The FDA indicated that, under certain conditions, it does not intend to take action for violations of certain federal Food, Drug, and Cosmetic Act (FDC Act) (21 U.S.C. §301 et seq.) provisions regarding new drug approval requirements, labeling with adequate directions for use, and compliance with current good manufacturing practice requirements (CGMP), by state-licensed nuclear pharmacies or federal facilities that compound or repackage radiopharmaceuticals. The agency also indicated conditions under which it will not take action against outsourcing facilities that compound or repackage radiopharmaceuticals for FDC Act violations relative to new drug requirements and labeling with adequate directions for use. The FDA issued two draft guidance documents (one specific to state-licensed nuclear pharmacies and federal facilities, and the other focused on outsourcing facilities) to clarify the agency’s current thinking on this topic. The FDA’s intent in promulgating the two draft guidance documents is to balance the need for patient access to radiopharmaceuticals and the potential risks posed by these drugs. The guidance on state-licensed nuclear pharmacies and federal facilities, when finalized, will supersede the May 1984 guidance on Nuclear Pharmacy Guideline Criteria for Determining When to Register as a Drug Establishment (Notice, 81 FR 96005, December 29, 2016; Notice, 81 FR 96011, December 29, 2016).
Terminology. Radiopharmaceuticals are radioactive sterile and non-sterile drugs used in nuclear medicine procedures to diagnose, monitor, and treat diseases. They are used in diagnostic procedures and for therapeutic purposes. A radiopharmaceutical is considered to be compounded when it is combined, admixed, mixed, diluted, pooled, reconstituted, or otherwise altered to create a drug. An FDA-approved radiopharmaceutical is considered to be repackaged when it is removed from the container in which it was distributed by the original manufacturer and is placed into a different container without further manipulation of the product. Repackaging also includes the act of placing the contents of multiple containers (e.g., vials) of the same finished drug product into one container provided the container does not include any other ingredients.
Compounding and repackaging of radiopharmaceuticals by state-licensed nuclear pharmacies and federal facilities. Under current law, radiopharmaceuticals compounded by entities that are not registered with the FDA as outsourcing facilities, and repackaged radiopharmaceuticals, are subject to all applicable provisions of the FDC Act related to the production of drugs. Congress explicitly excluded radiopharmaceuticals from section 503A of the FDC Act; therefore, compounded radiopharmaceuticals are not eligible for exemption under sections 503A, 505 (new drug approval requirements), 502(f)(1) (labeling with adequate directions for use), and 501(a)(2)(B) (current good manufacturing practice requirements). For example, radiopharmaceuticals are subject to the premarket approval, misbranding, and adulteration provisions of the FDC Act, including sections 505, 502(f)(1), and 501(a)(2)(B). The FDA recognizes that although radiopharmaceuticals are not eligible for exemptions under 503A, there are circumstances in which state-licensed nuclear pharmacies and federal facilities compound or repackage radiopharmaceuticals to meet patient needs. Accordingly, the agency developed a draft guideline to delineate the conditions under which it does not intend to take action against certain FDC Act violations (i.e., sections 505, 502(f)(1), and 501(a)(2)(B)) by state-licensed nuclear pharmacies and federal facilities that are not outsourcing facilities, that compound or repackage radiopharmaceuticals. The draft guideline sets forth the specific conditions in two categories: (1) Radiopharmaceuticals Compounding that Involves Manipulation other than Minor Deviations; and (2) Radiopharmaceutical Compounding that Constitutes Minor Deviations, and Repackaging.
Compounding and repackaging radiopharmaceuticals by outsourcing facilities. The Drug Quality and Security Act of 2013 added a new section 503B to the FDC Act, which established a new category of compounders—outsourcing facilities. Section 503B details the specific conditions under which human drug products compounded by or under direct supervision of a licensed pharmacist in an outsourcing facility may qualify for exemption under sections 502(f)(1) (labeling with adequate directions for use), 505 (drug approval requirements), and 505e (drug supply chain requirements). Outsourcing facilities that compound radiopharmaceuticals are subject to section 503B of the FDC Act. If an outsourcing facility fails to compound a drug in compliance with 503B, none of the outsourcing facility’s compounded drugs, including radiopharmaceuticals and non-radiopharmaceuticals, qualify for 503B exemptions. Section 503B does not apply to pharmaceuticals repackaged by outsourcing facilities. Additionally, repackaged pharmaceuticals are generally not exempted from the provisions of the FDC Act related to the production of drugs, including the premarket approval, misbranding, and adulteration provisions of the Act, including sections 505, 502(f)(1), and 501(a)(2)(B). The draft guidelines outline the specific conditions under which the agency does not intend to penalize violations of the FDC Act relative to new drug approval requirements and labeling with adequate directions for use, by outsourcing facilities that compound and repackage radiopharmaceuticals.
Comment period. The comment period on the FDA’s two draft guidance documents closes in 60 days.
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