EMA NIRS Guideline, Reference

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2 EMA NIRS Guideline, Reference 27 January 2014 EMEA/CHMP/CVMP/QWP/17760/2009 Rev2 Guideline on the use of near infrared spectroscopy by the pharmaceutical industry and the data requirements for new submissions and variations In operation from 27 July 2014 The guideline should be read in conjunction with: Directive 2001/82/EC and Directive 2001/83/EC Ph. Eur. Monograph Near-infrared Spectroscopy Ph. Eur. Monograph demonstration of uniformity of dosage units using large sample sizes ICH Q2(R1) guideline on validation of analytical procedures Guideline on process validation ICH Q8, Q9, Q10 and ICH guideline Q8, Q9 and Q10 - questions and answers IFPAC LUNDSBERG - EMA's 2014 NIRS Guideline 2

3 Scope of the guideline The regulatory requirements for marketing authorisation applications and variation applications submitted for medicinal products for human or veterinary use, which include the use of NIRS Outlines the requirements for applications in which NIRS is used for qualitative and quantitative analysis or in PAT Approaches other than those described in this guidance may be used, if appropriately explained and justified The chemometric principles described may also be applicable to other analytical techniques NIRS for non-regulatory purposes, such as generating process knowledge, is out of scope of this guideline IFPAC LUNDSBERG - EMA's 2014 NIRS Guideline 3

4 Definitions NIRS Procedure NIRS Method NIRS Model Describes how the NIRS method and model are being used for the intended purpose Describes the key elements that enable the NIRS measurement of the analyte of interest. This includes for example, the equipment and spectrophotometer type (e.g. FT, grating etc), the sample measurement interface (e.g. probe, sample stage etc), the number of scans or measurements and the spectral range of the instrument Describes how the NIR spectral data are related to the analyte property of interest or the intended use of the procedure Ref: EMA Guideline on NIRS, EMEA/CHMP/CVMP/QWP/17760/2009 Rev2 IFPAC LUNDSBERG - EMA's 2014 NIRS Guideline 4

5 NIRS Scope The guideline introduces the concept of the NIRS procedure scope to facilitate continuous improvement and lifecycle management Changes within the approved scope of the NIRS procedure would be subject to GMP only (should be handled by own PQS) Changes outside of the approved scope of the NIRS procedure would be subject to variation application IFPAC LUNDSBERG - EMA's 2014 NIRS Guideline 5

6 The iterative nature of NIRS Ref: EMA Guideline on NIRS, EMEA/CHMP/CVMP/QWP/17760/2009 Rev2 IFPAC LUNDSBERG - EMA's 2014 NIRS Guideline 6

7 NIRS Procedure IFPAC LUNDSBERG - EMA's 2014 NIRS Guideline 7

8 Element Specific requirements, examples Qualitative (ID, qualification, conformity) Quantitative Chemometric algorithm X X Sample collection and population Calibration X X Calibration set X Number of samples >> # latent variables Internal validation set X X External validation set - Cover entire calibration range incl normal commercial process variation (incl end-point) - Positive and Negative samples included Risk assessment X X X Reference Analysis Number of replicates to be justified # of Latent variables - Understand variability, prediction variance components - Of the order of number of significant sources of variations (understand the main feature of the variables) - Co-linearity Calibration model assessment - SEP, SEC, SECV - Plot SEP and SEP versus # latent variables - Plot ref versus prediction - Suitability of model SEP/SEL - Calibration Range > 10 x SEP Acceptance limits/criteria X X IFPAC LUNDSBERG - EMA's 2014 NIRS Guideline 8

9 Model validation Element Qualitative method Quantitative method Specificity X X Linearity and range X Range X Accuracy X Precision X Robustness X X Limit of detection When relevant Limit of quantification When relevant IFPAC LUNDSBERG - EMA's 2014 NIRS Guideline 9

10 Addendum 27 January 2014 EMA/CHMP/CVMP/QWP/63699/2014 Addendum to EMA/CHMP/CVMP/QWP/17760/2009 Rev 1: Defining the Scope of an NIRS Procedure A fictitious example of the scope for an NIRS procedure used for release testing for assay and CU of the active substance in a finished product (uncoated tablet) and how changes to this scope would be managed according to the guideline IFPAC LUNDSBERG - EMA's 2014 NIRS Guideline 10

11 Approved method scope for an assay and CU NIRS procedure, example IFPAC LUNDSBERG - EMA's 2014 NIRS Guideline 11

12 Changes within the scope IFPAC LUNDSBERG - EMA's 2014 NIRS Guideline 12

13 Changes outside the scope IFPAC LUNDSBERG - EMA's 2014 NIRS Guideline 13

14 Conclusion The guideline is helpful and outlines which data to submit in relation to a NIRS procedure and a PAT application The NIRS Procedure will evolve over time so a practical lifecycle management approach is important The Addendum helps to understand the purpose of the NIRS Scope and how to handle the lifecycle management Based on current experiences from the industry and inspections it would be beneficial to evaluate the appropriateness of the addendum and the proposed variation approaches, aiming at a faster and more efficient lifecycle management approach IFPAC LUNDSBERG - EMA's 2014 NIRS Guideline 14

15 Thank you for your attention! Line Lundsberg, PhD Lundsberg Consulting Ltd Lundsberg, QbD and PAT in Manufacturing, Ann Sym