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Quality by Design applications in biosimilar pharmaceutical products

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Abstract

A process is well understood when all critical sources of variability are identified and explained, variability is managed by the process design and monitoring, and product quality attributes are accurately and reliably predicted over the design space. Quality by Design (QbD) is a systematic approach to product development and process control that begins with predefined objectives, emphasizes product and process understanding, and sets up process control based on sound science and quality risk management. The Food and Drug Administration (FDA) and the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) have recently started promoting QbD in an attempt to curb rising development costs and regulatory barriers to innovation and creativity. QbD is partially based on the application of multivariate statistical methods and a statistical Design of Experiments strategy to the development of both analytical methods and pharmaceutical formulations. In this paper, we review the basics of QbD and their impact on the innovative, generic, and biosimilar pharmaceutical industry. In particular, we consider the challenge of mapping the control space in biotechnological processes and how advances in statistical methods can contribute to QbD.

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Abbreviations

API:

Active pharmaceutical ingredient

CQA:

Critical quality attribute

DP:

Drug product

FDA:

Food and Drug Administration

ICH:

The International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use

QbD:

Quality by Design

VoC:

Voice of the customer

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Authors and Affiliations

  1. KPA Ltd., Raanana, Israel

    Ron S. Kenett

  2. University of Torino, Torino, Italy

    Ron S. Kenett

  3. Teva Pharmaceutical Ind. Ltd., Rehovot, Israel

    Dan A. Kenett

Authors
  1. Ron S. Kenett
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  2. Dan A. Kenett
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Corresponding author

Correspondence to Ron S. Kenett.

Appendix: software products for simulations and QbD statistical analysis

Appendix: software products for simulations and QbD statistical analysis

Simulation experiments:

Statistical design of experiments:

Multivariate methods:

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Kenett, R.S., Kenett, D.A. Quality by Design applications in biosimilar pharmaceutical products. Accred Qual Assur 13, 681–690 (2008). https://doi.org/10.1007/s00769-008-0459-6

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  • DOI: https://doi.org/10.1007/s00769-008-0459-6

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