With this update, we have covered and provided Food and Drug Administration (FDA), Drug Enforcement Administration (DEA), and state boards of pharmacy actions related to COVID-19 for more than one month. This update will provide our usual summary of recent actions as well as highlight some trends observed from the regulatory agencies over the past month.

DEA

The DEA continues to allow flexibility regarding controlled substances to ensure providers have the necessary medications available to treat patients. For the duration of the public health emergency, the DEA is allowing DEA-registered hospitals and clinics to handle controlled substances at satellite hospitals and clinics that are nonregistered locations. Additionally, the DEA is allowing distributors to ship controlled substances directly to these satellite hospitals and clinics, even though they are nonregistered locations.

The DEA also provided an exception to the “five percent rule.” For the duration of the public health emergency, “A DEA-registered practitioner that complies fully with all other requirements of 21 CFR 1307.11 may now distribute controlled substances beyond five percent of the total number of dosage units of controlled substances distributed and dispensed during the same calendar year without being required to register as a distributor in order to make such distributions.” This means that under certain circumstances, hospitals, pharmacies or physicians may distribute controlled substances among one another.

Trending from the DEA is the continued flexibility it is providing in response to the extraordinary circumstances resulting from COVID-19.

HHS

Despite one leading senator’s characterization of pharmacists as not medical professionals, which was later walked backed, the U.S. Department of Health and Humans Services (HHS) recognized that “[p]harmacists are trusted healthcare professionals with established relationships with their patients” when it authorized “licensed pharmacists to order and administer COVID-19 tests, including serology tests, that the FDA has authorized.” With this authorization, pharmacists qualify as ‘covered persons’ under the Public Readiness and Emergency Preparedness Act (PREP Act) and may receive immunity under the PREP Act with respect to all claims for loss caused by, arising out of, relating to or resulting from the administration or use of FDA-authorized COVID-19 tests. Whether a pharmacist can order and administer COVID-19 tests, of course, is dependent on the state’s pharmacy scope of practice.

FDA

FDA Warnings

The FDA has issued an astounding 34 warning letters related to COVID-19 since March 6. Warning letters have focused on unapproved and misbranded products related to COVID-19. As of April 20, there is no FDA-approved therapeutic for the treatment of COVID-19. FDA warning letters have originated from the FDA’s review of website, social media accounts and labels. Products that have been subject to FDA warning letters include CBD products, homeopathic drug products, antiviral drug products, essential oils, beverage concentrates, hemp products and an industrial bleach promoted by a church. The FDA often has included a 48-hour time frame within which the firm receiving the warning letter must respond. Before marketing any product related to COVID-19, firms should carefully review the requirements found in the Food, Drug, and Cosmetic Act, specifically regarding new drug approval and misbranding provisions.

Diagnostics and Serological Tests

Diagnostic tests diagnose whether a patient is positive for the SARS-CoV-2 virus, which causes a COVID-19 infection. Serological tests help identify individuals who have developed an immune response to the virus. The FDA clarified the difference between the two tests in its letter to healthcare providers. As of April 17, more than 100 laboratories have notified FDA that they have validated their own COVID-19 test and have started patient testing. Additionally, eight commercial manufacturers have notified the FDA that they have validated and are distributing test kits under the Policy for Diagnostic Tests for Coronavirus Disease-2019 during the Public Health Emergency. Thirteen laboratories have notified the FDA that they have validated and are offering serology tests, but the FDA has not yet authorized any serology laboratory test. So far, 97 manufacturers have notified the FDA that they have validated and are offering serology tests, but the FDA has authorized only two serology tests. The most up-to-date information on diagnostics and serology testing is available on FDA’s FAQs on Diagnostic Testing for SARS-CoV-2.

Drugs

Just in the past two weeks, six drugs identified by HHS as priority drugs used in COVID-19 patients have been added to the FDA drug shortage list: azithromycin tablets, propofol injectable emulsion, dexmedetomidine injection, etomidate injection, midazolam injection and cisatracurium besylate injection. The FDA drug shortage list now includes almost twenty drugs commonly used in an intensive care unit (ICU) that are identified by the FDA as being in shortage.

In response to a number of reports related to increased demand and supply interruptions involving FDA-approved drug products used in the treatment of hospitalized patients with COVID-19, the FDA issued the Temporary Policy for Compounding of Certain Drugs for Hospitalized Patients by Outsourcing Facilities During the COVID-19 Public Health Emergency. In this policy, the FDA outlines conditions under which it does not intend to take action against an FDA-registered 503B outsourcing facility for compounding a drug product that is essentially a copy of an approved drug, for using a bulk drug substance that is not on the FDA’s 503B Bulk Drug Substances List or for not meeting current good manufacturing practice (CGMP) requirements with regard to product stability testing. All requirements of the policy must be met for the outsourcing facility to receive enforcement discretion, most notably that the compounded drug product must be listed in the appendix to the policy. However, the policy does not preclude an outsourcing facility from following typical 503B CGMP requirements to provide extended dating based on stability testing.

