Navigating Drug Approvals

Have you ever wondered why regulatory affairs can feel so complex? Why so many approvals and oversight? History is full of lessons. Many, painful. ➡️ Regulations exist because of past failures. ➡️ Tragedies shaped approvals, risk checks, and oversight. ➡️ From toxic drugs to faulty devices, every rule has a story. Here are the big scandals and their regulatory impact- listed chronologically: 1️⃣ Sulfanilamide Disaster (1937) → The Birth of Drug Safety Requirements - Imagine buying a liquid antibiotic, trusting it will help.   - It contains diethylene glycol, the same ingredient in antifreeze.   - In the 1930s, over 100 people in the U.S. died from this toxic drug.  💡 The regulatory impact? - The U.S. passed the 1938 Federal Food, Drug, and Cosmetic Act. - This act required drug safety testing before market release. - Other countries followed with stricter pharmaceutical laws. 2️⃣ Thalidomide Tragedy (1950s-1960s) → Global Pharmacovigilance & Stricter Drug Approvals - A drug for morning sickness caused a major disaster.   - Over 10,000 babies were born with severe birth defects due to this drug.   - The tragedy highlighted the critical need for stricter drug testing regulations. 💡 The regulatory impact? - USA started to ask proof of safety and efficacy before marketing a drug. - Europe strengthened clinical trial regulations, leading to EMA in 1995.   - The WHO improved global pharmacovigilance to detect risks earlier. 3️⃣ HIV-Contaminated Blood Scandal (1980s-1990s) → Blood Safety Regulations Get Tougher - Thousands were infected with contaminated blood. - The outbreak spread to France, Japan, the USA, the UK, and beyond. - Regulators failed to act quickly enough, resulting in widespread health crises. 💡 The regulatory impact? - FDA mandated HIV screening for all blood donations. - The EU Blood Directive (2002/98/EC) set strict standards for blood donation and processing. - Global blood safety programs were reinforced to prevent future outbreaks. 4️⃣ The Vioxx Scandal (2004) → Post-Market Surveillance Gets Serious - Vioxx (rofecoxib) was a blockbuster painkiller. - It was linked to thousands of heart attacks and strokes. - Despite early warnings, the drug remained on the market for years. 💡 The regulatory impact? - FDA introduced Risk Evaluation and Mitigation Strategies (REMS). - Contributed to stronger pharmacovigilance regulations by EMA. - WHO encouraged real-world evidence to track post-approval drug risks. - More focus on cardiovascular safety in drug development. - Stricter transparency requirements for clinical trial results. Did I miss any? Would you add any more scandals which shaped the regulations? Write a comment! 👇 ----- I am Ceren. I am passionate about making regulatory affairs clear, accessible and easy-to understand. If you like my posts, follow me and ring the 🔔 in my profile.

🔥 European Medicines Agency - mHealth data for real world evidence in regulatory decision making 📢 This expert report prepared within the context of the Big Data Steering Group of the European Medicines Agency and Heads of Medicines Agencies reviews relevant literature related to the use of mHealth data in the context of medicine regulation and aims to discuss its utility for regulatory uses. While mHealth tools can also be used during clinical trials, this report focuses on their use in real-world settings (i.e. in clinical care or the daily life of patients), to generate RWE for regulatory decision-making. 🚀 mHealth data was found to be useful for EU medicine regulation in three domains: 🔹 to support planning and validity of applicant studies (design & feasibility, representativeness & validity) 🔹 to support the understanding of clinical context (disease epidemiology, clinical management, drug utilisation) 🔹 to investigate associations of products on safety and efficacy outcomes and impacts of regulatory actions (effectiveness & safety studies, impact of regulatory actions) 🐸 Obviously, challenges will need to be overcome: 🔹 Data protection, accessibility and a complex regulatory landscape were identified as main operational challenges. 🔹 In terms of technical challenges, mHealth data quality can suffer from environmental conditions, the accuracy and placement of sensor and ability of patient to use the tool correctly. Interoperability of mHealth data is impacted by the different data sharing standards used by device developers and the sometimes unstructured and unlabelled data sets. 🔹 Several methodological challenges must be considered when using mHealth data. 🔹 Younger and wealthier populations are more likely to frequently use digital devices to measure their health, raising issues around the representativeness of mHealth data, although at the same time it may be useful for collecting more complete data from specific populations. 👣 In conclusion EMA is considering following points for future action: 1. Leverage work on patient experience data and expedite access to mHealth data 2. Increase discoverability of data sources and studies using mHealth data 3. Ensure compliance with data protection and ethical use of mHealth data 4. Engage and collaborate with all actors and relevant initiatives in the healthcare sector 5. Engage with EU and international standards for mHealth data 6. Increase the understanding and tracking of the use of mHealth data in EU Medicine Regulation 7. Support the development of mHealth derived measures to meet regulatory standards #digitalhealth #mhealth #rwe #interoperability #dataprotection

