Bulk drug substance management

With the rising need for novel therapies - and, based on the changes in the disease landscape as most currently highlighted by COVID - the global biopharmaceutical industry is evolving, and market needs are shifting. 

We are seeing an increasing number of drug products and APIs produced by an equally growing number of pharmaceutical and biopharmaceutical companies, as well as third-party CMOs.

The following article aims to take a closer look at the term “bulk drug substance” and its meaning, as well as to investigate smart solutions to shorten the phase between development and blockbuster production.

It furthermore aims to give a concise definition alongside an extended view on the daily challenges in biopharmaceutical processing.  

Micro to macro - from lab to commercial scale

Once a newly developed product has been approved for the market, manufacturers are faced with having to scale up, so they can move from preclinical to commercial scale manufacture. This is a complex process concerning the entire supply chain that needs to be well managed, as it is not without its challenges. Furthermore, no two production sites are the same and the chemistry processes differ from manufacturer to manufacturer. 

The obstacles and challenges are manifold, and they apply to scientific as well as to technical aspects, while legal regulations and standards have to be adhered to and complied with. Additionally, moving from micro to macro might lead to the the Food and Drug Administration having to newly approve the entire process.

And if this was not complicated enough, the different departments involved in research, development and production may be spread out across various sites. Even if they all operate within the same organization, they may be geographically removed from each other.

These are all factors that influence the outcome of any project, and so they should be considered early on, with 

• clear steps determined for the scale-up process and 
• clearly assigned responsibilities for all individuals involved

While during research, medicinal chemists are focused on whether a certain idea is feasible, once they move ahead, they are more concerned with the scale-up of procedures and logistics. Good Manufacturing Practice (GMP) is key, and strict regulations mandate extensive documentation to safeguard both quality and traceability. 

Single-use technology - the modern, agile choice for drug substance logistics

While the challenges of scaling up the production process for bulk drug substances are obvious, all parties concerned are constantly working on improving existing technologies or coming up with new approaches to make life easier. One such development is the use of single-use components, which was first employed in lab environments.

Single-use technology has become an accepted standard in small-scale environments such as the lab and when administering the drug to the patient. However, their modular design allows for great flexibility and as well as scalability, which is why is becoming increasingly common as an agile solution in all areas - all the way to large-scale commercial production.

The utilization of disposable equipment allows manufacturers to transfer the entire process - ranging from early-stage development to final product and logistics - relatively easily and without any major risks. The system, which involves both technology and equipment (including bags, connectors, tubings and assemblies) can be scaled up and adapted relatively easily thanks to the nature of the single-use components employed.

Trend: decentralized manufacturing means growing complexity

The biopharmaceutical industry has always been a fast-paced and challenging field but with an increased rate of new developments and growing decentralization, the already existing complexity is only bound to increase. 

Teams spread out over geographically removed sites have to collaborate and work together, which has been made possible or easier thanks to a growing degree of digitization. Digitization can be seen as one of the reasons for ever-increasing levels of decentralization, as well as outsourcing to third-party CMOs or CDMOs. 

These developments bring with them a growing need for standardized processes that are flexible and reliable in equal terms. They need to be compatible so as to ensure uniform processes across all sites and phases.

Thanks to its modular nature, single-use technology is ideal when it comes to finding innovative solutions for the design of bioreactors and decentralized biopharma manufacturing processes. 

While in the past disposable production methods have generally been used for lower volume manufacturing and processing for clinical and commercial requirements, they are on the rise for large-scale production purposes and are set to become an established industry standard.

Conclusion

Where innovation and technology are working hand in hand, they can come up with revolutionary solutions that in turn allow to improve the time to market. However, this is only possible with a comprehensive and sustainable approach and by considering long-term prospects. 

A newly developed medical drug is only as good as the entire process surrounding it. In other words, the initial work in the lab can be negligible if the required basic conditions have not been thought through and set up well in advance.

Single-use bioprocessing offers ideal premises for the development and production of bulk drug substance: Single-use systems are modular, thus allowing for the highest possible degree of agility. Flexible and scalable solutions are the future, and single-use is the way forward.