(428a) Indicator-Based Supply Stability Analysis of Pharmaceutical Excipients: Method and Application

Pharmaceuticals contain multiple excipients to enhance their functionality and manufacturability, e.g., corn starch as diluent, titanium oxide as colorant, magnesium stearate as lubricant. In R&D of pharmaceuticals, experts select excipients on an empirical basis¹ considering product efficacy as the major criteria. In order to stabilize the global supply chain issues in the pharmaceutical industry², systematic consideration of supply aspects is needed. Several studies have assessed the supply of drug materials, e.g., model-based minimization of cost/environmental impacts of pharmaceutical materials such as general pharmaceuticals³ and vaccines⁴. However, a common approach is yet to be established for the evaluation of supply stability for pharmaceuticals.

This work presents an indicator-based method for supply stability analysis of pharmaceutical excipients and its application to commercial pharmaceutical products in Japan. The method quantifies the potential supply risk of the excipient compounds in a product mainly from the resource distribution perspective. The method defines the five steps: (i) list the excipient compounds of the drug products in scope, (ii) identify raw materials of each compound and collect data, (iii) calculate supply stability indicator at the element level, (iv) extend the indicator calculation to the compound level, and (v) evaluate the supply stability of the product. Herfindahl-Hirschman Index (HHI^5,6) provides the basis of the supply stability indicator, which quantifies how evenly the materials are distributed in the world. We extended HHI to consider governance of the countries where the element is originated, and also newly defined the compound-level indicator. As a case study, the method was applied to all products (n > 14,000) in the Japanese pharmaceutical market. The analysis revealed potential risks of several specific excipients. It also elucidated that the supply stability of pharmaceuticals varied depending on the dosage forms or target diseases. These finding would be useful especially in the early phase of drug development (e.g., excipient selection or even dosage form determination), which can contribute to the sustainable supply of pharmaceuticals.

References

1. Bejarano, A., Hewa Nadungodage, C., Wang, F., Catlin, A. C. & Hoag, S. W. Decision Support for Excipient Risk Assessment in Pharmaceutical Manufacturing. AAPS PharmSciTech. 2019;20:1-16.

2. Sayarshad, H. R. Personal protective equipment market coordination using subsidy. Sustain Cities Soc. 2022;85:104044.

3. Goodarzian, F., Hosseini-Nasab, H. & Fakhrzad, M. B. A multi-objective sustainable medicine supply chain network design using a novel hybrid multi-objective metaheuristic algorithm. International Journal of Engineering, Transactions A: Basics. 2020;33:1986-1995.

4. Chowdhury, N. R., Ahmed, M., Mahmud, P., Paul, S. K. & Liza, S. A. Modeling a sustainable vaccine supply chain for a healthcare system. J Clean Prod. 2022;370:133423.

5. Herfindahl, O. C. CONCENTRATION IN THE STEEL INDUSTRY. 1950;p.9.

6. Hirschman, A. O. The Paternity of an Index. 1964;54:761.