ICH Q12 Examples – Pharmaceutical Product Lifecycle Management Examples – FDA Guidance
One of the main things to consider after the QbD development phase is the Post Approval Change Lifecycle Management. ICH Q12 guidance addresses this phase. For us QbD and PAT scientists, it would be good to prepare for this before and during scale up or tech transfer phases. This also shows the regulatory agency’s push for QbD and PAT driven solutions in the industry.
On May 11, 2021, FDA (Food and Drug Administration) published examples for the industry entitled “Q12 Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management.” This new guidance provides a framework and examples to facilitate the management of post-approval CMC (chemistry, manufacturing, and controls) changes for new and marketed pharmaceutical drug substances and drug products, including chemical and biotechnological or biological products.
ICH Q12, which was adopted as an ICH Guideline in November 2019, established which parts of an application are considered necessary to require a regulatory submission – if changed postapproval. The guidance includes ICH regulatory tools that should enhance the manufacturer’s ability to manage CMC changes effectively under the company’s Pharmaceutical Quality System (PQS) with less need for extensive regulatory oversight prior to implementation.
The Q12 guidance is intended to complement the existing Q8(R2)-Pharmaceutical-Development, Q9-Quality-Risk-Management, Q10-Pharmaceutical-Quality-System, and Q11-Development-and-Manufacture-of-Drug-Substances guidances. And as usual, guidances should not be used as a template or the only justification for regulatory submission.
What is in the updated ICH12 Example guidance:
This updated ICH Q12 document contains:
- Manufacturing process examples for a small molecule – Powder Blending Unit Operation
- Manufacturing process examples for a large molecule – Monoclonal Antibody
- Production Culture
- Anion-Exchange Chromatography
- Analytical Procedures
- Examples of Post Approval Change Management Process (PACMP) for Manufacturing Site Transfers
- An example of Product Lifecycle Management (PLCM) document
- A structured approach to analytical procedure changes
The document illustrates the use of ICH 12 through the progression of three categories:
- Minimal Parameter-Based Approach
- Enhanced Parameter-Based Approach
- Performance-Based Approach – performance-based control strategy
The final category of the Performance-Based Approach gives examples of using performance-based control strategies such as NIR analyzers to monitor the ECs in real-time.
Takeaways:
Enhanced knowledge reduces uncertainty, demonstrating that a material attribute or process parameter initially considered potentially critical in a minimal approach is not actually critical—i.e., does not have an impact on product quality and, therefore, is not an Established Condition.
Risk management activities could lead to different reporting categories—e.g., a change from prior approval (PA) to a notification for a change to a critical process parameter (CPP). Where the performance-based approach is used, some process parameters may not be classified as ECs due to assurance of quality being provided by online monitoring.
In this circumstance, the typical operating conditions for process parameters are provided as supportive information. During manufacture, the process parameters may be adjusted to deliver the expected outcome. The risks related to the in-line Process Analytical Technology (PAT) tests (e.g., near-infrared (NIR)) should be appropriately managed throughout the lifecycle. In-line PAT tests used for quality control are considered ECs.
Increased knowledge and understanding from more development approaches lead to a reduction of uncertainty and improved management of risk. As a result, Established conditions (EC)s could become less extensive and reporting categories more flexible.