Questions and Answers on Current Good Manufacturing Practices, Good Guidance Practices, Level 2 Guidance - Returned and Salvaged Drug Products
- Obtaining supply chain information, including knowing the names and addresses of all suppliers and distributors of a drug (including components and packaging) to determine if there is a reasonable possibility that such materials were stored under improper conditions.
- Determining details such as the timeframe, duration, nature, scope, and location of exposure as well as identity of all lots potentially subjected to the improper conditions (e.g., ramifications of a natural disaster such as power disruptions should be considered to assure a complete risk assessment).
- Obtaining certification (either on the certificate of analysis or as a separate statement) declaring that drug lots, including components and packaging, were not subjected to improper storage conditions.
For more information, see references below.
- 21 CFR Part 211.208, Drug Product Salvaging
- FDA Import Alert 99-33 - Detention Without Physical Examination of Products from Japan Due to Radionuclide Contamination http://www.accessdata.fda.gov/cms_ia/importalert_621.html
- FDA Public Health Focus - Radiation Safety http://www.fda.gov/NewsEvents/PublicHealthFocus/ucm247403.htm
- Food Safety: The EU Reinforces Controls on Imports from Japan http://europa.eu/rapid/pressReleasesAction.do?reference=IP/11/362
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 from, e.g., the accidental release of radioactivity
Some general concerns about radionuclide contamination from nuclear accidents include, but are not limited to, the following:
- Drug products and/or components may become contaminated with radionuclides from various sources, including contaminated atmospheric fallout, ground water, soil, or naturally-derived raw materials.
- A contaminated water supply used in drug manufacture may result in poor-quality products that fail to meet specifications.
- 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.
- 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).
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, including:
- CFR Part 211.65, Testing and Release for Distribution
- CFR Part 211.84, Testing and Approval or Rejection of Components, Drug Product Containers, and Closures
- CFR Part 211.94, Drug Product Containers and Closures
- CFR Part 211.208, Drug Product Salvaging
Contact for further information
Larry A. Ouderkirk, Consumer Safety Officer
Dr. Frank W. Perrella, Chemist
Division of Manufacturing and Product Quality (HFD-320): CGMP Subject Contacts