The healthcare industry which is R&D-intensive is a highly competitive market and quality cannot be compromised at any manufacturing level to ensure safe and effective medications are delivered to patients. The progress we see today is revolutionizing how we diagnose, treat and cure disease, saving patients’ lives and improving quality of life. In this new era of personalized medicine, many diseases previously regarded as deadly are now manageable and potentially curable. To achieve this, biopharma companies utilize ‘Quality by Design’ approach at various unit operations to optimize the processes, increase productivity and ensure the good quality of products. Various tools and techniques are employed to develop a robust process, and the corresponding instruments and methods require significant investments at industrial level. Biologic molecules the cornerstone of personalized medicine are big and complex as compared to small molecules of traditional medicines, and their manufacturing process requires broad spectrum of sophisticated analytical tools and techniques. To keep up with the desired quality and have a budget control over the investments, biopharma companies must adopt procedures that provide flexibility and ability to cover both of the above. Since different types of analytical tools could be used in biologics production, choosing an appropriate analytical method is important so that it is able to provide continuous or at-line process information about critical process parameters of interest, in an accurate, reproducible and robust manner.
Process analytical technique (PAT) is one such method or framework which ensures consistent product quality. PAT offers real-time monitoring of process parameters and product quality attributes during the production process, as well as timely control of process parameters from raw materials to completed drug product, to ensure final product quality. In contrast to offline testing, which involves manually extracting samples from the process and analyzing them in an analytical laboratory, the core of PAT is the integration of analytical technologies into the biomanufacturing process to monitor process parameters and quality attributes in real time. While chromatography, mass spectrometry, vibrational spectroscopy, and multivariate data analysis (MVDA) are routinely employed as PAT tools in biomanufacturing, these techniques should only be used after a comprehensive examination of their capabilities, limits, and intended purpose of use in the bioprocess. Furthermore, a PAT tool evaluation should be performed based on its commercial value and return of investment in industrial implementation.
To evaluate the application of PAT tools to the development and commercialization of a bioprocess, Nadine Hazelwood from the BioPhorum Operations Group in London in collaboration with other investigators from pharmaceutical industry conducted a benchmarking survey of biopharmaceutical companies and published the results in Biotechnology and Bioengineering journal. The co-authors who contributed to the study are Christopher Gillespie and George Zhou from MSD, Dhanuka Wasalathanthri from Bristol‐Myers Squibb, Diana Ritz from GlaxoSmithKline, Keith Davis from Pfizer and Thomas Wucherpfennig from Boehringer Ingelheim Pharma. The study is considered the first of its kind in which investigators assessed fifteen companies receiving seventeen responses from them and evaluated more than 20 different types of PAT tools in manufacturing using an industry-wide assessment to identify and rank the tools based on technological attributes such as technology maturity, ability to enable process control, and ease of implementation, as well as their business value such as simplicity of implementation, lead time, and cost reduction. Upstream and downstream unit operations were evaluated under r the development and manufacturing space. Assessment was done ‘in-line’ where samples are measured within the process stream, ‘on-line’ where samples are diverted automatically for analysis and ‘at-line’ which includes removal of samples from the process stream.
The findings of the survey revealed that on-line liquid chromatography (LC), in-line Raman, and MVDA, etc. had high business value, particularly in upstream processing at the production bioreactor unit at commercial scale. In the downstream Protein A purification and polishing processes, in-line variable path length UV/VIS measurements, online LC(/MS), multi-angle light scattering (MALS), and automated sampling have great business value at commercial scale. Authors gave an insightful perspective on the creation and application of some of the PAT tools based on their expertise in commercial biologics production. The results obtained in the survey can guide scientists and new manufacturers in terms of quality product development and all the stakeholders including funding agencies to assess the business value of tools and techniques employed during biologics manufacturing.
Gillespie C, Wasalathanthri DP, Ritz DB, Zhou G, Davis KA, Wucherpfennig T, Hazelwood N. Systematic assessment of process analytical technologies for biologics. Biotechnology and Bioengineering. 2022 Feb 1.