Compounding
Rachel Balick
Hospital and community compounding pharmacists will have more flexibility thanks to FDA guidances aimed at easing drug shortages during the COVID-19 pandemic. In five guidances released over 6 weeks, the agency announced that it will use discretion in enforcing certain standards for 503A and 503B compounding.
Pharmacists who qualify as 503A compounders under the Federal Food, Drug, and Cosmetic (FD&C) Act are state-licensed pharmacists, licensed physicians, or federal facilities that compound drugs that do not require new drug applications and are exempt from current good manufacturing processes (CGMP). These facilities are limited to dispensing compounded products for home use and are not allowed to compound large batches.
Compounding facilities that fall under the 503B section of the FD&C Act manufacture larger batches of compounding products with or without prescriptions to be sold to health care facilities for office use. Those that provide patient-specific medications are held to higher regulatory standards. These facilities are required to maintain full compliance with CGMP.
Enforcement discretion
Among the most notable of FDA’s clarifications is that medications on the agency’s drug shortage list are effectively considered “not commercially available,” freeing 503A and 503B compounding facilities from limits on compounding drugs that are “essentially a copy” of a product already available on the market. That means a compounding pharmacist could copy an otherwise commercially available drug, as long as it is for a specific patient or meets other conditions.
Compounders must meet other conditions to benefit from the enforcement discretion in the guidances. These include proscribed record keeping, limited beyond-use dates, and limiting affected compounding to drugs listed under Appendices A of both the 503A and 503B guidances (see sidebar). In addition, pharmacies must notify their state boards of pharmacy, and, if different, the hospital’s state board, and the board must not object.
Non-outsourcing compounders
April 10 temporary guidance focused on the use of nonstandard personal protective equipment (PPE) for 503A sterile compounders. FDA said it will not take action on what would normally be considered “insanitary conditions,” as long as compounders employ and document mitigation strategies to avoid product contamination, as well as keep records of when products were compounded without standard PPE and when sterilization approaches change. Mitigation strategies include use of expired PPE that is not visibly damaged or soiled and reuse of disinfected masks and gloves.
Additional temporary guidance granted flexibility for pharmacists to compound certain necessary medications under 503A for nonspecific patients hospitalized due to COVID-19. View the guidance at https://apha.us/TempGuidance.
FDA also announced it does not intend to take action if a 503A facility fills orders for a compounded drug that is essentially a copy of an approved drug that has been discontinued and is no longer marketed.
Outsourcing compounders
Temporary FDA guidance granted enforcement flexibility for 503B outsourcing facilities that compound drugs in shortage for patients hospitalized during the COVID-19 public health emergency. View that guidance at https://apha.us/OutsourcingGuidance.
In addition to using enforcement discretion of “essentially a copy,” guidance also states that FDA will use discretion on requirements on 503B bulks lists and stability studies. Hospitals must attempt to obtain FDA-approved drugs before turning to 503B compounders, and compounded products must have a 28-day beyond-use date.
Shortages
Drugs in shortage vary widely across states and regions, as many drugs are being diverted to areas that are harder hit by COVID-19. I.V. drugs used to maintain patients on ventilators, such as midazolam and propofol, are particularly affected by supply chain disruptions related to the pandemic. View FDA’s list of drugs in shortage at https://apha.us/DrugsInShortage.
Pharmacists and others affected by shortages can report them to FDA at drugshortages@fda.hhs.gov.