The Focal Point: Tuesday, December 3, 2019
- FDA Delays Release of Several Proposed Rulemakings
- FDA Unveils Draft Guidance on How to Request a Certificate of Confidentiality
- FDA Releases Guidance on Adaptive Designs for Clinical Trials of Drugs and Biologics
- Australia’s TGA Issues Advertising Guidance for Businesses Involved with Stem Cells and Other Human Cell or Tissue Products
- RichSource Stem Cells Receives an Untitled Letter from FDA
- GREFI Receives an Order to Cease Manufacturing
- President Signs Continuing Resolution to Keep Goverment Funded Through Dec. 20
- CMS Issues Final Rule Requiring Hospitals to Make Standard Charges Public
- White House Releases Annual Report on U.S. Global Health Security Efforts
- WHO Prequalifies Ebola Vaccine
- Researchers Develop AI-Based Stem Cell Quality Control Method
The latest regulatory agenda for the US Food and Drug Administration (FDA) was released, announcing the delays of several proposed rulemakings, and one new proposed rule allowing the importation of prescription drugs.
The Unified Agenda of Regulatory and Deregulatory Actions reports on the actions administrative agencies plan to issue in the near and long term. Released by the Office of Information and Regulatory Affairs, the Agenda demonstrates the commitment to fundamental regulatory reform and reducing unnecessary regulatory burdens on the American people.
Some of the rulemakings of interest to eye banks include:
- Biologics Regulation Modernization – regulations will be updated to clarify existing requirements and procedures related to BLAs, expected December 2019
- Definition of the Term “Biological Product” – expected to be finalized in January 2020
- Biologics License Applications and Master Files – expected to be finalized in February 2020
- Harmonizing and Modernizing Regulation of Medical Device Quality Systems – proposed rule expected in April 2020.
- Human Tissue Intended for Transplantation – proposing to revoke 21 CFR part 1270 in June 2020, since no tissues recovered before May 25, 2005 are remaining in inventory.
- Postmarketing Safety Reporting Requirements for Human Drug and Biological Products – expected to be re-proposed next June
- Requirements for Determining Donor Eligibility and Donation Suitability of Blood and Blood Components Intended for Transfusion or for Further Manufacturing Use – expected June 2020
- Institutional Review Board Waiver or Alteration of Informed Consent for Minimal Risk Clinical Investigations – expected to be finalized in September 2020
- Post Approval Changes to Approved Drug and Biological Applications– expected in September 2020
The FDA released draft guidance explaining how sponsors can request certificates of confidentiality (CoCs), which can prevent researchers from being compelled to disclose identifiable, sensitive information about research participants.
For non-federally funded research, FDA has been issuing discretionary CoCs on a case-by-case basis since the enactment of the 21st Century Cures Act, which also made the CoCs for federally funded research mandatory. This draft guidance describes the revised, streamlined process for submitting requests for discretionary CoCs.
FDA suggests that sponsors ask themselves four questions before submitting a request for a CoC, including:
- Does the human subject research collect identifiable, sensitive information?
- Is the requestor a sponsor or sponsor-investigator or authorized representative?
- Does the human subject research involve the use or study of a product subject to FDA’s jurisdiction and subject to FDA’s regulatory authority?
- Are the requestor’s research measures sufficient to protect the confidentiality of the identifiable, sensitive information?
After FDA reviews a request, the agency will send an electronic response letter to the requestor indicating whether the CoC has been granted. If granted, that letter will serve as the CoC.
FDA released a final guidance entitled Adaptive Designs for Clinical Trials of Drugs and Biologics, which finalizes the draft guidance issued in October 2018.
This document provides recommendations to sponsors and applicants submitting investigational new drug applications (INDs), new drug applications (NDAs), biologics license applications (BLAs), or supplemental applications on the appropriate use of adaptive designs for clinical trials to provide evidence of the effectiveness and safety of a drug or biological product. The guidance describes important principles for designing, conducting, and reporting the results from an adaptive clinical trial.
Australia’s Therapeutic Goods Administration (TGA) recently issued a guidance to assist businesses involved with stem cells and other human cell or tissue (HCT) products in complying with therapeutic goods advertising restrictions. The TGA noted that the agency has become aware that the term “stem cells” is being used in advertising human cell or tissue products. Because these products are regulated as biologicals in Australia, they cannot be advertised to the public.
