FDA Regulatory News and Trends

Welcome to FDA Regulatory News and Trends, designed to help you identify significant legal developments and navigate the evolving business, legal and regulatory world.

HHS expands monkeypox public health emergency to permit EUAs for diagnostic tests.  On September 7, HHS expanded the August 9 monkeypox public health emergency determination to extend to detection and diagnostic medical countermeasures.  FDA immediately released a guidance document to assist test developers in preparing emergency use authorizations (EUAs) for monkeypox, including template submission requirements and general clinical and analytical testing parameters.  Simultaneously with publishing this guidance on September 8, FDA also issued the first EUA for a monkeypox diagnostic PCR test to Quest Diagnostics Nichols Institute.  As in the early days of the COVID-19 public health emergency in 2020, FDA is permitting test developers to make testing, including laboratory developed tests, available with 30 days notification to FDA, and is requiring that commercial test developers submit an EUA to FDA.  At this time, FDA believes that only lesion swabs are an appropriate specimen type, but the agency is indicating its willingness to consider alternative validated specimen types in consultation with test developers.  We will monitor this closely and report on our experiences as we work with a number of companies to prepare and submit test EUAs to FDA in the coming weeks. 

Retests after negative home COVID-19 tests are recommended. On August 11, the FDA issued a safety communication advising people to perform repeat, or serial, testing following a negative result on any at-home COVID-19 antigen test. If repeat testing is not performed after a negative result, the FDA said, an infection may be missed and people may unknowingly spread the SARS-CoV-2 virus to others, especially if they are not experiencing symptoms. The FDA in fact recommends repeat testing following a negative result whether or not a person has COVID-19 symptoms. “The FDA’s new recommendations for at-home COVID-19 antigen tests underscore the importance of repeat testing after a negative test result in order to increase the chances of detecting an infection. These recommendations are based on sound scientific evidence and a result of the FDA’s collaboration with government and academic partners to assess at-home COVID-19 antigen test performance and ensure public health remains a top priority, particularly as the school season approaches. Throughout the pandemic, we have continued to learn about COVID-19 and the impact of variants on the performance of diagnostic tests designed to detect the virus, and we are committed to keeping the public updated so they can make the most informed health care decisions,” said Jeff Shuren, director of the FDA’s Center for Devices and Radiological Health.

FDA user-fee reauthorization is still not close, and some fear layoffs. Bloomberg News reported September 1 that employees of the FDA’s Center for Drug Evaluation and Research will be the first to get layoff warnings this month if the agency doesn’t hear quickly that congressional leaders are close to an agreement to reauthorize the user fees that help keep the FDA afloat. The fees must be reauthorized every five years, and the current period expires September 30. This must-pass bill has been delayed on Capitol Hill for a number of reasons, including many members’ desires to use it to add new requirements for the agency. FDA watchers say that if the authorization from Congress doesn’t come in time, the agency risks losing key staff who help with medical product reviews as it continues to cope with many ongoing health issues that affect Americans.  DLA Piper’s Alex Pinson and Jamie Gregorian will present critical updates on the FDA user-fee reauthorization process on September 28 at the Biocom Regulatory Affairs Committee Meeting.

Florida sues FDA over Canadian drug import program. On August 31, Florida Governor Ron DeSantis announced that the state is suing the FDA, alleging the agency has delayed Florida’s attempts to import cheaper prescription drugs from Canada. The lawsuit, filed in the US District Court for the Middle District of Florida, claims that for two years, the FDA has held up Florida’s application to start receiving medications to treat diabetes, hepatitis C, HIV and other illnesses from Canada. Florida was the first state in the country to apply for the Canadian drug importation program in November 2020. DeSantis had personally lobbied then-President Donald Trump to give final authorization to the plan that year, which is expected to save Florida residents an estimated $150 million in prescription drug costs annually. DeSantis said at a press conference, “It’s our view that we’ve waited long enough. The clock’s been ticking. We have a right to know what the FDA has been doing the last two years to ensure [whether] they are putting politics over patients [or] putting the interests of Big Pharma over the interests of average Floridians.”

