The Medicines Control Authority of Zimbabwe (MCAZ) has expressed deep concern over the recurring cases of contaminated oral liquid formulations containing Diethylene Glycol (DEG) and Ethylene Glycol (EG), which, when consumed even in small amounts, can be fatal.
Disturbingly, reports of DEG and EG poisoning cases have emerged worldwide since 2022, with over three hundred deaths, the majority of which were children.
In a statement, the MCAZ said when DEG and EG concentrations in liquid dosage forms, such as cough syrups, allergy syrups, analgesic syrups, and antiemetic syrups, exceed 0.10%, they can cause toxicity and fatalities.
“Pharmaceutical manufacturers must take proactive measures to ensure that all oral liquid formulations in circulation are free from DEG and EG contamination. Failure to comply with these directives will result in severe penalties and regulatory action,” said MCAZ.
Regarding the contamination of DEG and EG, the MCAZ identified specific starting materials of concern that are considered high-risk for pharmaceutical formulations. These materials include Glycerine (Glycerol), Propylene Glycol, Maltitol Solution, Hydrogenated Starch Hydrolysate, Sorbitol Solution, and other pharmaceutical ingredients that may generate DEG and EG during their synthesis or degradation processes.
“In light of the above, pharmaceutical manufacturers using high-risk starting materials should conduct rigorous testing of such materials in accordance with the current Good Manufacturing Practices (cGMP) requirements. Specifically, they should test for DEG and EG contamination as outlined in the respective pharmacopeial monographs for each starting material,” explained MCAZ.
The purpose of issuing this circular is to outline the regulatory position and proactive measures that pharmaceutical manufacturers must undertake to ensure that all oral liquid formulations registered with the MCAZ are free from DEG or EG contamination.
“The Authority hereby instructs all finished pharmaceutical product (FPP) manufacturers of oral liquid formulations registered in Zimbabwe, which may potentially be contaminated with DEG and EG, to implement the following preventive measures immediately: Upon receiving raw materials from suppliers, FPP manufacturers must conduct thorough testing of all containers and lots of high-risk starting materials intended for pharmaceutical formulations.
Testing for DEG and EG contamination in these high-risk materials should be performed in accordance with the respective pharmacopeial monographs. Skip-lot testing of these materials will not be accepted. Proof of testing will be verified during routine cGMP audits,” the circular stated.
Furthermore, the circular highlighted that FPP manufacturers using high-risk starting materials should not solely rely on supplier Certificates of Analysis (COAs) for DEG and EG test results.
In cases where DEG and EG testing is outsourced, the COA from the contract laboratory must be accompanied by copies of raw data.
“Finished product testing for DEG and EG, as described in the International Pharmacopeia (currently stated in the WHO Working Document QAS/23.922/rev3), should be conducted on formulations containing high-risk starting materials,”
MCAZ also said FPP manufacturers should exclusively use pharmaceutical-grade starting materials, as the use of non-pharmaceutical grades, such as industrial-grade materials, will not be acceptable.
“Vendors and manufacturers of high-risk starting materials should possess adequate qualifications. FPP manufacturers must be able to trace the supply chain and custody of starting materials from the manufacturer to their warehouse. FPP manufacturers are obligated to test retention samples of oral liquid formulations currently on the market for DEG and EG if these batches were released without prior testing for DEG and EG,” the authority said
To ensure compliance, the MCAZ will continue to closely monitor the situation through regular inspections and audits.