The current system by the numbers: → 10–15 years from discovery to approval → $985M median capitalized R&D cost per approved drug (JAMA, 2020) → $2.6B fully loaded cost including failed programs → 90% of drugs that enter clinical trials never reach patients → Phase 2 alone runs 3.6 years and fails 60–71% of the time — almost entirely on efficacy, not safety → ~50 novel drugs approved per year in the US Phase 2 is where the system bleeds out. It exists almost exclusively to answer one question: does it work? Safety was largely established in Phase 1. What we're spending 3.6 years and tens of millions of dollars on is an efficacy determination — the exact determination this model would transfer to the innovator and the market. If the FDA's mandate narrows to safety, Phase 1 becomes the primary regulatory gate. Assume it still runs rigorously — 2.3 years, as it does today. A streamlined safety-clearance review replaces the full NDA. Call it 6 months. Total FDA-gated timeline: roughly 3 years versus 10–15 today. Then what? → Companies launch with safety clearance and real-world evidence obligations — structured outcomes tracking, mandatory biomarker reporting, transparent efficacy databases accessible to physicians and payers → Physicians prescribe based on emerging efficacy data, exactly as they do today with off-label use, but with better information → Payers negotiate based on demonstrated outcomes in real populations, not RCT averages that may not represent their members → Drugs that work for a subset of patients reach that subset years earlier → Drugs that don't work get rejected commercially The rough math on pipeline impact: The FDA approves ~50 novel drugs per year. The US has roughly 7,000 drugs in clinical development at any given time. If removing the efficacy gate allows even 20% more safe candidates to reach patients 5–7 years earlier, the access implications are profound — particularly for rare diseases and oncology, where time is measured in survival months. Of course, physicians can't always evaluate efficacy data independently. Pharma will market safe-but-useless drugs aggressively. Payers will deny coverage without RCT data. Vulnerable populations will be exploited. These are legitimate concerns. They are also, largely, infrastructure problems — solvable with mandatory real-world evidence reporting, independent efficacy clearinghouses, and outcome-linked reimbursement frameworks. None of them require keeping the current system, which by its own metrics fails 90% of the patients it was designed to protect — not by approving bad drugs, but by never letting good ones through. The FDA was built to be a gatekeeper. The question worth asking in 2026 is whether a gatekeeper is still the right model — or whether a certifier of safety, paired with a transparent market for efficacy, gets more of the right drugs to more of the right patients faster. The arithmetic suggests it might.

It is a common misconception that real-world evidence (RWE) only matters once a medicine is approved. Of course, RWE plays an important role after launch, offering insights into safety, effectiveness and patterns of use in routine practice. But viewing it solely through a post-launch lens overlooks where it can have some of its greatest impact. The earlier RWE is integrated into discovery and development, the more powerful it becomes. It sets the trajectory for everything that follows: regulatory strategy, access planning and, ultimately, how quickly innovation reaches the patients who are waiting. That is why, at #Astellas, every medicine in our portfolio has, in some way shape or form, included RWE during the end-to-end development process: - Discovery: RWE helps refine our understanding of disease pathways, patient experience and unmet need, challenging assumptions before momentum builds in the wrong direction  - Development: As programmes progress, RWE can be used to simulate scenarios and strengthen overall trial design. This ranges from helping to identify trial sites and shaping clinically meaningful endpoints to providing historical or synthetic control arms in situations where placebo-controlled studies are neither feasible nor appropriate, such as in rare diseases.  - Access: Beyond regulatory approval, RWE complements clinical trial data by revealing local standards of care, treatment pathways, patient preferences and healthcare resource, providing a fuller picture of value within real-world systems. - Scientific exchange: Even in the field, RWE keeps adding value, strengthening conversations with healthcare professionals by adding real-world context to clinical data. Embedding RWE in this way does not happen organically. It requires early coordination across Development, Medical Affairs, Marketing and Market Access aligned around a shared strategy which is shaped from the outset by the needs of regulators, clinicians, payers and patients. Because only when that degree of coordination is in place from the very beginning can RWE fulfil its true potential — connecting early scientific insight with regulatory, access and clinical decisions in the real world.  #RealWorldData #RealWorldEvidence #PatientInsights 

