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Multiobjective Design Method for the Use Processes of Pharmaceutical Excipients Considering Quality and Cost-Effectiveness

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Abstract

Purpose

Achieving cost-effectiveness while maintaining strict quality regulations is an emerging topic in pharmaceutical manufacturing. With a focus on the use process of excipients, e.g., reception, storage, testing, and actual usage, this paper presents a multiobjective design method for determining the optimal process setup.

Method

The method consists of setup of the problem, creation of models for quality and economic evaluation, and finally multiobjective optimization. A case study was performed using benzyl alcohol, an oxidation-sensitive material; we designated the amount of oxidized impurities and the costs associated with testing as the quality and economic objectives, respectively. The process was simulated, considering container volume and purchase frequency as the design variables, and also the use of Raman spectroscopy as an alternative to conventional identification testing.

Results

The multiobjective evaluation indicated options on the Pareto frontier, i.e., the set of non-dominant options. Here, the process with larger containers and less frequent purchases resulted in reduced testing costs but more impurities and vice versa for the opposite combination. The use of Raman spectroscopy was more effective in reducing the cost of identification testing than in preventing the degree of oxidation by not opening the container.

Conclusions

Through the case study, we showed that the method was capable of identifying the promising process settings, especially with the aid of graphical analysis on the Pareto frontier. The method, which is currently focused on excipients, could be extended to similar design cases using raw materials for pharmaceutical manufacturing.

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Acknowledgments

The authors are grateful for the discussions with the industrial experts from F. Hoffmann-La Roche Ltd. in Basel/Kaiseraugst as well as the International Society of Pharmaceutical Engineering (ISPE), Japan. Financial support by Grant-in-Aid for Young Scientists (B) No. 26820343 from the Japan Society for the Promotion of Science as well as Research Grant 2014 from Nagai Foundation Tokyo are gratefully acknowledged. T. I. thanks the Program for Leading Graduate Schools, “Global Leader Program for Social Design and Management (GSDM),” by the Ministry of Education, Culture, Sports, Science and Technology for financial support.

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Authors and Affiliations

  1. Department of Chemical System Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-8656, Tokyo, Japan

    Takayuki Iida, Kosuke Ota, Tomohito Sasozaki & Hirokazu Sugiyama

Authors
  1. Takayuki Iida
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  2. Kosuke Ota
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  3. Tomohito Sasozaki
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  4. Hirokazu Sugiyama
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Corresponding author

Correspondence to Hirokazu Sugiyama.

Additional information

Teaser: This paper presents a multiobjective design method for determining the optimal setup of excipients use processes, e.g., material reception storage testing and actual usage considering quality and cost-effectiveness.

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Iida, T., Ota, K., Sasozaki, T. et al. Multiobjective Design Method for the Use Processes of Pharmaceutical Excipients Considering Quality and Cost-Effectiveness. J Pharm Innov 10, 313–323 (2015). https://doi.org/10.1007/s12247-015-9228-3

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