BIOPROCESSING

The digital age of bioprocessing and how manufacturers are benefi tting from advancements in the sector.

STREAMLINING

BIOPHARMA MANUFACTURING

Author: KEVIN

SEAVER - general manager, Bioprocess Automation and Digital, Bioprocess Program at Cytiva Discovering and making a new drug can take up to 10 years before regulatory approval. We have an opportunity to use tools in the digital world to shrink this timeline dramatically, but our industry is slow to take advantage. This is partly due to cybersecurity concerns as well as clinical and regulatory changes, but we can mitigate risk by turning custom bioprocessing projects into products. Without this advancement, the industry will fail in its responsibility to improve human health.

Companies can mitigate some of this risk by engaging early with drug manufacturers and using laboratory and testing facilities to lay the groundwork for the complicated processes involved. Lessons learned from the labs and testing facilities can be transferred and scaled up for a full-scale manufacturing plant.

The standard operating procedures (SOP) for bioprocessing plants currently require custom designed

e ture of bioprocessing lies in equipment that harnesses digitised records for realtime analytics and predictive analysis and maintenance.

software and fi rmware that run bioprocessing equipment. In a highly regulated and audited industry, the fi nancial and time investments needed to write and validate code for these projects can be immense. Even using some standard code base, the scope of a project can change rapidly as the development process advances.

Turning custom bioprocess projects into standardised products allows customers to choose from a catalogue of hardware which can be integrated with other functions in the manufacturing process. Having bioprocess equipment that is more of a product than a project that has already completed the development cycle, and that fi ts the functional and user specifi cations, allows manufacturers to pre-test the equipment in a variety of environments and provide clear documentation and validation ahead of an expensive project.

Instead of having to plan a new manufacturing system from the ground up, changes from developers can be accommodated relatively easily as only the updated parameters would need to be validated rather than the entire system. Extensive pretesting increases the overall quality of the system because of the comprehensive equipment testing required, which helps deliver nearly off -the-shelf bioprocess manufacturing capabilities. Another benefi t of bioprocessing equipment products is a reduction in time to set up a bioprocess plant. It no longer takes years to design, test, update, and re-test equipment as all of the testing and regulatory hurdles have been passed before the project begins.

With the use of bioprocessing equipment products, records can easily be digitised and integrated. In this digital age, paper remains a constant in drug manufacturing, and the development of a single product can produce hundreds or thousands of paper documents. The transition to digital not only reduces some of this material production but makes records easier to audit and track. This helps speed up the validation of systems and can reduce time to product release down to months or even days. Additionally, digitising records allows manufacturers to apply a deeper analysis or simulation than they would normally get from paper documents.

Bringing drug development into the digital age also allows for the use of digital twins – a virtual representation of a real-world plant or piece of equipment – a testing simulation which has been used in other industries over the last decade. Digital twins allow technicians to test various parameters to reduce costs, proactively anticipate issues, and optimise performance. The goal

is to develop a “golden batch,” a benchmark for the most productive batch possible. With drug batches costing upwards of $1 million, there is little room for mistakes, and the digital twin model helps drive maximal improvements in yield.

These innovations mark a new phase of digitisation for bioprocessing plants. Most plants in the industry are – according to the Digital Plant Maturity Model (DPMM) – at level one or level two, meaning that they mostly run on paper records. Getting to a level three plant off ers an increasingly automated system with more connectivity that requires standardised equipment that a standard bioprocessing equipment plant off ers. This approach provides a high-quality plant that saves drug developers money because of its quick set up time.

A major challenge in digitising and automating these highly regulated drug manufacturing facilities is connecting them to the internet. Cybersecurity remains a primary concern because cyber-attacks can shut down an entire facility and cost millions to address. Cyber-espionage and the security of proprietary information and processes is another concern. Taking a standardised approach is one way to address this with builtin security and extensive testing to validate a piece of equipment.

The future of bioprocessing lies in equipment that harnesses digitised records for real-time analytics and predictive analysis and maintenance. Standardised bioprocessing equipment allows for a rigorously tested plant to be put together in less time with higher quality outputs. As the industry continues to undergo a digital transformation, this platform off ers integrated predictive capabilities and big data analytics that can help streamline the drug development process.

The benefi ts precision dispensing technology can off er biopharma manufacturers thanks to its versatility and customisability.

Thanks to the everincreasing demand for its services, the biopharmaceutical industry has found itself at the centre of global attention and is growing every day. The far-reaching eff ects of the Covid-19 pandemic have left biopharma manufacturers under increasing pressure to bring quality lifesaving drugs to market faster. It is this pressure that is driving demand for rapid innovation and the simplifi cation of complex workfl ows – all while maintaining safety and reducing costs. This is no easy task, especially when handling complex raw materials.

As a result, single-use bioprocessing technologies have risen to the fore as a means for biopharma manufacturers to adopt new setups. These single-use systems have become an important tool for the industry – helping to streamline complex workfl ows, while off ering the fl exibility needed for on-demand and fl uctuating capacity requirements; enabling manufacturers to keep pace with the ever-changing landscape.

WHAT ARE SINGLE-USE SYSTEMS?

Single-use technologies come in all shapes and forms from tubing, capsule fi lters, ion exchange membrane chromatography devices, bioreactors and product-holding sterile bags, to connection devices and sampling receptacles. Despite the recent growing interest in this type of technology, “single-use” is not a new phenomenon. First emerging in the early 1980s, biopharmaceutical manufactures utilised it in their production processes as the industry started to produce drugs in larger quantities. However, it is the advances in single-use systems that have resulted in its increasing popularity today.