💊 Bridging the Gap: Real-World Evidence in European Oncology Decision-Making A recent Value in Health publication reviewed how real-world evidence (RWE) is being integrated into European regulatory and health technology assessment (HTA) decisions for oncology medicines. 🔍 Objectives The study examined how the European Medicines Agency (EMA), NICE (UK), HAS (France), and G-BA (Germany) have used and accepted RWE between 2020–2022, highlighting areas of alignment and divergence.4 📊 Main Findings 🔹 RWE was included in 31% of EMA oncology reports and between 24–45% of HTA appraisals. 🔹 It was mainly used as external controls, benchmarks, or contextual evidence to support single-arm trials or supplement efficacy/safety data. 🔹 Acceptance varied: EMA and NICE often accepted RWE as supportive evidence, while G-BA frequently judged it “not adequate.” 🔹 Only one medicine—Phelinun (melphalan, hematologic malignancies such as multiple myeloma)—had RWE accepted as primary evidence. 🔹 Divergences were common: Lumykras (sotorasib, KRAS G12C-mutated NSCLC) was supported by EMA/NICE but rejected by G-BA due to methodological concerns. ⚠️ Limitations The review highlights methodological biases, lack of standardization in data sources, language barriers (not all G-BA data in English), and subjectivity in interpreting reviewer comments. It also only assessed RWE referenced in final documents, leaving out evidence in manufacturer dossiers. ✅ Conclusions & Recommendations 🔹 RWE use is increasing in Europe, with EMA and NICE more receptive than G-BA. 🔹 Still, inconsistent standards hinder equitable access to oncology therapies. 🔹 With the EU Joint Clinical Assessment in 2025, synergetic standards are essential to ensure RWE complements randomized trials and accelerates access. 💡 My Reflections The findings mirror broader challenges I describe in my undergoing policy work: fragmentation remains a key barrier. Yet most attention goes to RWE used for labels or HTA, while the far greater volume of pre- and post-marketing studies is less scrutinised. These studies shape perceptions of unmet need and product value, but who ensures their design and analyses are reliable? Without better oversight, we risk overlooking a critical part of the evidence ecosystem. #RealWorldEvidence #RWE #Oncology #HTA #EMA #NICE #HAS #GBA #RegulatoryScience #PatientAccess #HealthPolicy #RWD #DrugDevelopment Disclaimer: This post is a personal summary and interpretation of the published paper (Value in Health, 2025;28(1):31–41) combined with my own reflections. For full details, please refer to the original publication.

