New ICH Topic Q14 and Revision of Q2

Recommendation

5-7 November 2024
Hamburg, Germany

GMP meets Development
GMP and FDA Compliance in Pharmaceutical Development and IMP Manufacturing

The ICH recently announced that the Q2(R2)/Q14 Expert Working Group (EWG) will develop a new ICH Quality Guideline, ICH Q14, on Analytical Procedure Development, and revise the ICH Q2(R1) Guideline on Validation of Analytical Procedures. These proposed guidelines (Q2(R2) and Q14) are intended to complement the existing ICH Q8 to Q12 guidelines, as well as the on-going ICH Q13 guideline for Continuous Manufacturing.

Background to the Proposal

According to ICH, an EWG composed of experts with expertise in the area of analytical chemistry and pharmaceutical control will work on the new Analytical Procedure Development guideline (Q14), which will be relevant for the sections S4, P4 and P5 of the CTD and which will complement with Q8(R2) and Q11. Using the enhanced approach for analytical procedures can contribute to resource-efficient drug development and post-approval CMC changes. The revised Q2(R1) guideline will also be relevant for the sections S4, P4 and P5 of the CTD with emphasis on systematic Analytical Development. As analytical development activities are followed by analytical validation activities, the two tasks will be conducted by one EWG.

 Q2(R1) Revision

According to ICH, the current Q2(R1) “Guideline on Validation of Analytical Procedures: Text and Methodology” does not cover modern analytical procedures, (e.g., Near Infrared (NIR) Spectroscopy or Raman Spectroscopy). The lack of guidance for these analytical methods can lead to submissions with inadequate validation data for such analytical procedures, resulting in recursive information requests and responses, which can delay application approval. This is particularly the case for procedures reliant on multivariate models, a category for which currently no ICH validation guideline exists. NIR or Raman Spectroscopy are commonly used in process control and real time release testing (RTRT) using multivariate analysis methods. According to ICH, the scope of the revision of ICH Q2(R1) will therefore specifically address validation of modern analytical procedures including a discussion of statistical aspects in validation together with common validation characteristics for procedures, like NIR, nuclear magnetic resonance spectroscopy (NMR), and hyphenated techniques, for example CE-MS, CE-ICP-MS, LC-NMR, GC-MS, LC-MS.

Q14 Analytical Procedure Development Guideline

Since there is currently  no ICH guideline on Analytical Procedure Development, applicants often report analytical validation results alone and rarely present performance evaluation with analytical development outcomes. This makes regulatory communication ineffective especially when non-conventional analytical procedures are employed (for example, RTRT and multivariate models for process control). Additionally, the lack of guidelines precludes the applicant from an opportunity to present scientific basis for flexible regulatory approaches (e.g., Quality by Design (QbD) concept) to post-approval analytical procedure changes.

According to ICH, the new guideline is proposed to harmonize the scientific approaches of analytical procedure development, and to provide the principles relating to the description of the analytical procedure development process. The new guideline is intended to improve regulatory communication between industry and regulators and facilitate more efficient, sound scientific and risk-based approval as well as post-approval change management of analytical procedures.

Issues to be addressed

Q14 Analytical Procedure Development guideline
Main technical and scientific elements, which require harmonization, include:

• Submission of analytical procedure development and related information in CTD format,
• The concept and strategy of enhanced approaches for analytical procedures,
• Performance criteria of analytical procedures,
• In line with ICH Q8 and ICH Q11, a greater understanding of analytical procedures can create the basis for more efficient, sound science and risked-based lifecycle management (e.g., using analytical QbD (AQbD) principles),
• Key elements and terminology,
• Demonstration of suitability for RTRT.

Q2(R1) Revision
For procedures reliant on multivariate methods the following will be addressed:

• Definition of validation characteristics applicable to multivariate methods which may differ with the area of application (e.g., identification vs. quantitation, batch vs. continuous process, dosage form assay vs. blending monitoring),
• Important method parameters (e.g., the number of latent variables) established during method development,
• Robustness which is well understood, however does not have a quantitative measure,
• Inclusion of post-approval verification and maintenance considerations as a part of the validation (control strategy),
• Requirements for validation data sets.

The possible Step 2a/2b endorsement for both guidelines is currently expected for spring 2020. More information can be found on the ICH Quality Guidelines webpage.