COMPOUND WITH CONFIDENCE: PCCA Membership, $795/month.
Stay current on PCCA news and events, market trends, and all things compounding!
By Dylan Herr, Eagle Business Development Specialist
The content below was based on an earlier proposed version of USP General Chapter 795. However, USP has since released a newer version of the chapter. To see our most current content about the new version of the chapter, please read our blog post Proposed Changes to USP 795. "
On March 30, 2018, the Compounding Expert Committee of the United States Pharmacopeial Convention published proposed revisions to USP chapter <795> Pharmaceutical Compounding – Nonsterile Preparations. The revised chapter was open to public comments until July 31, 2018, and is expected to become official on December 1, 2019. Major revisions to the chapter include, but are not limited to, the following:
Of the proposed revisions, the expansion of requirements for assigning BUDs in the absence of stability information has the most potential to affect the way that compounders practice pharmacy. The current USP chapter <795> only requires that “when assigning a BUD, compounders shall consult and apply drug-specific and general stability documentation and literature when available.”2 To meet this requirement, many compounding pharmacies use peer-reviewed journal articles and other literature references in order to provide a scientific justification for extended BUDs.
The revised chapter, however, states that BUDs may be extended past the maximum BUD by type of preparation in the absence of CNSP-specific stability information (as outlined in Table 3) “if there is a stability study (published or unpublished) using a stability-indicating assay for the specific API, CNSP (compounded nonsterile preparation), and container-closure that will be used.”1 The inclusion of these requirements will make finding peer-reviewed journal articles and other literature references more challenging, as many of them are not formulation or container-closure specific.
Stability-Indicating Methods Additionally, the revised chapter requires the use of a stability-indicating assay for stability studies. Historically, many compounding pharmacies have collected data to support extended BUDs for their formulations by having a contract analytical laboratory test the potency of the preparation at certain time-point intervals over the proposed BUD. This type of potency-over-time testing, however, does not meet the requirements of a stability study and of the revised USP <795> chapter, as it is not conducted using a stability-indicating assay to measure the potency of the active ingredient(s). While all stability-indicating assays measure the potency of an active ingredient, not all potency testing methods are stability-indicating.
One of the primary differences between a potency test and a stability study comes down to the analytical testing method used. While a potency testing method is reliable at quantitatively determining the concentration of a drug in a preparation at the time of compounding, not all potency testing methods are capable of separating the intact drug from its degradation products. As a result, these other substances could potentially mask or simulate the analytical behavior of the intact drug, resulting in an inaccurate concentration of the active ingredient. Results from this type of testing cannot be interpreted to determine that the product is stable over time, as there may have been degradant products or changes in the concentration of the active drug that were present, but not detected.
As a comparison, a stability-indicating assay is a potency testing method that is specifically developed and validated to differentiate between the active ingredient and the presence of other substances, such as impurities, degradation products and excipients. A stability-indicating assay is typically developed by forcibly degrading the compounded preparation through exposure to conditions known to produce decomposition, such as light, heat, oxidation, acids and bases. The stability-indicating assay is then validated in the presence of the resulting degradation products, which provides assurance that any increases or decreases in the active ingredient represent actual changes in the concentration of the drug. Conclusion All of this means that the requirements for extending the BUDs of nonsterile compounded preparations will likely become more stringent on December 1, 2019. We recommend that compounding pharmacies start developing strategies for establishing extended BUDs for their preparations now so as not to interrupt patient access to compounded medications.
PCCA has already invested the resources in their FormulaPlus™ program to provide members access to formulations with extended BUDs that have undergone testing using stability-indicating assays. PCCA members can access the complete list of FormulaPlus formulations here.
Furthermore, at Eagle, not only can we develop, validate and execute stability-indicating assays for most sterile and nonsterile compounded preparations, but we also offer consulting services on all aspects of testing and regulatory compliance. If you have questions about any of these matters, please contact us at 800.745.8916.
A version of this article was originally published the Summer 2018 issue of the Apothagram, PCCA’s quarterly, members-only magazine.
References 1. United States Pharmacopeial Convention. (2018). <795> pharmaceutical compounding –Nonsterile preparations [In-process revision: General chapters]. Pharmacopeial Forum, 44(3). Retrieved from http://www.usppf.com/pf/pub/ 2. United States Pharmacopeial Convention. (2017). <795> pharmaceutical compounding –Nonsterile preparations. In United States pharmacopeia and national formulary (USP 41st ed. & NF 36th ed.). Rockville, MD: United States Pharmacopeial Convention, Inc.