Usp General Notices and Requirements 7.20

Section 7.20 of USP 32-NF 27`s General Notes on significant numbers and rounding states: “Observed or calculated values shall be rounded to the number of decimal places corresponding to the limit expression.” This would result in a maximum unrounded result of 0.14%, which corresponds to the specification of 0.1%, while a maximum unrounded result of 0.104% would correspond to the specification of 0.10%. On December 27, 2013, USP published the general notices for the second addendum to USP 37-NF 32. The final amendment concerns Article 5.60.30 on elemental impurities. The requirements of General Chapters and will come into effect on December 1, 2015. In the future, “General Communications” will also include an amended section 6.80.30 on temperature meters. This section states that temperature measuring instruments used for pharmacopoeia testing must meet the specifications, i.e. be traceable to a NIST standard or equivalent. Conventional liquid thermometers, analog or digital devices for temperature measurement (such as resistance temperature devices) are some of the measuring instruments that can be used. The table in section 8.2.40 entitled “Weights and Measures” is a new part of “General Communications”; This table lists the different units, including the International System of Units (SI), and the symbols used for each unit. Section 7.20 on rounding rules remains unchanged.

What needs to be rounded? When does a result match? When not? It seems generally unknown that these provisions relating to rounding of test results appear in the general communications of each issue of the USP-NF. The borderline test was included in the identification section at the request of the FDA. This makes a difference if the detection and quantification of DEG is considered part of the identification test or only a standard of strength, quality or purity, especially from a regulatory perspective. Under the federal Food, Drug and Cosmetic Act (FDCA), a drug whose name is recognized in USP-NF must meet standards of officinal identity or be considered adulterated, mislabeled, or both. If the detection and quantification of DEG is part of the identification test, the cGMP regulations of 21 C.F.R. § 211.84(d)(l) would require drug manufacturers to detect and quantify existing DEGs. In addition, glycerin manufacturers could not deviate from the DEG limit, as this would be an aspect of identity. If, on the other hand, the detection and quantification of DEG is exclusively part of a purity test (impurity test), a manufacturer is not required to include in his identity check the need to detect DEG in glycerin.

In addition, in terms of FDA enforcement, a manufacturer could deviate from the impurity requirements set out in the monograph by labeling the product to indicate that it deviates from USP testing requirements in this regard. In summary, an identity/identification test provides a more robust standard, both in terms of the compendal standard itself (including FDA enforcement under FDCA 501(b)) and FDA cGMP (enforced by FDA under FDCA 501(a)). Yes, the FDA has asked USP to take the same approach so that these monographs are consistent with the glycerin monograph. 12. In January 2009, the FDA submitted a letter to USP requesting a review of sorbitol solution and propylene glycol similar to glycerin. USP is also updating other monographs listed in the high-priority appendix provided 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 Product Monographs for propylene glycol and sorbitol solution.) For more information, see the full USP General Notes and Requirements document.

The Glycerin Product Monograph Review Bulletin became official on May 1, 2009. This revision bulletin replaces the Product Monograph for USP 32–NF 27 and USP 32–NF 27 First Supplement. The revision bulletin is published in printed form in 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`s initial application to USP to revise the USP Product Monograph and the Industrial Testing Guidelines for Glycerol for Diethylene Glycol. For identification B, it is not necessary to determine the moisture content, as this applies to qualitative use.