Not every drug that is researched and developed in the United States makes its way onto the shelves of your local drugstore. This is for good reason: to ensure that Americans may only access drugs with demonstrated efficacy in clinical trials that can safely treat a specified condition or illness.[1] Safety and efficacy concerns can also create certain hurdles to promoting drug diversity and accessibility in the U.S. Limiting the drugs that make it through major clinical-research milestones and approval pathways reduces product variety and options for Americans. On the other hand, lowering safety and efficacy thresholds for introducing drugs into markets could pose greater risks and costs to consumers, but it may also incentivize innovation and greater investments in research from risk-averse pharmaceutical manufacturers.[2] Competition between similarly effective drugs could also drive down product prices to the benefit of consumers.[3] Yet, decreased safety and efficacy standards could lead to needless and increased marketing of drugs with little to no medical benefit, imposing greater costs on patients while incentivizing manufacturer-imposed limitations on drug innovation.[4] In other words, there are clear tradeoffs between lax and stringent regulations. The Food and Drug Administration (FDA) considers these tradeoffs and imposes a controlled review process to limit the number of drug approvals each year. Whether the review is lenient or stringent in the end, the FDA universally cites safety and efficacy concerns under its statutory mandate[5] as reasons for not certifying many drugs.[6]
The FDA is right to carry out its statutory mandate of enforcing safety and efficacy standards when approving drug applications. But does the FDA adequately balance necessary consumer protection concerns with countervailing desire for affordable and accessible drugs? The FDA recently and controversially approved a drug, Aduhelm, after years of intensive research and clinical studies that were aimed at finding a treatment for Alzheimer’s disease. [7] This approval was significant partially because it had been eighteen years since a drug had been approved to treat Alzheimer’s.[8] On the other hand, many scientists were critical of the FDA’s apparent leniency in approving the drug for a broader range of uses than was clinically tested.[9] Additionally, the FDA ignored key committee suggestions by prominent scientists not to approve the drug without additional supporting evidence.[10] Apparently, the FDA’s interest in approving a new drug for treating Alzheimer’s won over these concerns. This might be because, during that eighteen-year period between Alzheimer’s drug approvals, at least ninety-eight applications for FDA review and approval of other drugs went through and failed FDA clearance guidelines.[11] These rejections, however, were not outliers—the FDA rejects most drug applications.[12]
Though approval rates for new generic drugs have rapidly increased in recent years,[13] some still argue that these rates still are not responsive enough to consumer needs and market demand.[14] In addition, other regulatory innovations attempted by the FDA, including expedited development and approval programs, can have an unclear impact on the number of yearly drug approvals and total drug development times.[15] The push and pull between cautionary regulations and standards supporting drug innovation is clearly as lively as ever in the U.S. Rather than create a clear and satisfactory answer for what values should be prioritized in drug development, the FDA sometimes struggles to accommodate these conflicting interests.[16] The modern challenge facing the FDA is finding a more beneficial balance between safety, efficacy, and innovation that does not compromise one for another.
The European Union (EU) has an interesting answer to this challenge. Whereas the FDA oversees and regulates the domestic drug market in the United States as an individual and unitary government agency, the CE Mark system in the EU implements a decentralized collection of reviewing offices based in the various member states.[17] A CE Mark functions in the EU much like an FDA approval does in the US.[18] However, given the confederate and semi-autonomous nature of member states in the EU, the CE Mark system has limited authority to implement standards on its members uniformly.[19] Different European countries have greater flexibility to interpret the EU standards in the CE Mark system as strictly or leniently as they see fit, as long as their interpretation remains consistent with EU law.[20] Moreover, the collaborative purpose of the EU requires that member states recognize and affirm each other’s drug approvals made in pursuance of those standards.[21] As a result, drug manufacturers can and frequently do forum shop for the CE Mark office with less stringent approval requirements.[22] This institutional design allows drugs to be vetted under the least intensive standards available in the EU, which is a marked departure from the FDA’s uniform standards and approval pathways. Although the CE Mark system looks at product safety before market approvals, it also sometimes relaxes entry efficacy requirements for items similar to previously approved products, only requiring examination of that standard in post-market approval clinical studies.[23] The lack of an upfront efficacy requirement may stem from cost concerns, a desire for administrative efficiency, efforts to reduce governmental accountability, or broad public trust in the reliability of the medicine. Whatever the reasons may be, these standards have remained largely consistent over time,[24] suggesting the EU has firmly taken a position in favor of expediting drug development pathways at the cost of initial oversights and strict safety standards.
The issue of drug accessibility and pricing in the US remains a hotly debated problem across the political spectrum. This article does not advocate overhauling, repealing, or changing portions of FDA administration to address this challenge. However, the CE Mark system offers valuable insight into what realignment of FDA standards in favor of leniency could accomplish or risk for the drug market. The balance the EU has chosen has benefits in simplifying drug development procedures and reducing entry costs in the drug market, but this reduced oversight can still create concerning risks to consumer safety and health. The EU’s solution may be a shining example of progress, or it could be a cautionary tale of what government action should be avoided. The FDA should consider the merits and shortcomings of taking a firm position in the innovation-regulation debate, as the EU seems to have done in their CE Mark system. This will better ensure the FDA successfully carries out its statutory mandate to provide consumers safe and effective medical solutions when and where they are needed.
[1] Agata Dabrowska & Susan Thaul, Cong. Rsch. Serv., R41983, How FDA Approves Drugs and Regulates Their Safety and Effectiveness 5 (2018); Russell Katz, FDA: Evidentiary Standards for Drug Development and Approval, 1 NeuroRx 307, 307 (2004).