FDA sent an untitled letter to Florida-based manufacturer RichSource Stem Cells, Inc. over unsubstantiated claims for its RICHGEN allograft product.
RichSource’s website describes RICHGEN as “a combination of amniotic fluid and membrane, Wharton’s jelly, and placental tissue,” and claims the product can treat various diseases including cancer, diabetes, Lyme’s disease, asthma, arthritis, neuropathy and joint pain, as well as for topical wound healing.
According to FDA, RICHGEN does not meet all the criteria in 21 CFR 1271.10(a), and are not regulated solely under section 361 of the PHS Act and the regulations in 21 CFR Part 1271. As such, RICHGEN is regulated as a drug and a biological product and would require a valid biologics license application (BLA) to be legally marketed.
FDA also notes that the product raises significant safety concerns as it is marketed to treat serious and life-threatening conditions and “because the product is administered by various higher risk routes of administration, including via spinal injections, their use, if contaminated could cause a range of adverse events.”
FDA has ordered Gynecology, Reproductive Endocrinology and Fertility Institute (GREFI) of San Juan, Puerto Rico to immediately cease manufacturing due to significant violations of FDA regulations.
GREFI performs donor screening, is responsible for donor testing, and determines the eligibility of anonymous and directed donors of reproductive HCT/Ps. FDA found that they did not provide adequate protections against the risks of communicable disease transmission and that the HCT/Ps manufactured pose a danger to health.
They were ordered to immediately cease all manufacturing of HCT/Ps from directed or anonymous reproductive tissue donors until compliance with the regulations in 21 CFR Part 1271 has been achieved and you have been provided with written authorization from FDA to resume operations. Additionally, they were requested to notify all recipients of these reproductive tissues.
President Trump signed a Fiscal Year (FY) 2020 Continuing Resolution (CR) that prevented a government shutdown. This bill provides continuing FY2020 appropriations to federal agencies through December 20, 2019 and extends several expiring health programs.
Congressional leaders still need to reach agreement on over 12 appropriations bills for the rest of fiscal 2020. Disagreements over border wall spending have largely delayed progress on the budget, with the possibility of another short-term or even a full-year CR, or a government shutdown before the end of the year.
The Centers for Medicare and Medicaid Services (CMS) issued a final rule last Friday requiring hospitals to provide patients with “clear, accessible” information about standard charges for hospital services, including laboratory and pathology services, through the use of standardized data elements. Beginning Jan. 1, 2021, CMS will require hospitals to make their charges public through a comprehensive, machine-readable file and through a public display of shoppable services in a consumer-friendly manner.
The White House released the annual report, Advancing the Global Health Security Agenda: Results and Impacts of U.S. Government Investments, detailing U.S. progress on global health security, including efforts to contain outbreaks of Ebola, Zika, and other high-threat diseases. The President’s budget request for fiscal year 2020 proposes resources specifically dedicated to protecting the United States and its partners abroad from deadly infectious disease threats.
The world’s first Ebola vaccine, rVSV-ZEBOV (Erverbo, Merck) recently received prequalification from the World Health Organization (WHO), meaning the vaccine meets WHO standards for quality, safety and efficacy. This announcement comes less than 48 hours after the European Commission decision to grant a conditional marketing authorization for the vaccine, following the recommendation from the European Medicines Agency (EMA).
WHO prequalification allows United Nations agencies and Gavi, the Vaccine Alliance, to procure the vaccine for at-risk countries. A WHO statement noted that this is the fastest vaccine prequalification process ever conducted by the organization. The vaccine is currently in use in the ongoing outbreak in the Democratic Republic of the Congo under a compassionate use.
Investigators from the National Eye Institute and National Institute of Standards and Technology have developed an image analysis method that uses artificial intelligence (AI) to evaluate stem cell-derived “patches” of retinal pigment epithelium (RPE) tissue for implanting into the eyes of animals with age-related macular degeneration (AMD). The patches successfully preserved vision in the animals. The findings were published recently in the Journal of Clinical Investigation.
The researchers’ AI-based validation method used quantitative bright-field absorbance microscopy (QBAM) and deep neural networks (DNNs) to non-invasively predict tissue function and cellular donor identity.
This study demonstrates that AI can be utilized to scale up manufacturing of therapies from induced pluripotent stem cells, which may lead to precise, reproducible measurements of tissue quality.