be a setback, but it is also can be a roadmap. It is an official document that says: "Here is what is missing; come back when you have fixed it."

Why are CRLs so important?

CRLs carry enormous significance because they sit at the intersection of science, business, and public health. Consider:

1. Strategic pivot points for companies

A CRL forces a company to decide: Do we invest more time and money to address the FDA's concerns, or do we walk away? Sometimes the deficiencies are minor and easily fixable; at other times, they are so fundamental that continuing to do so makes little sense.

2. Market-moving disclosures

Because the market places great value on new product approvals, the news of a CRL often leads to sharp drops in a company's stock price — especially if the drug was seen as a major pipeline asset.

3. Impact on patients

For patients waiting for new treatment options, CRLs can feel like an unexpected delay. Understanding the nature of the deficiency can help patients and advocates see whether it is a temporary hurdle or a sign of deeper problems.

4. Scientific learning

Each CRL is a detailed FDA critique of a drug's data and the sponsor's responses. While usually kept confidential, if shared, they can become case studies that improve drug development as a whole.

The current situation: Confidential by default

Under U.S. law, CRLs are part of a company's regulatory correspondence and thus are treated as confidential commercial information. Sponsors may choose to disclose the fact that they received a CRL — and often do, given that it's material information for investors — but the actual content is rarely released in full.

Instead, companies often issue press releases summarizing the FDA's concerns. Unfortunately, these summaries can be selective, vague, and overly optimistic:

• Selective: emphasizing easily fixable manufacturing issues and omitting more serious efficacy concerns

• Vague: using language like "additional analyses requested" without context

• Optimistic: framing the CRL as "a minor setback" even if the letter itself is more critical

This practice makes it hard for outside observers — including investors, clinicians, and patient groups — to understand what really happened.

The significance of CRLs being more publicly released

CRLs regularly released in full, could have a profound effect on how new therapies are evaluated, understood, and debated. Here's why:

1. Transparency builds trust

Our industry struggles with perceptions of secrecy. Polished summaries are shared and that is fine but if they are the only data released, it is impossible to know if the sponsor is downplaying serious concerns. Releasing more complete CRLs shows the unfiltered FDA perspective, which can reassure the public that approvals are based on thorough, science-driven review.

2. Better information for stakeholders

Investors could better assess the real risk of resubmission and approval. Clinicians could understand why certain drugs were not approved — whether due to safety concerns in specific populations or inadequate evidence of benefit. Patients and advocacy groups could advocate more effectively if they knew the precise barriers.

3. Industry-wide learning

Drug development is full of repeated mistakes: inadequate trial design, poor endpoint selection, underpowered studies, or manufacturing gaps. Public CRLs can serve as detailed case studies, allowing future sponsors to avoid similar pitfalls.

4. Accountability

Public CRLs help ensure that sponsors fully address the FDA's concerns before resubmitting, rather than trying to sidestep them with minimal new data. They also keep the FDA accountable, making its reasoning transparent and open to scientific debate.

Potential drawbacks and industry concerns

Of course, releasing CRLs is not without controversy. Key concerns include:

1. Proprietary data

CRLs often contain detailed discussion of clinical trial data, manufacturing processes, and commercial plans. Sponsors argue that full disclosure could benefit competitors or harm competitive advantage.

2. Misinterpretation

FDA reviews are technical documents, and taken out of context, statements in a CRL could be misread by the public or sensationalized by the media.

3. Chilling effect on communication

If sponsors know that every word in their submissions could become public, they might be less candid, potentially limiting open dialogue with regulators.

4. Impact on innovation

Some fear that too much transparency could discourage small biotech firms — already operating under tight timelines and budgets — from pursuing high-risk programs.

The evolving conversation

The debate is not purely academic. In recent years:

• Some sponsors have voluntarily released CRLs, especially when the market reaction to vague summaries was worse than anticipated.

• Regulatory advocates and transparency groups have pushed for routine publication, arguing that CRLs, like European Public Assessment Reports (EPARs), could help demystify the approval process.

• The FDA itself has signaled interest in improving transparency, though it is constrained by existing confidentiality laws.

The conversation reflects a broader trend in medicine: moving from "trust us" to "show us." Patients, payers, and clinicians want to see the data and the reasoning behind it, not just the headline.

International context

The U.S. FDA is not alone in grappling with this issue. European regulators, through the EMA, publish relatively detailed assessment reports once a drug is approved, but not if it is rejected. Similarly, Health Canada has taken steps to publish "Summary Basis of Rejection" documents for drugs that are not approved.

These models demonstrate that it is possible to balance transparency with the protection of confidential information, although it requires careful policy design.

A path forward

So, what would be the ideal outcome?

• Routine publication of redacted CRLs: Share the FDA's reasoning while redacting truly proprietary data, like detailed manufacturing process steps.

• Standardized summaries: Even if full letters aren't released, require sponsors to issue standardized, FDA-reviewed summaries that accurately reflect the deficiencies.

• Educational context: Provide plain-language explanations alongside CRLs, so clinicians, patients, and journalists can understand the technical details.

Such steps could bring real benefits without undermining innovation.

Why it matters

At its heart, the significance of CRLs being released is about more than a document. It is about shining light on critical moments in the life of a new therapy: the point where data meets judgment. When companies keep those moments private, the public can only guess at what went wrong. When CRLs are shared, everyone from researchers designing the next trial to patients hoping for a breakthrough can see, learn, and plan accordingly.

Transparency is not a cure-all. It won't eliminate uncertainty, disappointment, or risk. However, in a field where trust is essential and decisions affect both lives and balance sheets, sharing the FDA's reasoning is a powerful way to build confidence, foster learning, and ultimately bring better medicines to the people who need them.

If your organization is grappling with CRLs or needs help avoiding them, please contact us at Metis Consulting Services: Hello@MetisConsultingServices.com.

For more info, see our website www.MetisConsultingServices.com

Matlock’s Misguided Take on the Opioid Crisis

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.