Maximizing and validating the stability of a drug is critical throughout its life cycle, beginning in the development phase of an active pharmaceutical ingredient (API), continuing through the final formulation process, and following commercialization as part of post-marketing product analysis.
The assessment of a compound’s chemical and physical characteristics, potency, activity, solubility, and appearance after storage under a variety of defined conditions can guide decision making on which experimental candidate to take forward, or may signal the need to reengineer a lead compound to enhance its stability before initiating costly preclinical and clinical studies.
The stability of a drug, whether a small molecule or a larger biopharmaceutical such as a protein, is an essential part of analytical testing to ensure the identity and activity of the API, assess the final formulation, and detect degradation products or aggregates that might contribute to increased risk of adverse effects and toxicity.
Two years ago, the ICH Steering Committee endorsed the establishment of a Quality Implementation Working Group to monitor the consistent, global implementation of the Q8 (Pharmaceutical Development), Q9 (Quality Risk Management), and Q10 (Pharmaceutical Quality System) guidelines that were established in 2003. These recommendations represented a departure from traditional approaches to quality guidance and emphasized a quality system built on risk- and science-based strategies.
Stefan Adam, Ph.D., director of analytical development and quality control at LifeCycle Pharma, emphasized the importance of applying ICH Q8, Q9, and Q10 guidelines to the early phases of small molecule drug development in his presentation at Bharat Book’s “Stability Testing” conference held earlier this month in London. The outcomes of early-stage testing, including analysis of a compound’s chemical or physical incompatibility, could then be applied to the selection of excipients for formulating the API into a drug product. This type of risk management-based approach can benefit from close interaction between the analytical, formulations, and manufacturing teams.
Risk management is an important component of a proactive stability program, in Dr. Adam’s view. The ability to predict probability of success by performing sound risk assessment at every step of developmentis a valuable tool that can save companies time, resources, and money. For example, from the beginning a company should perform diligent forced-degradation and excipient-compatibility studies and use the results together with data obtained from bulk stability testing and evaluation of the packaging material to predict early on a long-term stable formulation.