FDA Releases Trio of Compounding Guidances Just Days After DQSA Signed into Law


The DQSA contains two sets of measures: One intended to better secure the pharmaceutical supply chain, and the other to more rigorously regulate the compounding pharmacy sector after a series of major lapses in quality.  The legislation creates a voluntary registration system by which compounding facilities can sign up to be inspected by FDA. The hope of legislators is that facilities will have a greater incentive to purchase supplies from these facilities, and in turn incent companies to become registered with FDA in the first place.

The legislation also bans compounders from making “essentially a copy of a marketed and approved drug,” and gives FDA new authority to inspect compounding facilities in accordance with a “risk-based schedule.” Companies, in turn, will be required to report adverse events to FDA.  However, the bill’s compounding provisions mostly leave intact the patchwork of regulations that critics have contended allowed deficient compounding practices to harm patients in the first place. Compounders that continue to operate within state lines will still be regulated by state boards of pharmacy—not FDA.

The bill was signed into law by Obama on Wednesday, 27 November 2013.

New Guidance

The legislation had long been in the works, affording FDA an unusually long lead time to develop guidance. Even then, the release of the guidance just days after the signing of the legislation marks an unusual—perhaps even unprecedented—speed for the agency, which can sometimes take years to release guidance.  The agency has been clamoring for more authority with which to confront the compounders since an October 2011 outbreak of fungal meningitis from a Massachusetts-based compounding pharmacy, the New England Compounding Center (NECC), and the speed may reflect its desire to move forward as quickly as possible.

The three draft guidance documents are relatively short, and cover three distinct topics:

  • who is regulated by Section 503A of the Federal Food, Drug and Cosmetic Act (FD&C Act)
  • who needs to register as an “outsourcing facility” under Section 503B of the FD&C Act
  • interim product reporting by outsourcing facilities and which information must be submitted under Section 503B of the FD&C Act

New Section 503A Provisions

The DQSA removed certain provisions from the statute that the court had found to be unconstitutional, and FDA said it was “necessary to explain FDA’s current thinking with regard to section 503A.”  In Pharmacy Compounding of Human Drug Products Under Section 503A of the Federal Food, Drug, and Cosmetic Act, FDA explains the conditions under which a compounded product must be produced in order to be exempt from other relevant provisions of federal law.

Specifically, the drug must:

  • be made for an individual identified patient based on a valid prescription by a practitioner
  • be made by a licensed pharmacist in a licensed (state or federal) facility or by a licensed individual physician
  • be compounded in compliance with US Pharmacopoeia standards or in compliance with an established monograph or other FDA bulk drug substance list
  • be accompanied by valid certificates of analysis
  • not be a compounded version of a drug that has been withdrawn from the market due to reasons of safety or efficacy
  • not be a product identified by FDA as being unsuitable for compounding
  • not be an exact copy of a commercially available drug product

FDA also said drugs may be compounded in “limited quantities” prior to the receipt of a prescription provided it has historically received valid orders for the product.

Regulators also listed several other statutory provisions which they said have not yet gone into full effect. For example, FDA has not yet finalized a list of products which compounders may not create due to demonstrable difficulties in assuring safety or efficacy. Those provisions will not go into effect until a final rule is promulgated.

Compounded drugs will also be subject to quality standards, and a failure to meet those standards will subject the compounder and its products to regulatory enforcement by FDA and federal authorities. FDA said it will in general employ a risk-based enforcement approach.

An earlier 1998 guidance document on compounding has been withdrawn.

What’s an Outsourcing Facility?

A second draft guidance, Registration for Human Drug Compounding Outsourcing Facilities Under Section 503B of the Federal Food, Drug, and Cosmetic Act, reflects a new category of “outsourcing facilities” under the DQSA.

Such facilities will be inspected by FDA regulators more similarly to traditional (i.e. conventional) pharmaceutical manufacturers. Outsourcing facilities must register with FDA annually between 1 October and 31 December and provide to FDA a list of all products they intend to compound in the next year, and drugs on FDA’s shortage list, and whether they compound sterile drugs or drugs in bulk. In addition, companies need to provide information about the location and mailing address of each facility, as well as a unique facility identifier.

Companies who elect to register should be compounders of sterile drugs, FDA said.

What Needs to be Reported?

A third draft guidance document, Interim Product Reporting for Human Drug Compounding Outsourcing Facilities Under Section 503B of the Federal Food, Drug, and Cosmetic Act, is also intended to outline the requirements for outsourcing facilities. In particular, the guidance clarifies that outsourcing facilities under 503B of the FD&C Act must submit to FDA a list of all drug products compounded by the facility during the previous six-month period. The list must be submitted twice per year, in June and December.

Each submission must contain specific information.

  • the active ingredient and strength of active ingredient per unit
  • the source of the active ingredient (bulk or finished drug)
  • the National Drug Code (NDC) number of the source drug or bulk active ingredient, if available
  • the dosage form and route of administration
  • the package description
  • the number of individual units produced
  • the NDC number of the final product, if assigned

Reports should be made through FDA’s electronic drug registration and listing service in structured product labeling (SPL) format.

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