🔥 𝗦𝗮𝘂𝗱𝗶 𝗙𝗗𝗔 𝗷𝘂𝘀𝘁 𝗿𝗮𝗶𝘀𝗲𝗱 𝘁𝗵𝗲 𝗯𝗮𝗿. 𝗔𝗻𝗱 𝘁𝗵𝗲 𝗶𝗻𝗱𝘂𝘀𝘁𝗿𝘆 𝗻𝗲𝗲𝗱𝘀 𝘁𝗼 𝗽𝗮𝘆 𝗮𝘁𝘁𝗲𝗻𝘁𝗶𝗼𝗻. 🇸🇦 The SFDA - هيئة الغذاء والدواء published its Framework on the Use of Real-World Data (RWD) and Real-World Evidence (RWE) for Marketing Authorization of Medicinal Products. 𝗩𝗲𝗿𝘀𝗶𝗼𝗻 𝟭.𝟬. 𝗔𝗽𝗿𝗶𝗹 𝟮𝟬𝟮𝟲. The SFDA isn’t just borrowing from FDA or EMA playbooks. They’re building their own. And they’re doing it thoughtfully, covering everything from fit-for-purpose data standards, to target trial emulation, to transportability of global trial results to the Saudi population. That last point is underrated. 🔸In a region where most pivotal trials were never designed with MENA populations in mind, local RWD becomes a strategic regulatory asset, not just a nice-to-have. 🔸The framework also takes a clear stance on bias and confounding. Propensity scores, hdPS methods, target trial emulation: this is serious methodological thinking. Not checkbox regulation. What does this mean practically? If you’re running trials in the GCC or seeking marketing authorization in Saudi Arabia, RWE strategy is no longer optional. 𝗜𝘁 𝗻𝗲𝗲𝗱𝘀 𝘁𝗼 𝗯𝗲 𝗽𝗮𝗿𝘁 𝗼𝗳 𝘆𝗼𝘂𝗿 𝗱𝗼𝘀𝘀𝗶𝗲𝗿 𝘁𝗵𝗶𝗻𝗸𝗶𝗻𝗴 𝗳𝗿𝗼𝗺 𝗱𝗮𝘆 𝗼𝗻𝗲. 𝗙𝗼𝗿 𝘆𝗲𝗮𝗿𝘀, 𝗥𝗪𝗘 𝗵𝗮𝘀 𝗯𝗲𝗲𝗻 𝗽𝗼𝘀𝗶𝘁𝗶𝗼𝗻𝗲𝗱 𝗮𝘀 𝗰𝗼𝗺𝗽𝗹𝗲𝗺𝗲𝗻𝘁𝗮𝗿𝘆 𝘁𝗼 𝗿𝗮𝗻𝗱𝗼𝗺𝗶𝘇𝗲𝗱 𝗰𝗹𝗶𝗻𝗶𝗰𝗮𝗹 𝘁𝗿𝗶𝗮𝗹𝘀. The framework clearly moves beyond definitions. It sets expectations around: 🔹 Fit-for-purpose data (not just “available data”) 🔹 Study design rigor (including target trial emulation and hybrid models) 🔹 Explicit handling of bias and confounding 🔹 Direct use in regulatory decision-making (not just exploratory insights) This is a regulator actively shaping how evidence should be generated, interpreted, and trusted. But here’s the part I find most interesting 👇 The framework openly acknowledges something the industry has struggled to operationalize for years: 👉 Evidence is no longer only generated in controlled environments. 👉 It is continuously produced across healthcare systems, patients, and digital tools. And yet, not all data deserves to become evidence. 𝗧𝗵𝗲 𝗲𝗺𝗽𝗵𝗮𝘀𝗶𝘀 𝗼𝗻 𝗳𝗶𝘁-𝗳𝗼𝗿-𝗽𝘂𝗿𝗽𝗼𝘀𝗲 𝗥𝗪𝗗, 𝗱𝗮𝘁𝗮 𝗾𝘂𝗮𝗹𝗶𝘁𝘆, 𝗮𝗻𝗱 𝗺𝗲𝘁𝗵𝗼𝗱𝗼𝗹𝗼𝗴𝗶𝗰𝗮𝗹 𝗿𝗼𝗯𝘂𝘀𝘁𝗻𝗲𝘀𝘀 is where the real shift is happening. Because this is where most organizations fail today. We are entering a phase where: The question is no longer “Do you have data?” It’s “Can your data survive regulatory scrutiny?” This framework makes one thing very clear: 🌟 If your data cannot demonstrate quality, traceability, and methodological integrity, it will not support market access, no matter how innovative your solution is. #ClinicalTrials #RealWorldEvidence #RWD #RWE #SFDA #DrugDevelopment #DigitalHealth #RegulatoryScience #GCC #EvidenceBasedMedicine #Pharma #HealthTech

📊 New Insights on How the EMA Uses Real-World Evidence in Drug Approvals A new study published in JAMA Network Open sheds light on the evolving role of real-world evidence (RWE) in regulatory decision-making at the European Medicines Agency (EMA). Despite the growing global momentum around RWE, the study found that fewer than 10% of EMA approvals between 2020–2023 incorporated RWE. Most of these studies were cohort-based, drawing primarily from registries and electronic health records, with oncology being the most represented therapeutic area. A key takeaway is the lack of consistency and transparency in how RWE is defined, evaluated, and integrated into benefit–risk assessments. Without clear guidance, applicants remain uncertain about how RWE contributes to regulatory decisions. However, Europe is moving in the right direction. Initiatives such as DARWIN EU and expanded national health data systems in countries like Germany and France are strengthening the region’s data infrastructure—laying the groundwork for greater RWE adoption in future EMA assessments. As health systems advance toward more data-driven regulation, high-quality RWE will become increasingly essential for bridging evidence gaps, enhancing patient relevance, and supporting faster, more informed decisions.