In a similar response for compounded drugs, the FDA issued the Temporary Policy for Compounding of Certain Drugs for Hospitalized Patients by Pharmacy Compounders not Registered as Outsourcing Facilities During the COVID-19 Public Health Emergency. Under this temporary policy, pharmacies may compound a drug that is essentially a copy of a commercially available drug or provide a drug to a hospital without obtaining a patient-specific prescription if all conditions of the policy are followed. Like the policy for outsourcing facilities, the policy for pharmacy compounders requires that the compounded drug product be listed in the appendix to the policy. Currently, the list of drugs is identical for both the outsourcing facility policy and the pharmacy compounder policy. One condition for pharmacy compounders is that they must be informed by the hospital it is providing the drug to that the hospital has made reasonable attempts to obtain and has not been able to obtain adequate supplies of both an FDA-approved drug product and a drug product made by an outsourcing facility containing the same active ingredient for the same route of administration. The beyond-use dates that pharmacy compounders may label product with are shorter than the beyond-use dates FDA-registered outsourcing facilities may label product with. Pharmacy compounders also must notify and receive permission from the state authority that regulates pharmacy compounding in the state where the pharmacy is located, and if the hospital the pharmacy is supplying compounded drug product to is located in a different state, then the state authority that regulates compounding in the state where the hospital is located also must be informed and must provide notice to the pharmacy that it does not object to the practice.

Continuing its efforts to increase the drug supply, the FDA also issued product-specific guidances for the generic drug development of chloroquine phosphate and hydroxychloroquine sulfate.

Clinical Trial Guidance

The FDA updated the Question-and-Answer Appendix in the Guidance on Conduct of Clinical Trials of Medical Products During the COVID-19 Public Health Emergency. Previously, the FDA addressed submitting protocol amendments, documenting protocol deviations, initiating virtual clinical trial visits for monitoring patients, making changes to ship investigational products directly to patients, and obtaining and documenting informed consent from patients in isolation due to COVID-19. This update includes new content on conducting remote clinician-reported outcome or performance outcome assessments; remote site monitoring; electronic common technical document requirements; investigational product administration by a local healthcare provider that is not a subinvestigator; and information for sponsors on whom they should contact at the FDA regarding certain changes to ongoing trials. Updates also include information on obtaining informed consent from a patient who is unable to travel to the clinical trial site due to COVID-19 illness or travel restrictions.

State Boards

The Centers for Disease Control and Prevention (CDC) updated its considerations for pharmacies during the COVID-19 pandemic, which are applicable and should be used as guidance for pharmacies in all states. The guidance is intended for pharmacy staff to minimize their risk of exposure to the virus and to reduce the risk to customers. Updates include that everyone entering the pharmacy should wear a face covering, regardless of symptoms. Pharmacists and pharmacy technicians always should wear a face mask for source control while they are in the pharmacy. Additionally, the CDC is recommending that pharmacies reschedule or postpone routine clinical preventive services that require face-to-face encounters, such as adult immunizations.

The California Board of Pharmacy compiled a resource for sources of compounded products in high demand due to COVID-19 and drug shortages. The list includes California-licensed outsourcing facilities and compounded preparations that may be available from the facilities. California also issued additional pharmacy law waivers. California is now extending the reassessment/revalidation/reevaluation requirements for sterile compounding staff competencies up to an additional 90 days.

Ohio updated its emergency rules for the dispensing of chloroquine and hydroxychloroquine. For those patients on chloroquine or hydroxychloroquine discharged from inpatient treatment for COVID-19 and those discharged from an emergency department for a probable COVID-19 diagnosis, the prescription is limited to no more than a seven-day supply, with zero refills. Urgent care facilities are not included in the definition of an emergency department under the emergency rule. Additionally, Ohio issued guidance on drug shortages, this guidance includes a discussion of the difference between outsourcing facilities and Ohio compounding pharmacies. The guidance also notes the Ohio provision for occasional wholesale sales, which “permits any terminal distributor (not just pharmacies) to engage in the sale (even a no-cost sale) of dangerous drugs that are on the FDA’s drug shortage list. This allows the purchase of drugs in shortage from non-pharmacy licensees such as EMS agencies, ambulatory surgical centers, clinics.”

Pennsylvania responded to HHS’s authorization of pharmacists to order and administer COVID-19 tests. The Pennsylvania Board of Pharmacy provided a waiver for pharmacists to order and administer COVID-19 tests. Specifically, “[t]here is nothing in the Pharmacy Act or the Board’s regulations that prohibits pharmacists from ordering and administering tests. A pharmacist is a healthcare practitioner who may administer tests if administration of the test is delegated by a medical doctor. Therefore, for the purposes of preparing for and mitigating any effect of COVID-19 testing, licensed pharmacy practitioners are granted the requisite authority needed to carry out end-to-end COVID-19 testing, including but not limited to: ordering; testing; and communicating results.”

Takeaways

Rapid response in the life sciences and pharmacy sectors continues to occur at both the federal and state levels to address the threat of the new coronavirus. We expect to see continued activity in this space and will keep you updated as we become aware of developments.