US Food and Drug Administration (USFDA) has recommended testing of samples from containers of all lots of high-risk drug components like glycerin and propylene glycol before it is used in the manufacture or preparation of drug products.
The advisory comes after dozens of deaths were reported from Uzbekistan and Gambia after children consumed cough syrups with high levels of diethylene glycol (DEG) and ethylene glycol (EG) that were supplied by some Indian manufacturers. The agency has, however, clarified that no contaminated products connected to the recent international incidents have entered the U.S. drug supply chain. The recommendations are advisory in nature and not mandatory.
The US FDA stated the guidance is intended to alert pharmaceutical manufacturers, compounders, repackers, and suppliers to the potential public health hazard of glycerin and other high-risk drug components as these deaths were caused due to the presence of DEG- or EG-contaminated components in the products. The guidance states even if DEG and EG tests are not included in the identification test of the US pharmacopoeia monograph the manufacturer can carry out tests to detect and quantify DEG and EG. It has asked the drug product manufacturers to maintain current knowledge of their supply chain and all personnel in pharmaceutical manufacturing facilities be made aware of the importance of proper DEG and EG contamination testing, and the potential hazards.
It has also advised the repackers, and others who distribute and prepare high-risk components for use in drug products to test the high-risk components that are used, sold for use, or intended for use in drug products.
According to the US FDA, one of the major problem areas was the reliance of the manufacturers of the liquid drug products containing contaminated glycerin on the certificate of analysis (COA) provided by the supplier of the glycerin. “The origin of the glycerin was not readily apparent from the COA. The COA obtained by the manufacturers of the liquid drug products was often a copy of a COA on the letterhead of the distributor from whom they had purchased the glycerin and not the COA provided by the original manufacturer of the glycerin. The chain of custody or distribution history of the glycerin was also not readily known, often because the glycerin might have been sold multiple times between its manufacture and its use in manufacturing the finished drug product, the guidance note said.
As a remedial measure, the agency has recommended that accurate and complete COAs that identify the original manufacturer of the components be issued for each component lot shipment. US FDA also states that these recommendations are also ‘important precautions when determining supplier and lot acceptability of other components (e.g., polyethylene glycol 40 castor oil) that may be at risk for DEG or EG contamination and are not specifically named in this guidance’.
