Abstract
Drug products undergo many chemistry, manufacturing, and control (CMC) changes throughout their lifecycle, making the overall process costly and time consuming. The pharmaceutical industry and regulatory agencies rely on biopharmaceutics tools to make critical product quality performance decisions as part of drug product’s life cycle management. The application of these biopharmaceutics tools, and the requirements to support CMC, are described in several regulatory guidances1. However, the pharmaceutical industry has encountered many challenges in implementing current regulatory guidance describing the paths for waiving e.g., the bioequivalence requirements following moderate/major CMC2. In addition, there are no published guidelines on establishing the in vitro in vivo link, essential for the development of clinically relevant drug product specifications (CRDPS)/patient centric drug product quality. Recognizing these challenges, new tools and approaches are needed to decrease regulatory burden and enable flexibility in regulatory assessment (e.g., reducing the need for human experimentation). To this end, the concept of safe space has gained popularity among the scientific community, including regulatory agencies, as a more inclusive tool that does not precisely require the building of an in vitro-in vivo correlation (IVIVC) in support of major CMC changes3.
This presentation will discuss the concept of safe space and focus on:
- General considerations in the establishment of safe space via implementation of physiologically based biopharmaceutics/pharmacokinetics (PBBM/PBPK) modeling
- Data needed (IVIVC vs. IVIVR)
- Factors affecting the likelihood of success (i.e., regulatory approval)
- Considerations in PBBM development/validation and regulatory requirements
- Safe space regulatory applications
- Case studies (success and failure)
By Sandra Suarez-Sharp