[2] Rena Conti, Richard G. Frank & Jonathan Gruber, Addressing the Trade-Off Between Lower Drug Prices and Incentives for Pharmaceutical Innovation, Brookings (Nov. 15, 2021), https://www.brookings.edu/essay/addressing-the-trade-off-between-lower-drug-prices-and-incentives-for-pharmaceutical-innovation/.
[3] How Can Improved Competition Lead to Lower Drug Prices?, UMass Chan Medical School: Commonwealth Medicine (Oct. 25, 2018), https://commed.umassmed.edu/blog/2018/10/25/how-can-improved-competition-lead-lower-drug-prices; Toon van der Gronde, Carin A. Uyl-de Groot & Toine Pieters, Addressing the Challenge of High-Priced Prescription Drugs in the Era of Precision Medicine: A Systematic Review of Drug Life Cycles, Therapeutic Drug Markets and Regulatory Frameworks, 12 PLoS ONE 1, 12 (2017). But see Ameet Sarpatwari et al., Competition and Price Among Brand-Name Drugs in the Same Class: A Systematic Review of the Evidence, 16 PLoS Med. 1, 7, 9 (2019).
[4] See Donald W. Light et al., Institutional Corruption of Pharmaceuticals and the Myth of Safe and Effective Drugs, 41 J. L., Med., and Ethics 590, 591-93 (2013).
[5] Is It Really ‘FDA Approved’?, U.S. Food & Drug Administration (May 10, 2022), https://www.fda.gov/consumers/consumer-updates/it-really-fda-approved#:~:text=To%20receive%20FDA%20approval%20for,effective%20for%20their%20intended%20uses; Dabrowska & Thaul, supra note 1, at 5; Katz, supra note 1, at 307.
[6] Unapproved Drugs, U.S. Food & Drug Administration (June 2, 2021), https://www.fda.gov/drugs/enforcement-activities-fda/unapproved-drugs.
[7] FDA Grants Accelerated Approval for Alzheimer’s Drug, U.S. Food & Drug Administration (June 7, 2021), https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-alzheimers-drug.
[8] Kelly Servick, Alzheimer’s Drug Approved Despite Doubts About Effectiveness, Science (June 7, 2021), https://www.science.org/content/article/alzheimer-s-drug-approved-despite-doubts-about-effectiveness#:~:text=The%20antibody%20aducanumab%20today%20became,the%20United%20States%20since%202003.
[9] Id.
[10] Id.
[11] C. Kwon Kim et al., Alzheimer’s Disease: Key Insights from Two Decades of Clinical Trial Failures, 87 J. Alzheimer’s Disease 83, 84 (2022).
[12] What Does It Take to Get a Medication Approved Through the FDA?, Nationwide Childs.’: 700 Childs.’ (Jan. 7, 2021), https://www.nationwidechildrens.org/family-resources-education/700childrens/2018/03/what-does-it-take-to-get-a-drug-approved-through-the-fda#:~:text=Each%20year%2C%20the%20FDA%20reviews,begin%20clinical%20trials%20in%20humans.
[13] Angelika Batta et al., Trends in FDA Drug Approvals Over Last 2 Decades: An Observational Study, 9 J. Fam. Med. Prim. Care 105, 107, 109 (2020); Mayookha Mitra-Majumdar et al., Analysis of Supportive Evidence for US Food and Drug Administration Approvals of Novel Drugs in 2020, 5 JAMA Network Open 1, 2 (2022).
[14] Richard A. Deyo, Gaps, Tensions, and Conflicts in the FDA Approval Process: Implications for Clinical Practice, 17 J. Am. Board Fam. Prac. 142, 145-46 (2004).
[15] Jonathan J. Darrow et al., FDA Approval and Regulation of Pharmaceuticals, 1983-2018, 323 JAMA 164, 169-71 (2020).
[16] See Batta et al., supra note 13, at 109; Darrow, supra note 15, at 169.
[17] What is CE Marking?, ASQ, https://asq.org/quality-resources/ce-marking (last visited Dec. 23, 2022).
[18] Dan Conley, Two Paths for Medical Device Approval: FDA vs. CE, 15 HealthManagement 1, 1-2 (2015); Dan Z. Reinstein & A. John Kanellopoulos, CE Mark Versus FDA Approval: Which System Has it Right?, CRSTEurope (Feb. 2015), https://crstodayeurope.com/articles/2015-feb/ce-mark-versus-fda-approval-which-system-has-it-right/; John Campbell, Strategies for Navigating Medical Device FDA and CE Approval, Sterling Med. Devices (Nov. 17, 2021), https://sterlingmedicaldevices.com/strategies-for-navigating-medical-device-fda-and-ce-approval/#:~:text=The%20main%20difference%20between%20a,member%20states%20of%20the%20EU.
[19] EU Legislation and CE Marking, Int’l Trade Admin. (Aug. 24, 2020), https://www.trade.gov/country-commercial-guides/eu-eu-legislation-and-ce-marking.
[20] Baylie M. Fry, Comment, A Reasoned Proposition to A Perilous Problem: Creating a Government Agency to Remedy the Emphatic Failure of Notified Bodies in the Medical Device Industry, 22 Willamette J. Int’l L. and Disp. Resol. 161, 161-63 (2014).
[21] Id.
[22] Id.
[23] Conley, supra note 18, at 2; Campbell, supra note 18.
[24] What is CE Marking?, ASQ, https://asq.org/quality-resources/ce-marking (last visited Dec. 23, 2022).
Tom Romanchek
Tom Romanchek is a 3L GW Law student and a Kahan Health/FDA Law Fellow. He is pursuing concentrations in health law and intellectual property.