By Tim Freeman, Managing Director, Freeman Technology 

In recent decades, the pharmaceutical industry has employed innovative, cutting edge technology to undertake research, and to develop new drugs which deliver immense value to society. In comparison, there has been relatively little emphasis on manufacturing processes, so many of these products are still typically produced using batch processes that have been developed empirically and that are also relatively inefficient. The introduction of initiatives such as Quality by Design (QbD) and Process Analytical Technology (PAT) by the Food and Drug Administration (FDA) are encouraging the industry to apply its considerable skills to address this imbalance in order to positively transform process operations and improve overall manufacturing efficiency. One of the areas that will be crucial to this transformation is a better understanding of powder behavior, since almost all pharmaceutical products are handled in powder form at some point during the manufacture cycle. Modern powder characterization techniques will make an important contribution to better understanding by providing process relevant data that can then be used to convert process experience, or fundamental information about a specific product, into more valuable knowledge. 

ICH (International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use) Guideline Q8: Pharmaceutical Development describes the principles of QbD. It suggests that the industry should switch from an approach that uses retrospective testing to assess quality, to one that proactively targets quality metrics throughout the product development and manufacturing processes. PAT is an FDA initiative which is designed to facilitate the implementation of new analytical technologies. Its aim is to encourage improvements in efficiency by reducing the regulatory burdens that restrict the adoption of novel innovations in the processing arena.

The underlying message of both QbD and PAT is that the industry needs to improve understanding and adopt a knowledge-based approach to product development, process optimization and manufacturing. QbD and PAT are symbiotic rather than distinct. QbD encourages a better understanding of both the materials and the process at the earliest possible stage, as well as the identification of Critical Process Parameters (CPP) that need to be closely monitored and controlled. Relevant analytical technologies enable the gathering of information during the pilot stage, and enhance understanding throughout the manufacturing life cycle, thereby augmenting the knowledge base.

However, neither QbD nor PAT is yet a regulatory requirement, so what incentives are there for pharmaceutical companies to adopt this new way of working? The simplest answer is that the previous approaches are not sustainable in the long term. The pharmaceutical industry needs to bring new products to market more quickly, but without compromising quality, in order to recoup the increasing costs of research and development. A greater understanding of products and processes is likely to require additional investment in the initial stages, but ultimately it will accelerate time to market and facilitate the reliable scale-up of operations. This enhanced understanding will also help to optimize process efficiency leading to increases in both productivity and profitability, which is becoming increasingly important as patents expire, and as the growing generics industry continues to exert intense commercial pressure.

Changes in regulatory perspectives will also provide a further incentive. Out of necessity, the regulators are now required to adopt an approach based on risk analysis, with the focus being on products and processes that present the greatest potential for harm. Companies that can demonstrate the application of robust QbD and PAT approaches, in order to manufacture products with optimised and well-defined performance, using processes that are clearly understood, will ultimately benefit from a more supportive relationship with regulatory bodies.

So there are very good reasons for change but it will undoubtedly require significantly better fundamental knowledge and a much greater understanding of materials and processes. The industry will need to implement new ways of working as well as adopt new tools that deliver access the information it requires.

Author Biography

Tim Freeman, Managing Director, Freeman Technology

Tim Freeman is Managing Director of powder characterisation company Freeman Technology for whom he has worked since the late 1990s. He was instrumental in the design and continuing development of the FT4 Powder Rheometer? and the Uniaxial Powder Tester. Through his work with various professional bodies, and involvement in industry initiatives, Tim is an established contributor to wider developments in powder processing.

Tim has a degree in Mechatronics from the University of Sussex in the UK. He is a mentor on a number of project groups for the Engineering Research Center for Structured Organic Particulate Systems in the US and a frequent contributor to industry conferences in the area of powder characterisation and processing. A past Chair of the American Association of Pharmaceutical Scientists (AAPS) Process Analytical Technology Focus Group Tim is a member of the Editorial Advisory Board of Pharmaceutical Technology and features on the Industry Expert Panel in European Pharmaceutical Review magazine.  Tim is also a committee member of the Particle Technology Special Interest Group at the Institute of Chemical Engineers, Vice-Chair of the D18.24 sub-committee on the Characterisation and Handling of Powders and Bulk Solids at ASTM and a member of the United States Pharmacopeial (USP) General Chapters Physical Analysis Expert Committee (GC-PA EC).

www.freemantech.com.cn

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Introduction

Following Tim Freeman's articles on Powder Flow,

understanding powder behaviour to optimise process performance, increase productivity and improve quality.

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Tim Freeman's Powder Flow Feature: Exploring the Impact of Particle Size on Bulk Powder Properties

Tim Freeman's Powder Flow Feature: What Makes a Powder Flow?

Tim Freeman's Powder Flow Feature: Understanding Powders

Tim Freeman's Powder Flow Feature: Exploring the Impact of Particle Shape on Bulk Powder Properties

Tim Freeman’s Powder Flow Feature: Exploring the Impact of Humidity on Bulk Powder Properties