Bioprocess and Continuous Manufacturing

Next-Gen Therapies Driving Process Innovation

The biopharma market has enjoyed near exponential growth over the last few decades, which has boosted total revenues by over 6,000% from USD 4 billion since the 1990s to $275 billion today [i]. With biopharmaceuticals now comprising 25% of the total pharma market, the pressure is on to maintain this growth and innovation.

As a result, pharmaceutical companies have shifted focus to more and more complex therapies including biologics, cell and gene therapies, and high-potency APIs (HP-APIs). In turn, this requires new, innovative biomanufacturing processes to accelerate development from bench to bedside.

Innovation in bioprocessing and manufacturing is being driven by a need for flexibility, cost efficiency and speed to market. There
has been some movement on new bioprocesses, as seen in the rapid rise in single-use technologies, especially for HP-APIs. Additionally, as continuous manufacturing enters the biomanufacturing space, it will add new transparency and automation to the traditional biomanufacturing process – offering benefits to new, patient-centric treatments such as gene and cell therapies.

Spotlight on Single-Use Systems

Due in part to the dramatic increase in global bioreactor capacity to meet the demands of manufacturers, adoption of single-use technologies has grown exponentially over the past decade. Grand View Research, in a May 2018 market research report on single-use technologies in bioprocessing, forecast a compound annual growth rate of 13.6 percent through 2025 for the $9.71 billion single-use global market.[ii]

Single-use systems have been applauded for their cost reduction, realized from minimized cleaning steps and reduced risk of cross-contamination. There is also a reduction in labor costs as additional hold-times and validation steps can be eliminated.

Another area where single-use systems are in high demand is HP-APIs – owing to the increased demand for antibody-drug conjugates (ADCs). The ADC market, itself driven by the increased demand for new oncology drugs, is estimated to be a $8-10 billion business by 2025 and growing at a substantial rate [iii] [iv]. Single-use systems have proven to be effective at significantly reducing the risk of cross-contamination of HP-APIs as single-use flexible isolators can be used for handling solids (toxic APIs) during synthesis and in downstream

Additionally, single-use systems have allowed companies to work with smaller quantities and in a more time-efficient way, as no additional
cleaning steps need to be implemented. These single-use platforms are also more amenable to automation; there has been considerable discussion on automation and the increase in transparency that new software will bring – potentially filling a substantial gap in the
processes of today.

The Evolution of Biomanufacturing

With monoclonal antibodies well established in the industry, the biopharmaceutical manufacturing world could be perceived as mature, when in fact it is still evolving. Between October 2018 and September 2019, a total of 618 new (original) investigational new drug
applications (INDs) had been filed with the FDA and, of those, more than 150 were for cell or gene therapy products [v]. It is the development of these personalized medicines that has paved the way for more automation, and inclusion of the patient in supply chain considerations.

Kiran Chin, managing partner and CEO at MKA Insights, stated at a BioProcess Insider panel discussion on bottlenecks in biomanufacturing that “there is greater risk in not having a level of transparency. The risk to a single patient is so much greater than if you’re building out batches and testing and validating [them] because you have a direct line to a person that you’re hoping to help.”

Until recently, most of the bioprocess manufacturing occurred in discrete units (separate control structures) and often didn’t talk to any
centralized system. However, it is believed that almost 50 percent of such manufacturing now incorporates a distributed control system with centralized, electronically based batch records. This system also helps with reporting, as having a centralized data lake makes for easier reporting to regulatory agencies that expect product monitoring to continue through the product life cycle.

Towards Continuous Manufacturing

If the biopharma market generally is mature, and upstream processes used in biopharma manufacturing are evolving, the downstream segment – still experiencing bottlenecks – is most open to innovation. Recent advances in downstream process capabilities are bringing continuous manufacturing to downstream operations.

The US National Institutes of Health (NIH) has begun awarding grants in the area of continuous manufacturing [vi] in bioprocess and in July 2019, the University of Delaware, the National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL), and the FDA entered into a Collaborative Research and Development Agreement (CRADA) focused on biopharmaceutical manufacturing investment and research.

Kelvin Lee, institute director at NIIMBL, has noted that biopharmaceuticals are certainly more challenging to manufacture than traditional pharmaceuticals. The CRADA will establish a foundation for FDA engagement within NIMBL projects as NIIMBL seeks to enhance patient access by helping developments in biopharmaceutical manufacturing technologies and processes. [vii]

As equipment, materials, data, analytics platforms, and people are more connected via the Industrial Internet of Things, digital manufacturing will enable greater transformation of pharmaceutical manufacturing, BCC Research predicts in its 2019 report, Bioprocess
Optimization and Digital Bio-manufacturing: Global Markets. [viii]

It is clear that the biopharmaceutical industry sees increased use of automation as a potential solution to making their manufacturing
processes more time and cost efficient and reduce or eliminate risk. While the ultimate goal is to get safe and efficacious medicines to patients as quickly as possible, the sheer complexity of next generation therapy will require many different approaches with respect to adopting and deploying automation solutions.

Eager to learn more about the future of bioprocess and continuous manufacturing? Join us at CPhI North America in Philadelphia, September 9-11, 2020, to meet with more than 500 exhibitors and 5000+ visitors from across the Pharma supply chain, and to attend our free on-site conference. With more than 30 hours of content from thought leaders across drug development, delivery and manufacturing, don’t miss the opportunity to update your knowledge on key industry trends and developments.