Industry Collaborates to Advance Continuous Bioprocessing

Continuous or integrated bioprocessing has taken big steps towards adoption with a first biosimilar mAb having cleared Phase 1 clinical trials this Spring¹. The benefits of fully or partially integrated bioprocesses have been shown by several manufacturers where economic improvements, process intensification and time to market are repeatedly highlighted. In recent conferences, companies like Alvotech (Iceland), Sanofi Aventis (Germany) or Wuxi Biologics (China) have presented data of successful technical runs with integrated continuous technologies under GMP conditions.  

With the industrial adoption quickly advancing, finding a common language and a harmonized approach with regards to continuous manufacturing principles is a main step. This simplifies the implementation of this new bioprocessing approach and reduces the hurdles for other manufacturers that intend to walk that path in the future. 

An efficient way to collect and develop experience or lessons learnt from the industry is to bring together early adopters from the industry, experts from universities and the key suppliers. In other words, let’s learn from each other’s experience. This is exactly what the DECHEMA aims to do. This non-profit society connects over 5800 scientists, engineers and professionals from the chemical and biopharmaceutical industry. The goal is to drive scientific exchange, identify emerging technology trends, and support knowledge transfer from academic to industrial production. 

A group of experts from the DECHEMA group for “Single-use technology in biopharmaceutical manufacturing” kicked-off a project on integrated bioprocessing in 2018 for peers: scientists and developers of integrated bioprocesses. After two years of work, the result is a summary of industry experience on continuous processing from cell thawing in upstream processing (USP) all the way to final formulation in downstream (DSP)², see Figure 1. The group designed a model process based on a 500 L mAb production in single-use equipment and assessed all processing steps with regards to 1) state-of-the-art of technical implementation, 2) potential risks or uncertainties and 3) current mitigation strategies.

Figure 1: Process steps for the continuous model process as defined by the DECHEMA expert group. The model process is the basis for the risk analysis of integrated bioprocessing steps. (Image source: DECHEMA², 2020)

Since the industry is moving towards implementation for biologics production under cGMP, the main focus of the work was on risk management according to regulatory requirements, such as the ICH Q9³. The failure mode and effects analysis (FMEA) is a good and recognized tool to systematically identify and prioritize risks. As a result, the work describes most prominent risks for every processing step. Most of the risks are linked to the operating and validation principles, dynamic process changes, process interruptions, or the limited lifetime of modules and filters.

For these risks, the expert group suggests various strategies that summarize experience from early adopters, references from regulatory authorities or input from other industry collaborations. Strategies for more general topics that address the entirety of the process such as bioburden control, virus safety, long-term equipment suitability or process control are discussed in a second part of the publication.

In summary, the work shows that many areas of continuous processing which are commonly perceived as risks or uncertainties of integrated biomanufacturing have already been successfully addressed in the industry or can be mitigated through different strategies.

The collaboration of various industry partners – from manufacturers to universities and suppliers – is a key aspect to advancing new technologies and manufacturing concepts. While many risks or questions raised and discussed in the publication are shown to have a mitigation strategy, some areas such as regulatory aspects or advanced process control options require further developments. Further work of industry groups, like the one shown here, has the potential to facilitate the adoption of integrated biomanufacturing and with that, allows us to make vital drugs accessible to patients faster and cheaper.

Learn more about The Origins of Continuous Bioprocessing and what it offers the pharma sector in the blog post by Dr Levison.

References

¹ Biosana Pharma, "Biosimilar Development," 2020. [Online]. Available Here

² DECHEMA, “Technical State-of-the-Art and Risk Analysis on Single-Use Equipment in Continuous Processing Steps”, 2020. [Online].

Available Here

³ ICH Harmonised Tripartite Guideline, "Quality Risk Management Q9," 2005.