ICH Q12 Product Life Cycle Management
The ICH Q12 topic was endorsed by the ICH Steering Committee in September 2014 and the draft ICH Q12 Guideline on Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management was published for comment in December 2017. The final ICH Q12 Post-Approval Changes Guideline including two Annexes has been adopted in November 2019. The guideline aims to promote innovation and continual improvement, and strengthen quality assurance and reliable supply of product, including proactive planning of global supply chain adjustments.
The next phase will be the implementation of ICH Q12 across the ICH regions. However, especially in the EU, revision of local regulations (e.g. the EU Variations Regulation) will have to be performed to fully implement the concepts of Q12.
The new guideline has been developed to complement the existing ICH Q8 to Q11 guidelines, especially to enable full realization of more flexible regulatory approaches to post-approval CMC changes. The guideline applies to pharmaceutical drug substances and products (both chemical and biological). The guideline also applies to drug-device combination products that meet the definition of a pharmaceutical or biological product and to analytical methods.
In order to ensure a standardized approach, the guidance defines the categorization of Post-Approval CMC changes, Established Conditions (ECs), Post-Approval Change Management Protocols (PACMPs), and Product Lifecycle Management (PLCM) concepts. In particular, the guideline emphasizes the relationship between Regulatory Assessment and GMP Inspection.
Furthermore, the guideline describes how ECs are identified as well as what information can be designated as supportive information that would not require a regulatory submission, if changed. Guidance is also included for managing revisions of the ECs over a product’s lifecycle.
Conference presentations, case studies and open discussions will help participants learn more about the lifecycle management of pharmaceutical products and provide a forum for discussing ICH´s new Guideline.
Participants will thus have the opportunity to give feedback and ask questions directly to ICH´s Q12 Expert Working Group (EWG) members on how to move forward with the transition to and implementation of the lifecycle approach.
The meeting will also address topics such as:
- What are “Established Conditions” for Manufacture and Control?
- How could Postapproval Change Management Protocols look like?
- What is the impact of ICH Q12 on analytical method and process validation and transfer?
- What are the views and expectations of assessors and inspectors?
ICH Q2/ICH Q14 Analytical Procedure Life Cycle Management
As early as 2018, the ICH announced that the Q2(R2)/Q14 Expert Working Group (EWG) would develop a new ICH quality guideline, ICH Q14, for the development of analytical methods and revise the ICH Q2(R1) guideline for the validation of analytical procedures. This will complement the existing ICH Q8 to Q12 guidance and the current ICH Q13 guidance for continuous manufacturing. The new Analytical Procedure Development Guideline (Q14) will then be relevant for sections S4, P4 and P5 of the CTD and should be seen together with Q8(R2) and Q11 as a supplement to the guidelines. The use of the enhanced approach to analytical procedures development and validation can contribute to resource-efficient drug development as well as submission process or facilitate changes after CMC approval. The revised Q2(R1) guideline will also be relevant for sections S4, P4 and P5 of the CTD, with an emphasis on systematic analytical development. As development and validation are linked and subsequent steps, both guidelines will be worked on by the same Expert Working Group, with a potential to combine both documents into one.
The current Q2(R1) „Guideline on Validation of Analytical Procedures: Text and Methodology“ does not yet include modern analytical methods (e.g. near infrared (NIR) spectroscopy or Raman spectroscopy). This gap can lead to insufficient validation data for submissions and thus to additional official queries and thus to a delay in the approval of the application. This applies in particular to methods based on multivariate models, a category for which there is currently no guidance in ICH Q2(R1). NIR or Raman spectroscopy is often used in process control and real-time release testing (RTRT) using multivariate analytical methods. Therefore, the revision of ICH Q2(R1) will specifically serve the validation of modern analytical methods, including a discussion of statistical aspects. Common validation characteristics for methods such as NIR, nuclear magnetic resonance spectroscopy (NMR) and hyphenated techniques such as CE-MS, CE-ICP-MS, LC-NMR, GC-MS, LC-MS will also be considered.
Q14 Analytical Method Development Guide
As there is no ICH guideline for the development of analytical methods yet, it is often the case that applicants only report on analytical validation results and seldom present a performance evaluation with analytical development results. This makes communication with the regulatory authorities more difficult, especially when unconventional analytical methods are used (e.g. RTRT and multivariate models for process control). In addition, the lack of guidelines excludes the possibility for the applicant to provide a scientific basis for flexible regulatory approaches (e.g. Quality by Design (QbD) concept) to change analytical methods after approval.
According to ICH, the new directive is proposed to harmonise the scientific approaches to analytical process development and to provide the principles for the description of the analytical process development process. The new guideline should improve communication between industry and regulators and allow for more efficient, sound scientific and risk-based authorisation and change management for post-authorisation changes to analytical methods.
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 to ICH Q12, 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.
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,
- Requirements for validation data sets.