Draft guidance document issued on how to conduct studies during drug development. On August 26, the FDA issued a nonbinding draft guidance document that provides recommendations that are intended to promote a consistent approach in designing, conducting, and interpreting enzyme- or transporter-mediated in vitro and clinical drug-drug interaction (DDI) studies during the development of a drug or other therapeutic product. A consistent approach, the agency said, will reduce uncertainty for the pharmaceutical industry to meet the requirement of multiple regulatory agencies in a variety of nations and lead to more efficient utilization of resources. The draft guidance was prepared under the auspices of the International Council for Harmonisation, including laboratory developed tests.

FDA issues guidance on identification policies for Class I and unclassified medical devices. On July 22, the FDA issued a final guidance titled “Unique Device Identification: Policy Regarding Compliance Dates for Class I and Unclassified Devices, Direct Marking, and Global Unique Device Identification Database Requirements for Certain Devices.” This final guidance includes the FDA’s compliance policy regarding Global Unique Device Identification Database (GUDID) submission requirements for certain Class I devices that are considered consumer health products. A Class I device is one that is considered to present low to moderate risk of patient harm. The guidance also explains that at this point the FDA does not intend to enforce GUDID submission requirements for Class I and unclassified devices, other than implantable, life-supporting, or life-sustaining devices, regardless of whether they are consumer health products, before December 8, 2022. This is a 75-day extension of an existing FDA compliance policy that was published in the July 2020 version of this guidance.

Draft guidance for industry on new oncology review program. On July 22, the FDA issued a draft guidance for industry titled “Real-Time Oncology Review (RTOR).” The purpose of this guidance is to provide recommendations to applicants on the process for submission of selected new drug applications (NDAs) and biologics license applications (BLAs) for review under the FDA’s RTOR program. The FDA Oncology Center of Excellence, in collaboration with its Office of Oncologic Diseases, began the RTOR program in February 2018 to facilitate earlier submission of topline results (in other words, efficacy and safety results from clinical studies before the study report is completed) and datasets, after database lock, to support an earlier start to the FDA application review for drugs and biologics that have a potential action against cancer. The intent of RTOR is to provide FDA reviewers earlier access to data, to identify data quality and potential review issues, and potentially provide early feedback to the applicant, which can allow for a more streamlined and efficient review process.

FDA issues a series of warning letters related to current Good Manufacturing Practice compliance. Common citations include failure to establish and follow written procedures, inadequate supervision, and failure to investigate complaints in a timely fashion.

• On August 19, 2022, FDA issued a Warning Letter to Green Wave Analytical, LLC, a contract testing laboratory in San Diego, California, for blocking inspection and falsely claiming that the firm did not perform cGMP testing of finished drug products or components under contract. The warning letter noted five violations – that the company (1) failed to establish and document test methods; (2) failed to maintain accurate laboratory records; (3) failed to assure that only authorized personnel institute changes in master production and control records; (4) failed to establish a system for monitoring environmental conditions in aseptic processing areas; and (5) failed to establish and give sufficient authority and procedural structure to a quality control unit.
• On August 17, 2022, FDA issued a Warning Letter to Gordon Laboratories Inc., a contract manufacturer of artnaturals Scent Free Hand Sanitizer, based in Carson, California. This warning letter comes after last year’s voluntary recall due to the presence of benzene, acetaldehyde, and acetal contaminants. Earlier this year, FDA inspected the drug manufacturing facility and found the firm (1) failed to investigate the root cause of the benzene, acetal, and acetaldehyde impurities; (2) failed to test samples of each component for identity and conformity; and (3) failed to establish adequate written procedures for production and process control.
• On June 30, 2022, FDA issued a Warning Letter to Bi-Coastal Pharma International, a generics manufacturer based in Shrewsbury, New Jersey, over supervision and quality control issues. According to the Warning letter, the firm (1) failed to establish and follow adequate written procedures describing the handling of all written and oral complaints regarding a drug product; (2) failed to establish adequate written procedures for the quality control unit; and (3) failed to ensure adequate supervision.
• Finally, on July 18, 2022, a Warning Letter for significant deviations from cGMP for active pharmaceutical ingredients (API) was issued to Jost Chemical Co., of St.Louis, Missouri, for “gross mold failure.” The warning letter listed four violations: (1) failure to investigate and resolve quality-related complaints; (2) failure to establish adequate written procedures for cleaning equipment and its release for use in manufacture of API; (3) failure to establish scientifically sound and appropriate test procedures; and (4) failure to ensure data integrity.

