Testing of Glycerin, Propylene Glycol, Maltitol Solution, Hydrogenated Starch Hydrolysate, Sorbitol Solution, and Other High Risk Drug Components for Diethylene Glycol and Ethylene Glycol

The FDA has issued a final guidance to help manufacturers prevent the use of glycerin and other high-risk drug components contaminated with the toxic substances diethyleneglycol (DEG) or ethyleneglycol (EG), to combat a rise in fatal consumer #poisonings.

FDA has received and continues to receive (most recently in early 2023) reports about fatal poisonings of consumers who ingested drug products in a liquiddosage form (such as cough, allergy, analgesic, and antiemetic drug products) that were manufactured with DEG- or EG-contaminated components.

These cases reveal the following similarities:

➡️The manufacturers of the liquid drug products that contained contaminated glycerin did not perform full identity testing on the glycerin raw material, including tests to quantify the amount of DEG present and to verify the purity of the glycerin received.

➡️The manufacturers of the liquid drug products containing contaminated glycerin relied 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.

cGMP requirements - Dont apply Skip testing

21 CFR 211.84(b) requires that a representative sample of each shipment of each lot be collected for testing and describes that the number of containers to be sampled shall be based upon appropriate criteria.

Because DEG contamination presents a serious hazard and FDA has seen wide variability of DEG and EG contamination from container to container, the Agency recommends that the representative sample collected for testing is of each container of each lot.

Regulatory Perspective:

💡Ensure the specific identity analysis for each lot, which includes a limit test for DEG and EG, incorporates testing of samples from all containers of all lots of a high-risk drug component before the high-risk drug component is used in the manufacture or preparation of drug products.

💡For high-risk drug components where the DEG and EG tests are not included in the identification test of the USP-NF monograph for the component,32 a manufacturer uses a suitable and equivalent procedure that includes a test to detect and quantify DEG and EG. The Agency recommends that any tests to detect and quantify DEG and EG use a safety limit for DEG and EG of NMT 0.10%.

💡Drug product manufacturers maintain current knowledge of their supply chain for high-risk drug components (ie., the identity of the original manufacturer of the component and any subsequent repackers or distributors).

💡All personnel in pharmaceutical manufacturing facilities (especially personnel directly responsible for receipt, testing, and release of components) be made aware of the importance of proper DEG and EG contamination testing, and the potential hazards if this testing is not done.

💡Repackers, and others who distribute and prepare high-risk components for use in drug products, test the high-risk components that are used, sold for use, or intended for use in drug products. Accurate and complete COAs that identify the original manufacturer of the components should be issued for each component lot shipment

Click here to read full FDA guidance 

Top Regulatory Affairs Pharmacy Courses launched on Udemy 📖👨‍🎓👩‍🎓✌

1) New USFDA Electronic Submission Gateway Course-Regulatory Affairs

👉Apply Coupon Link: Click here

2) Title : Pharmaceutical Clinical Research course

👉Apply Coupon Link: click here

3) Title: Pharma Drug Regulatory Affairs Course

👉Apply Offer link : Click here

4) Title: Pharma eCTD & CTD preparartion + Sumbmission course

👉Apply Coupon Link: Click here