Resumen de Quality by design through multivariate latent structures

Daniel Gonzalo Palací López

• The present Ph.D. thesis is motivated by the growing need in most companies, and specially (but not solely) those in the pharmaceutical, chemical, food and bioprocess fields, to increase the flexibility in their operating conditions in order to reduce production costs while maintaining or even improving the quality of their products. To this end, this thesis focuses on the application of the concepts of the Quality by Design for the exploitation and development of already existing methodologies, and the development of new algorithms aimed at the proper implementation of tools for the design of experiments, multivariate data analysis and process optimization, specially (but not only) in the context of mixture design.

  Part I - Preface, where a summary of the research work done, the main goals it aimed at and their justification, are presented. Some of the most relevant concepts related to the developed work in subsequent chapters are also introduced, such as those regarding design of experiments or latent variable-based multivariate data analysis techniques.

  Part II - Mixture design optimization, in which a review of existing mixture design tools for the design of experiments and data analysis via traditional approaches, as well as some latent variable-based techniques, such as Partial Least Squares (PLS), is provided. A kernel-based extension of PLS for mixture design data analysis is also proposed, and the different available methods are compared to each other. Finally, a brief presentation of the software MiDAs is done. MiDAs has been developed in order to provide users with a tool to easily approach mixture design problems for the construction of Designs of Experiments and data analysis with different methods and compare them.

  Part III - Design Space and optimization through the latent space, where one of the fundamental issues within the Quality by Design philosophy, the definition of the so-called 'design space' (i.e. the subspace comprised by all possible combinations of process operating conditions, raw materials, etc. that guarantee obtaining a product meeting a required quality standard), is addressed. The problem of properly defining the optimization problem is also tackled, not only as a tool for quality improvement but also when it is to be used for exploration of process flexibilisation purposes, in order to establish an efficient and robust optimization method in accordance with the nature of the different problems that may require such optimization to be resorted to.

  Part IV - Epilogue, where final conclusions are drawn, future perspectives suggested, and annexes are included.