Multiple regulatory agencies continue to do their part in the fight against COVID-19. This week, the U.S. Drug Enforcement Administration (DEA) and Food and Drug Administration (FDA) and state boards of pharmacy all acted to address shortages of necessary medical supplies and drugs. The Centers for Disease Control and Prevention (CDC) made a substantial change in its advice to the public and now “recommends wearing cloth face coverings in public settings where other social distancing measures are difficult to maintain (e.g., grocery stores and pharmacies) especially in areas of significant community-based transmission.” The face masks recommended for the general public are different from the FDA-cleared face masks and respirators worn by healthcare professionals. In addition, a report issued by the U.S. Department of Health and Human Services Office of Inspector General has set the stage for increased regulatory activity regarding measures aimed at increasing supplies for use in the public health emergency, as there are still severe shortages of testing supplies, widespread shortages of personal protective equipment, shortages of critical supplies and anticipated shortages of ventilators.
In response to reports and letters citing the need for certain controlled substances, used particularly for patients with COVID-19 who are on ventilators, the DEA increased the aggregate production quotas (APQ) for certain controlled substances listed in Schedule II of the Controlled Substances Act and the assessment of annual needs (AAN) for List I chemicals such as ephedrine, pseudoephedrine and phenylpropanolamine. An APQ is the general umbrella-like quota which represents the national need for a substance and is set annually by the DEA. The APQ reflects medical, scientific, research, industrial, export and reserve needs of the United States. The AAN is analogous to the APQ, but the AAN applies to List I chemicals. DEA increased the 2020 APQ by 15% for certain substances needed for the treatment of COVID-19, including fentanyl, morphine, hydromorphone, codeine, ephedrine, pseudoephedrine and certain controlled substance intermediates which are essential to their production. The DEA also increased the APQ for methadone to ensure that opioid treatment programs have enough supplies to treat patients suffering from opioid use disorder.
The DEA also announced that it is increasing the authorized amounts of certain Schedule III and IV controlled substances to be imported into the United States that are necessary for patients on ventilators, including ketamine, diazepam, midazolam, lorazepam and phenobarbital.
These announcements provide the flexibility for DEA registrants like manufacturers and 503B outsourcing facilities to apply for increases to their manufacturing, procurement and import quotas.
The FDA has now placed two additional drugs used for patients with COVID-19 on the FDA drug shortage list. Furosemide, which is a diuretic, and midazolam, a benzodiazepine, were both added to the FDA drug shortage list. Both drugs are critical for patients in the intensive care unit. Placing a drug on the FDA drug shortage list activates statutory safeguards for the nation’s drug supply – FDA-registered 503B outsourcing facilities may now compound essential copies from bulk drug substances of the commercially available products for the duration of time the drugs appear on the FDA drug shortage list. This allows these facilities that operate under the same current good manufacturing practices as drug manufacturers to produce drug products to increase patient access when a drug is in short supply.
Similar to how FDA issued guidance on the Conduct of Clinical Trials of Medical Products during COVID-19 Pandemic, FDA recently released guidance with recommendations for sponsors conducting ongoing studies to support new animal drug development during the COVID-19 public health emergency. In this guidance, FDA discusses what sponsors should do for ongoing studies that may be affected by COVID-19. Options include protocol amendments to modify data collection methods or, if necessary, documentation of protocol deviations. FDA recommends that sponsors consider remote monitoring programs to maintain oversight of clinical sites because remote monitoring is acceptable, as appropriate, to ensure safety for everyone involved in the conduct of the study and to maintain scientific integrity of the data. Early and open communication with the agency may be necessary to continue new animal drug development during the public health emergency.
FDA was busy updating enforcement policy and issuing updated emergency use authorizations (EUAs) for face masks and respirators. FDA revised the Enforcement Policy for Face Masks and Respirators to help expand the availability of general-use face masks for the public and of particulate-filtering facepiece respirators for healthcare professionals during this pandemic. FDA does not intend to object to the distribution, importation and use of respirators identified in the CDC recommendations that are not in compliance with various FDA regulations. FDA also described its approach for issuing EUAs for the decontamination of face masks and filtering facepiece respirators as well as EUAs for face masks intended for a medical purpose, surgical face masks and N95 respirators.
