Conclusion

Conclusion

In the previous edition of this volume a conclusion was not presented. Even for the novice to pharmaceutical process engineering the technical and practical review presented was structured in a self-explanatory manner and represented the summary of thinking over many decades in chemical and mechanical engineering. A conclusion would have added little to enlighten the reader.

This edition is intended to suggest that while many of the engineering principles described previously have not changed and, indeed, are as relevant as they have ever been, the control of the quality of the product in a demonstrable and scientifically sound fashion has become a substantial consideration in the way that processes are managed. The Quality by Design (QbD) principles espoused by regulatory bodies, unlike the fundamental engineering consid-erations, are evolving and are based on relatively new developments in the fields of multivariate statistics and risk management. The danger in introducing these novel concepts to an introduction to engineering principles is to dilute the clarity and well-defined nature of the former with the more general essence of the latter. However, it would be irresponsible to suggest, particularly to those coming to this topic for the first time or with limited background, that engi-neering principles alone are of relevance to pharmaceutical process engineering at this juncture. There can be no question that the most substantial future developments will be in new methods of analysis or data collection that can be applied through QbD strategies involving information management and sta-tistical assessment to deliver rapid solutions to processing problems and in all probability to give real-time control of the variations in product output by manipulation of input variables.

It would be difficult to do justice to the principles of QbD, statistical exper-imental design, and Process Analytical Technology (PAT) without expanding the present text to a series of volumes on pharmaceutical process engineering. However, by including them as overviews, sufficient attention is given to these topics to give the novice a framework from which to continue to evolve an understanding, as their importance in product development activities increases.

In concluding this volume, a model is proposed for the relationship between the various components described and their application to process develop-ment. Figure 20.1 depicts the unit operations, shown originally in Figure 20.1 of chapter 1, and indicates the role that well-designed experiments followed by monitoring and control strategies may play in assuring the quality of the product and, thereby, ensuring both the safety and efficacy of dosage forms released for use in disease therapy.

The future of pharmaceutical process engineering will relate closely to developments in material science, analytical and information technology. It is anticipated that many new developments, particularly with respect to bio-technology, will be driven by efficiency in resource utilization, time, and expense to address the medical needs of more narrowly defined patient pop-ulations, as pharmacogenomics and the principles of individualized dosing begin to drive requirements for smaller but more controlled production than that of the 20th century. 

FIGURE 20.1 Monitoring and control of elements of the manufacturing process relating to product quality.

Indeed, while it may be many years before it is a common strategy, it can be anticipated that following statistically designed optimization, continuous processes under direct feedback monitoring and con-trol could routinely be used to produce product on any required scale (for example, gram to many kilogram quantities) to supply the demand without the need for serious depletion or accumulation of stock based on the arbitrary scale of batch production. Linking production to demand based on well controlled and predictable manufacturing represents an efficient commercial strategy.