Addressing Today’s Top Biopharma Manufacturing Trends
Biopharma industry trends such as the demand for biosimilars, monoclonal antibodies and continuous process manufacturing are impacting the type of technologies being adopted by the industry. From Quality by Design (QbD) to Process Analytical Technology (PAT), data analytics plays a significant role.
This article is posted on our Science Snippets Blog
The biopharmaceutical industry continues to grow and adapt as it faces ongoing challenges in areas such as development timelines, drug prices and a changing regulatory environment. New technologies and therapeutics are being introduced, and the ongoing response to the Covid-19 pandemic has created additional pressure (and fast-tracked development approaches). Companies are being pushed to do more with less, while making productivity improvements wherever they can.
A key factor underlining all of the advances and changes is the ongoing pressure to bring products to the market quickly and to thoroughly document process design, streamline bioprocessing and ensure product quality using improved assays and analytical technologies. The push toward continuous processing and adoption of single-use equipment continue to drive instrumentation selection.1
Whether it’s embracing the principles of Quality by Design (QbD), incorporating Process Analytical Technology (PAT) or optimizing the supply chains, data analytics plays a significant role in the current trends in biopharma manufacturing.2
Process Improvement Drives Industry Needs
Among biopharma manufacturers, there is an ongoing trend toward technological advances in bioprocessing, especially in upstream technology, with a growing push to extend the reach of advancement downstream as well. Companies are looking for ways to create cost-effective purification along with improvements in productivity.
In a 2020 survey report from Bioplan Associates,1 the top new technologies or new product development areas that biomanufacturing companies said they are working on were:
- Bioprocess development/optimization services/bioprocess modeling
- Automation software
- Continuous chromatography/ downstream bioprocessing
- Bioreactor control
- Continuous upstream bioprocessing
These are currently outranking other areas that dominated ten years ago, such as: disposable/single-use bioreactor bags/consumables, disposable/single-use filtration, and single use chromatography, which, nevertheless, remain drivers in the industry.
The survey also found that:
There is widespread latent dissatisfaction with many current bioprocessing technologies and equipment, coupled with an apparent recognition that innovation in bioprocessing has slowed in recent years.
– Bioplan Associates (2020 Survey Report)
Technology advances continue in many areas from expression systems and bioreactors to bioprocess improvements and continuous bioprocessing.
Biosimilars Driving Need for Data Analytics
Success in the biosimilar market means being able to develop a manufacturing process that not only meets the critical quality attributes (CQA) of the original biologic, but also to do it in a cost-effective way through an efficient manufacturing process.
Optimizing production at full scale is impractical, which makes a Quality by Design (QbD) approach using a reliable scale-down model of the process an attractive alternative. Creating a well-documented process in line with ICH guidelines3 starts with using multivariate data analysis (MVDA) and Design of Experiments (DOE) to create robust models.
Traditionally, process characterization has involved a two-step experimental design involving low-resolution screening followed by response surface design and exploration. MVDA allows the creation of a one-step method for cell culture processes. Using a combination of MVDA and DOE allows complex dataset comparisons for process changes, technology transfer, and process scale-up.
Continuous Process Manufacturing Addresses Trends
Continuous process manufacturing is a trend that has been increasing over the last half decade and is now an important way that biopharma companies meet the growing demand for novel therapeutics and the ever-increasing pressure to reduce manufacturing costs. Following process intensification and the move towards single-use equipment, continuous operation is the next logical step in the evolution of bioprocesses.
Single-use or disposable bioprocessing equipment is now used for more than 85 percent of pre-commercial pharmaceutical production. 4
One downside of single-use systems is lower output. The maximum operating volume for single use bioreactors is about 4,000 liters. As a result, the industry is turning to process intensification and continuous process manufacturing to increase the output while reducing the cost of goods for the process.
PAT sensors and advanced data analytics are essential elements of success for continuous process manufacturing. Sensors make it possible to do more inline and online measurements rather than relying on offline measurements completed in a far-away quality control lab.
Toward Digital Transformation and Biopharma 4.0
A key trend over the last decade is the continuous push toward digitalization of processes.
Consider these statistics:
- Companies use only 4% of the data they have available
- Only 20% of biopharma companies are digitally mature, whereas 80% are in the early stages or still developing
- The IDC estimates that by 2024 over 50% of all IT spending will go toward digital transformation
- Across all industries, 70% of companies either have a digital transformation strategy in place or are working on one, according to a Tech Pro Research survey
- The 2020 State of Tech Spend report showed that digital transformation was expected to be the top budget item for IT expenditures in 2020.
Digital transformation offers a mechanism for companies to revise their business models, to improve production processes, and even to design and discover innovative drugs and treatments faster by using artificial intelligence to screen compounds. From process automation to using data analytics in clinical trials, leveraging digital transformation helps to create more efficient processes as well create services that fully engage and provide value to key stakeholders.
Another area where digital transformation helps biopharma companies improve manufacturing is using the vast quantities of data generated from bioprocessing to help predict (and prevent) future process deviations. By using advanced data analytics to create accurate models of cause and effect from past production runs or batches, companies are able to create models for how future batches should operate, predict outcomes based on key performance indicators and set process parameters.
Some Predictions for the Future
If we look at where this is heading in the future, we expect that:
- Accelerated regulatory approvals will lead to a growth in demand for cell and gene therapy products.
- The increase in demand and need for quick scale-up will lead to more cell and gene therapy developers looking to outsource.
- Outsourcing to CDMOs will continue to grow, and the selection criteria may come down to portfolio breadth, ability to incorporate advanced data analytics, regulatory compliance and cost.
- As development phases accelerate (as with COVID-19 vaccines and treatment), being ready for full-scale manufacturing and commercialization means creating scale-ready processes from the start.
- Quality by design using DOE and MVDA will become integral to all PAT technologies, and essential for rapid scale up.
References:
1. 17th annual Report and Survey of Biopharmaceutical Manufacturing Capacity and Production, Bioplan Associates, April 2020. https://www.bioplanassociates.com/17th
2. FDA, Advancing Regulatory Science at FDA: Focus Areas of Regulatory Science, 2021. https://www.fda.gov/media/145001/download
3. ICH Q11. Pharmaceutical quality system. 2012. http://www.ich.org/products/guidelines/ quality/article/qualityguidelines.html. Accessed 23 Feb 2019.
4. Eric S. Langer and Ronald A. Rader, Biopharmaceutical Manufacturing is Shifting to Single-Use Systems. Are the Dinosaurs, the Large Stainless Steel Facilities, Becoming Extinct?, October 23, 2018 https://www.americanpharmaceuticalreview.com/Featured-Articles/354820-Biopharmaceutical-Manufacturing-is-Shifting-to-Single-Use-Systems-Are-the-Dinosaurs-the-Large-Stainless-Steel-Facilities-Becoming-Extinct/
