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Confusion From the FDA on Compounding

Agency Tries to Expand List of Useable “Bulk Drug Substances”
Stephen Barlas

The efforts of the Food and Drug Administration (FDA) to come up with an expanded list of active ingredients that can be compounded in hospitals and drugstores in the absence of a formal “bulk drug substances” list have come under heavy fire. The agency has been slow to establish the bulk list. In its absence, compounders can use only a limited number of substances. But the agency cracked open a political hornet’s nest in October when it issued a draft guidance policy that allows hospitals and retail drugstores to use additional substances that will be entered on what will be known as List 1.

Compounders can use only substances that meet one of two criteria: 1) they are components of drugs approved under Section 505 of the Federal Food, Drug, and Cosmetic Act, or 2) they are the subject of United States Pharmacopeia (USP) or National Formulary (NF) monographs. That restriction applies to what are referred to as 503A pharmacies regulated by the states, typically retail and hospital pharmacies. Outsourcing facilities, a new type of entity regulated by the FDA that sells bulk products to retail and hospital pharmacies, must comply with additional requirements. These 503B pharmacies have to use substances that meet the two tests above as well as one other: The bulk drug substance must appear on an FDA “clinical needs” or “drug shortage” list.

Here’s where the new controversy comes in. In an interim policy the FDA issued in October 2015, it loosened the requirements for both 503A and 503B facilities by allowing them to use additional bulk substances that meet two conditions.1,2

The conditions are ostensibly being applied to 740 substances that were submitted to the FDA in 2014 for consideration on the bulk list that the FDA was obligated to establish according to the 2013 Drug Quality and Security Act (DQSA). That list has not been created, nor is it likely to be established any time soon. So rather than restrict compounders to substances that meet the “approved by FDA or USP/NF” interim criteria, the FDA decided to take some of those 740 nominees, measure them against the October 2015 expanded criteria, and put them on one of three lists. Substances put on List 1 meet the two “expanded” criteria the FDA announced last October. There are about 60 substances on List 1, which differs somewhat for 503A and 503B facilities. List 2 contains substances that cannot be used because of questions related to safety or efficacy. List 3 has substances still being evaluated.

Pharmacy groups are highly critical of the FDA’s moves, mostly for reasons of process. “Congress made it very clear that FDA must take all bulk drug nominations through its Pharmacy Compounding Advisory Committee (PCAC),” says Dagmar Anderson, Vice President of Communications at the International Academy of Compounding Pharmacists. “This appears to be an additional attempt by the FDA to circumvent congressional intent.”

The 740 nominations were submitted prior to the appointment of a PCAC, which, according to the DQSA, was supposed to have a significant say in any “expanded” list. The first PCAC meeting was held in January 2015. The PCAC voted on 19 of the 740 substances during three meetings in 2015. But the FDA only published its draft guidance with the rules for the three “lists” in October 2015. The PCAC had no role in developing that guidance. It is not clear how many of the 19 substances the PCAC voted on in 2015 were approved for List 1, which has 60 substances on it, or even where those 60 substances came from.

An FDA press spokesman was unable to provide answers to the above questions. Jurgen Venitz, MD, PhD, Vice Chairman of the Department of Pharmaceutics at Virginia Commonwealth University School of Pharmacy and Chairman of the PCAC, did not respond to an email.

Michael Carome, MD, Director of the Public Citizen’s Health Research Group, is a member of the PCAC. Dr. Carome states there are at least 12 substances on List 1 that should be on List 2 because of reasons having to do with either safety or effectiveness, or both. In all 12 instances, either FDA reviewers recommended against putting the substance on the yet-to-be-established bulk list and/or the PCAC concurred. In any case, Dr. Carome believes that List 1 substances should only be allowed to be used for a short period, perhaps six months. There was one compounding industry representative on the PCAC, and his term ended in October 2015. Most of the members of the committee are academics with a clinical pharmacy background or physicians.

The FDA’s justification for creating the new lists is “to avoid unnecessary disruption to patient treatment while the agency considers the bulk drug substances that were nominated with sufficient support to permit FDA to evaluate them and promulgates the regulations required under section 503A.”

“But this justification is substantially outweighed by the public health threat posed by allowing widespread production of unapproved new drugs from these bulk drug substances for many years to come,” Dr. Carome says.

Author bio: 
Mr. Barlas is a freelance writer in Washington, D.C., who covers issues inside the Beltway. Send ideas for topics and your comments to


  1. Food and Drug Administration. Pharmacy Compounding of Human Drug Products Under Section 503A of the Federal Food, Drug, and Cosmetic Act: Guidance. October 26, 2015. Available at: Accessed January 29, 2016.
  2. Food and Drug Administration. Interim Policy on Compounding Using Bulk Drug Substances Under Section 503B of the Federal Food, Drug, and Cosmetic Act: Guidance for Industry (Draft). October 26, 2015. Available at: Accessed January 29, 2016.