In GMP Trends Issue #1150, a noteworthy observation was reported regarding a bulk API manufacturer who validated a change in the batch size of a product but failed to put samples on stability. The specific observation reads as follows:
The process validation for …. Increase in batch size was inadequate….There was no provision for placing validation batches on stability
This oversight raises an essential question for quality assurance teams: Does your validation protocol explicitly require a stability study for validation batches, particularly in cases of process scale-up?
For any change in process, stability data serves as a safeguard, ensuring that product quality remains consistent throughout the product’s shelf life. Failing to place validation batches on stability testing can result in undetected issues that might affect product safety and efficacy once distributed.
A scale-up often involves variations in processing parameters and equipment usage that may affect the product. The conditions under which a larger batch is manufactured could introduce unexpected variances in quality attributes, which might not be apparent in smaller-scale productions. Stability testing allows for the verification of these attributes, identifying any degradation patterns unique to the larger batch size and ensuring that the product remains within specification.
In this instance, the manufacturer’s failure to include the scaled-up validation batches in stability studies is an example of a common GMP compliance gap. While the process change was validated, the absence of stability testing leaves an essential compliance element unaddressed. Quality assurance teams should review and, if necessary, revise their protocols to include a stability study requirement for all validation batches, especially during scale-up or process modifications.
Always remember:
- Review Your Protocol: Ensure your validation protocols mandate stability studies for all validation batches, particularly in cases of process scale-up.
- Incorporate Stability Testing Early: Establish stability study parameters before initiating scale-up to capture relevant data throughout the batch’s shelf life.
- Maintain Comprehensive Documentation: Proper documentation of stability data for scaled-up batches not only supports compliance but also strengthens product reliability and consumer trust.
- Update Procedures as Needed: Regularly update procedures to align with industry best practices and regulatory expectations.
By incorporating stability studies into validation protocols, manufacturers can better assure regulators and customers that each product batch—regardless of size or process adjustments—meets quality standards throughout its lifecycle.