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The amount of regulation needed in drug approval is a very fine line. Not enough regulation and adverse effect reporting increases, signifying consumers who were negatively affected by the drug. Too much regulation and the pipelines of biopharma companies become blocked, meaning important treatments can’t reach those in need. The task, therefore, that governmental regulatory agencies are faced with, is facilitating drug approval while also keeping people safe.

Over the past three decades the FDA has implemented 5 programs to hasten drug approval:

1. Accelerated Approval

The 1992 FDA Accelerated Approval Program is intended to allow for “earlier approval of drugs that treat serious conditions, and that fill an unmet medical need based on a surrogate endpoint”.[1] The use of surrogate endpoints instead of real clinical endpoints accelerates the review process. For example, in oncological treatment, a shrink in tumour size (surrogate endpoint) rather than the overall patient survival rate (clinical endpoint).

2. Fast Track

Introduced by the FDA Modernization act of 1997, Fast Track is meant to expedite the approval of drugs which treat life-threatening or severe diseases. Requirements for a drug to be Fast Tracked include superior effectiveness to, avoiding serious side effects of and less toxicity than an existing drug. Its ability to address a major public health need is also assessed.[2]

3. Priority Review

Title XI of the Food and Drug Administration Amendments Act of 2007 created the priority review voucher (PRV) program for neglected tropical diseases. The program grants a voucher to drug developers who are eligible for priority review, increasing the profitability of a drug and acting as incentive to develop treatments for diseases that are otherwise unprofitable.[3] In 2012, the Food and Drug Administration Safety and Innovation Act extended the program by including eligibility for rare pediatric diseases and, in 2016, ‘medical countermeasures’ for terrorism were included as well.[3]

 

aramis-khorchidian-chart

Figure 1[4]Since their inception, the highly coveted PRVs have been sold to drug manufacturers for large sums, the going rate for a PRV currently seems to be around $130M (figure shows data between 2014 and 2018; 2017 alone has seen 5 transactions)

 

4. Breakthrough Therapy

The aforementioned 2012 Food and Drug Administration Safety and Innovation Act also introduced Breakthrough Therapy designation for drugs. Drugs are given this designation if “preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s)”.[5]

5. Regenerative Medicine Advanced Therapy (RMAT)

Section 3033 of the 21st Century Cures Act adds another designation for drugs that grants a speedier approval. Request for an RMAT designation requires the treatment to be a regenerative medicine therapy (e.g. cell therapy) and for preliminary clinical evidence to show that it has “the potential to address unmet medical needs”.[6]

Overall, all these programs, except for Accelerated Approval, grant similar advantages to a drug manufacturer, such as frequent meetings with, and intensive guidance from, the FDA, a ‘rolling’ review schedule and eligibility for Accelerated Approval.[2] So the advantage is huge and can result in equally huge shifts in profit margins.

But how well are these policies working?

The effects of these programs are cumulative and it’s clear from the numbers that the FDA’s efforts to speed up the approval process hasn’t gone in vain.

The table below shows the number of expedited drug approvals, per year, since the inception of Fast Track:

 

aramis-khorchidian-chart2

Figure 2[7]

 

If we compare this to the annual total number of approvals, we see a significant percentage of drugs having been expedited in their approval:

 

 

aramis-khorchidian-chart3

Figure 3

 

The percentage values on the orange series show the percentage of all drug approvals that were expedited. In 1998 (the year Fast Track was introduced) to 2000, the percentage was small, however as the policy gained traction, it saw a steady climb, reaching a high 42.6%. In other words, in 2007-09 nearly half of all drug approvals were expedited.

On one hand, it looks like the policies are working just as they were meant to and important life-saving drugs are reaching market as quick as possible. On the other, adverse event reporting may be on the rise as a result, but this is a totally separate discussion (one that I may write about in the near future).

 

Bibliography

[1] “Fast Track, Breakthrough Therapy, Accelerated Approval, and Priority Review – Accelerated Approval.” US Food and Drug Administration Home Page, 15 Sept. 2014, www.fda.gov/ForPatients/Approvals/Fast/ucm405447.htm. Accessed 28. Dec. 2017.

[2] “Fast Track, Breakthrough Therapy, Accelerated Approval, and Priority Review – Fast Track.” US Food and Drug Administration Home Page, 30 Mar. 2017, www.fda.gov/ForPatients/Approvals/Fast/ucm405399.htm. Accessed 28. Dec. 2017.

[3] Gaffney, Alexander, et al. “Regulatory Explainer: Everything You Need to Know About FDA’s Priority Review Vouchers.” RAPS, Regulatory Affairs Professionals Society, 19 Dec. 2017. Accessed 28. Dec. 2017.

[4] Ridley, David. “Priorityreviewvoucher.org.” Priorityreviewvoucher.org, priorityreviewvoucher.org/. Accessed 28. Dec. 2017.

[5] “Fast Track, Breakthrough Therapy, Accelerated Approval, and Priority Review – Breakthrough Therapy.” US Food and Drug Administration Home Page, 15 Sept. 2014, www.fda.gov/ForPatients/Approvals/Fast/ucm405397.htm. Accessed 28. Dec. 2017.

[6] Center for Biologics Evaluation and Research. “Cellular & Gene Therapy Products – Regenerative Medicine Advanced Therapy Designation.” US Food and Drug Administration Home Page, Center for Biologics Evaluation and Research, 16 Nov. 2017. Accessed 28. Dec. 2017.

[7] Chary, Krishnanvengadaraga. “Expedited drug review process: Fast, but flawed.” Journal of Pharmacology and Pharmacotherapeutics, vol. 7, no. 2, 2016, p. 57., doi:10.4103/0976-500x.184768.