Pharmaceutical manufacturers are reeling under the demands of growing competition, quality and safety concerns and diminishing margins. Companies are under more pressure than ever to increase capacity utilization, reduce cycle times and improve manufacturing efficiencies. The difference between success and failure often lies in the ability to adapt to changing market trends and embrace new technologies and methodologies.
By nature, pharmaceutical processes are complex, with potential for product variability to occur due to variations in both operating conditions and raw materials. Final drug quality is influenced by everything that happens during manufacturing. Each step in the process and each ingredient, as well as the condition of the equipment and even subtle changes in the manufacturing environment, can lead to variations in product quality.
In the face of all these challenges, Process Analytical Technology (PAT), an FDA initiative, is well positioned to have a significant impact on pharmaceutical manufacturing and drive greater efficiency, utilization and first-time quality. PAT is a framework for innovative pharmaceutical development, manufacturing and quality assurance. With the goal of understanding and controlling the manufacturing process, Process Analytical Technology provides an opportunity to move from the current quality paradigm that focuses on the testing of finished product to a continuous quality assurance paradigm. PAT is underscored by the belief that quality cannot be "tested in" to products it should be built-in by design.
A Difficult Production Environment
Pharmaceutical companies still suffer from excessive rework and discarded product, high work-in-process, low capacity utilization, prolonged cycle times and laboratory bottlenecks. According to an AMR Research report , the industry average for both rework and discarded product is 50%; on-hold product inventories are at the 40- to 60-day level on average; and on-hold inventories of 100 days are not unheard of.
In addition, plant utilizations run at 40-50% and average cycle times in the industry are in the 30- to 90-day range. In non-conformance scenarios, cycle times typically double. Further complicating the situation, laboratory bottlenecks can add as much as 75% to the cycle time, and sometimes more when an investigation prevents routinely scheduled activities.
The Right Time for PAT
PAT is already a proven approach in continuous manufacturing process industries such as oil and gas refining, where quality problems need to be corrected before they contaminate large volumes of product. Given its success in these areas, PAT is currently gaining momentum in pharmaceutical and biotech production environments, where it can be used to reduce product and process variability, ensure conformance, and decrease discards. A single batch of product can represent a revenue opportunity of at least $3-4 million.
Based on four principles process understanding, risk-based approach, regulatory strategy to accommodate innovation and real-time release PAT can be used to analyze and control manufacturing processes by measuring quality attributes of raw and in-process materials. It eliminates error-prone manual intervention, helps to accurately produce to demand, and ensures in-process quality checks. PAT can be achieved by inline measurement of performance attributes, real-time or rapid feedback control that focuses on prevention, and an in-depth understanding of process.
Where to Start with PAT?
Two schools of thought exist regarding implementing Process Analytical Technology introduce PAT at the product/process development stage, or institute it in commercial-scale manufacturing. If PAT is implemented in product/process development, the process will be more robust when scaled up to commercial manufacturing. This does not mean that PAT cannot be utilized in commercial manufacturing. In fact, it would be easier to use in commercial manufacturing, as there would be more data to draw upon.
To successfully adopt PAT, it is essential to establish a team that will work together to accomplish the following:
- Understand the existing process at a detailed level prior to implementing changes, in order to ensure that any change results in minimal disruption and has a clear, quantifiable benefit over the previous process; and
- Ensure that any program is part of an overall improvement strategy that is focused on quality improvement, cost reduction and the elimination of compliance issues.
Ideally, PAT should be implemented through a series of pilot projects. Each project should document the results of the pilot study and should be followed by a thorough analysis of the results prior to scale-up of products. This pilot approach offers quality and efficiency improvement to products at all stages in the product lifecycle, from new to mature items.
Benefits of PAT
Compliance continues to be a major challenge in life sciences industries, and PAT helps to ensure compliance with regulatory standards. Other benefits of PAT in pharmaceutical R&D and manufacturing include providing a deeper scientific and engineering-oriented understanding of manufacturing processes, reducing product development times, enabling robust licensing packages, and facilitating faster scale-up and faster time-to market for new products.
From a manufacturing perspective, utilizing PAT brings about reduced waste, right-first-time manufacturing, higher production asset utilization and real-time quality assurance and validation. It also supports Lean manufacturing practices for reductions in raw material usage, work-in-progress and finished goods inventories, while also helping to provide a more robust product supply to the public.
Any way you look at it, Process Analytical Technology is here to stay. In addition to support from FDA, the potential for pharmaceutical manufacturers to improve their bottom-line profitability is driving PAT's success. To fully reap its benefits, companies must implement PAT in a modular, methodical manner to ensure minimal disruption to the pharmaceutical manufacturing process.
- "Pharmaceutical Quality: Build it into the process," Alison Smith and Roddy Martin, AMR Research, May 2004
About the Author
Pradep Nair leads the Global Life Sciences and Healthcare Practice at HCL Technologies, one of India's leading global IT services companies. Nair holds a BE in Electronics from an Indian university and an MBA from Northwestern University's Kellogg School of Management.