ATMPs

Step 1: Review EMA Guidelines for ATMPs

Begin by thoroughly reviewing the EMA guidelines for ATMPs, such as the “Guideline on Quality, Non-clinical and Clinical Requirements for Investigational Advanced Therapy Medicinal Products in Clinical Trials.” These guidelines provide specific requirements for stability testing, including storage conditions, testing intervals, and acceptance criteria. Access these documents on the EMA website: EMA Guidelines.

Step 2: Develop a Stability Protocol for ATMPs

Create a comprehensive stability protocol that aligns with EMA guidelines. The protocol should outline the study design, storage conditions (e.g., cryopreservation at -150°C or below, refrigerated at 2°C to 8°C), testing intervals, and sample sizes. Specify the quality attributes to be tested, such as cell viability, potency, sterility, and identity. Ensure that the protocol addresses any specific requirements related to the ATMP’s formulation, such as its sensitivity to temperature changes, light, or pH fluctuations.

Step 3: Select Representative Batches for Testing

Select at least three primary batches of the ATMP for stability testing. These batches should be manufactured using the same process, formulation, and packaging intended for commercial production. Document all relevant details about the batches, including batch numbers, manufacturing dates, and any changes in the manufacturing process.

Step 4: Conduct Stability Testing Under Defined Conditions

Conduct stability testing under the defined storage conditions using validated stability chambers that maintain the required temperature levels. Perform tests at defined intervals to monitor the stability of the ATMP. Use validated analytical methods to test samples for all specified quality attributes, ensuring compliance with EMA guidelines.

Step 5: Analyze and Interpret Stability Data

Analyze the stability data using appropriate statistical methods to evaluate the product’s shelf life and storage conditions. Ensure that the data meets the acceptance criteria outlined in the stability protocol and supports the proposed shelf life. Consider factors such as cell viability, potency, identity, and the biological activity of the ATMP.

Step 6: Prepare a Comprehensive Stability Report

Compile a detailed stability report summarizing the study results, data analysis, conclusions, and any recommendations for the ATMP’s shelf life and storage conditions. Ensure that the report complies with EMA submission requirements and is suitable for submission to regulatory authorities.

Practical Tips and Resources

Tip 1: Use Cryopreservation Techniques

Implement cryopreservation techniques to maintain cell viability and stability during storage and transportation, especially for cell-based ATMPs.

Tip 2: Regularly Monitor Critical Quality Attributes

Regularly monitor critical quality attributes, such as cell viability, potency, and biological activity, throughout the stability study to ensure the ATMP maintains its intended quality.

Reference to Regulatory Guidelines

For more details on stability testing for ATMPs, refer to the EMA Guidelines.

Summary

Conducting stability testing for Advanced Therapy Medicinal Products involves understanding EMA guidelines, developing a tailored stability protocol, selecting representative batches, conducting tests under specified conditions, analyzing data, and preparing a comprehensive report. By following these steps, manufacturers can ensure compliance and facilitate successful regulatory submissions for ATMPs.