Special FDA designations for drug development: orphan, fast track, accelerated approval, priority review, and breakthrough therapy.
Over the past decades, US Congress enabled the US Food and Drug Administration (FDA) to facilitate and expedite drug development for serious conditions filling unmet medical needs with five special designations and review pathways: orphan, fast track, accelerated approval, priority review, and breakthrough therapy.
This study reviews the FDA's five special designations for drug development regarding their safety, efficacy/clinical benefit, clinical trials, innovation, economic incentives, development timelines, and price.
We conducted a keyword search to identify studies analyzing the impact of the FDA's special designations (orphan, fast track, accelerated approval, priority review, and breakthrough therapy) on the safety, efficacy/clinical benefit, trials, innovativeness, economic incentives, development times, and pricing of new drugs. Results were summarized in a narrative overview.
Expedited approval reduces new drugs' time to market. However, faster drug development and regulatory review are associated with more unrecognized adverse events and post-marketing safety revisions. Clinical trials supporting special FDA approvals frequently use small, non-randomized, open-label designs. Required post-approval trials to monitor unknown adverse events are often delayed or not even initiated. Evidence suggests that drugs approved under special review pathways, marketed as "breakthroughs", are more innovative and deliver a higher clinical benefit than those receiving standard FDA approval. Special designations are an economically viable strategy for investors and pharmaceutical companies to develop drugs for rare diseases with unmet medical needs, due to financial incentives, expedited development timelines, higher clinical trial success rates, alongside greater prices. Nonetheless, patients, physicians, and insurers are concerned about spending money on drugs without a proven benefit or even on drugs that turn out to be ineffective. While European countries established performance- and financial-based managed entry agreements to account for this uncertainty in clinical trial evidence and cost-effectiveness, the pricing and reimbursement of these drugs remain largely unregulated in the US.
Special FDA designations shorten clinical development and FDA approval times for new drugs treating rare and severe diseases with unmet medical needs. Special-designated drugs offer a greater clinical benefit to patients. However, physicians, patients, and insurers must be aware that special-designated drugs are often approved based on non-robust trials, associated with more unrecognized side effects, and sold for higher prices.
Michaeli DT
，Michaeli T
，Albers S
，Boch T
，Michaeli JC
... -
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Expedited Programs for Serious Conditions: An Update on Breakthrough Therapy Designation.
Our aim was to describe the regulatory pathways made available by the US Food and Drug Administration (FDA) to expedite the drug development and approval process, with a focus on the benefits and limitations of the Breakthrough Therapy Designation (BTD) pathway.
Published materials consisting of journal articles, press releases, government documents, and news articles from pharmaceutical publishers were identified through online databases (ie, Medline and Scopus), the FDA website, and Internet search engines (eg, Google).
To encourage pharmaceutical innovation and increase the number of products being approved each year, the FDA has introduced 4 expedited regulatory pathways to accelerate the drug development and approval process. The most recent program, enacted in July 2012, was BTD that is given to drugs that treat a serious or life-threatening disease or condition; and preliminary clinical evidence suggests the potential for these drugs to provide a substantial improvement over the current standard of care. The primary basis for the creation of BTD is to provide patients with serious conditions with earlier access to FDA-approved medications. In 2014, 22% of the new molecular entities approved within the Center for Drug Evaluation and Research had BTD status, as opposed to only 11% in 2013, which indicates both the popularity and success of this expedited pathway. Additionally, the creation of BTD has produced a more collaborative working relationship between the pharmaceutical industry and the FDA because both parties have a vested interest in the drug's success. Some of the more notable concerns surrounding these approved breakthrough therapies have been the abbreviated tolerability and efficacy evidence available from accelerated clinical development programs, ensuring the manufacturing aspects keep pace with these accelerated clinical programs, and finally, managing the strain on resources for both the pharmaceutical companies and the FDA.
BTD has already had many positive and negative impacts on various stakeholders, including sponsors, investors, regulatory agencies, third-party payors, and patients. The ultimate goal of the BTD program is to identify promising drug candidates early in the clinical development timeline, expedite the development and review processes via intensive guidance from the FDA, and provide patients access to approved therapies as quickly as possible. With the first few batches of BTD product approvals, the FDA and other stakeholders have been working collaboratively to address the various expected and unexpected challenges that have arisen during the BTD process in order to refine and improve this already successful program.
Kwok M
，Foster T
，Steinberg M
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ResearchGate
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钛学术
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