This Week at FDA: Bardoxalone strikes out at adcomm; Updated device consensus standards

Regulatory NewsRegulatory News | 10 December 2021 |  By 

Happy Friday – this week we’re juggling lots of end-of-year activity from the US Food and Drug Administration (FDA). Today and in the next week, look for our contributors to highlight several draft and final guidance documents and to provide analysis and background on industry’s reactions to other guidances whose comment periods have recently closed.
The Center for Drug Evaluation and Research (CDER) released its fall/winter 2021 regulatory science news update today. The 6-page newsletter gives updates on COVID-19-related actions such as updates to emergency use authorizations (EUAs) for therapeutics to treat the virus, and includes a reminder not to use the deworming treatment ivermectin to treat COVID-19. Highlights of recently published research from CDER authors, a notice of job and internship openings with CDER, and a summary of three “impact stories” round out the newsletter.
FDA also gave its manual of policies and procedures (MAPP), Conducting Effective Meetings in CDER: Remote Access Considerations, a post-pandemic refresh. The revised MAPP now notes the agency’s pandemic procedures for limiting social gatherings in the workplace and replaces reference to WebEx, Adobe, and Skype with MS Teams and ZoomGov for hosting meetings.
Two new draft guidance documents reached the Office of Management and Budget (OMB) for review, signaling their possible release in the near future if the White House signs off on the documents. The guidances cover the development of non-opioid analgesics for acute pain and notifying the agency of medical device shortages and discontinuations under Section 506J of the Federal Food, Drug, and Cosmetic Act.
CDER published a case study this week showing how physiologically based pharmacokinetic (PBPK) modeling of bioequivalence (BE) can support FDA approval of a topical generic drug. In the case study, the modeling approach supported the approval of generic diclofenac sodium topical gel based on “an alternative BE approach in lieu of the comparative clinical endpoint BE study” FDA would recommend ordinarily.
The agency has updated its compendium of clinical outcome assessments (COAs), “to encourage the development and implementation of patient-focused clinical outcome assessments” for use in clinical trials. The latest updates include COAs from new molecular entity and biologics license application labels from July 2017 to June 2018, as well as from efficacy supplements through June 2018 and measures qualified by CDER.  
Adcomms and authorizations
An FDA advisory committee gave a unanimous thumbs down to Reata’s bardoxalone methyl for the treatment of chronic kidney disease caused by Alport syndrome. The Cardiovascular and Renal Drugs Advisory Committee cited safety concerns and the selection of estimated glomerular filtration rate as the primary endpoint in the pivotal phase 3 trial, among other considerations.
At press time, the meeting of the Neurological Devices Panel of CDRH’s Medical Devices Advisory Committee is underway. The committee is considering a premarket approval application for BrainsGate’s Ischemic Stroke System, designed to increase blood flow during the brain in some patients with acute ischemic stroke who cannot receive intravenous clotbusters or endovascular thrombectomy.
Also this week, FDA authorized a new combination of monoclonal antibodies for emergency use as pre-exposure prophylaxis against COVID-19 in some immunocompromised people and people who are not recommended to receive COVID-19 vaccines.  AstraZeneca’s Evusheld (tixagevimab co-packaged with cilgavimab and administered together) is administered by intramuscular injection, and is authorized for ages 12 and up within the indicated population.
Enforcement Corner
On the enforcement side, FDA posted a warning letter sent to Kentucky-based Induction Therapies, LLC last month over its promotion of an unauthorized microneedling device. Despite the company’s claim that its “Collagen P.I.N. is a Class 1 FDA registered medical device for Percutaneous Collagen Induction Therapy,” FDA says the device was distributed without approval, clearance or authorization and is both adulterated and misbranded.
The agency also released a 483 it handed to generic drugmaker Dr. Reddy’s detailing eight observations identified during an inspection of the company’s Duvadda plant in Andhra Pradesh, India. The 483 notes issues with the company’s adherence to quality control procedures, laboratory controls, and validation of testing performed by its suppliers. It also notes issues with the site’s aseptic processing areas and procedures for preventing microbial contamination.
In device news, FDA updated its list of recognized consensus standards for medical devices this week, adding, withdrawing or modifying dozens of standards on the listing. Device manufacturers may opt to declare conformity to the recognized standards to meet certain requirements for their devices as part of premarket review submissions or for other purposes.
CDRH has released a list of COVID-19 tests that may be impacted by the omicron variant. The center highlights two tests, Meridian Bioscience’s Revogene SARS-CoV-2 and Tide Laboratories DTPM COVID-19 RT-PCR tests, with reduced ability to detect the variant. It also advises that 26 tests with S-gene drop out may be impacted by the omicron variant. “A specific deletion in the spike (S) gene (Δ69-70) results in an S-gene drop out, also referred to as an S-gene target failure (SGTF), where the genetic target that covers the portion of the S-gene where the deletion occurs fails to detect the virus,” CDRH explains.
The agency also issued a final order denying a petition to exempt class II “powered patient transport devices, all other powered patient transport” regulated under product code ILK from 510(k) requirements.
Additionally, FDA continued its streak of de novo device classifications, issuing final orders classifying five devices into class I and class II. The devices include pressure ulcer management tools, temporary coil embolization assist devices, ingested, transient, space occupying device for weight management and/or weight loss, negative pressure wound therapy device for reduction of wound complications, and transcutaneous electrical nerve stimulation for attention deficit hyperactivity disorder.
FDA released minutes from three rounds of negotiations around the reauthorization of the Medical Device User Fee Amendments (MDUFA V) this week. The minutes of the May and June meetings relate discussions about FDA’s calculations of its staffing needs, how COVID-19 supplemental funding will be used, and where industry feels MDUFA resources could best be used at FDA. The minutes, more detailed than those for most of the user fee negotiation meetings, make for interesting reading.
What else we’re reading
This story in Fierce Healthcare that cites a recent Deloitte report on physician attitudes toward wearable health tech. Physicians and other health care providers cite lack of interoperability and concerns about accuracy as continuing reasons for skepticism about how wearables can be integrated into health care delivery.
As reported today in Focus, FDA is facing an onslaught of cell and gene therapy submissions but continues to struggle with chronic staffing shortages that are largely attributable to federal-private sector salary discrepancies.  The agency’s Center for Biologics Evaluation and Research (CBER) posted a job opening for a cell and gene therapy reviewer this week, imploring applicants to “Become a part of an agency that touches the lives of every American!” Doctorally prepared candidates are encouraged to apply for the staff fellow position.


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