Single-use technology is dominating the biopharma market, and is thought to currently be used in over 85% of preclinical and clinical manufacturing processes. With no signs of slowing down, the market is predicted to grow at an annual growth rate of 17.5% between 2020 and 2025, according to research from Market Data Forecast. Even with the success of single-use though, stainless steel workfl ows are unlikely to disappear, and so manufacturers must seek innovative ways to ensure their setup is as effi cient and versatile as possible. That’s where precision dispensing technologies hold promise. These precise, fl exible, disposable solutions do not require a complete overhaul of a facility and can achieve a wide range of effi ciencies as part of diff erent manufacturing setups and processes. Especially suited to applications like raw material handling, they can also minimise the amount that a product must be manipulated within a workfl ow to safeguard its integrity.

Single-use bioprocessing technologies have risen to the fore as a means for biopharma manufacturers to adopt new setups.

Author: UDO LOSEHAND

- head of Global Technical Developers at Roquette

THE RISE OF PRECISION DISPENSING T ECHNOLOGY

6 WAYS PRECISION DISPENSING TECHNOLOGY CAN BENEFIT YOU

Easily integrated into new or existing workfl ows, precision dispensing solutions bring fresh opportunities for manufacturers that are still reliant on stainless steel, single-use, or hybrid systems and can have a real impact on process effi ciencies and your bottom line.

Reduced handling time Products can be introduced at all steps of manufacturing, from the earliest stages at which ingredients are weighed and measured to their storage and transfer between diff erent parts of a facility. Drug products must be handled, stored and manufactured using validated processes and equipment to protect the integrity of the fi nal product, and assure the health and satisfaction of the end

THE RISE OF PRECISION DISPENSING T ECHNOLOGY

consumer. This can be extremely time and labor-intensive, requiring additional procedures to be put in place, and increasing the margin for risk or contamination. With precision dispensing technologies, raw materials are pre-weighed and packaged according to manufacturing requirements, eliminating the process of having to manually weigh out diff erent quantities of product from large drums – reducing handling time and thus increasing effi ciency for manufacturers.

Lower contamination risk By reducing the need to handle or manipulate raw materials, precision dispensing technology removes any inadvertent errors that can occur when manually weighing materials. Not only this, but manufacturers can also benefi t from the minimised risk of external product contamination from handlers, equipment, and the surrounding environment – a crucial requirement to guarantee the safety of the fi nal drug formulation. This is achieved via a clean connection and dust-free transfer of the product from the containment packaging to the bioreactor. In addition, precision dispense packaging that complies with extractables and leachables regulation for single-use technologies, can also minimise the introduction of contaminants via the packaging itself.

Customisability Precision dispensing technology off ers numerous benefi ts to manufacturers through its closed architecture and customisability. Single-use packaging, for instance, can be tailored to suit specifi c fi ll and weight requirements, so products can be matched to the desired chemistries and processes. Containers are typically available for a wide range of fi ll types and weights, while outlet port sizes can be changed to suit equipment design. Such attributes allow for a fully customised solution, and off er complete assurance of a controlled delivery, allowing processors to seamlessly discharge the right amount of raw material into the bioreactor for a given formulation.

Increased productivity To avoid contaminating extremely valuable batches of product, manufacturers must implement extensive cleaning and sterilisation-inplace (CIP, SIP) workfl ows. This can be challenging as CIP and SIP workfl ows require time, monetary investment, energy and space, and force manufacturing downtime. Equipment must be completely shut down while it is cleaned, sterilised and validated – all of which can result in up to two weeks of downtime between batches, creating a signifi cant bottleneck in pharmaceutical production. Precision dispensing technologies help to overcome these issues by reducing the time spent handling materials, sampling, dispensing and processing, as well as reducing the signifi cant downtime that comes with cleaning and validating product containers. This means manufacturers are able to process more batches per year, resulting in increased productivity.

Ease of integration Thanks to its range of customisable “plug and play” options available to suit numerous applications, precision dispensing technology can be quickly and easily integrated into existing manufacturing processes. This off ers new opportunities for manufacturers reliant on either stainless steel or single-use equipment and ensures the fl exibility needed to keep up with industry as well as guarantee they remain cGMP and FDA compliant. Technologies such as this also reduce the amount of training required to operate the systems, reducing the amount of work hours in streamlining workfl ows, whilst also off ering the same benefi ts regardless of setup specifi cs and further enhancing process effi ciencies.

Greater compliance and control Manufacturers should look for single-use packaging solutions that are produced in line with the highest standards of production (ICH Q7 GMP) to further reduce contamination and ensure greater compliance. Meanwhile, precision dispensing technology from a vertically integrated supplier with a single point of audit can off er additional advantages in terms of assurance too, by delivering high levels of transparency and compliance, as well as the added benefi t of having extensive knowledge of the raw material science and its provenance.

LOOKING AHEAD

As the industry moves away from the ‘blockbuster’ mindset, we expect the popularity of single-use systems to continue to rise. The growing focus on personalised medicines and smaller populations increases the complexity of pharmaceutical manufacturing and requires the swift repurposing of existing assets – making it critical to optimise effi ciency wherever possible. Throughout the Covid-19 pandemic, the world looked to the biopharma and pharmaceutical industry for a swift response and the progress made this year in terms of vaccine formulation has forever changed the way the industry will continue to develop.