Adding to the growing list of EUAs, FDA issued an EUA for imported non-NIOSH-approved disposable filtering facepiece respirators (FFRs) manufactured in China. As with previously issued EUAs, manufacturers or importers must request that their products be added to the list of authorized products under the EUA. Here, FDA outlined three conditions of eligibility for a disposable non-NIOSH-approved respirator manufactured in China: (1) It is manufactured by an entity that holds one or more NIOSH approvals for other models of FFRs produced in accordance with the applicable standards of authorization in other countries that can be verified by FDA; (2) it has a regulatory authorization under a jurisdiction other than China that can be authenticated and verified by FDA; or (3) it demonstrates acceptable performance with respect to applicable testing standards as documented by test reports from a recognized independent test laboratory that can be verified by FDA. Following this EUA, FDA published a list of authorized imported, non-NIOSH-approved respirators manufactured in China, which includes four manufacturers and more than 10 respirator models.
In step with the issuance of the updated Enforcement Policy for Face Masks and Respirators and the EUA authorizing imported non-NIOSH-approved disposable FFRs manufactured in China, FDA clarified that “the guidance applies to KN95 respirators as well. It explains that for the duration of the pandemic, when FDA-cleared or NIOSH-approved N95 respirators are not available, the FDA generally would not object to the importation and use of respirators without an EUA, including KN95 respirators, if they are on the CDC list of respirator alternatives during the COVID-19 pandemic.” This statement clarifies that an EUA is not necessary for face masks that appear on CDC’s list of respirator alternatives.
FDA also updated the list of authorized ventilators, ventilator tubing connectors and ventilator accessories under the EUA for ventilators, anesthesia gas machines modified for use as ventilators, positive pressure breathing devices modified for use as ventilators, ventilator tubing connectors and ventilator accessories.
Evidencing FDA’s concern not only for patient safety but also for the safety of workers manufacturing medical devices, FDA issued recommendations for medical device manufacturers to protect the health and safety of medical device manufacturing personnel during COVID-19. Among others, these recommendations include implementing basic infection prevention measures, policies and procedures for prompt identification and isolation of sick employees, and regular cleaning and disinfection practices.
Due to fever being a common symptom of COVID-19, FDA issued an Enforcement Policy for Clinical Electronic Thermometers. Typically, manufacturers of clinical electronic thermometers are required to submit a premarket notification to FDA and receive FDA clearance prior to marketing these devices. These devices are regulated as Class II devices with the product code FLL. Like other enforcement policies during COVID-19, this policy allows the distribution and use of clinical electronic thermometers that are not currently 510(k) cleared without compliance to various regulatory requirements. The policy also provides standards and labeling that the devices should adhere to for enforcement discretion.
Two other notable FDA policies are the Enforcement Policy for Infusion Pumps and Accessories During COVID-19 and the Enforcement Policy for Extracorporeal Membrane Oxygenation (ECMO) and Cardiopulmonary Bypass Devices. FDA recognizes that patients infected with COVID-19 may require continuous infusion of medications, nutrition or other fluids. FDA thus is creating flexibility for manufacturers that make device modifications to address manufacturing limitations or supply shortages for infusion pumps and accessories. Similarly, FDA recognizes the importance and utility of increased availability of ECMO devices for patients during COVID-19, as an acute respiratory or cardiopulmonary failure may necessitate long-term extracorporeal membrane oxygenation. FDA therefore does not intend to object to limited modifications to the indications for and design of FDA-cleared or FDA-approved ECMO devices and cardiopulmonary bypass devices listed in the policy.
Consistent with its issuance of policies enabling telemedicine so that healthcare professionals and patients can practice social distancing, FDA issued an Enforcement Policy for Remote Ophthalmic Assessment and Monitoring Devices. This policy describes ophthalmic assessment devices that may be used in telemedicine. Particularly, FDA does not intend to object to limited modifications to the indications for or functionality, hardware or software of certain devices that would enable the practice of telemedicine. Specific devices and modifications are listed in the policy. The devices include visual acuity charts, visual field devices, general-use ophthalmic cameras and tonometers.
Ohio again leads the way, now authorizing a pharmacist, pharmacy intern and certified pharmacy technician to administer FDA-approved COVID-19 diagnostic tests. This move not only will expand testing in Ohio, but it is also a significant step toward advancing the practice of pharmacy.
Like many other states, Arizona is allowing pharmacists and technicians to work remotely. Pharmacies do not need to gain prior approval to implement remote access, nor do they need to have an inspection prior to doing so.
The CDC issued Considerations for Pharmacies during the COVID-19 Pandemic, which is applicable to 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 reduce the risk for customers.
Rapid response in the life sciences and pharmacy sector 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.