Last week FDA published a much needed guidance document addressing compounding by outsourcing facilities of shortage medications for patients confined to hospitals. Yesterday FDA took an unprecedented step (see Section 503A guidance) and recognized, during the COVID emergency (or until FDA withdraws the policy), Section 503A compounders may compound certain identified shortage medications for patients in hospitals without a prescription for an individually identified patient. Section 503A has always permitted compounders to compound copies of shortage medications (which are not, by definition, “essential copies” of commercially available drug products). Never before has FDA permitted Section 503A pharmacies to compound such medications for so-called “office use.” There are some important caveats, however, to what seems like a generous policy during this unprecedented and critical time.
FDA does not intend to take action against a Section 503A pharmacy for compounding a shortage medication, or for providing a drug to a hospital without obtaining a patient-specific prescription, if all of the circumstances in the guidance are present (and the other conditions of Section 503A are met).
Some important highlights: (1) The hospital must attempt to first obtain the product from an outsourcing facility; (2) if the hospital and pharmacy are not owned or controlled by the same entity, the pharmacy must note the COVID emergency on the order, and must request and obtain from the hospital within one month the “records” of the patients for whom the products are used (state law permitting); and (3) pharmacies must pay particular attention to some the very short beyond use dates set forth in the guidance (that are inclusive of any sterility tests) (Attachment B).
Thus, FDA is not “dispensing” altogether with the prescription/order requirement; instead, it is permitting pharmacies not affiliated with a hospital to obtain patient information “later.” Although FDA has not permitted this in the past (although compounders have both requested and engaged in obtaining patient names “after the fact”), one does wonder whether this limitation is necessary to “protect” patients right now (given the other limitations such as short beyond use dating).
FDA’s conditions under this temporary policy include the following:
- The compounded drug product must appear on the Appendix A list and contain only one of the active ingredients listed there.
- The compounded drug is provided directly to a hospital, which informs the pharmacy that:
- The hospital is treating patients with COVID-19; and
- The hospital has made reasonable attempts and has not been able to obtain:
- Adequate supplies of an FDA-approved drug product containing the same active ingredient for the same route of administration, and
- Adequate supplies of a product made by an outsourcing facility containing the same active ingredient for the same route of administration.
- The compounded drug product is labeled with a default beyond-use-date (BUD) in accordance with the table in Appendix B, except that the pharmacy uses a shorter BUD:
- If literature/scientific information, or commercially available product labeling for a similar drug indicates that the drug product may not be physiochemically stable for the duration of the default BUD period, in which case the pharmacy uses such shorter BUD, or
- If the pharmacy has been unable to obtain a sufficient supply of personal protective equipment (PPE) that it typically relies on to assure compliance with the insanitary condition provision in the FD&C Act (or PPE that is equivalent or better), in which case the pharmacy applies BUDs of 24 hours for products stored at room temperature and 3 days for products stored refrigerated. (See guidance for PPE and compounding here)
- If the pharmacy and hospital are not owned/controlled by the same entity, the pharmacy: (1) marks the order with a notation indicating that the drug is provided to the hospital to treat patients during the COVID-19 public health emergency; and (2) requests that the hospital provide, to the extent allowed by applicable laws, the records that identify the patients to whom the drugs were administered and document such request within one month of sending the compounded drug to the hospital.
- Before providing the drug product to the hospital, a State-licensed pharmacy notifies the following State authorities, and the State authorities inform the pharmacy that they do not object:
- The State authority that regulates pharmacy compounding in the State where the pharmacy is located, and,
- If different, the State authority that regulates pharmacy compounding in the State where the hospital is located.
The following substances – products that are aqueous solutions for injection (like the Section 503B limitation) – may be used in compounding (see Appendix A). Compounders should check the list frequently for additions or subtractions to the list.
- Cisatracurium besylate
- Dexmedetomidine hydrochloride
- Fentanyl citrate
- Hydromorphone hydrochloride
- Ketamine hydrochloride
- Midazolam hydrochloride
- Norepinephrine bitartrate
- Rocuronium bromide
- Vancomycin hydrochloride
- Vecuronium bromide
Note that compounders (under Sections 503A and 503B) are always permitted per the relevant statutory sections to compound drug products on FDA’s published shortage list because those listed products are not “commercially available.” The big difference here is FDA’s temporary waiver of the prescription requirement for Section 503A pharmacies, under the specific conditions listed in the guidance.