Page 14 - CuttingEdge April 2023

Key Changes in USP <621>

evaluation of system sensitivity rmulae are not in line with up analysis, and reducing
for the respective compendial test the updated USP <621>, it waste. The updated USP<621>
methods through a protocol. After is recommended to use EP Chromatography mandates the
completing the protocol study, formulae or manual calcu- 'system sensitivity' check, which
suitability of the test method to lations. However, software ensures the accurate quantification
include sensitivity solution shall updates will be released before of trace level impurity analysis. In
be evaluated through regulatory USP <621> effective to fulfil addition, the latest revision allows
notification. For new products, it the USP requirements. us to adjust column dimensions
is suggested that development lab for gradient separations, which is a
should evaluate the sensitivity check 9. Summary significant advance. Although these
during the method development and Advances in technologies over the provisions are welcomed, one must
include it in the SST run. Analytical past number of years have enabled be mindful of the requirements or
development function when the development of new, effective, limits of the allowable changes
transfers the analytical method to and efficient chromatographic and the verification work that
QC lab, system sensitivity shall methods. The updated version underpins our demonstration of
be evaluated. This procedure shall of USP Chapter <621> reflects equivalent performance of the
provide the confidence of lamp these method and technological adjusted method. Although in
performance w.r.t. specific product advances. The updated USP <621> theory these changes avoid the
analysis on a regular basis and is also part of the United States necessity for full revalidation of the
thus ensure accurate reporting of Pharmacopeia’s harmonisation analytical method, it is often that
impurities/degradation products initiative. That initiative involves when making extensive changes to
in the drug substances and drug the US Pharmacopeia working the method, the verification work
products tested and released to with other organisations, including required will approach that of a full
market. the European Pharmacopeia and revalidation. The end user must
Japanese Pharmacopeia, to achieve assess the benefits of change versus
8. Way Forward the international harmonisation the work required to prove method
o In general, USP<621> chroma- of pharmacopeial standards. performance equivalence.
tography, revised changes Every year USP updates various Acknowledgements
are applying specifically to monographs and general chapters. 1. BNV Ganapati Rao, Head - CQC &
Compendial methods, however, However, while the revisions from ASAT,
may also be applied to other year-to-year may not be significant, Dr. Reddy’s Laboratories Limited
methods. if you are working with USP 2. Ramesh Nethala, Specialist - CQC,
monograph methods, it is strongly
o If the other test methods not recommended to pay attention to Dr. Reddy’s Laboratories Limited
meeting the revised requirements, each new USP-NF. 10. References
a detailed technical assessment System suitability testing (SST) is
shall be performed to provide required by USP and FDA to check 1. USP-NF 2022, General chapter <621>
Chromatography, official 01 Aug 2017 to 30
justification. In parallel alternate and ensure ongoing performance of Nov 2022.
method shall be developed and an analytical systems and methods. 2. USP-NF 2022, General chapter <621>
validated to comply the revised Both USP and EP have chapters Chromatography, official as of 01 Dec 2022.
changes. with recommendations for system 3. Leveraging Empower Software Solutions
to Manage Upcoming USP Chapter 621
suitability tests that are enforced changes, released on Aug 2022.
o All the current ongoing verifi- by FDA and EMA. 4. <621> Chromatography Notice and Chapter
cations and validations as per (posted 28-Oct-2022; official 01-Dec-2023)
USP are to be revisited to ensure In summary, the new General 5. Tony Tailor, Allowable Changes to
that they are in-line with the Chapter <621> Chromatography Chromatography Methods for HPLC – More
Freedom for Chromatographers Granted by
new calculations for system does reflect the excellent work of the Pharmacopeia’s February 3, 2023, LCGC
suitability. the pharmacopeia’s in supporting Blog
chromatographers to use more 6. Robert Pritchard, Mark Sharpiro,
o As an example, If the current modern technology for their Considerations for Replacing Deuterium
Lamps in HPLC Systems, March, 2019,
chromatography software fo- regulated methods, speeding AR&D, Cambrex, USA
C E
14 Spinco Biotech April 2023