- 21 CFR Part 212, titled Current Good Manufacturing Practice for Positron Emission Tomography Drugs, is a specialized section of the U.S. Food and Drug Administration’s (FDA) regulations that outlines the Good Manufacturing Practice (CGMP) requirements specifically for the production of Positron Emission Tomography (PET) drugs. PET drugs are radiopharmaceuticals used in medical imaging procedures, particularly for diagnosing and monitoring diseases such as cancer, neurological disorders, and cardiovascular conditions. Due to the unique nature of PET drugs—including their short half-lives, small batch sizes, and on-demand manufacturing—the FDA recognized the need for a tailored set of GMP standards distinct from those for conventional pharmaceutical products.
- The purpose of Part 212 is to ensure that PET drugs are produced in a manner that guarantees their safety, identity, strength, quality, and purity. The regulation became effective in December 2011 and applies to all PET drug manufacturers, including hospital-based or academic PET centers and commercial PET drug producers. It is designed to be practical and flexible while maintaining essential quality standards, acknowledging that PET drugs are often made in small quantities and administered to patients within minutes or hours of production.
- Part 212 is structured to cover the key elements of pharmaceutical manufacturing, adapted for the PET environment. It mandates that facilities have an effective quality assurance system that includes procedures for preventing contamination, ensuring proper labeling, and maintaining batch consistency. Personnel involved in PET drug production must be adequately trained and qualified, and written standard operating procedures (SOPs) must be established for all critical operations.
- The regulation includes provisions for quality control testing, requiring that each batch of PET drug be tested for identity, strength, purity, and quality before it is released for patient use—unless certain conditions for parametric release are met, such as validated sterilization processes. Given the extremely short half-lives of some PET drugs (e.g., fluorine-18 or carbon-11), the regulation allows for release prior to completion of sterility testing, provided that the batch is manufactured under strict aseptic conditions and that sterility test results are reviewed retrospectively.
- Recordkeeping is also a major component of 21 CFR Part 212. Manufacturers must maintain accurate and complete records for each batch, including production logs, equipment calibration records, and quality control data. These records must be retained for at least one year after the expiration date of the drug, or for three years if no expiration date is provided.
- Part 212 also outlines requirements for equipment, facilities, and materials. Equipment must be suitable for its intended use and properly cleaned and maintained. Facilities must be designed to prevent contamination and cross-contamination, with designated areas for radioactive and non-radioactive components. Materials used in production must be clearly identified, tested, and stored under appropriate conditions.
- Importantly, 21 CFR Part 212 distinguishes itself from traditional GMP regulations found in Parts 210 and 211 by offering a risk-based and streamlined approach appropriate for the scale and immediacy of PET drug production. This allows compliance without unnecessary regulatory burden, while still ensuring that PET drugs administered to patients are of high quality.
- In summary, 21 CFR Part 212 is a specialized GMP regulation tailored to the unique needs of PET drug production. It ensures that these short-lived, high-precision radiopharmaceuticals are produced in a consistent, controlled, and safe manner, balancing the rigors of pharmaceutical quality assurance with the operational realities of PET drug manufacturing. The regulation reflects the FDA’s commitment to public health while fostering innovation in nuclear medicine and molecular imaging.
