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August 16, 2023
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By all accounts, the COVID-19 pandemic was a major disruptor that altered the routine of everyday life. Perhaps no other sector experienced upheaval more acutely than the public health infrastructure. It might be said that the U.S. Food and Drug Administration (“FDA”) was at the metaphorical epicenter of that upheaval. It prioritized reviewing the safety and efficacy of vaccines submitted under an emergency use authorization directive following the declaration of a public health emergency for COVID-19.1
Q3 2023 Healthcare Quarter in Review Read Now
With the disruption of the pandemic over, the FDA is again committed to meeting the standard review expectations as defined by two laws: 1) the Prescription Drug User Fee Act (“PDUFA”) for pharmaceuticals and biologics, and 2) the Medical Device User Fee Act (“MDUFA”) for certain medical devices.2, 3 Under these laws, the FDA is mandated to complete license application reviews within a certain prescribed time frame. The “clock“ starts ticking when the agency receives a complete submission and stops if there are any gaps in data or any issues with the quality of the submission.4
In terms of expediting, the FDA provides manufacturers with four pathways designed to get specific types of pharmaceuticals and biologics into the hands of doctors and their patients earlier than the PDUFA mandate.5 Manufacturers can also leverage internal operational opportunities to speed up both the clinical and submission development processes.
What follows are questions that pharma, medical device and biotech firms may be asking about the submission process as the world continues to move on from the pandemic, and the demand for new drugs and devices grows.
Q. Coming out of COVID-19, what are the priorities in the FDA submission process for new drugs or devices that I should know about?
A. With the FDA’s resources focused on COVID-19, the review process for new products was strained. Now the agency is dedicated to returning to the routine timelines outlined in the PDUFA and MDUFA mandates and those that apply to the four accelerated submission pathways.6 Accelerated pathways are designated as such:
- Fast Track: for drugs that “treat serious conditions and fill an unmet medical need”7
- Breakthrough Therapy: for drugs that “demonstrate substantial improvement” over those currently on the market8
- Accelerated Approval: for drugs that offer a “clinical benefit”9
- Priority Review: for a first-time drug or one that “has advantages over existing treatments”10
Understanding the nuances of these designations can help a firm meet FDA expectations during the approval process. Equally important is knowing how to assess and best present clinical data, as well as how to prepare the application itself for review. Any hiccup during the agency’s review can stop the clock and delay review, or worse, result in a Clarifying Response Letter, which kicks the application back from the FDA and starts the review clock all over again.
Q. How can I best facilitate the clinical phase of the development process?
A. The best way is to have a preliminary discussion with the FDA during the pre-submission (“pre-sub”) process to vet potential endpoints and align on clinical research targets before the data collection process begins. That way once the trial is underway, only patient test results that support these endpoints are collected. In certain cases, favorable interim trial outcomes may permit accelerated submission of the new drug or biologic application. Nothing can guarantee approval but effective communication with the FDA is essential for exploring all options.
Q. How can I facilitate the submission development phase?
A. It’s critical to understand the expectations of regulators and create a compelling case for approval based on the data. Applicants can then determine an appropriate filing strategy. Some regulatory leads take a risk-based approach. Examples include writing at risk, assuming certain outcomes will be achieved, or adopting a minimum viable product (“MVP”) approach to submission. With MVP, applicants file an initial packet that is purposely incomplete but nonetheless sufficient to start the agency’s official review period. With the applicant’s careful planning, the missing information — typically outcomes data — can be provided at a later date when other information is requested by regulators, without stopping the PDUFA clock.11
Q. How does digital transformation come into play for drug- and device-makers in the submissions process?
A. Digitization is rapidly improving efficiency and leading to better governance in clinical trials. Once the data is in, companies can leverage techniques to streamline core submissions processes and reduce cycle times. These include improved governance and access to robust regulatory analytics and dashboards to proactively accelerate submissions and improve submission quality.
Q. What’s all this I hear about virtual clinical trials?
A. We all know that COVID-19 accelerated the telehealth movement. Clinical trials have also evolved with the migration from traditional brick-and-mortar trial sites to decentralized and virtual methods. According to one report, “83% of all clinical trials are now partially or entirely virtualized.”12 This trend is made possible by tools such as “wearables,” which enable continuous monitoring of patient vital signs, or via smartphone-based apps that permit effective and timely patient-reported outcomes through the use of emojis or other means. This movement could potentially cut years off a study by removing the logistical barriers associated with recruitment and management of a conventional trial.
