Touted to be the next best thing to GMP and cGMP, Process Analytical Technology (PAT) is an FDA guideline which is making its mark, writes Beatrijs Van Liedekerke
Encompassing the potential to deliver significant shifts in the economics of the pharmaceutical sector, pharma-ceutical manufacturing is slowly entering the era of PAT.
Though many companies are high up on the overall PAT learning curve, they are grappling with the challenge of determining the best way to define the manufacturing vision of the future; incorporating PAT and selecting the right tools and infrastructure.
Where and how PAT is implemented is crucial in realising multiple benefits. One of the most important benefits that PAT can bring is increased process understanding resulting in efficient production processes, higher yields, less waste, consistent product quality and hence a positive effect on patient safety. With more consistency in product quality, companies minimise the risk of product recalls and brand damage. In addition, PAT also diminishes the cost of overall quality control and compliance.
When applied to process development, PAT speeds up time to market with an immediate positive effect on economics. PAT also alters process validation, eliminates validation time and thereby costs. It also facilitates technology transfer and reduces the time to realise the same. In summation, PAT leads to real time release, consequently resulting in reduction of inventory, and consequently of warehousing space, inventory manipulations and the risk of mistakes. On the economics side, it frees up working capital as it reduces intermediate products and raw material.
Even though benefits are many, all of them may not all apply to every PAT implementation. Therefore, it becomes important to calculate the return on investment (ROI) to motivate a PAT investment. PAT implementation can start at a small scale with minor investments, but with the ultimate vision of real time release in mind. Some processes may not require PAT implementation, but it is essential to analyse the current processes and identify hidden benefits. An important point to note is that the most obvious area of PAT implementation is for new processes for products under development. This might require new approaches in R&D as well as in manufacturing.
A PAT initiative should ideally start by setting up a PAT strategy with ultimate business objectives that connect all the underlying projects together and prioritise them. The crucial element in this process is to calculate the business case for each of the proposed implementations.
The challenge in starting a PAT initiative is to establish a PAT strategy that supports the manufacturing vision of the future. PAT ultimately should lead to “quality by design”, and requires more than replacing lab analyses by in-line measurements. Some companies get lost in the fact that in order to achieve this “quality by design” that they need to combine different disciplines: process engineering, process chemistry, analytical chemistry, multivariate data analysis, IT etc. If these disciplines are effectively combined, PAT implementation becomes easier.
Once the PAT strategy is established, specific projects can be identified and ROIs need to be calculated in order to prioritise projects. This presents yet another challenge as companies do not know where to begin and think that they need to start with investing a lot of money. However, they can start small and gradually evolve towards a comprehensive PAT infrastructure to avoid high investments early that may not have the best fit with the overall plan. To calculate ROI, there is usually a lot of process data available that can be used. However, companies often are not using the wealth of information that is residing in different databases or logs. Going back to basic data will facilitate the identification of the optimal starting location. This is part of a prioritisation exercise that not only maximises ROI but makes the introduction of PAT manageable.
The pharmaceutical industry should also take advantage of the significant PAT experience accumulated by other industries. Although the pharmaceutical industry does not like to be compared with other industries, companies can definitely benefit from the PAT knowledge that the petrochemical, chemical, electronics, aviation and aeronautics industries have built.
Critical success factors
As PAT demands a multidisciplinary approach, all skills need to be represented in the project team working towards a common goal. Skill-set requirements will change significantly. For example, instrumentation and electrical engineering skills will play a key role
PAT gains for the pharmaceutical industry are potentially significant and the rewards depend on robust PAT implementation. The technology that comes with PAT like mathematical modelling, real-time or near real-time measurement, and multivariate data acquisition and analysis is impressive. But as the adage goes, ‘the system is only as good as the people who run it’ remains as true as ever. The introduction of PAT also represents a significant people change. Quality control, for example, moves from the laboratory to the production floor with an attendant shift in responsibility and need for both procedural change and people change. A cascade of reactions has to happen for implementation to be successful. As PAT demands a multidisciplinary approach, all skills need to be represented in the project team working towards a common goal. Skill-set requirements will change significantly. For example, instrumentation and electrical engineering skills will play a key role. Enterprise-wide data management, retrieval and querying will be vital. There is a need to extend pharmaceutical scientific skills into understanding the supportive database structure and managing knowledge retrieval systems in an efficient, usable and timely manner. Against a background of possible job uncertainty, people need to be guided through the change. Timely and clear communication about the PAT strategy and its ultimate objectives should re-assure people as part of and also ensure a successful implementation.
A mature project management organisation is a key aspect. Once the PAT initiative is started, multiple projects might be running at the same time. When many interdependencies are identified, it is crucial to have a mature project management that is capable of dealing with this complexity.
Change or fashion trend?
Although the PAT guidance is not mandatory, the FDA is taking a clear direction. This was also confirmed by Dr Janet Woodcock, FDA’s Chief Medical Officer in her keynote address at IFPAC 2007. She discussed the Critical Path Initiative and PAT’s role in improving the overall drug development and manufacturing process. So it is clear that “quality by design”/PAT is the way forward where companies that do not take this path will be in a weak market position and loose the license to operate. Companies with an existing PAT strategy or in the process of developing a strategy will gain competitive advantage.
If low cost countries implement PAT, they will increase the advantage of being low cost while also providing a guarantee of consistency and high quality; the latter being an often heard defensive remark from the Western countries when competing with low cost countries like India and China. Implementing PAT could be the tool that facilitates the quantum leap forward with respect to quality in low cost countries.
The pharmaceutical industry is gradually getting convinced of the multiple business benefits that PAT brings. Although some of them are still struggling to implement PAT, a lot of pharmaceutical multinationals are progressing and investing step-by-step. It has become clear over the last couple of years that PAT is no fashion, but an irreversible direction taken to ensure product quality. If low cost countries like India and China succeed in implementing PAT, they will solidify their position of low cost sourcing while providing high quality products.
(The writer is Associate Director at PricewaterhouseCoopers Advisory Services – Process Improvement practice in Beijing, China)