Product Stability Issues

Book chapter – Steam Sterilization: A Practitioner’s Guide (Ch.23)

Chapter summary

BACKGROUND

Pharmaceutical products may exhibit thermal degradation. When developing and implementing a sterilization cycle, it is necessary to limit or balance the amount of product degradation while still using sufficient thermal input to achieve the desired sterility assurance level (SAL).
Some product types, e.g., low concentrations (
1%) saline, are extremely heat stable. Overkill-based sterilization cycles may be used to achieve the desired SAL. This is the typical approach used for many products manufactured
in Europe. Other products, however, are adversely affected by thermal input.
Degradation can lead to the final product not having the required potency, or the creation of degradation products in unacceptable levels. There are several ways to minimize the thermal degradation to the product while still achieving the desired SAL. This chapter discusses some of the requirements for sterilization-related stability studies and methods to reduce the thermalrelated product degradation when subjecting the product to a terminal sterilization cycle.

STABILITY TESTING REQUIREMENTS

– Maximum Fo
– Methods to Reduce Thermal Degradation of Product
– Change in Sterilization Process
– Presterilization of Some Components or Difficult-to-Sterilize Areas of the Product
– Changes in the Sterilization Model Utilized
– Aseptically Filling the Product Prior to Terminal Sterilization
– Reduce the Allowable Presterilization Bioburden
– Change in the BI for the Process

HIGHER TEMPERATURE – SHORTER TIME CYCLE

CHANGES TO A COMBINATION OF PARAMETERS

CONCLUSION

When evaluating the effects of the sterilization cycle on product stability, it is important to recognize that Fo alone cannot be correlated to product stability. For example, cycles using any of the sterilization models, any BI, and a variety of sterilization times and temperatures can all yield the same total Fo for a cycle. The effect on the product for each variation of the cycle may yield vastly different product degradation profiles. It is useful to perform some stability studies early in the product formulation development process to identify products that may be potentially subjected to a terminal sterilization cycle.

                                                                                                                                Courtesy of DHI Publications.