FDA Publishes Compounding Guidance, but Where Are the Regulations?

By Susan Bizzell and Nicholas Gonzales

Executive Summary

The Food and Drug Administration (“FDA”) released five regulatory and guidance documents pertaining to compounding in an effort to provide clarity to pharmaceutical stakeholders.  The documents, issued pursuant to the Drug Quality and Security Act (“Act”), describe expectations regarding compliance with current good manufacturing practices (“cGMPs”) for compounding outsourcing facilities and standards for compounding pharmacies, request nominations to the lists of bulk drug substances that can be used in compounding in those facilities and propose to update the list of drugs withdrawn from the market for safety or efficacy reasons.


The FDA recently released five documents related to compounding pharmacies and outsourcing facilities pursuant to the Act.  The documents focus on Sections 503A and 503B of the Food, Drug, and Cosmetic Act, which was amended by the Act.  Section 503A places restrictions on compounding pharmacies that generally sell their products to specific patients within a single state.  The Act adds Section 503B that creates “outsourcing facilities,” which do not face the same geographic restrictions as 503A compounding pharmacies but must register with the FDA and meet strict operational requirements.


Section 503A – Compounding Pharmacies

The FDA released two documents pertaining specifically to 503A compounding pharmacies.  One is a final guidance document titled, “Guidance:  Pharmacy Compounding of Human Drug Products under Section 503A of the Federal Food, Drug, and Cosmetic Act.”  When this and the other guidance documents include provisions not currently found in laws and regulations, they are not binding but represent the FDA’s current thinking.  Under this document, drugs compounded in accordance with the Act are exempt from approval, labeling and manufacturing process requirements, although other requirements still apply.  To be eligible for these exemptions, compounded drugs must meet certain requirements.  Among other things, the drug must:

  • Be made by a licensed pharmacist or physician;
  • Be compounded for an identified patient based on a valid prescription or in limited quantities before the receipt of a prescription for such individual patient under certain circumstances;
  • Be compounded in compliance with the United States Pharmacopoeia (“USP”) chapters on compounding using bulk drug substances that comply with the standards of a USP or National Formulary monograph, if one exists.  If a monograph does not exist, the substance must be a component of an FDA-approved drug.  If neither of these circumstances exists, the substance must appear on an FDA list of substances approved for compounding as further explained below (“FDA-Approved List”);
  • Be compounded using approved bulk drug substances;
  • Not be on the list of drugs that have been withdrawn from the market due to safety or efficacy reasons as further explained below; and
  • Not be a drug identified by the FDA as presenting demonstrable difficulties for compounding that demonstrate an adverse effect on the safety or effectiveness of the drug.

Further, the pharmacist or physician must not regularly or in inordinate amounts compound any drug that is a copy of a commercially available drug.  The guidance imposes limits on the distribution of compounded drugs outside of the state in which they are compounded.

The FDA also published in the Federal Register a revised request for nominations to be included in the FDA-Approved List.  The FDA previously called for such nominations but was not satisfied with the responses it received.  The FDA requests that commenters resubmit proposals with very specific supporting evidence for each nominated substance.  Nominations are open until September 30, 2014.

Section 503B – Outsourcing Facilities

Section 503B creates a new category of compounding entities known as “outsourcing facilities.”  These facilities do not need to be licensed as pharmacies by the states in which they operate, but they are required to register with the federal government and abide by applicable laws if they wish to be exempt from approval, labeling requirements and requirements of the Drug Supply Chain Security Act.  Two documents released by the FDA pertain specifically to outsourcing facilities.  One is a draft document titled, “Guidance for Industry:  Current Good Manufacturing Practice – Interim Guidance for Human Compounding Outsourcing Facilities Under Section 503B of the FD&C Act” on which the FDA seeks comments by September 2, 2014.

Drugs compounded within outsourcing facilities must be compounded in accordance with cGMPs.  In the future, the FDA will issue regulations pertaining to cGMPs within these facilities; in the meantime, the draft guidance provides insight into the FDA’s thoughts on the subject and generally requires many strict controls to be maintained throughout the compounding process.

The second document related to outsourcing facilities calls for nominations by September 30, 2014, for the list of bulk drug substances that can be used for compounding within 503B outsourcing facilities and is similar to the call for nominations with respect to 503A facilities described above.

Drugs That Have Been Withdrawn from the Market

The FDA also issued a proposed rule to amend its list of drug products that may not be compounded by 503A and 503B facilities because the drug products have been withdrawn from the market after either the drug product or components were found to be unsafe or ineffective.  Specifically, twenty-five drug products would be added to the list and one product would be modified.  Comments are due by September 2, 2014.


Next Steps

The public has an opportunity to submit comments and potentially influence the final language of four out of five of these proposed rules and the draft guidance documents.  Operators of 503A and 503B facilities should be aware of these proposed rules and guidance documents as they are the best indications we currently have of the FDA’s expectations.

This article was initially published in the Indiana Pharmacist, is educational in nature and is not intended as legal advice.  Always consult your legal counsel with specific legal matters.

Susan Bizzell and Nicholas Gonzales are attorneys with Hall Render.

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Ben Keeton

Publisher at Medical News
Ben is the publisher of Medical News and focuses on the business of healthcare in Kentucky.
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