Stability in early-stage development

Stability is essential in early-stage product development because it helps predict how a drug will perform over its intended shelf life, under various conditions.  Identifying potential stability issues early allows researchers and developers to make informed decisions about formulation, packaging, and storage, ultimately saving both time and money. This proactive approach minimizes the risk of costly failures later in the development process, ensuring that the product remains effective and safe for its intended use. Balancing thorough stability testing with efficient resource use is key to achieving the best outcome and optimising the investment in the early stages of development.

Time and money….critical elements in early-stage development as companies continuously weigh the risks and rewards of their drug development investment.  We understand effective stewardship and carefully designed experiments are crucial for navigating these challenges.  In the early stage development, companies may opt to sacrifice formality to achieve a more nimble and flexible process.  Decision points in early development could be more frequent which may have immediate impact on a particular direction requiring the study to pivot, or return to start again.  We’ve provided some insight into a streamlined approach to early-stage development below:

  • When planning your stability study, the design elements should be implemented with a clear understanding of the product and objective. Understand what the goal is, then focus on the process to get there.  It is not a straight line…
  • Collect comprehensive information such as active constituent, formulation type, dose, proposed packaging material, size and fill volume. Understanding the composition of the product may assist to identify any unique characteristics that might influence stability;
  • Talk to the active constituent supplier, search literature (patents, journals) for greater understanding of the active ingredients and formulation specifics helps identify potential stability issues. Factors like chemical reactivity, interactions, and environmental sensitivity should be considered.
  • Understand what you are working with – how much active constituent is available, how long does it take to source, what is the best use for what you have available?
  • Be mindful of the volume of product available for stability, sometimes this can be quite limited. Choose to fill smaller volume packaging that reflects the intended packaging ie. similar surface exposure and headspace, same closure;
  • Have sufficient product available to perform the required testing at each timepoint, but most importantly, have sufficient packs available to extend the study if needed. This avoids interruptions if the study needs to be extended;
  • Design R&D studies with shorter stability timepoints initially (days, weeks), having additional product available to extend into months. Keep the information flowing to the development team;
  • Consider the opportunities and risks of using accelerated stability protocols eg. 40°C/ 75% relative humidity; This can assist predict how the product will fare under long-term storage conditions more quickly;
  • Focus on test parameters that will provide essential stability data, such as active ingredient concentration and physical changes;
  • Use fit-for-purpose analytical methods – analytical methods used do not need to meet full regulatory validation standards at this stage but should be adequate for assessing the key stability parameters;
  • Define clear goals for the stability study (both short and long-term);
  • Be prepared for potential setbacks. Understanding that failure can provide valuable insights helps in managing the R&D process effectively;
  • Review and communicate outcomes clearly and regularly (even if it is disappointing news);
  • Maintain objectivity, have more than one expert opinion available at review;
  • Identify milestones and criteria for making decisions about whether to continue or alter the study. Having clear exit points ensures timely decisions and efficient resource use.

At Pia Pharma we understand that by carefully managing these elements you can gain valuable insights into the stability of your candidate formulations while keeping the development process efficient and within budget.  We are always available to discuss your development options, mindful we have formulation and regulatory expertise that can accelerate this process beyond expectation to get your project further faster.