Diethylene Glycol and Ethylene Glycol High-Risk Drug Components Testing
Are you up-to-speed on FDA’s Final Guidance issued May 9, 2023 relating to the testing of “high-risk” drug components (raw materials) for the presence of Diethylene Glycol and Ethylene Glycol contamination? If not, read on since FDA is recommending the immediate implementation of new sampling and testing protocols for “high-risk” raw materials.
Background Information
For the purposes of this discussion, FDA provides a definition of “high-risk drug components” as being raw materials, through historical experience, which have been found to be at higher risk of Diethylene Glycol (DEG) and Ethylene Glycol (EG) contamination as compared to other drug components. Examples of “high-risk” materials include but are not limited to Glycerin, Propylene Glycol, Maltitol Solution, Sorbitol Solution, Polyethylene Glycol (MW<1000 only), Diethylene Glycol Stearates, Polysorbate 20/40/60/80, Nonoxynol 9 and Octoxynol 9.DEG and EG are highly toxic compounds which can cause death in humans who ingest them. The US Food, Drug and Cosmetic Act (FD&C Act) was enacted in 1937, largely in response to an outbreak of DEG poisoning whereby 107 people (mostly children) died after ingesting an oral liquid drug (Sulfanilamide) in which DEG had been added as a solvent. Although DEG and EG are no longer permitted for use as added ingredients in US food, drug, or cosmetic products, both continue to present a health risk since they may be present as contaminants in certain “high-risk” raw materials. Even at very low levels, DEG and EG have been proven harmful to human health, which is why FDA has established a limit of not more than (NMT) 0.10% for DG and EG (individually) in “high-risk” raw materials and drug products themselves.
FDA Final Guidance Issued May 9, 2023
On May 9, 2023 FDA issued a Final Guidance entitled “Testing of Glycerin, Propylene Glycol, Maltitol Solution, Hydrogenated Starch Hydrolysate, Sorbitol Solution, and other High-Risk Drug Components for Diethylene Glycol and Ethylene Glycol.” This Final Guidance is actually a revision of a Guidance Document first issued in 2007, relating to testing for low levels of DEG in certain raw materials. Although FDA had previously instructed the United States Pharmacopeia – National Formulary (USP-NF) to add Limit Tests for DEG and EG to the monographs of “high-risk” raw materials, this Final Guidance introduces new sampling and testing protocols for immediate implementation.What are the new FDA-recommended/required sampling and testing protocols included in this Final Guidance?
1、For “high-risk” raw materials where DEG and EG Limit Tests are included in the Identification Test of the USP-NF monograph, drug manufacturers can no longer rely on DEG and EG test results as reported on the Certificate of Analysis issued by the vendor of that material. The drug manufacturer is required to conduct DEG and EG testing (or arrange for it to be conducted) on samples taken from every container of every shipment of every lot of a “high-risk” raw material. The limit is NMT 0.10% for DEG and EG, individually.
3、Drug manufacturers should maintain current knowledge of their supply chain for “high-risk” raw materials, whereby the identity of the original manufacturer and any subsequent repackers or distributors are known.
4、Manufacturers, repackers and distributors of “high-risk” raw materials for use in drug products must now test such materials for DEG and EG and indicate these values on each Certificate of Analysis that it issues for each Lot of material.
5、All personnel in pharmaceutical manufacturing facilities (especially those responsible for the receipt, testing and release of raw materials) should be made aware of the importance of proper DEG and EG contamination testing and the potential hazards if it is not performed.
6、Pharmacies that use “high-risk” raw materials in compounding drug products should test each Lot of “high-risk” material for DEG and EG content or ensure that such testing was properly performed by a reliable supplier. (Note that drug manufacturers are not provided with this option.)
PTS Testing Service as Consumer Product Safety Certification Testing Laboratory（CPSC Lab） has provided clients with accurate testing for DEG and EG contamination in numerous “high-risk” raw materials used in drug and cosmetic products. Our state-of-the-art Analytical Chemistry Lab and its well-seasoned staff of experts is at your disposal to discuss not only ‘routine’ DEG and EG testing of “high-risk” raw materials, but also the testing of drug and cosmetic products for these same contaminants.
PTS Testing Service as Consumer Product Safety Certification Testing Laboratory（CPSC Lab）, For enterprises and cross-border e-commerce around the world to provide one-stop authoritative third-party product certification and testing services. (including CE(LVD/EMC/RED/RoHS/REACH/EN71)、CPC(CPSC/CPSIA/ASTM F963/Ca Prop 65/FCC/UL)、CCPSA(SOR/2011-17)、AS/NZS ISO 8124、GB6675、LFGB、FDA、GB 4806、GB 18401、GB 31701、QB/T 1333、QB/T 2155, Formaldehyde, AZO, Carcinogenic Sensitized Dyes, Organotin, Phthalates, Heavy metals, Nickel release, Salt spray corrosion, High temperature aging, component analysis Report). We serve a wide range of industries: contained on textile, footwear, bags, Toys, electronics, arts and crafts, cosmetic, Watches, Eyewear, Jewelry & Accessories ,Glass, Children products, Garment, Furniture, Lighting fixture, Beauty & Cosmetic Electric, Care Massage Product Field, Adult products Sex toys Products, electronic and many other fields.
