The Food and Drug Administration on May 4 issued a advisory to warn drugmakers, suppliers and health professionals that a counterfeit additive may be illegally used to replace or contaminate more expensive glycerin, a sweet syrup used in over-the-counter medicine like cough medications, fever medication and injectable drugs.
The FDA suggests, but not requires that drug manufacturers test glycerin for possible contamination of diethylene glycol or DEG, a known poison that is used in antifreeze and as a solvent.
No evidence indicates that glycerin used in the
US has been tainted with the poisonous industrial solvent, the FDA says.
But caution needs to be excised to ensure glycerin used in the country is free of DEG.
The warning was issued as cases of death associated with use of tainted glycerin have been reported to the FDA since last October.
Panama has recently confirmed 100 deaths from the DEG contamination and another 200 are waiting to be confirmed.
Today, the New York Times reported in a lengthy article that the DEG responsible for the deaths in
Panama probably originated from some Chinese suppliers.
Although it can't be 100 percent certain, the newspaper found that some chemical traders often sell industrial grade DEG as 95.5 percent pure glycerin to make a ludicrous profit.
Inhalation of diethylene glycol can cause cough and dizziness and contact with it can lead to redness on the skin and the eyes. Ingestion of the poison causes abdominal pain; confusion; dizziness; downiness; nausea; unconsciousness; and vomiting. In serious cases, it can cause kidney failure and nervous damage or even deaths.
Haiti, 85 children died in 1996 through glycerin contaminated with DEG in paracetamol syrup produced by Pharval Laboratories, a Haitian company, which did not verify the authenticity of the glycerin supplied by a Dutch company, Vos from a manufacturer in
China, according to Wikipedia.
In October 20006, the Centers for Disease Control and Prevention and the Ministry of health of Panama found toxic levels of diethylene glycol in a sugarless liquid expectorant during an investigation of 46 deaths from a syndrome characterized by gastrointestinal symptoms, renal failure and paralysis.
Between 1990 and 1998, according to the FDA, similar incidents of DEG poisoning reportedly occurred in
Nigeria and resulted in hundreds of deaths.
US, the FDA says, more than 100 people died in 1937 after ingesting DEG-contaminated Elixir Sulfanilamide, a drug used to treat infections, which triggered the enactment of the Federal Food, Drug, and Cosmetic Act. However, no death in the country has been linked to DEG contamination in any medicine.
The FDA says that it "is emphasizing the importance of testing glycerin for DEG due to the serious nature of this potentially fatal problem in combination with the global nature of the pharmaceutical supply chain and problems that continue to occur with this kind of contamination in some parts of the global supply of glycerin."
The FDA recommends that:
Drug product manufacturers perform a specific identity test that includes a limit test for DEG on all containers of all lots of glycerin before the glycerin is used in the manufacture or preparation of drug products because of the serious hazard associated with DEG contamination.3.
The relevant safety limit for DEG is 0.1%, as recognized by the USP monograph for glycerin.
The Agency recommends that a manufacturer perform the identity tests, including the limit test for DEG, which appear in the USP monograph for glycerin.
Alternatively, a manufacturer may use an equivalent identification procedure that includes a test to detect and quantify DEG provided it meets the relevant safety limit.
One alternative procedure is a thin-layer chromatography (TLC) method published in the Journal of AOAC International. 4.
This identification test is done in accordance with the CGMPs, which require that each lot of a component undergo testing to confirm its identity before use in drug product manufacturing (21 CFR 211.84(d)(1) requires that “[a]t least one test shall be conducted to verify the identity of each component of a drug product.
Specific identity tests, if they exist, shall be used”).
A specific identity test for glycerin is found in the United States Pharmacopeia (USP) monograph. 5.
The USP monograph for glycerin provides a two-part identity test:
test A using “Infrared Absorption” and test B using gas chromatography that references the “Limit of Diethylene Glycol and Related Compounds.”
The infrared absorption test identifies glycerin and DEG, but does not distinguish between the two.
Test B distinguishes glycerin from DEG. 6.
Drug product manufacturers know their supply chain for glycerin (i.e., the manufacturer of the component and any subsequent distributor(s)).
All manufacturers take every opportunity to ensure proper testing of glycerin for DEG contamination.
All personnel in pharmaceutical manufacturing facilities (especially personnel directly responsible for receipt, testing, and release of glycerin) should be made aware of the importance of proper testing and the potential hazards if the testing is not done.
Repackers, and others who distribute and prepare glycerin for use in drug products, test glycerin that is used, sold for use, or intended for use in drug products.
Pharmacies that use glycerin in compounding drug products either test the glycerin for DEG content or ensure that such testing was properly done by a reliable supplier.
Bulk or repackaged glycerin intended as an excipient or other component of a drug product is a drug as defined by section 201(g)(1) the Act (21 U.S.C. 321(g)(1)).
Section 501(a)(2)(B) of the Act (21 U.S.C. 351(a)(2)(B)) requires that the methods used in, or the facilities or controls used for a drug’s manufacture, processing, packing, or holding conform to CGMP.
Testing bulk or repackaged glycerin for DEG content is consistent with good manufacturing practice required under the Act.
For other components, such as propylene glycol, that in the past were found to be contaminated with DEG, precautions should also be taken to identify reliable suppliers and secure shipment to prevent similar occurrences. 7.