In-use stability and compatibility studies are often used in biotherapeutic development to assess biologic drugs with diluents and/or administration components. The studies are done in conditions that are relevant for the target route of administration (usually intravenous, subcutaneous, or intramuscular) to ensure that patient safety and product efficacy are maintained during clinical use.
To understand the current industry position on these studies, BioPhorum’s Development Group Formulation Workstream collaborated on five benchmarking surveys for biologic drugs.
The results have been published in An Intercompany Perspective on Compatibility and In-Use Stability Studies to Enable Administration of Biopharmaceutical Drug Products.
Douglas Kamen, Associate Director of Formulation Development at Regeneron Pharmaceuticals, said that the questions “were developed by the authors, who are researchers in the field and wanted the answers for themselves. They developed a set of practices that work, but not a single set of best practices. Because all these methods work, you can select what is best for the particular needs of your own company’s clinical program”.
To provide a comprehensive picture of common industry practices, the surveys assessed areas including
- Regulatory strategies and feedback
- Clinical in-use formulation, patient, and site considerations
- Clinical blinding, masking, and placebo approaches
- Study setup, execution, and reporting
- Clinical and in-use stability testing.
The results indicated diverse practices in all these areas but noted that the different approaches supported successful clinical studies. The varied practices may stem, in part, from the different molecular modalities, routes and modes of administration, the stability profiles, and the different therapeutic areas and clinical needs for which they are designed.
George Crotts, Director at GlaxoSmithKline, elaborated: “The diversity in approaches is not a bad thing. This group of authors has identified the allowable variability and flexibility in approaches, while at the same time providing insight for the boundaries on times, volumes, temperatures and other parameters utilized across the industry. This cross-company collaboration is an excellent way to significantly improve product quality.”
Published in the Journal of Pharmaceutical Sciences, the paper also presents various approaches that can be used to guide the strategy and design of an in-use stability and compatibility program based on clinical and biomolecule needs.
“What we learned is that there is no single guidance,” said Chakravarthy Narasimhan, Senior Principal Scientist at Merck, “but instead there are multiple ways to conduct these studies, and regulatory bodies are accepting a variety of methods. This diversity of approaches means that there is a clear need to propagate this information to pharmaceutical companies, so they can develop robust injectable products.”
With the increased complexity of biopharmaceutical modalities, study sponsors and stakeholders must develop appropriate in-use stability and compatibility practices. This paper provides insights for biopharmaceutical companies into the practicalities of these studies and how they are being used to support the administration of biologics from early clinical programs to marketed products.