With COVID-19 cases on the rise in the United States, some hospitals have faced shortages of FDA-approved drug products used to treat the disease. To fill that gap, the FDA recently announced a “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,” which enables state-licensed compounding pharmacies (aka 503A pharmacies) to compound these needed medications.
Under the Federal Food, Drug, and Cosmetic Act (FD&C Act), state-licensed pharmacies that have not registered as outsourcing facilities under section 503B of the FD&C Act may not compound drugs that are essentially copies of commercially available drugs, and also may not compound a drug for a hospital without first obtaining a patient-specific prescription. In the Temporary Policy, the FDA relaxed these prohibitions by stating it will not take action against state-licensed pharmacies that compound a limited number of commercially available drugs (listed in Appendix A of the Temporary Policy) needed to fight COVID-19 so long as those pharmacies comply with certain requirements.
This Temporary Policy provides an excellent opportunity for both hospitals (to access difficult-to-find drugs) and pharmacies (to fill this-much needed gap), but it also creates risk for both sets of facilities. Below are four things every hospital and compounding pharmacy should know before engaging in compounding under the Temporary Policy, including risk mitigation strategies.
Hospitals must exhaust other options before using state-licensed compounding pharmacies.
The Temporary Policy permits 503A pharmacies to compound drugs for hospitalized patients, but the guidance makes clear the FDA is not providing a full-throated endorsement of hospitals' using such facilities. The FDA recommends that hospitals first try to obtain FDA-approved drugs through manufacturers. If that is not possible, the FDA recommends hospitals next turn to outsourcing facilities that are “subject to more robust quality standards” than state-licensed pharmacies (i.e., 503A pharmacies). In fact, the Temporary Policy does not permit a state-licensed pharmacy to compound drugs for a hospital unless and until the hospital states that it first made “reasonable attempts” to obtain the drugs from a manufacturer and outsourcing facility.
Recommendations
Hospitals should document their unsuccessful efforts to obtain the drugs before ordering them from a compounding pharmacy. This should include, at a minimum, documenting communications with manufacturers/distributors and outsourcing facilities and maintaining copies of rejected invoices and/or website or other notifications indicating the drugs are not available.
Pharmacies should insist that, prior to any order, a hospital state, in writing, that (1) it is treating COVID-19 patients and (2) it has made reasonable attempts to obtain the drugs from FDA-approved sources and outsourcing facilities, and that those attempts were not successful.
The Temporary Policy does not completely eliminate the requirement that state-licensed pharmacies compound drugs for specific patients.
The Temporary Policy states that the FDA will not take action against a state-licensed pharmacy that provides a drug to a hospital without first obtaining a patient-specific prescription (as required by section 503A(a) of the FD&C Act). However, the pharmacy must still request that the hospital identify the patients to whom the drugs are administered within one month of the order. When sending the drugs, the pharmacy must also make a notation indicating that the drugs have been provided to treat patients during the COVID-19 public health emergency.
[NOTE – These requirements do not apply when the hospital and the pharmacy have common ownership.]
Recommendations
Hospitals should ensure that they have sufficient processes in place to track the movement of the compounded drugs and identify which patients receive them. Depending on a hospital's medication management system, a best practice will likely include segregating the drugs received from a compounding pharmacy in the hospital's own storage cabinet or area. Failure to provide information to pharmacies about the patients who received the drugs could result in sanctions (though the FDA does not identify any in the Temporary Policy) or other exposure/liability, especially if a hospital has any indemnification obligations to the pharmacy or if the hospital promises to provide the information but does not.
Pharmacies should, at the time the order is sent, make a request in writing that the hospital identify the patients who receive the drugs. This request should include, at a minimum, (1) a clear request for the patient names, (2) a clear request for records sufficient to identify the patients, (3) a date and time stamp, and (4) a deadline for receipt of the requested information that is one month from the date the order is sent. To ensure that hospitals comply, pharmacies should provide a secure way for the hospital to send the records, and should also follow up with any hospitals that have not provided sufficient documentation one week before the documentation is due.
State authorities must weigh in before a pharmacy can provide compounded drugs.
Before a pharmacy may provide a compounded drug to a hospital, it must first notify appropriate state authorities of the compounding activities, and those state authorities must provide notices that they do not object to the pharmacy's compounding and providing the drug. Specifically, the pharmacy must notify and get permission from the authority that regulates pharmacy compounding in both the state in which the pharmacy is located and the state in which the hospital is located.
Recommendations
Hospitals should request that the pharmacy provide evidence that it has submitted this notice to the state authorities and received the requisite non-opposition(s). Although these obligations are imposed on the pharmacy and not the hospital, a hospital should not accept an order from a pharmacy that has not fully complied with this process.
Pharmacies should reach out to the necessary state authorities immediately upon being contacted by a hospital for such an order so that the authorities have sufficient time to respond. (It goes without saying that the pharmacy should not send the order without first receiving a response from the state authorities). A pharmacy's notice to a state authority should, at a minimum, (1) list the specific drug products and volume that the hospital has requested, (2) make clear that it intends to provide the drugs without first obtaining patient-specific prescriptions pursuant to the FDA's Temporary Policy, and (3) explicitly request that the authority provide its non-opposition in writing. When the hospital is located in a different state than the pharmacy, the pharmacy should consult the pharmacy laws and regulations in that state to learn any local requirements.
Drug products compounded under the Temporary Policy must be used quickly.
The Temporary Policy requires compounding pharmacies to assign shorter-than-usual Beyond-Use-Dates (BUDs) to the drugs they compound. Appendix B to the Temporary Policy provides BUDs ranging from four to 22 days based on how the drug was processed/sterilized and whether it was subjected to a sterility test. However, the Temporary Policy requires the pharmacy to label the drug with an even shorter BUD if (1) literature or scientific information indicates that the drug may not be physicochemically stable for the duration of the BUD in Appendix B (in which case, the shorter BUD from the literature must be used) or (2) if the pharmacy does not have a sufficient supply of personal protective equipment and is, therefore, compounding pursuant to the FDA's “Temporary Policy Regarding Non-Standard PPE Practices for Sterile Compounding” (in which case, the BUD must be 24 hours for products stored at room temperature and three days for products stored in refrigeration).
Recommendations
Hospitals should ask for, in writing, the compounding pharmacy's basis for the BUD that appears on the drug product. If the BUD is 24 hours or three days because the compounding pharmacy is low on PPE and operating under the FDA's Non-Standard PPE Practices, the hospital should engage in further follow-up with the pharmacy to ensure the aseptic processing and disinfecting practices they are using are sufficient to justify confidence in the sterility of the drugs.
Pharmacies should maintain files containing all of the documentation that justifies the BUDs they affix to the drugs. This documentation should include, at a minimum, (1) a copy of Appendix B to the Temporary Policy, as it existed at the time the drugs are sent; (2) copies of any articles, literature or other information concerning the drugs' stability on which the pharmacy relied in determining the BUD; and (3) in the event the pharmacy is compounding pursuant to the FDA's Non-Standard PPE Practices, documentation of compliance with that policy (e.g., more frequent cleaning logs, expanded environmental monitoring, etc.).
Originally published 4/23/2020
The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances.
