New ICH quality guidelines proposed

Sandra Maguire, Senior Manager, Regulatory Affairs at G&L, looks at new guidelines issued by the ICH and outlines the objectives and potential benefits of the proposals on Analytical Procedure Development.

Background:

New guidelines aimed at making it easier for manufacturers to switch analytical methods for testing medicines post-approval have been issued by the International Council for Harmonization (ICH).

It is also hoped that once introduced, the procedures will promote more robust analytical processes.

Two proposals have been issued by the European Medicines Agency (EMA) for public consultation - Q14 Analytical Procedure Development Guideline is a brand-new guideline while Q2 Validation of Analytical Procedures is a Revision of the previously issued proposition.

Both mark a major milestone in their respective fields as before their release, there was no ICH guideline on analytical procedure development. Previously, applicants had to report analytical validation results alone without any data to support analytical development outcomes.

This distinct lack of framework made it impossible for applicants to present a scientific basis for flexible regulatory approaches to post-approval analytical procedure changes.

The proposals:

Q14 is designed to harmonize the scientific approaches to Analytical Procedure Development and provide the principles relating to the description of Analytical Procedure Development process.

The guideline describes science- and risk-based approaches for developing and maintaining analytical procedures suitable for the assessment of the quality of drug substances and drug products.

It applies to new or revised analytical procedures used for release and stability testing of commercial drug substances and products (chemical and biological/biotechnological).

It can also be applied to other analytical procedures used as part of the control strategy following a risk-based approach.

Q14 is intended to complement ICH Q2 Validation of Analytical Procedures which has been completely revised to include more the recent application of analytical procedures.

These include validation principles that cover analytical use of spectroscopic or spectrometry data (e.g., NIR, Raman, NMR or MS) as well as continuing to provide a general framework for the principles of analytical procedure validation applicable to products mostly in the scope of Q6A[i]and Q6B[ii].  

Q2(R2) and Q14 are intended to complement ICH Guidelines Q8 to Q12, as well as ongoing ICH Q13 for Continuous Manufacturing 

Guideline objectives/expected benefits:

The ICH summarizes the objectives and expected benefits of the revised Q2 and Q14 as follows[iii]:

Q2(R2) objectives:

• Presents a discussion of elements for consideration during the validation of analytical procedures included as part of registration applications submitted within the ICH member regulatory authorities.
• Guidance and recommendations on how to derive and evaluate the various validation tests for each analytical procedure.
• Serves as a collection of terms and their definitions.
• Bridge the differences that often exist between various compendia (BP, EP, USP, JP) and documents of the ICH member regulatory agencies.
• Indicates the data which should be presented in a regulatory submission.

Q2(R2) expected benefits:

• Encouragement of the use of more advanced analytical procedures leading to more robust quality oversight by pharmaceutical drug manufacturers
• Adequate validation data, resulting in the reduction of information requests and responses, which can delay application approval. Not only could a Q2 which overarches and ameliorates divergent compendial requirements reduce the risk of agencies seeking additional validation data, but an internationally recognised method of validation could also allow for greater harmonisation of the product dossier in different regions.
• Modernisation of general methodology to include analytical procedures and data evaluation for biotechnological products and statistical/multivariate data evaluations.
• Incorporation of the principles described in ICHQ8-Q10 which did not exist when Q2 (R1) was issued.

Q14 objectives:

• Describes science and risk-based approaches for developing and maintaining analytical procedures fit for intended use, in line with the systematic approach suggested in ICH Q8 and using principles of ICH Q9.
• Specifies a minimal approach and elements of an enhanced approach for analytical procedure development.
• Describes considerations for the development of multivariate analytical procedures and real-time release testing (RTRT).
• Provides principles to support change management of analytical procedures based on risk management, comprehensive understanding of the analytical procedure and adherence to predefined criteria for performance characteristics.
• Includes submission considerations of analytical procedure development and related lifecycle information in the Common Technical Document (CTD) format.

Q14 expected benefits:

• Harmonization of scientific approaches, key factors, and terminology for analytical procedure development.
• Increased understanding of analytical procedure.
• Employing predefined performance characteristics guides development and facilitates regulatory change management of analytical procedures.
• Enabling preventative measures and facilitating continual improvement by using more analytical procedure knowledge.
• Reducing the amount of effort across the analytical procedure lifecycle.
• Guidance on demonstration of the suitability for real-time release testing.

Deadlines:

Comments on the proposals are currently being accepted by the EMA and will help shape the final draft of the guidelines.

The public consultation closes on 31 July 2022 with the targeted implementation of the guidelines in May 2023.

The comments form can be found here

[i] Q6A - Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products

[ii] Q6B - Specifications: Test Procedures and Acceptance Criteria for Biotechnology/Biological Products

[iii] ICH Q2(RE2) Q14 Step 2 Presentation 24 March 2022