SUPPLEMENTARY INFORMATION:

I. Background

FDA is announcing the availability of a guidance for industry entitled “Insanitary Conditions at Compounding Facilities.” ^[1] Under section 501(a)(2)(A) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 351(a)(2)(A)), a drug is adulterated if it has been prepared, packed, or held under insanitary conditions whereby it may have been contaminated with filth or rendered injurious to health. Drug products compounded under insanitary conditions could become contaminated and cause serious adverse events, including death, in patients. Although sections 503A and 503B of the FD&C Act (21 U.S.C. 353a and 353b) provide exemptions for compounded drugs from specified provisions of the FD&C Act if certain conditions are met, neither section provides an exemption from section 501(a)(2)(A) of the FD&C Act. Any drug that is prepared, packed, or held under insanitary conditions is deemed to be adulterated under the FD&C Act, including drugs produced by a compounding facility.

Since the 2012 fungal meningitis outbreak associated with injectable drug products that a pharmacy compounded and shipped to patients and healthcare providers across the country, the Agency has identified insanitary conditions at many of the compounding facilities that it has inspected, and numerous compounders have voluntarily recalled drug products intended to be sterile and also temporarily or permanently ceased sterile operations because of these findings. Generally, State licensed pharmacies do not register with FDA unless they are outsourcing facilities. As a result, the Agency is often not aware of these pharmacies, their conditions and practices, and potential problems with the quality of their drug products. Although FDA does conduct some surveillance inspections, FDA does not inspect the vast majority of State licensed pharmacies in the United States unless, for example, FDA receives a complaint, such as a report of a serious adverse event or product quality issue. FDA does, however, routinely inspect outsourcing facilities registered with FDA.^[2] Regardless of whether a facility is routinely inspected by FDA, it is critical that both State licensed pharmacies and outsourcing facilities identify and remediate, as well as work to prevent, the occurrence of insanitary conditions within their facilities. Because insanitary conditions can result in drug contamination and patient injury, corrective action should be implemented expeditiously in order to prevent the recurrence of such conditions.

In the Federal Register of September 26, 2018 (83 FR 48631), FDA announced the availability of a revised draft guidance for industry entitled “Insanitary Conditions at Compounding Facilities.” The revised draft guidance provided examples of conditions that the Agency has observed at compounding facilities it has inspected and considers to be insanitary conditions. The revised draft guidance also described corrective actions that compounding facilities should take when they identify such conditions and the regulatory actions FDA may take in response to identified insanitary conditions.

FDA received comments on the revised draft guidance from various ( printed page 71350) stakeholders ( e.g., physicians, pharmacies, outsourcing facilities). Several comments were submitted concerning the implications of the policies described in the revised draft guidance for physicians who compound or repackage drug products or mix, dilute, or repackage FDA-licensed biological products in their offices. In response to these comments, FDA made changes, where appropriate, in the final guidance. The changes include adding a footnote to state that “processing of beta-lactams” does not refer to mixing, reconstituting, or other such acts that are performed in accordance with the directions contained in FDA-approved labeling; adding a footnote to reflect that the FDA does not generally object to rapid movement temporary blocking or disruption of first air in the ISO 5 area when necessary for the safe handling of radiopharmaceuticals to minimize radiation exposure, and revising the language in a footnote concerning the scope of physician compounding or repackaging activities to state that FDA generally does not intend to take action under section 501(a)(2)(A) of the FD&C Act against a physician who is compounding a drug product, repackaging an FDA-approved drug product, or who is mixing, diluting, or repackaging an FDA-licensed biological product, provided that it occurs in the physician's office for in-office administration to the physician's patients; and adding recommendations encouraging compounders to use risk evaluation strategies and risk management tools to develop appropriate controls necessary to prevent the occurrence of insanitary conditions at their facilities. In addition, editorial changes were made to the guidance for clarity.

This guidance is being issued consistent with FDA's good guidance practices regulation (21 CFR 10.115). The guidance represents the current thinking of FDA on “Insanitary Conditions at Compounding Facilities.” The examples described in the final guidance do not constitute an exhaustive list of conditions FDA considers to be insanitary conditions. It does not establish any rights for any person and is not binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations.

II. Paperwork Reduction Act of 1995

This guidance contains no collection of information. Therefore, clearance by the Office of Management and Budget (OMB) under the Paperwork Reduction Act of 1995 (PRA) (44 U.S.C. 3501-3521) is not required.

However, this guidance refers to a previously approved FDA collection of information. This collection of information is subject to review by OMB under the PRA. The collections of information in 21 CFR part 7 pertaining to FDA's recall regulations have been approved under OMB control number 0910-0249.

III. Electronic Access

Persons with access to the internet may obtain the guidance at either https://www.fda.gov/​Drugs/​GuidanceComplianceRegulatoryInformation/​Guidances/​default.htm or https://www.regulations.gov.