FDA approves innovative treatment for a form of psoriasis. On September 1, the FDA approved the first treatment option for generalized pustular psoriasis (GPP) flares in adults. Distinct from the much more common plaque psoriasis, GPP is a rare and potentially life-threatening skin disease characterized by episodes of widespread eruptions of painful, sterile pustules. It is estimated that one out of every 10,000 Americans has the disease. The new drug, called Spevigo, is a novel, selective antibody that blocks the activation of the interleukin-36 receptor, a key part of a signaling pathway within the immune system shown to be involved in GPP. The drug is manufactured by Boehringer Ingelheim and has an orphan drug designation for this indication. The FDA approval comes with certain post-market clinical study requirements.

Marinus Pharmaceuticals’ Ztalmy qualifies for priority review voucher. On September 7, the FDA announced the issuance of a priority review voucher to the sponsor of a rare pediatric disease product application. The Federal Food, Drug, and Cosmetic Act, as amended by the Food and Drug Administration Safety and Innovation Act (FDASIA), authorizes the FDA to award priority review vouchers to sponsors of approved rare pediatric disease product applications that meet certain criteria. The FDA is required to publish notice of the award of the priority review voucher. The agency announced it has determined that Ztalmy (ganaxolone), manufactured by Marinus Pharmaceuticals, Inc., meets the criteria for a priority review voucher. This means, under the FDA’s voucher program, that the company qualifies for a voucher that can be redeemed to receive a priority review of a subsequent marketing application for a different product.

FDA INTERNATIONAL COLLABORATIONS

FDA launches Operation Lascar website.  The FDA has launched a public website in support of Operation Lascar, a pilot initiative between the US and UK started in 2017  that focuses on the movement of illicit FDA-regulated products. Since the initiative was launched, there have been five joint Operation Lascar initiatives with the UK. In addition, Operation Lascar has been responsible for initiating more than 80 new FDA criminal investigations and has identified more than 3,000 violative shipments of illicit medicines intended for the US. In May 2022, the FDA’s Europe Office and the OECD introduced the whole-of-governments approach during a nonpublic meeting with officials from 19 countries, who met again in July 2022 to discuss illicit product transshipments and trends in the EU.  This week, the FDA’s Europe Office and OECD are scheduled to hold a two-day public workshop on September 15 and 16 to discuss this initiative.

Examining the effect of European privacy law on the FDA’s work. On August 9, the FDA’s Office of Global Policy and Strategy published “How a European Data Law Is Impacting FDA,” a “Global Perspective” FDA publication. The article examines how the European Union’s General Data Protection Regulation (GDPR) may be impacting the FDA’s public health activities. The publication explained that the FDA has been closely following the impact of the GDPR on its work. So far, according to the article, the FDA’s bioresearch monitoring program, which oversees the conduct and reporting of FDA-regulated research, has been most affected by the law. Overall, the article finds that the GDPR is an ongoing area of concern to the agency and that the Regulation’s impact will no doubt continue to change as the US and the EU Union continue negotiating a new data agreement and as the overall legal and policy landscape in the EU continues to evolve. The FDA’s Europe Office, the article concluded, will be closely tracking GDPR developments in the months and years ahead.

Agreement with Ecuador on shrimp imports. On August 19, the FDA signed a confidentiality commitment with Ecuador’s Vice Ministry of Aquaculture and Fisheries in Guayaquil, Ecuador. The agreement will allow for the exchange of confidential information, including inspection records, draft rulemaking and guidance, and other non-public documents, between the two countries. According to the FDA, the agreement is an important step in preparing Ecuador for participation in a three-country pilot program designed to ensure the safety of shrimp imported to the United States. In FY 2021 and FY 2022, Congress provided $6 million to develop and implement options for regulating shrimp imports, including imports from the three largest exporting countries by volume over the last three calendar years. Currently, these three countries are India, Ecuador, and Indonesia. The FDA is preparing to evaluate the effectiveness of a new form of arrangement, a Regulatory Partnership, in these countries. The partnership aims to leverage commodity-specific oversight systems– in this case, involving shrimp – along with data and information, to strengthen food safety before and at the port of entry.