Regulatory Spotlight - Compendia Updates: USP <621> and USP <1220>
Srividya Ramanathan, Principal Scientist, Technical Consulting and Support Services; Heather Cawley, Principal Scientist, Pharmaceutical Raw Materials
Compendia publications are periodically updated in order to align with industry trends and harmonize with global regulatory practices. Staying abreast of these changes well before they are implemented, and being ready to adapt as necessary, is in the best interest of any bio/pharmaceutical testing laboratory. At Eurofins BioPharma Product Testing (EBPT), monitoring of compendia updates is a continuous effort. Our organization is prepared for changes and strives to remain in full compliance when updates or new guidance become effective. Recently the USP implemented two significant, general chapter changes. Eurofins BPT was well prepared to implement measures to adopt these updates quickly within all impacted testing areas.
New general chapter <1220> Analytical Procedure Life Cycle, became effective on May 1, 2022. This text holistically considers the validation activities that take place across the entire life cycle of an analytical procedure and provides a framework for the implementation of the proposed guidance. This chapter also incorporates Quality by Design concepts described in the ICH guidelines. According to <1220>, the overall approach to the lifecycle management of an analytical procedure involves three stages:
Stage 1 – Procedure development and optimization based on the desired Analytical Target Profile (ATP) of the material under test. This stage may involve Design of Experiments (DOE) and appropriate risk assessments in order to establish robustness and a Method Operable Design Region (MODR) for the analytical procedure.
Stage 2 – Procedure performance qualification consists of studies designed to demonstrate that the procedure is suitable for its intended purpose, i.e. confirmation that reportable values meet the ATP criteria through traditional validation, verification, and transfer studies.
Stage 3 – Ongoing procedure performance verification (OPPV) involves monitoring the analytical procedure during routine use and confirming that the performance continues to meet ATP criteria. Monitoring ensures that the performance of the procedure is maintained at an acceptable level over the procedure lifetime.
Eurofins BPT already had a robust, established Standard Operating Procedure that describes our approach to validation, qualification, transfer, and verification activities. Additionally, guidelines and tracking tools are in place for monitoring and trending system/method performance based on client established criteria for KPI (Key Performance Indicator) reporting. As a result of the published chapter updates, an internal team has been identified to monitor industry requirements and gather stakeholder input in order to strengthen our plan for further integration of the proposed guidelines for procedure lifecycle management.
While the current guidance presented in <1220> is optional, Eurofins BPT will consider the chapter content as best practice where relevant, especially for Drug Products, Bulk Drug Substances, and Active Pharmaceutical Ingredients. The extent of implementation will be based on the criticality of the quality attribute being measured. We are committed to align with this guidance with an overall policy, while still allowing flexibility to meet our clients’ unique requirements and develop customized approaches on an as needed basis.
A revision to general chapter <621> Chromatography became effective on December 1, 2022. This chapter describes general procedures, definitions, and calculations of common parameters and various requirements for system suitability. In preparation for this change, a committee of experts from representative analytical departments assessed the updates to the chapter. The result was generation of a detailed memo that was distributed to all of our existing clients in November, ahead of the effective date for the revised chapter. The memo, based on information gathered from relevant industry stakeholders and internal SME’s, outlines our strategy to comply with new calculations and criteria with minimal impact to any existing, established chromatographic testing.
Our team is also working closely with the USP to propose solutions for any testing that does not meet suitability criteria following these chapter updates. We are proactively evaluating delayed sections of <621> and providing feedback to the USP as necessary. USP members visited our facility at the beginning of March 2023 and requested that experts from our team sit on their councils to provide insight for future revisions. This collaboration will ensure a smooth implementation of potential modifications to the general chapters from the lens of a contract laboratory.