The Drugs Regulatory Authority of Pakistan (DRAP) has issued another drug impurity alert regarding a chemical that is being used as an anti-freezing agent in various medicines, particularly cough syrups, which may potentially harm the kidneys.
This is the second alert of this type, with the first one having been issued in October.
Earlier this week, DRAP issued a new advisory to pharmaceutical companies directing them to ensure that solvents such as glycerine, propylene glycol, and sorbitol used in oral preparations are tested for the presence of any toxic or lethal impurities, including diethylene glycol (DEG) and ethylene glycol (EG).
In an earlier advisory on October 21st, DRAP had advised recalling any product(s) that were reported to be out of specifications after testing and analysis of already-manufactured batches, warning that strict regulatory action would be taken if this was not done.
Given the widespread consumption of oral solutions such as cough syrups, any DEG contamination is a serious cause for concern and requires immediate action. The fact that DRAP has had to issue a second drug impurity alert within a two-month period is indicative of the potential scale of damage that may have occurred during this time.
Sorbitol, glycerin, and propylene glycol (PG) are commonly used solvents in pharmaceutical products, but they have the potential to be mixed or contaminated with DEG. The clinical effects of DEG poisoning are known to be neurotoxic, hepatotoxic, and nephrotoxic. Elevated cerebrospinal fluid protein concentrations in victims of DEG poisoning may be linked to apparent kidney injury.
DEG is converted into hydroxy ethoxy acetic acid and causes acidosis, which can severely damage kidney cells responsible for filtration and lead to an increase in creatinine levels in the blood, disrupting the biochemical balance in the body and brain. In the past, diethylene glycol has caused widespread deaths in various countries, and a well-known company’s toothpaste containing DEG has also led to the spread of various diseases.
According to DRAP’s advisory, it has received multiple responses from various pharmaceutical manufacturers and their associations explaining that testing facilities for these impurities are not available and requesting more time to develop the necessary testing provisions.
It is worth noting that the Central Drugs Laboratory (CDL) in Karachi has the capability to test for these impurities. Therefore, DRAP has advised all relevant stakeholders, including pharmaceutical manufacturers and regulators, to ensure that when purchasing these solvents, they confirm that the supplier or vendor has tested all batches in the consignment for specific impurities, including DEG and EG, using the limit test.
The companies will also be responsible for impurity testing of solvents such as glycerin, sorbitol, and propylene glycol on every batch, either by using their own in-house facility or by paying the required fee to have the tests conducted at the Central Drugs Laboratory in Karachi. Such testing will not result in regulatory action and will be limited to preventing the use of adulterated solvents in manufacturing. The Federal Inspectors of Drugs have been advised to conduct risk-based sampling of these solvents for testing by the CDL in Karachi to check for the presence of any impurities.
Drug Lawyers’ Forum Chairman, Noor Mahar, praised DRAP’s advisory on drug impurity, stating that these steps will help save lives because diethylene glycol has properties similar to glycerin and is therefore used as a cheaper substitute. If it enters the body in excess, it can damage the kidneys and cause other diseases. Cough syrups containing this chemical have the highest over-the-counter sales in Pakistan.
Noor Mahar noted that there are no formal laws in Pakistan for testing these hazardous elements, but DRAP’s notice will ensure that all batches of glycerine, sorbitol, and propylene glycol are tested before being purchased by pharmaceutical companies.
