| August 29, 2022 | By
Pharmaceutical industry groups praised aspects of the International Council for Harmonization (ICH) Q14 and Q2(R2) draft guidelines, but questioned how improving knowledge of analytical methods should be conveyed in regulatory submissions and whether small businesses would have the resources to invest in the improved approach in Q14.
Other groups had questions related to the use of multivariate modeling in the development of analytical methods. In addition, calls have been made for better integration of the two guidelines.
The comments were submitted in response to the European Medicines Agency’s (EMA) call for comments on the two guidance documents. (RELATED: ICH publishes draft guidelines on the development of analytical methodsRegulatory guidance March 31, 2022)
The guidelines should make it easier for manufacturers to switch analytical methods to test drugs after approval and aim to promote more robust analytical processes.
Meanwhile, the U.S. Food and Drug Administration (FDA) on Friday released ICH Q14 and Q2(R2) for public comment, along with a slew of other ICH guidance documents.
The Q14 guideline would harmonize scientific approaches for the development of analytical procedures while the Q2(R2) document covers validation principles for the use of analytical procedures such as near infrared (NIR) based analysis and spectroscopy. Raman, which often require multivariate statistical analyses. .
EFPIA: Q14 framework is reasonable
The European Federation of Pharmaceutical Industries and Associations (EFPIA) said that the ICH Q14 guidelines “provide a reasonable framework for the development of analytical procedures and the management of the life cycle of methods” and that the examples provided in the annexes are “very useful”.
However, the EFPIA said it was unclear how improved knowledge should be conveyed in a submission. “The guide is short on expected/anticipated content to communicate enhanced knowledge in a submission. This must be globally accepted for appreciable benefit. Great value will exist in future implementation training case studies to ensure alignment between industry and regulators on regulatory change management expectations.
The 64-page ICH Q14 document proposes to harmonize scientific approaches for the development of analytical procedures by describing a minimal or improved approach. It also describes the elements of an Analytical Target Profile (ATP) that is incorporated into the enhanced approach.
Parexel wonders how small regulators will review multivariate approaches
Parexel said it is unclear how smaller regulators will consider the multivariate models required in the development of analytical procedures in ICH Q14. The company wrote that using these models “will require specialized review staff. Traditional CMC reviewers are chemists or biologists, not trained in complex analytical mathematics. The company added that “smaller agencies may not to be able to manage this type of information”.
Instead, Parexel suggested that multivariate approaches should be optional and that summaries of these approaches should be written “in language understandable to non-experts.”
EFPIA said the guidance should provide more examples showing how multivariate models can be used for training purposes.
Adoption of Q14 questioned by small businesses
Similarly, Jazz Pharmaceuticals wondered if smaller companies would have the time and resources to implement the improved method validation approach.
“The additional time and resources required to apply the improved approach will likely be more difficult for smaller biopharmaceutical companies to integrate, and therefore less likely to be used. A risk-benefit assessment of the methods will be needed to identify where this approach would be applied most effectively and most beneficial for lifecycle management when resources are limited,” Jazz wrote.
More integration with ICH Q2
The European Compliance Academy Foundation/European QP Association called for more alignment between Q14 and ICH Q2, saying that ICH “has failed to write a single, integrated document to provide a comprehensive approach to the development, validation and operational use of procedures Integrate ICH Q2 with Q14. ”
The EFPIA agreed, writing that “a better link is needed between Q2 and Q14, both in terms of the relationship between the guidelines and agreement on the terms and concepts used”.
For example, there should be additional text providing cross-references to Q14 in the introduction as well as more consistent use of the term ‘performance criteria’.
In other areas, the International Society for Pharmaceutical Engineering (ISPE) found several sections of the draft ICHQ2(R2) revision “difficult to follow because information on related validation points is spread across different sections and , in some cases, details are not well aligned between sections.
The company offers mixed praise for Q2 (R2)
Fujifilm Diosynth Biotechnologies Denmark expressed both support and criticism of Q2(R2).
The company wrote that “there are a lot of improvements in the guideline in terms of clarifying R1’s issues and making the guidelines much clearer.”
However, the guidelines must take into account the progress made in statistical software. “Nearly 30 years have passed since the first trio of Q2As were published and, among other developments, statistical software for designing and evaluating validation studies has grown tremendously over this time.”
FDA begins consultation
The agency also released the final ICH E14 and S7B versions. question and answer guide on clinical and non-clinical evaluation of QT/QTc interval prolongation and proarrhythmic potential.
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