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FDA Releases Compounding Guidance


What is regulatory guidance?
Federal agencies release guidance to set forth and describe the agency’s thinking on a particular subject. Guidance may be released by an agency when required by new legislation or when the agency believes it necessary to clarify how it will implement its existing authorities

On Nov. 27, President Barack Obama signed the landmark Drug Quality and Security Act, a law that aims to improve the safety of the U.S. pharmaceutical supply. Title I of the act contains important updates to oversight systems for pharmaceutical compounding, and on Dec. 3, the U.S. Food and Drug Administration, or FDA, released for public comment six guidance and regulatory documents for implementing the new law. These documents:

  • Implement reinstated FDA authority: The Drug Quality and Security Act reinstates Section 503A of the Food, Drug, and Cosmetic Act, which exempts pharmacies engaged in traditional compounding1 from federal regulations applied to drug manufacturing. The enforceability of 503A was called into question by a Supreme Court decision in 2002 that left FDA with little clarity on how to regulate traditional compounding. The recently released guidance explains the reinstated authority in 503A and how FDA will proceed in executing that authority, such as by establishing a list of drugs that are too dangerous to compound. 
  • Define the registration process and interim reporting for outsourcing facilities: The Drug Quality and Security Act creates a category of human drug compounders called outsourcing facilities. These facilities will volunteer to register with FDA, meet more rigorous quality standards, and submit to FDA inspections.2 FDA guidance provides technical instructions regarding facility registration, as well as how outsourcing facilities should report which products they compound—another requirement under the law. Outsourcing facilities will not have to report these products immediately if they register before June 2014.
  • Call for “do not compound” suggestions: FDA has asked for suggestions regarding drug products that “present demonstrable difficulties for compounding.” Due to their complexity, there is a risk that compounding such drugs will result in an unsafe or ineffective product. FDA will review the responses and develop a list of drugs that may not be compounded.
  • Request nominations for bulk substances: Outsourcing facilities will be allowed to compound drugs from bulk drug substances, or active ingredients, if the drugs are in shortage or on a list approved by FDA. The agency is calling for suggestions on what substances to include on that list. In a separate guidance, FDA calls for suggestions for a similar list for traditional compounding pharmacies; these pharmacies, however, are less restricted in their use of bulk drug substances.  

Public responses to the guidance will be accepted in February and March. Detailed information and comment deadlines for each document follow.


Summary of FDA’s Drug Quality and Security Act guidance and regulatory documents

Draft Guidance: Pharmacy Compounding of Human Drug Products Under Section 503A of the Federal Food, Drug, and Cosmetic Act (Docket ID: FDA-2013-D-1444)

Comments due: Feb. 3, 2014

The Drug Quality and Security Act reinstates Section 503A of the Food, Drug, and Cosmetic Act and the authority it grants FDA. This draft guidance describes the requirements of 503A and notes areas where FDA will promulgate further guidance or regulation as part of the full implementation of 503A. Among the notable provisions:

  • Section 503A states that a compounder may use only bulk drug substances that are part of an approved drug application, are described in a United States Pharmacopeial Convention, or USP, monograph, or are on a list set by FDA. The agency issued a proposed list of these bulk drug substances in 1999 but will now reconsider the list. Until FDA promulgates a final rule, compounders should use only bulk drug substances that are components of an approved drug or have a USP monograph.
  • FDA has the authority under Section 503A (as well as the new Section 503B) to establish lists of drug products that present demonstrable difficulties for compounding. The law prohibits compounders from making these products, but this restriction is not enforceable until FDA issues a regulation.
  • Section 503A says that unless a state has a memorandum of understanding with FDA to address the interstate distribution of inordinate amounts of compounded drugs, a pharmacy located in that state may ship only an amount of compounded drugs equal to 5 percent of its total prescriptions out of the state. FDA had released a draft memorandum in 1999 but will reissue a new draft for comment to replace it. FDA will not enforce the 5 percent limit on interstate shipments until 90 days after the agency finalizes the memorandum of understanding and makes it available to the states for consideration and signature.
  • FDA underscores that if a compounding pharmacy violates any of the 503A provisions, the pharmacy ceases to receive its Food, Drug, and Cosmetic Act exemptions and can be cited by FDA for violation of good manufacturing practices,3 provisions on drug approval, and misbranding.
  • FDA will withdraw existing guidance on compounding known as the Compliance Policy Guide, which was released in 2002 when section 503A’s enforceability was called into question by a Supreme Court decision, Thompson v. Western States. FDA will also withdraw an earlier, 1998 guidance.

