FDA issued a much needed guidance document addressing compounding by outsourcing facilities for hospitalized patients during the COVID-19 emergency. Like its other recent guidance documents addressing the COVID-19 pandemic, this guidance sets forth FDA’s temporary policy — for compounding certain drug products for hospitalized patients by outsourcing facilities that have registered with FDA under FDCA section 503B (21 U.S.C. § 353b). It will remain in effect for the duration of the emergency or until withdrawn by the Agency.
FDA states that many hospitals are currently “experiencing difficulties accessing FDA-approved drug products used for patients with COVID-19.” Guidance at 3. Because a significant number of cases of individuals suffering from COVID-19 involve hospitalizations, certain FDA-approved drug products may become unavailable. FDA typically addresses drug shortage situations through working with the global supply chain, but due to the “unprecedented disruptions to, and demands on” the supply chain, and in order to better respond to “evolving regional conditions,” FDA asserts that flexibility is needed, on a temporary basis, to ensure that patients received needed treatment when hospitals cannot obtain FDA-approved drugs. Thus,
[a]s a temporary measure during the public health emergency related to COVID-19, or until FDA otherwise withdraws or revises this guidance, FDA does not intend to take action against an outsourcing facility for compounding a drug product that is essentially a copy of an approved drug, for using a bulk drug substance that is not on FDA’s 503B Bulks List, or for not meeting CGMP requirements with regard to product stability testing and the establishment of an expiration date … when all of the [circumstances listed in the guidance] are present.
Guidance at 3-4 (emphasis added).
These circumstances include:
- The compounded drug product appears on the list, attached as Appendix A to the Guidance, of drugs used for hospitalized patients with COVID-19 and contains only one of the active ingredients listed there.
- The compounded drug product is provided directly to a hospital that informs the outsourcing facility it: (i) is treating patients with COVID-19, and (ii) has made reasonable attempts to obtain an FDA-approved drug product containing the same active ingredient for the same route of administration and has been unable to do so. (We recommend that the outsourcing facility maintain documentation of communications concerning the hospital’s “reasonable attempts” to obtain the FDA-approved drug product, although FDA’s guidance does not specifically require such documentation.)
- The bulk drug substances that the outsourcing facility uses to compound the drug product must be in compliance with section 503B(a)(2)(B) through (D), regarding conformance with applicable USP monographs, sourcing from facilities registered with FDA under FDCA section 510, and must be accompanied by certificates of analysis (as is required for any bulk substance used by an outsourcing facility notwithstanding the COVID-19 emergency). For reference, the text of FDCA section 503B is attached here.
- The outsourcing facility’s practices regarding stability testing and expiration dates must meet the conditions for enforcement discretion described in Appendix B to the guidance (Stability/Expiration Dating For Compounded Drug Products) and Appendix C (Conditions Under which FDA Generally Does Not Intend to Take Regulatory Action Regarding Stability Testing and Expiration Date Requirements).
Any outsourcing facility undertaking to compound drug products pursuant to this guidance should pay particular, careful attention not only to FDA’s list of permissible ingredients (Attachment A), but also to the guidance’s details concerning stability testing and expiration dating for products set forth in Attachments B and C.
Because the list of substances in Attachment A may be updated throughout the crisis period, those intending to rely on the guidance for compounding should frequently check Attachment A for additions or deletions to it. As with other guidance, the Agency has published during the public health emergency, the guidance is being implemented immediately, but it remains subject to comment in accordance with the Agency’s good guidance practices. FDA provides the following email address to the extent there are questions concerning the guidance: firstname.lastname@example.org.