Radioactive materials (radionuclides) release radiation, also called "ionizing radiation," as high-energy particles or electromagnetic energy (e.g., gamma rays) as their unstable atoms transition to a more stable state. Low levels of radiation occur naturally in the environment (as "background radiation"), but elevated levels may occur, for example, during or following a nuclear reactor accident. Radioactive materials released into the environment by such an accident may contaminate drug products, components, or packaging materials. In these circumstances, firms should determine if any of these articles has become contaminated with radionuclides. If a drug product has been subjected to improper storage, including contamination with radioactive material, the product must not be salvaged and returned to the marketplace (21 CFR 211.208). Similarly, contaminated drug components and packaging materials should not be used or salvaged to manufacture drug products. It is important for manufacturers to know the origin and complete supply chain of a drug product, component, or packaging to better enable an assessment for possible contamination arising , e.g., the accidental release of radioactivity
Some general concerns about radionuclide contamination nuclear accidents include, but are not limited to, the following:
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Drug products and/or components may become contaminated with radionuclides various sources, including contaminated atmospheric fallout, ground water, soil, or naturally-derived raw materials.
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A contaminated water supply used in drug manufacture may result in poor-quality products that fail to meet specifications.
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Certain dosage forms, such as injectable and inhalable drugs, may present greater risk to patients if contaminated with radionuclides, because these drugs more directly enter into the bloodstream.
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Drug products and/or drug components contaminated with radionuclides may result in poor- quality products that fail to meet stability specifications (e.g., reduced efficacy).
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Manufacturers of finished drugs must assure that their products comply with FDA regulations, which includes assurance that the components are of appropriate quality (see, e.g., 21 CFR 211). In addition, manufacturers of drug components and primary containers must also assure the quality of their material. FDA expects drug manufacturers and distributors to be extra vigilant and to take enhanced measures to assure the quality and safety of their drugs that may have been exposed to radioactive contaminants. It may be appropriate for a firm to undertake measures to prevent purchase of at-risk materials as well as to increase testing of incoming components and finished products before final release. See Title 21 Code of Federal Regulations (CFR), Part 211
