Top stories: FDA denies new dietary ingredient application for Oleandrin. Legislation seeks to bolster public confidence in FDA vaccine decision with transparency. Legislators question communications process for EUA modifications. BIO, biotech executives advocate for ‘historic independence’ of FDA. Is the FDA’s approach to quality metrics due for a comeback?
Welcome to our COVID Weekly Recap, AgencyIQ’s weekly wrap-up of the top regulatory developments related to COVID-19. The following analysis was available to AgencyIQ subscribers earlier this week as part of our daily regulatory intelligence briefings, as well as dozens of other pieces of analysis. Contact us to find out how you can become a subscriber to AgencyIQ.
FDA denies new dietary ingredient application for Oleandrin
By Lily Rosenfield and Alexander Gaffney, MS, RAC
September 3, 2020
In a letter made public yesterday, the FDA denied a company’s application to market Oleandrin, an extract from the oleander plant, as a dietary supplement. The ingredient has recently been floated by some as a potential treatment for COVID-19—without clinical evidence.
- Oleandrin is a cardiac glycoside, steroid ester and steroid saponin derived from the poisonous oleander plant. It has been examined in studies for lung cancer treatments and chemotherapeutic agent toxicity, though overall human trial data is sparse.
- Phoenix Biotechnology had filed a New Dietary Ingredient application with the FDA seeking the agency’s determination that the ingredient would be safe for use when taken orally by adults in an amount of less than 25 micrograms per day. The NDI filing is required for supplement products not marketed prior to October 1994, when Congress passed the Dietary Supplement Health and Education Act (DSHEA). (AgencyIQ subscribers can learn more about the NDI process here)
- FDA: This is not a dietary supplement: The FDA found that Oleandrin is excluded from the legal definition of a dietary supplement, which excludes any “article authorized for investigation as a new drug, antibiotic, or biological for which substantial clinical investigations have been instituted and for which the existence of such investigations has been made public” which was not already marketed as a dietary supplement.
- Oleandrin had previously been investigated as a new drug and was not marketed as a dietary supplement prior, thereby excluding it from the definition of a dietary supplement. The FDA also faulted the evidence provided in the application, which it said did not establish the product as safe.
- Connected to COVID: Recently, Oleandrin has made news as a speculative treatment for COVID. Specifically, Andrew Whitney, an executive on the board of Phoenix Biotechnology, had meetings to discuss Oleandrin with President Donald Trump, according to media reports.
- Prior studies: A pre-print, non-peer-reviewed in vitro study from July claims that Oleandrin stops SARS-CoV-2 from replicating in monkey kidney cells in a test tube. While there is no other data to support Oleandrin as a COVID-19 therapeutic, studies have shown Oleandrin could be an effective treatment for breast cancer, stroke, and pancreatic cancer. Data also indicate that the ingredient is associated with significant safety risks.
- What’s next: Given FDA’s response, Oleandrin’s path to market will not be as a dietary supplement. The letter was issued to the company in June, prior to publicized White House meetings on the topic.
Legislation seeks to bolster public confidence in FDA vaccine decision with transparency
By Aaron Badida, JD
August 31, 2020
New legislation introduced in Congress this month seeks to pre-emptively ensure that any vaccine authorized for use by the FDA through its Emergency Use Authorization (EUA) process is subject to transparency efforts.
- Emergency Use Authorization is a process by which the FDA can “authorize”—not approve—the use of a product based on preliminary evidence suggesting that a product “may be” effective for a given purpose. The FDA has indicated in its guidance that it would be willing to make use of this process to authorize a vaccine for COVID-19. “[F]or a vaccine for which there is adequate manufacturing information, issuance of an EUA may be appropriate once studies have demonstrated the safety and effectiveness of the vaccine but before the manufacturer has submitted and/or FDA has completed its formal review of the biologics license application.”
- The concern: That an EUA wouldn’t adhere to the FDA’s usual transparency efforts, which can include an advisory committee and other opportunities for the public to see information related to a product’s authorization after it happens.
- The Safe Authorization for Vaccines during Emergencies (SAVE) Act would require there to be an emergency meeting whenever an EUA is requested for a vaccine intended to treat a disease that is the subject of a declared public health emergency. The FDA and vaccine sponsor would be required to present data to the Vaccines and Related Biologic Products Advisory Committee (VRBPAC). There is an exception that would allow the HHS Secretary to forego the meeting, but instead submit a report to Congress detailing the reason for the decision.
- Additional efforts to obtain approval: The bill also would effectively create a “conditional authorization” process, by which the authorization would be “conditioned on the sponsor seeking licensure of the product” within a certain amount of time. This would incentivize sponsors to maintain current development efforts.
- ACIP hearing: SAVE also would require that a vaccine given an EUA for a disease for which there is a public health emergency be evaluated by the Advisory Committee for Immunization Practices (ACIP) within 15 days of EUA issuance. SAVE would amend the Public Health Service Act to require ACIP to issue recommendations about priority populations for an authorized vaccine or request more information from HHS to make that determination.
- The bill may be more for public confidence.Vaccine hesitancy has been a concern among public health officials, who fear that even if approved, people would be resistant to receiving a vaccine for the novel coronavirus. Discussing the SAVE Act, Maggie Hassan (D-N.H.) stated in a press release: “As we work to get a potential vaccine approved, produced, and distributed as quickly as possible, it’s critically important that the public is confident that the federal government followed the necessary protocols to ensure that the vaccine is safe and effective.” The bill is also sponsored by Sens. Mike Braun (R-Ind.) and Lisa Murkowski (R-Ark.).