🔬 FDA Breaks from Dogma: One Pivotal Trial Is Now the Default for Drug Approval 📰 In a landmark NEJM Sounding Board (Feb 19, 2026), FDA Commissioner Makary and Vinay Prasad announce that one adequate and well-controlled study, combined with confirmatory evidence, is now the FDA's default standard — formally ending the two-trial dogma. 🧬 The rationale: the two-trial requirement was designed for an era when biologic understanding was far more limited. Today, modern drug development establishes credibility in multiple ways, relying on both statistical and biologic inferences. Two trials are just one of many interlocking facets of clinical credibility. 📋 Critically, confirmatory evidence explicitly includes real-world evidence — alongside mechanistic science, data from related indications, and information from other drugs of the same class. This is a pivotal moment for the RWE community! 💡 The FDA is telling us that the quality of a single trial matters more than the quantity of trials. Instead of spreading finite reviewer time across multiple pivotal trials, the agency will focus on ensuring the one trial provides the most up-to-date and useful information for patients. 🌍 For those of us in real-world evidence, if one pivotal trial is the new default, then robust RWE becomes even more critical as confirmatory evidence — whether through external control arms built from natural history data, target trial emulation studies, or post-market surveillance. This dramatically elevates the value of strong disease natural history studies and high-quality real-world data. The reform is also paired with a strengthened postmarket initiative to collect robust data on all drugs and devices — where RWE will play an essential role. 💬 How do you see this shift changing your evidence generation strategy? Prasad V, Makary MA. N Engl J Med 2026;394:815-817. DOI: 10.1056/NEJMsb2517623 #RealWorldEvidence #FDA #ClinicalTrials #DrugDevelopment #RWE #EvidenceGeneration #RegulatoryScience #Pharma #NaturalHistory #OneTrialDefault

Yesterday’s revised #RWE medical device guidance from #FDA presages comparable changes for new drugs and biological products. If FDA's significant declaration that “it will accept RWE without requiring that identifiable individual patient data… always be submitted in a marketing submission” is applied to new drugs, sponsors won’t need to submit patient-level RWE data in their NDAs, BLAs or supplements- directly, through third-party agreement, or via Drug Master File (DMF) references.   ►FDA says to date only 35 drugs and biological products relied on RWE for approval - a poor showing a decade of congressional authorization, funding and encouragement, an Agency-wide RWE Framework, and multiple guidances. But is that true? By FDA’s own reckoning, it claims 57 product approvals, “safety related labeling changes” or “safety related actions.” Is the announcement undercounting shaving sponsor reliance on RWE? (See FDA’s own list below)   ► The revised device guidance retains this floor: “The need for review or adjudication of specific outcomes of interest (e.g. stroke or major bleeding) at the patient level may also be assessed.” Freeing sponsors from always submitting patient-level data to simply assuring access, if needed or desired, means FDA will always be able to look deeper into RWD datasets, assess missing data, data linkage and other issues. But could review delays arise if the data isn’t in hand? Will sponsors newly need to balance a tradeoff between the savings of foregoing submission of such data vs. needing to do so post-hoc and mid-review? Even more impactful, will this policy shift entail broader, wholesale acceptance of RWD sources and RWE analyses that do not allow for patient-level inquiries by FDA? That FDA will allow for reliance on large datasets that lack identifiers and linkages that enable it to scrutinize patient-level data in reviewing NDAs and BLAs? That isn’t clear: “[R]eviewers,” FDA says, “will now consider the strength of submitted RWE on an application-by-application basis.”   ► Finally, will shifting this baseline for new drugs require dramatic revisions to written guidance? The 2023 drugs “Considerations” final guidance says “Sponsors must ensure that they are able to submit patient-level data for any RWD…” Can “assure access” simply substitute for “submit”? #kendallsquarepolicy

This editorial from Blood Cancer Journal (2025) discusses the growing role of real-world evidence (#RWE) in #regulatory_approvals for multiple myeloma (MM) therapies. MM is a rare, incurable blood cancer with frequent relapses, making traditional randomized clinical trials (#RCTs) increasingly challenging. Regulatory agencies like the #FDA and #EMA have issued guidelines supporting the use of RWE—data derived from routine clinical practice, such as electronic health records—in regulatory submissions, especially for rare diseases and advanced treatment lines where RCTs may be impractical or unethical. Between January 2021 and April 2025, 44% of MM drug marketing applications approved by the FDA and EMA included RWE, mainly in advanced lines of therapy. RWE was used to demonstrate unmet medical need, support single-arm trials, and provide external comparator arms. However, the quality and reliability of RWE are critical; regulators have sometimes rejected RWE due to methodological limitations or data heterogeneity. The article emphasizes that sponsors should engage early with regulators and ensure data sources are fit-for-purpose, reliable, and generalizable. High-quality RWE is expected to remain essential for advancing MM therapies, especially where patient needs are most urgent. Citation Lockwood Taylor, Angela Chen, Amy Pierre. "Utilization of real-world evidence in regulatory approvals for multiple myeloma therapies." Blood Cancer Journal (2025) 15:210. https://lnkd.in/eiG-7d39