Regulatory and Financial Drivers Open the Door to Technology Innovation
It’s been almost 10 years since 21 CFR Part 11 appeared on the industry stage, and again the pharmaceutical community is buzzing with activity regarding recent guidance issued by the FDA – this time about Process Analytical Technologies or PAT. While 21 CFR Part 11 deals primarily with technology and its application, this new initiative has much farther-reaching objectives. Specifically, the FDA is attempting to transform the way drugs are made today and in the future. This represents a major cultural change for drug manufacturers with benefits that far outweigh the challenges that can come with applying new technologies. And, with major regulatory and financial drivers as incentive, PAT presents the opportunity to revolutionize the way drugs are made.
The Basics on PATIn the pharmaceutical industry, PAT has been around for years and has been applied for even longer in the chemical and petrochemical industries. Manufacturers have long recognized the need to understand their processes and how to apply technology. While the technology and its application may not be new, the acceptance and guidance by the FDA is new. The goal of the FDA guidance document from September 2004 is to promote a more scientific, risk-based approach to manufacturing drugs and to encourage innovation. This is a major departure from 21 CFR Part 11, which was viewed by many manufacturers as having the potential to stifle innovation.
PAT, which includes sensing technology but also much more, is an overall system for designing, measuring, controlling, analyzing and predicting a manufacturing process in real or near real time. The ultimate goal of a PAT solution is to provide a deep process understanding such that variability is understood and controlled, and quality attributes can be accurately predicted. The outcome of this is a process that is able to adjust in real time to deliver a product that meets quality specifications. The end result is a migration from batch manufacturing to continuous manufacturing of drugs. This is truly something to be excited about!
Drivers to Implementing PATIn the past, fear of non-compliance kept many drug manufacturers from applying innovative technology to the manufacturing process. As a result, pharmaceutical companies have fallen behind many other industries. But, when the FDA issued its PAT guidance document, it was effectively throwing its weight behind innovation and a new approach to manufacturing. The guidance document serves to promote innovation and alleviate manufacturers’ concerns about attempts at modernization. And, unlike 21 CFR Part 11, the FDA’s guidance on the PAT approach to manufacturing is voluntary. The agency is actively encouraging companies to look at the PAT approach to manufacturing without fear of reprisal. The approach to review and inspection can be more team based and less adversarial than in the past.
With the FDA making the PAT implementation process voluntary, drug manufacturers clearly need a compelling reason to undertake a PAT strategy. Despite the team-based approach to review and inspection and the genuine effort on the part of the FDA to stimulate innovation, there needs to be a financial driver for a drug manufacturer to take the necessary steps toward a PAT solution deployment. Fortunately, there are several with the opportunity for significant gains.In general, as pressure continues to build on pharmaceutical companies, they need to find alternatives to manufacturing drugs like they always have. Product recalls, shrinking pipelines, skyrocketing drug discovery costs, demands for government price controls and industry consolidation are all compounding factors. Manufacturing the same old way simply doesn’t cut it anymore.
A PAT solution can provide the answer, as one of the goals of PAT is achieving real-time release. When drugs are made today there are numerous quality checks all along the manufacturing process. Before processing begins, after blending, after drying, after compression, etc., drugs are tested to ensure that they meet quality requirements. At the end of a process, there are additional terminal quality tests performed prior to shipping the final product. All of this testing throughout the manufacturing process takes a typical cycle time of a day or so to manufacture a drug and turns it into six to eight weeks or more. The additional lab tests, paperwork and approvals can build non-value added time to the manufacturing process. Real-time release is the end result of a process that is well understood and in control to such a degree that the additional testing is unnecessary because the product is already known to be in compliance. Instead of numerous tests during manufacturing and a long delay following manufacturing, the product ships when it is complete. This results in a drastic reduction in manufacturing cycle time and finished goods inventory. Now, a batch that may be worth $1,000,000 can ship immediately and not be delayed.
As an example in one area, a PAT solution might be deployed on a blending operation. In the pharmaceutical industry today, documentation and predicate rules require that there is a procedure for blending. To achieve complete blend uniformity of a compound, a procedure might require the blend to occur for 1 hour at 85? F, regardless of how long it takes for the blend to become uniform. A PAT solution would install NIR sensors around the vessel to monitor blend uniformity and feed that sensor input into analytical and predictive software and ultimately into a control system. This PAT solution would monitor quality, predict the outcome of the chemical attributes of the compound and shut off the blend process when blend uniformity is achieved, regardless of how long it took. This solution drives non-value-add activities out of the process and reduces cycle times.
Beyond the benefits of cycle time reduction and reduced inventory, there are quality and waste reduction benefits as well. For the same reasons described above, product quality now becomes predictable, and the process will be known to produce a quality drug. Eliminating lost batches made to poor quality standards also reduces waste.
The wave of change that is sweeping the industry represents an enormous opportunity for drug companies, especially big pharma. Many drug manufacturers are quickly moving toward innovation to realize the benefits that PAT solutions can provide. With the FDA and industry working hand in hand toward innovation, it’s the perfect time to implement Process Analytical Technologies and get them down PAT.
By Bart Reitter, Life Sciences Management, GE Fanuc Automation
About the Author: Bart Reitter is Life Sciences Market Development Manager for GE Fanuc Automation, a unit of GE Infrastructure. Reitter has more than 11 years’ experience in manufacturing automation, providing both process and discrete solutions. His experience spans manufacturing hardware and software as well as enterprise-wide solutions. Reitter can be reached at firstname.lastname@example.org.