Legislators question communications process for EUA modifications
By Charles Friend
September 3, 2020
On Wednesday, Senator Elizabeth Warren (D-MA) wrote a letter to FDA Commissioner Stephen Hahn requesting information about the FDA’s process for communicating changes in—or revocations of—Emergency Use Authorizations (EUAs) to medical providers.
- EUAs allow unapproved medical products to be used in an emergency when there are otherwise no approved or available alternatives. The FDA is obligated to establish conditions for the use of medical products authorized under an EUA, including conditions ensuring health care providers and patients are aware of potential benefits and risks of said products.
- Expanded EUA use: The COVID-19 pandemic has resulted in an unprecedented expansion of the use of EUAs, with the FDA authorizing at least 270 EUAs during the COVID-19 pandemic compared to just 77 between 2005 and 2018.
- Modified or Revoked EUAs: However, the FDA has revoked or modified several of these EUAs due to new information, including revising which masks and other forms of PPE under EUAs may be safely decontaminated and re-used, which have caused confusion for certain healthcare providers. The letter expresses concern that changes and modifications to EUAs may continue to create confusion for healthcare professionals if they are not clearly communicated.
- Requested Information: The letter requests that the FDA provide information clarifying steps it takes to communicate information about EUA modifications or revocations to providers, including how the agency notifies healthcare providers and other entities using products authorized under EUA of EUA modifications or revocations as well as data suggesting a change in the products risks and benefits. The letter also requests information regarding how the FDA enforces compliance and levies consequences against organizations that continue to use products after the EUA authorizing them is revoked, and the role data collected by the agency from healthcare providers and patient advocates plays in decisions to modify or revoke an EUA.
BIO, biotech executives advocate for ‘historic independence’ of FDA
By Charles Friend
September 3, 2020
On Thursday, biotechnology industry executives associated with the Biotechnology Innovation Organization (BIO) released an open letter advocating that companies, politicians, and regulators take steps ensure that the development and regulatory approval of medicines to treat COVID-19 is data-driven and devoid of political influence.
- The letter, signed by BIO’s CEO Michelle McMurry-Heath and six other biotechnology industry executives, includes five recommendations for the industry, political leaders and the FDA.
- Clinical trials: The letter states that clinical trials should adhere to best practices and include the participation of a diverse population of subjects, noting that different subpopulations may react differently to treatments. Companies should ensure a data-driven approach to the development and use of new products.
- Release of data: The letter also notes that companies should be thoughtful in their release of clinical trial data. Data, the letter states, should be released at scientific meetings or in peer-reviewed journals—not via press release. Companies should ensure that any publicly released data should contain descriptions of key data points to avoid confusion or misinterpretation of results.
- FDA independence: The letter emphasizes that the agency’s decisions regarding the review and approval of new medicines must be free of external influence, and that politics should not influence regulatory decisions. The letter requests that political leaders take steps to assure the public that politics will not interfere with regulatory decision-making or the development of medicines.
What we’re watching
This extraordinary statement from the NIH’s COVID-19 Treatment Guidelines Panel, which reviewed the FDA’s decision to grant an Emergency Use Authorization to convalescent plasma and found the decision… lacking.
Based on the available data, which included the data available to the FDA, the Panel determined that “there are insufficient data to recommend either for or against the use of convalescent plasma for the treatment of COVID-19,” and that “Convalescent plasma should not be considered standard of care for the treatment of patients with COVID-19.”
That’s a major difference from what the HHS announced last week. “The FDA’s emergency authorization for convalescent plasma is a milestone achievement in President Trump’s efforts to save lives from COVID-19,” wrote Secretary Azar in a statement accompanying the FDA’s authorization announcement. FDA Commissioner Hahn said at a press conference announcing the decision that the data showed that plasma represented “a pretty substantial clinical benefit.”
The NIH doesn’t often weigh in on FDA decisions, let alone undercut them or second-guess them. We’ll be watching to see if this is a one-off occurrence or the start of a trend.
. . . .
This Tweet from the FDA’s top drug quality official, Michael Kopcha (@QualityKop), wondering aloud how patients and purchasers might consider “ratings of a manufacturing facility’s quality management authority.”
As we’ve argued for months now, the FDA sure appears likely to start moving back toward its old quality metrics approach, which was quietly shelved after significant industry pushback. We’ve looked at how the increased use of remote inspections during COVID might lead to this comeback. We’ve written about how it’s difficult to even define what good drug quality looks like. And we’ve written about how the FDA is surveying companies about benchmarks of effective quality systems, its desire to develop metrics for quality management, and its own use of quality metrics for a recent study.
Could we soon see the FDA publish those facility ratings? We’ll be watching.
The percentage of respondents to a recent poll conducted by the Harris Poll and STAT News who said they had concerns that “the vaccine approval process is being driven more by politics than science.” That included 82% of Democrats and 72% of Republicans. Just 68% of respondents said they were confident that “the FDA will only approve a COVID-19 vaccine if it is safe.”
“It is up to the sponsor [vaccine developer] to apply for authorisation or approval, and we make an adjudication of their application. If they do that before the end of Phase Three, we may find that appropriate. We may find that inappropriate, we will make a determination.”
FDA Commissioner Stephen Hahn, in an interview with the Financial Times describing the circumstances under which the agency might review and authorize a vaccine product for COVID-19 prior to the conclusion of a Phase 3 study. That language was generally consistent with what the FDA had previously communicated in its guidance on the development and review of vaccines for COVID-19.