Q. Is AI playing a role in clinical trials?
A. In January 2021, the FDA released its “Artificial Intelligence/Machine Learning Action Plan,” which created an initial framework, transparency initiatives and best practices for these powerful software tools.13
Given all the discussions around AI, regulators and industry players are moving slowly and deliberately — and rightfully so. It’s coming, no doubt, but in the end, AI is only as good as the data underlying the analysis. Until high volumes of accurate, real-world data are available to support analysis, the full benefits of AI will be limited.
Statutory Time Frames
- PDUFA (Prescription Drug User Fee Amendments) requires the FDA to process drug applications within 10 months of receipt.14
- MDUFA (Medical Device User Fee Amendments) has no specified timeline, but the FDA has a goal to process applications within 90 days.15
Footnotes:
1: “Emergency Use Authorization for Vaccines Explained,” U.S. Food and Drug Administration (November 20, 2020), https://www.fda.gov/vaccines-blood-biologics/vaccines/emergency-use-authorization-vaccines-explained.
2: “PDUFA legislation and background,” U.S. Food and Drug Administration (December 16, 2015), https://www.fda.gov/industry/prescription-drug-user-fee-amendments/pdufa-legislation-and-background.
3: “Medical device user fee amendments (MDUFA),” U.S. Food and Drug Administration (October 5, 2022), https://www.fda.gov/industry/fda-user-fee-programs/medical-device-user-fee-amendments-mdufa.
4: “FDA’s Drug Review Process: Continued,” U.S. Food And Drug Administration (August 24, 2015), https://www.fda.gov/drugs/information-consumers-and-patients-drugs/fdas-drug-review-process-continued.
5: “Fast Track, Breakthrough Therapy, Accelerated Approval, Priority Review,” U.S. Food And Drug Administration (June 12, 2023), https://www.fda.gov/patients/learn-about-drug-and-device-approvals/fast-track-breakthrough-therapy-accelerated-approval-priority-review.
6: “FAQs: What Happens to EUAs When a Public Health Emergency Ends?” U.S. Food And Drug Administration (May 12, 2023), https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/faqs-what-happens-euas-when-public-health-emergency-ends.
7: “Fast Track,” U.S. Food and Drug Administration (January 4, 2018), https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/fast-track.
8: “Breakthrough Therapy,” U.S. Food and Drug Administration (January 4, 2018), https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/breakthrough-therapy.
9: “Accelerated Approval,” U.S. Food and Drug Administration (February 24, 2023), https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/accelerated-approval?sm_guid=MTQ4NTAxfDExNjE0NjM5fC0xfGFubmZvbmZhQGFvbC5jb218ODcxMjMxfHwwfDB8MzM5MDE5NjV8ODM3fDB8MHw1.
10: “Priority Review,” U.S. Food and Drug Administration (January 4, 2018), https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/priority-review.
11: “FDA’s Drug Review Process: Continued,” U.S. Food & Drug Administration (August 24, 2015), https://www.fda.gov/drugs/information-consumers-and-patients-drugs/fdas-drug-review-process-continued.
12: “Accelerating Virtual Clinical Trials,” BioPharma Dive (February 22, 2021), https://www.biopharmadive.com/spons/accelerating-virtual-clinical-trials/595034/.
13: “FDA Releases Artificial Intelligence/Machine Learning Action Plan,” U.S. Food and Drug Administration (January 21, 2021), https://www.fda.gov/news-events/press-announcements/fda-releases-artificial-intelligencemachine-learning-action-plan.
14: “PDUFA legislation and background,” U.S. Food and Drug Administration (December 16, 2015), https://www.fda.gov/industry/prescription-drug-user-fee-amendments/pdufa-legislation-and-background.
15: “Medical device user fee amendments (MDUFA),” U.S. Food and Drug Administration (October 5, 2022), https://www.fda.gov/industry/fda-user-fee-programs/medical-device-user-fee-amendments-mdufa.
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August 16, 2023
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