The U.S. Food & Drug Administration’s (FDA’s) Accelerated Approval (AA) Program seems to be heading for a long overdue makeover. The House Energy and Commerce (HEC) Committee is considering a pair of rival bills, one Democratic and one Republican, to reform the AA process. Here’s a quick briefing.
The AA Program
Created in 1982 in response to the HIV/AIDS epidemic, the AA Program is designed to expedite the approval of novel treatments of serious health conditions not being adequately served by the current medical market. Drugs receiving accelerated approval can be removed from the market if post-approval (Phase IV) studies fail to confirm their intended clinical benefits.
The problem with this approve-now/confirm-later approach is that drug sponsors often delay the required Phase IV studies, leaving it to the FDA to initiate the slow and cumbersome approval withdrawal mechanism. Consequently, unproven drugs remain on the market for prolonged periods—and are sometimes never withdrawn at all. While criticism of the program is nothing new, things came to a head in 2021 when FDA pulled a surprise and used the AA to approve Aduhelm, the controversial Alzheimer’s treatment from Biogen. In response, Congress decided it was time to do something and held hearings on how to fix and speed up the process for withdrawing accelerated approvals of ineffective drugs.
The AA Program Reform Bills
Congressional representatives from each party have proposed bills to strengthen FDA’s powers to withdraw AA pathway drugs.
The Democratic bill, H.R. 6963, the Accelerated Approval Integrity Act of 2022, proposed by
HEC Committee chairman Frank Pallone, Jr. (D-NJ), would:
- Limit how long AA drugs could stay on the market without confirming clinical benefit to five years;
- Require manufacturers seeking accelerated approval to agree with FDA on a post-approval studies plan before AA Program approval is granted;
- Authorize FDA to require that post-approval studies be underway at the time of approval;
- Require sponsors to provide quarterly updates on post-approval studies; and
- Establish expedited procedures for withdrawing approval, which include notice, an opportunity for a written appeal to FDA, and an opportunity for public comment.
The Republican bill, H.R. 6996, the Accelerating Access for Patients Act of 2022, proposed by the HEC Committee’s ranking member, Cathy McMorris Rodgers (R-WA), would also beef up FDA withdrawal powers and sponsor obligations, but in a more limited way. Specifically, the Republican bill would require FDA to:
- Write specific regulations setting out a process for expedited withdrawals;
- Establish procedures for drug sponsors to develop a plan detailing how they will comply with accelerated approval requirements;
- Issue guidance on “the use of novel clinical trial designs” that may be used to satisfy post-market study requirements; and
- Approve or “specify changes” to a post-approval study protocol within 60 calendar days after the protocol is submitted.
Takeaway
While both bills give FDA authority to use expedited procedures to withdraw accelerated approval status if post-approval testing requirements aren’t met, the Democratic bill allows for withdrawal under two additional conditions, i.e., where the drug sponsor fails to either:
- Submit periodic progress reports for post-approval studies; or
- Achieve agreed upon enrollment targets, milestones, or timely post-approval study completion.
The Republican bill also imposes fewer obligations on drug sponsors regarding post-approval studies and compliance and places the onus on FDA to implement procedures to facilitate and enforce compliance with post-market study requirements.
Meanwhile, here are the important new FDA Emergency Use Authorizations (EUAs) and clearances announced in March 2022:
New FDA Emergency Use Authorizations (EUAs) & Approvals
| Manufacturer(s) | Product |
| Quest Diagnostics | EUA for Quest RC COVID-19 PCR DTC test |
| Quest Diagnostics | EUA for Quest PF COVID-19 PCR DTC test |
| Quest Diagnostics | EUA for Quest COVID-19 PCR DTC test |
| Helix | EUA for molecular test detecting SARS-CoV-2 from anterior nasal swab specimens self-collected without supervision using Helix COVID-19 Self-Collection Kit |
| Siemens Healthineers | EUA for Atellica IM SARS-CoV-2 Antigen test |
| Siemens Healthineers | EUA for and Advia Centaur SARS-CoV-2 Antigen test |
| BioMérieux | 510(k) clearance for Vitek MS Prime MALDI-TOF mass spectrometry identification system |
| Foundation Medicine | Approval of FoundationOne CDx test as companion diagnostic to identify NSCLC patients with EGFR exon 19 deletions or exon 21 alterations for treatment with EGFR inhibitors |
| Phase Scientific International | EUA for over-the-counter, at-home version of SARS-CoV-2 rapid test, called the Indicaid COVID-19 Rapid Antigen At-Home Test |
| Minute Molecular Diagnostics | EUA for DASH SARS-CoV-2/S molecular test |
AstraZeneca
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Merck | Approval for Lynparza (olaparib) as adjuvant treatment for early-stage breast cancer patients harboring germline BRCA1/2 mutations |
| Immucor | 510(k) clearance for Luminex Lifecodes single antigen Class I and Class II assays |
| Inspirata | 510(k) clearance for Dynamyx digital pathology software, using whole-slide images rather than traditional glass slides for primary diagnosis |
| AltPep | Breakthrough device designation for blood-based Soba-AD diagnostic test to detect Alzheimer’s disease |
| Oceanit | EUA for ASSURE-100 rapid COVID-19 test based on saliva spit samples |
| ChromaCode | Expanded EUA for HDPCR SARS-CoV-2 RT PCR test for use on new qPCR instruments and 384-well plates |
New CE Marks & Global Certifications
Notable European CE certifications announced during the period:
New CE Markings in Europe
| Manufacturer(s) | Product(s) |
| Biolytical Laboratories | iStatis COVID-19 Antigen Home Test |
| Illumina | TruSight Oncology Comprehensive (EU) assay |
| CardiNor | CardiNor Secretoneurin ELISA test for cardiovascular disease risk |
| MedMira | Reveal TP (Syphilis) test |
| Quotient Limited | MosaiQ Extended Immunohematology Microarray test |
| Luminex (DiaSorin) | xMap NxTag Gastrointestinal Pathogen Panel (GPP) |
| Sense Biodetection | Veros rapid, disposable COVID-19 molecular diagnostic test |
| Mawi DNA Technologies | HemaSure-Omics non-invasive collection device and NextSwab 100 percent injection-molded swab |
| Diadem | AlzoSure Predict plasma-based biomarker test for early prediction of Alzheimer's disease |
| SeekIn | SeekInCare Cancer Detection Kit |
Other international clearances announced during the period:
| Manufacturer(s) | Country(ies) | Product(s) |
| Cue Health | Canada | At-home molecular COVID-19 self-test run on portable Cue Health Monitoring System |
| Biolytical Laboratories | Canada | iStatis COVID-19 Antigen Test |
| Mawi DNA Technologies | UK | HemaSure-Omics non-invasive collection device and NextSwab 100 percent injection-molded swab |
| QuantuMDx | UK | SARS-CoV-2 RT-PCR test |
| LumiraDx | UK | LumiraDx SARS-CoV-2 RNA Star Complete rapid molecular test |
| Burning Rock Biotech | China | LungCure CDx nine-gene sequencing assay |
| Guardant Health | Japan | Guardant360 CDx liquid biopsy test for tumor mutation profiling |
