The Alliance for Pharmacy Compounding (APC) advocates for the responsible compounding and dispensing of "essentially copies" of FDA-approved drugs by compounding pharmacies when these drugs are listed as "currently in shortage" on the FDA Drug Shortage List, as permitted by FDA guidance. These best practices are specifically designed for 503A state-licensed compounding pharmacies. It is recommended that pharmacies seek legal counsel before compounding copies of FDA-approved drugs in shortage. APC does not guarantee that adherence to these best practices will protect a pharmacy from lawsuits, regulatory citations, or legal actions.
Background
Federal law outlines specific criteria for the active pharmaceutical ingredients (APIs) that may be used in compounded human-health medications. To be eligible for compounding, an API must have an applicable USP or National Formulary monograph, be a component of an FDA-approved product, or appear on the final or interim 503A or 503B Bulks lists published by the FDA. Generally, federal law prohibits the compounding of a medication that is a copy of an FDA-approved drug, with a few important exceptions, including during drug shortages. According to FDA guidance, a compounding pharmacy may prepare "essentially a copy" of an FDA-approved drug when that drug is listed as "currently in shortage" on the FDA drug shortage webpage. This exception is a crucial policy to ensure patients can continue to access necessary drug therapies when any FDA-approved drug is in shortage. Traditional compounding pharmacies have long played a vital role in ensuring the continuation of care by compounding copies of FDA-approved drugs based on patient-specific prescriptions from providers.
Best Practices When Compounding FDA-Approved Drugs Listed in Shortage
Pharmacies should review the FDA Drug Shortage List regularly. A 503A pharmacy may compound a copy of an FDA-approved product while it appears on the FDA Drug Shortage List. The active pharmaceutical ingredient and dosage form of the FDA-approved drug must be listed as "currently in shortage." Pharmacies should check the FDA drug shortage list before preparing a copy of an FDA-approved drug and maintain documentation to demonstrate to regulators that the drug was in shortage at the time it was compounded. For 503B outsourcing facilities, FDA guidance allows a 60-day period to continue compounding an essential copy after the drug comes off the FDA's shortage list. However, it is best practice for 503A pharmacies to cease preparing and dispensing copies of FDA-approved drugs immediately when the drug is removed from the shortage list.
Pharmacies may only source API from state-licensed wholesalers who purchase from FDA-registered manufacturers or order directly from FDA-registered manufacturers. They must verify that the manufacturer is registered with the FDA and that the API meets all the requirements of section 503A. If sourcing API from a new or unfamiliar wholesaler or manufacturer, the pharmacy should send a sample of the API for independent third-party testing of its potency and purity before preparing and dispensing it for the first time. Pharmacies should adhere to USP Chapter <797> testing requirements for sterility, endotoxin, stability, particulate, antimicrobial effectiveness, and container closure integrity studies.
Counseling must be offered to the patient or the patient's agent/caregiver. Providing written information to assist in understanding how to properly use the compounded medication is advised. Instructions should be written in a way that a layperson can understand, especially directions including dosage titrations and conversions between milligrams and milliliters or units. Multi-dose sterile vials should be labeled to be discarded 28 days after puncture. If a medication is to be shipped or delivered, temperature verification studies should be performed to ensure the medication can be kept at the proper temperature throughout the delivery process.
Pharmacies should ensure that physicians or other prescribers understand that for a compounded drug to be dispensed, the prescription must be written for the compounded API. They should make sure prescribers understand that the price of the compounded drug is not a legal basis for prescribing it in lieu of the FDA-approved drug. Like all medications, compounded drugs can only be prescribed in the presence of a valid patient-practitioner relationship and can only be dispensed by a pharmacy after receipt of a valid patient-specific prescription order. Pharmacists have a duty to question prescribers when orders are written in a way that is outside of the normal titration or dosing schedule of a medication.
Pharmacies should never claim or insinuate that any compounded drug is "FDA-approved" or claim to use "FDA-approved ingredients." They should never refer to a compounded preparation as "generic" or use the brand-name or image of the FDA-approved drug in any materials. Pharmacies should never make a direct comparison between a compounded medication and a generic or brand-name manufactured product. They should never make claims of safety or efficacy of the compounded product. Pharmacies should not use photos of the FDA-approved, brand-name product in their marketing. The pharmacy's website and other marketing may highlight accreditations, professional affiliations, testing protocols, patient-reported outcomes data, etc., that demonstrate the pharmacy's commitment to quality. Advertising that patients will or may save money using compounded medications compared to manufactured products is not allowed.
Following these best practices can help keep patients safe as compounders continue to meet the need for medications that are otherwise unavailable due to drug shortages.
MediZap as a corporate patron of APC continues to lobby the FDA and US federal legislators on expanding and improving the ability of real-time data on drug shortages being shared with the agency from sources such as GPO’s (e.g., Vizient and Premier Inc.), as compared to currently Big Pharma. Additionally, extending the time both 503A’s and 503B’s can compound a drug removed from the shortage list to encourage more compounders to support access to drugs that come at a significant cost to compounders to commercialize.