Category 2 of the Bulk Substances Nominated Under Sections 503A or 503B of the Federal Food, Drug, and Cosmetic Act
FDA finalized two guidances clarifying the agency’s proposed policies concerning the use of certain bulk drug substances in compounding by state-licensed pharmacies, federal facilities, and licensed physicians (under section 503A), and by outsourcing facilities (under section 503B):
- Guidance for Industry, Interim Policy on Compounding Using Bulk Drug Substances Under Section 503A of the Federal Food, Drug, and Cosmetic Act
- Guidance for Industry, Interim Policy on Compounding Using Bulk Drug Substances Under Section 503B of the Federal Food, Drug, and Cosmetic Act
The guidance documents describe three categories of nominated bulk drug substances. The bulk drug substances in category 2 were nominated for use in compounding under sections 503A or 503B with sufficient supporting information for FDA to evaluate them, but they raise significant safety risks. FDA would consider taking action against a compounder or outsourcing facility for compounding drug products with bulk drug substances listed in category 2 under its general enforcement policies.
Summary of the Safety Risks
Category 2 substance
Nominated with sufficient information under 503A or 503B or both
Date added to Category 2
October 27, 2015
Domperidone is associated with a serious risk of life-threatening cardiac arrhythmias and sudden cardiac death in all populations, including healthy lactating women. Domperidone is transferred into human breast milk, but it is unknown to what extent domperidone in breast milk is absorbed by the breastfed infant and what the resulting drug levels and drug side effects in the exposed infant would be.
Domperidone is available to treat certain gastrointestinal conditions that are refractory to standard treatment under an expanded access investigational new drug (IND) program.
June 9, 2016
Germanium sesquioxide is likely to be contaminated with highly toxic inorganic forms of germanium salts which can be toxic to the kidneys. Germanium has resulted in nephrotoxicity (kidney injury) and death, even at recommended use levels.
Quinacrine HCl for intrauterine administration
June 9, 2016
Quinacrine HCl is a known mutagen (causes changes in the DNA of a cell) and is associated with serious adverse reactions such as aplastic anemia, hepatitis, severe dermatitis, exacerbation or worsening of psoriasis, and psychosis. Safety risks associated with intrauterine administration of quinacrine HCl (e.g., for female sterilization) include increased risk for life-threatening reproductive tract malignancies.
July 30, 2018
The use of cesium poses significant safety risks (e.g., heart toxicity) and is potentially associated with death. Cesium chloride (CsCl) can cause irregular heartbeats, also called arrhythmias. There have been reports of humans experiencing serious heart problems after taking CsCl. CsCl is associated with a lower blood level of potassium, which is a mineral that is essential to normal heart function.