Draft Guidance: Registration for Human Drug Compounding Outsourcing Facilities Under Section 503B of the Federal Food, Drug, and Cosmetic Act (Docket ID: FDA-2013-N-1429).

Comments due: Feb. 3, 2014

The Drug Quality and Security Act establishes a new, voluntary category of FDA-regulated compounders known as outsourcing facilities that will register with FDA, meet more rigorous quality standards, and submit to FDA inspections that are scheduled to mitigate risks. This draft guidance outlines the registration process for these facilities. Among the notable provisions:

  • FDA has created a new “human drug compounding outsourcing facility” category in its current registration system.
  • FDA will allow compounders to register via email as an interim option.
  • No registration fees will be charged until Oct. 1, 2014.

Draft Guidance: Interim Product Reporting for Human Drug Compounding Outsourcing Facilities Under Section 503B of the Federal Food, Drug, and Cosmetic Act (Docket ID: FDA-2013-N-1428).

Comments due: Feb. 3, 2014

This draft guidance outlines the process for the new category of outsourcing facilities to report to FDA which products they are compounding. Among the notable provisions:

  • Registered outsourcing facilities must report product information upon initial registration and then twice a year (June and December).
  • If a facility registers before June 2, 2014, FDA does not intend to immediately enforce the requirement to report product information as long as the product report is submitted within two months.
  • Until FDA modifies its systems to allow electronic reporting of products, companies should email their lists in a Microsoft Excel file to FDA.

Request for Nominations: Drug Products That Present Demonstrable Difficulties for Compounding Under Sections 503A and 503B of the Federal Food, Drug, and Cosmetic Act (Docket No. FDA-2013-N-1523)  

Nominations due: March 4, 2014

FDA has the authority under sections 503A and 503B of the Food, Drug, and Cosmetic Act to prohibit pharmacists and outsourcing facilities from compounding drug products or categories of drugs that it deems to present demonstrable difficulties for compounding. FDA is requesting nominations for drugs or categories of drugs for inclusion in this list.

Request for Nominations: Bulk Drug Substances That May Be Used to Compound Drug Products in Accordance With Section 503B of the Federal Food, Drug, and Cosmetic Act, Concerning Outsourcing Facilities (Docket No. FDA-2013-N-1524).

Nominations due: March 4, 2014

FDA has the authority under Section 503B to establish a list of bulk drug substances, or active ingredients, that outsourcing facilities may use to compound drugs. Bulk drug substances not on this list may be used to make a drug only if it appears on FDA’s drug shortage list. The agency is requesting nominations for bulk drug substances for inclusion in this list and is asking for information about a nominated substance such as its chemical characteristics, safety, and efficacy, and the clinical need to compound from the bulk substance.

Withdrawal of Proposed Rule and Request for Nominations: Bulk Drug Substances That May Be Used to Compound Drug Products in Accordance With Section 503A of the Federal Food, Drug, and Cosmetic Act (Docket No. FDA-2013-N-1525).

Nominations due: March 4, 2014

FDA has the authority under Section 503A to establish a list of bulk drug substances that are neither the subject of a USP monograph nor components of FDA-approved drugs that may be used to compound drugs. FDA is withdrawing a 1999 proposed rule to list such drug substances and is requesting nominations for a revised list. The agency asks for information about a nominated substance, such as its chemical characteristics, safety, and efficacy.


End notes

1Traditional compounding is a practice in which pharmacists create or adjust a medication for a specific patient need, such as an allergy to an ingredient.
2Inspections are scheduled based on risks, such as a facility’s past compliance issues or the frequency of FDA inspections in the past.
3The term “good manufacturing practices” refers to regulatory standards that ensure proper design, monitoring, and control of manufacturing processes and facilities.

Date added:
Jan 24, 2014

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