The Glycerin Monograph Revision Bulletin became official on May 1, 2009. This Revision Bulletin supersedes the monograph appearing in USP 32–NF 27 and USP 32–NF 27 First Supplement. The Revision Bulletin will appear in print in the USP 32-NF 27 Second Supplement.
USP revised the Glycerin Monograph in response to a request from the Food and Drug Administration (FDA). For more information, see the FDA initial request to USP to revise the USP Monograph and the Guidance for Industry Testing of Glycerin for Diethylene Glycol.
On January 12, 2009, FDA submitted a letter to USP requesting revision of Sorbitol Solution and Propylene Glycol similar to Glycerin. USP also is updating other monographs listed as high priority on the attachment supplied with the FDA letter. These monographs are Maltitol Solution, Sorbitol Sorbitan Solution, and Noncrystallizing Sorbitol Solution. (See FDA's Request to USP to Revise the USP monographs for Propylene Glycol and Sorbitol Solution).
The Limit test was placed in the identification section per the request of the FDA. It makes a difference whether the detection and quantification of DEG is considered part of the Identification test or is considered solely a standard for strength, quality or purity, particularly from a regulatory standpoint. Under the Federal Food, Drug, and Cosmetic Act (FDCA), a drug with a name recognized in USP-NF must comply with compendial identity standards, or be deemed adulterated, misbranded, or both. In addition, if DEG detection and quantification is part of the Identification test, the cGMP regulations at 21 C.F.R. § 211.84(d)(l) would require that manufacturers of drug products detect and quantify any DEG present. Furthermore, manufacturers of glycerin could not deviate from the DEG limit since this would be an aspect of identity. In contrast, if DEG detection and quantification is solely part of a purity (impurity) test, a manufacturer need not include as part of its identity testing the need to detect and quantify DEG in the glycerin. In addition, in terms of FDA enforcement, a manufacturer could deviate from the impurity requirements established in the monograph by labeling the product to indicate that it deviates from the USP test requirements in this regard. In summary, a test for Identity/Identification provides a more robust standard, both in terms of the compendial standard itself (including FDA enforcement under FDCA 501(b)), and FDA cGMPs (enforced by FDA under FDCA 501(a)).
The test for the Limit of DEG and EG was validated for DEG and EG only. The purpose of the Limit test in the ID section is for identification of DEG and EG as contaminants/adulterants.
Yes, FDA requested USP follow the same approach for these monographs to be consistent with the Glycerin monograph.
According to section 7.20 of the General Notices in USP 32-NF 27 regarding significant figures and rounding, it states, “The observed or calculated values shall be rounded off to the number of decimal places that is in agreement with the limit expression.” This would translate into an un-rounded maximum result of 0.14% conforming to the 0.1% specification while an un-rounded maximum result of 0.104% would conform to the 0.10% specification.
For Identification B, there is no need to determine the water content as this is for qualitative use.