Client Alert – FDA Issues Draft Guidance on Bulk Compound Drug Substances

Mar 27, 2018
  • FisherBroyles News
  • Health Care
  • Pharmacy Law

In January of this year, and in response to concerns over the risks associated with the use of non-FDA approved, compounded drugs (particularly in the wake of the 2012 fungal meningitis outbreak that began with contaminated compounded injectable drugs), the U.S. Department of Health and Human Services Food and Drug Administration (FDA) issued a compounding policy priorities plan. The plan set out a number of 2018 actions targeted at compounders, including several planned guidance documents, rules, and a revised draft memorandum of understanding between the FDA and states.

As one of the initial steps in that plan, the FDA has issued a draft version of a Guidance covering drug compounding that is directed primarily at outsourcing facilities and their use of bulk active ingredients. Key provisions of the draft Guidance propose to limit the bulk substances that outsourcing facilities can use in compounding, and directs the FDA to develop a list of bulk drug substances (the “503B Bulks List”) for which there is a clinical need.

The primary focus of the draft Guidance is the FDA’s interpretation of the statutory phrase, “bulk drug substances for which there is a clinical need” and a proposed two-pronged test of what it describes as a clinical need analysis that it will use to determine which bulk substances are placed on the 503B Bulks List.

In regard to its interpretation of “clinical need,” the FDA proposes that outsourcing facilities be limited to compounding drug products using bulk substances that are included in the 503B Bulks List. FDA describes the process broadly as follows:

The first step of the FDA’s analysis involves the agency considering whether attributes of the approved drug may make it unsuitable to treat certain patients for particular conditions – and whether the compounded drug is intended to address that attribute. The FDA also intends to consider whether the drug product to be compounded must be produced from a bulk drug substance rather than an approved drug….

The draft guidance then describes a second step of the clinical-need analysis, which would apply to any bulk drug substances that are components of FDA-approved drugs that proceed through the first step, and to bulk drug substances that are not components of FDA-approved drugs. This analysis consists of a balancing test under which the FDA would weigh certain factors for each substance being proposed for use in a compounded drug product – specifically, its physical and chemical characterization, possible or known safety issues, evidence or lack of thereof of effectiveness, and historical use[i].

A full description of the clinical need analysis is described in III.B.ii of the draft Guidance.

FDA intends to maintain a current list of all bulk drug substances it has evaluated on its website, together with separate lists for bulk drug substances it has placed on the 503B Bulks List and those it has decided not to place on the list.  According to the draft Guidance, “FDA will only place a bulk drug substance on the 503B Bulks List where it has determined there is a clinical need for outsourcing facilities to compound drug products using the bulk drug substance. If a clinical need to compound drug products using the bulk drug substance has not been demonstrated, based on the information submitted by the nominator and the information considered by the Agency, the Agency will not place a substance on the 503B Bulks List.”

The full text of the draft Guidance is available at:

The FisherBroyles Pharmacy and Health Care Law team is pleased to keep you informed of important events related to the pharmaceutical and health care industries. We welcome your questions. Please contact any of the following attorneys:

Brian Dickerson, FisherBroyles Partner
Brian E. Dickerson
[email protected]

Anthony Calamunci, FisherBroyles Partner
Anthony Calamunci
[email protected]

Nicole Waid, FisherBroyles Partner
Nicole Hughes Waid
[email protected]

Amy Butler, FisherBroyles Partner
Amy Butler
[email protected]

I.               [1] Statement from FDA Commissioner Scott Gottlieb, M.D., on a key step in advancing FDA’s oversight of drug compounding and implementing new laws governing outsourcing facilities,

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