Case Study
Overview
A mid-size pharmaceutical company submitted commercial tablets for two dose strengths, but global regulatory agencies pushed back on the proposed dissolution specification and asked for stronger justification to avoid risks of manufacturing non-compliance. The company wanted a faster, more cost-efficient method to address regulatory questions than traditional clinical trials.
No
Delay to product launch
12x
Return on investment
Challenge
The sponsor’s proposed dissolution specification was Q80% at 45 minutes. Dissolution testing of production batches showed results close to or failing the proposed agency limits, creating the risk of:
- Out-of-specification (OOS) batches during routine manufacturing, projected at 5–10% of annual production, equating to an estimated $1M USD in losses per year.
- The possibility of being forced into a costly clinical trial program to justify dissolution specifications.
The company needed a solution that would provide robust regulatory justification without incurring prohibitive costs or delays
Solution
The team decided to use GastroPlus® physiologically based pharmacokinetic (PBPK) modeling, validated across clinical datasets, to predict drug performance under various dissolution conditions. By integrating this advanced modeling approach into their biopharmaceutics risk assessment and regulatory strategy, the company achieved outcomes that would have otherwise required costly, time-intensive clinical studies. Specifically, the PBBM was used to:
- Run virtual bioequivalence (VBE) trial simulations.
- Justify wider dissolution specifications for both dose strengths.
- Present regulators with mechanistic evidence supporting the proposed limits.
This approach required only a one-time cost of $0.2M USD, a fraction of the cost of running new clinical trials.
Results
The modeling-based submission was accepted by regulators, providing clear benefits:
- Avoided annual OOS losses of ~$1M USD.
- Eliminated the need for costly clinical studies, estimated at $7M USD plus $0.5M in manufacturing costs.
- Accelerated approval timelines, ensuring no delay to product launch.
By utilizing PBPK modeling, the sponsor not only secured regulatory approval but also demonstrated a strong return on investment (ROI)—between 12x and 45x, depending on the alternate route chosen.
Advanced modeling strategies can save time, reduce cost, and optimize commercial success.
