Process analytical technology (PAT) has long been recognised in manufacturing as an effective automated quality assurance tool. Used in pharma small molecule & biotech applications, it is increasing process effectiveness and productivity while reducing batch-testing requirements and minimising waste. New PAT based processes are introducing a more holistic working practice that is being applied to development, supply and manufacturing operations. The result is not just increased product quality and process efficiency, but reduced time to market for new drugs and generics.
Martin Gadsby, Director at Optimal Industrial Technologies, looks at how PAT can positively impact global health by speeding up the development and production of new drugs while exceeding the high-quality standards of regulatory compliance.
One of the time-saving features of PAT compared to traditional quality control is the elimination of multiple physical steps in the production cycle. Traditional quality control requires a QC hold point after most unit operations where samples are taken and transported to the lab for testing. The results must then be interpreted, and the product is either acceptable, requires rework or is scrapped. Termed “Testing Quality into the Product”, this QC step is evidently too late in the manufacturing process.
The application of a PAT based methodology and tools such as the market leading synTQ software suite from Optimal utilises sensor arrays on the production equipment to compare live test results with multivariate models, providing real-time quality predictions. In turn, these allow process adjustments to be made in real-time to assure product quality in a closed loop system.
Using a traditional quality control method means that if there are any issues with the manufacturing process, these may only become apparent after the unit operation or batch is finished, i.e. once time and resources have already been expended. In contrast, PAT-led production does not necessarily require post-quality-control testing since the quality is not tested into the product, rather it is built into it, therefore eliminating waste.
PAT provides a framework to understand and monitor the development (or chemistry) of the product and the manufacturing processes at every stage. Time efficiency is also improved by the system’s increased responsiveness. While post-quality-control may not clearly clarify what went wrong in production, PAT uses continuous quality monitoring to evaluate and control the process, plus instantly flag anomalies or issues, allowing the operator to promptly resolve them (if not done so automatically).
As PAT speeds up the whole production cycle, from development to large scale production, product approval and release occur faster too. Shortening the time required for a treatment to be developed, tested, produced and approved means increasing the time available within the product patent window, and saving precious time reaching patients in need of help.
For example, over 58,000 people die of resistant infections every month. Therefore, being able to shorten the time to release a new drug to combat antibiotic resistant bacteria and viruses by just one month, could make a great difference. In this sense, PAT-led production can be a game-changer for pharmaceutical companies and patients worldwide.
Increasing the product’s quality is another fundamental aspect in pharmaceutical manufacture. According to the UK’s MHRA website for example, nine alerts and recalls for sub-standard drugs and medical devices were posted during a five-day period from 2nd and 6th October 2017. Although it is impossible to reduce errors down to zero, shifting from traditional post-production quality control to PAT-led production can minimise errors and the circulation of substandard drugs by systematically increasing the overall quality of the final products.
In the traditional manufacturing paradigm, post-manufacturing quality control samples are analysed to test the quality of the whole batch. However, these samples may not be representative of the bulk, and sub-standard drugs or medicaments may enter the market and affect patients in need of them. With PAT you can have a holistic strategy, where the product quality is assured continuously throughout the production process and not just by a few samples after production.
In addition, as PAT reduces the amount of off-spec material in the system, the use of resources is maximised, and less waste is produced. Productivity improvements and waste reduction can be further improved by applying the PAT model down the line, and connecting PAT driven quality assurance processes from raw ingredient suppliers through to the manufacturer, hence saving more time and further reducing the likelihood of producing ineffectual drugs.
The use of PAT is empowering technologies such as continuous manufacturing in all areas of pharmaceutical manufacturing, where the savings in cost, time and improvements in the consistency of quality can perhaps be maximised. In areas such as flow chemistry, there are opportunities to change the synthesis technique, perhaps change and lower the cost of the starting raw materials and make drugs that would otherwise be unaffordable available to a much wider population.
Finally, lower work in progress, just-in-time manufacturing, faster product release, lower raw material usage during development, reduced cycle times, lower energy consumption, less off-spec material and lower quality testing costs are all factors that contribute to lowering the costs of developing and producing a new drug. Prescription drug costs are a burden for many; health organisations and patients mostly select cheaper drugs, and in some cases, the patients never collect their prescription due to the price. Potentially cheaper, yet reliable, medicines make it possible for these patients to afford the products they need.
Pharmaceuticals and bioscience are a global business and the examples provided show how PAT might improve world health by increasing the availability of medicines and potentially even save lives worldwide by lowering production costs, times, and improving the quality of medicines. However, it is fundamental to implement an appropriate PAT system to obtain these results.
One framework, whose tangible benefits have been proven worldwide, is synTQ by Optimal. The software is currently in use by over half of the global pharmaceutical manufacturing majors, and there have already been reports of production cycle times for existing drugs being reduced from weeks to hours and productivity rising by multiples.
PAT is the key emergent process technology that is allowing the pharmaceutical industry to create fully integrated, regulatory compliant, continuous production techniques. No implementation path is the same, as each product has its own manufacturing (and PAT) requirements. However, by using platforms like synTQ, we can unify necessary information to enable the control of processes like never before. Through the continued development of these platforms, the pharmaceutical industry will be able to make further advances in efficiency and bring more innovative and cost-effective products to market quicker than before.
Photo Caption: New PAT based processes are introducing a more holistic working practice that is being applied to development, supply and manufacturing operations.