Proposed Revisions to USP General Chapter <797>: Introduction of Category 3 CSP
Earlier this month, the USP announced an extension for public comment for the revisions to USP General Chapters <797> and <795> lasting until January 31st of 2022. Below is a review of the introduction of Category 3 CSPs and how it could impact your pharmacy operations.
Brief Background on General Chapter <797> Proposed Revisions
The Compounding Expert Committee (CMP EC) has been working on revisions to general chapter <797> since 2010. Two drafts have since been published for public comment, first in 2015 and again in 2018. Both versions received a combined total of over 10,000 comments. Following the review of all comments, USP published a final revision of <797> in June 2019, with an effective date of December 2019.
Numerous appeals from various stakeholders were submitted to USP regarding certain provisions (particularly Beyond Use Dating) in the revised 2019 standard. The Appeals Panel granted the appeals in March of 2020, remanding <797> to the CMP EC for further engagement on the issues raised by stakeholders.
Among the major edits included in the chapter, the renaming of CSP microbial risk levels and updated terminology to create the addition of Category 3 is one of the most significant.
Category 1 and 2 CSPs essentially stay the same and are distinguished primarily by the facility in which they are made and the length of time within which they must be used.
Category 1 CSPs have shorter BUDs and may be prepared in an unclassified segregated compounding area.
Category 2 CSPs have longer BUDs and must be prepared in a cleanroom suite.
Category 3 CSPs are those that may be assigned longer BUDs than the limits for Category 1 or Category 2 CSPs, up to 180 days, if additional requirements are met.
Category 3 CSP Requirements and Impacts
Category 3 extended BUD, in essence, is achieved through the following general areas:
Changing personnel competency requirements (Media Fill/Gown/Garb/GFT testing).
Requiring sterile garb and no skin exposure. Increasing environmental monitoring requirements.
Increasing the frequency of the application of sporicidal disinfectants.
Stability Data Requirements for Category 3 CSPs
The BUD assigned to a Category 3 CSP must be supported by stability data obtained using a stability indicating analytical method that is able to distinguish the active ingredient from its degradants and impurities (e.g., by forced degradation studies) and quantify the amount of the active ingredient.
The Category 3 CSP must be prepared according to the exact formulation (API and other ingredients of identical grade and procedures) from which the stability data are derived.
Category 3 CSP must be packaged and stored in a container closure of the same materials of composition as that used in the study.
The analytical method must be validated based on characteristics such as those described in USP Chapter〈1225〉 Validation of Compendial Procedures.
The compounding facility must have documentation of the stability study, including a description of the methodology (e.g., number of samples taken and storage conditions), validation of the method, the stability-indicating analytical method, and all the results of the study.
Additional Requirements to Consider:
If the Category 3 CSP is an injection (USP Chapter 〈788〉 Particulate Matter in Injections) or if it is an ophthalmic solution (USP Chapter 〈789〉 Particulate Matter in Ophthalmic Solutions), particulate-matter testing is conducted once per formulation with acceptable results. Once for each formulation and for each container closure system in which it will be packaged, the container closure system used is evaluated for and conforms to container closure integrity (see USP Chapter< 〈1207〉> Package Integrity Evaluation—Sterile Products).
Once for each formulation and for each container closure system in which it will be packaged, the container closure system used is evaluated for and conforms to container closure integrity (see USP Chapter < 〈1207〉> Package Integrity Evaluation—Sterile Products).