Charles River Laboratories

Luis Berrade is the Senior Director of Sales for Biologics Testing at Charles River, with over 14 years of experience in the biotech industry. After earning his PhD in the U.S., he joined a European Contract Development and Manufacturing Organisation (CDMO), specialising in biologic manufacturing and testing. He later transitioned to Charles River Laboratories, progressing from Cell Specialist to his current global leadership role. Luis has extensive expertise in biologics development, viral safety and clearance strategies for recombinant proteins and advanced therapies. His background in CDMO and testing services gives him unique insight into the challenges companies face in ensuring the safety and efficacy of their biologics.

In an interview with Pharma Tech Outlook Europe, Berrade emphasises the importance of biosafety in biologic manufacturing and the advanced technologies that are revolutionising biosafety testing.

Key Barriers to Biosafety in Biologic Manufacturing

Organisations manufacturing biologics, especially recombinant biologics such as antibodies, vaccines or advanced therapies, must navigate three critical biosafety barriers. Ensuring the safety and reliability of raw materials is essential.

Companies must carefully assess their resources and conduct thorough testing to detect and eliminate contaminants—viral, microbial or other harmful agents—that compromise the final product.

While ensuring the safety of raw materials, a robust testing strategy is also crucial to prevent contamination. Companies must establish key intermediates for testing, covering not only these intermediates but also the drug substance and the final product. The approach to viral safety and microbiological controls varies depending on the product and its manufacturing process.

The last key barrier to biosafety is viral clearance. Not all biologics allow for viral inactivation or removal steps during production. However, implementing viral clearance measures—such as inactivation or removal steps—is essential. For those that do, these processes are well established in the recombinant protein and antibody space, but they pose challenges for advanced therapies due to their sensitivity.

For cell and gene therapies, traditional viral inactivation methods—such as detergent treatment, low pH exposure or nano-filtration—may be unsuitable, as they can compromise the integrity of the product. This limitation makes stringent raw material sourcing and testing even more critical to prevent contamination.

New Milestones in Biosafety Strategies

For emerging modalities like viral vectors, specialised viral safety testing is required. Replication-competent assays must be implemented to ensure the absence of replicationcompetent viruses in adeno-associated viruses (AAVs), adenoviruses (AVs), lentiviruses (LVs) and retroviruses (RVs).

A significant advancement in biosafety is next-generation sequencing (NGS), which is poised to replace traditional viral safety methods. NGS can be an alternative to in vitro adventitious virus testing and legacy assays such as MAP, HAP and RAP for antibody testing. In the long term, NGS may surpass polymerase chain reaction (PCR)- based methods, becoming the standard for viral screening in the biotech industry.

“A major advancement in biosafety is next-generation sequencing (NGS), which is poised to replace traditional viral safety methods. NGS can be an alternative in vitro adventitious virus testing and legacy assays such as MAP, HAP and RAP for antibody testing”

Multi-Spike Approach for Greater Efficiency

Companies increasingly demand faster turnaround times to accelerate the release of critical intermediates and final drug products. NGS plays a key role in reducing these timelines. We also employ a rapid stability testing methodology called Celsius, which enables faster bio-burden and stability assessments than traditional methods, helping expedite the release process. Overall, NGS and Celsius are transforming biosafety testing, enhancing speed and efficiency.

In terms of viral clearance, we have implemented a multispike approach, allowing clients to spike their materials with Murine Leukemia Virus B (MVLB) and Minute Virus of Mice (MVM)—two widely used model viruses in the biotech industry—simultaneously. This allows both viruses to be processed in a single run, streamlining residual infectivity detection while reducing the amount of materials required, the number of runs and overall costs. This approach benefits advanced therapies, where lots are often small, making material conservation critical. The multi-spike strategy significantly improves cost efficiency in viral clearance studies by minimising the needed volume and lowering costs.

Enhancing Speed and Safety with Rapid Methods and AI

Rapid methods—including NGS and rapid stability testing— are key. More companies are adopting droplet digital PCR (ddPCR) over quantitative PCR (qPCR), which offers a significant advantage by reducing the volume of material needed for intermediate or drug product release.

We’re exploring the potential of AI-driven solutions to enhance speed further and minimise the number of samples required for drug release, ultimately optimising efficiency in the process.

It’s all about optimising our processes.We’re making a significant effort to become more digital, which will help us plan activities better and accelerate result release while maintaining full compliance with Good Manufacturing Practices (GMP). Since we operate in a highly regulated industry, quality always comes first and we will never compromise it for speed. However, we recognise that speed is critical, so every step we take aims to improve efficiency without sacrificing quality.

As a manager, I focus on staying closely connected with our clients, understanding their needs and effectively communicating them to our management team. This ensures we can implement new technologies and solutions that enhance speed and safety in drug testing and release.

At Charles River Laboratories (CRL), everything we do at the management level is aimed at helping clients bring their drugs to market faster and with the highest safety standards. This commitment aligns with our global strategy and our management team remains dedicated to driving innovation in this direction. We will continue working to provide faster, more efficient, and safer solutions for our clients.

Key Advice for Aspiring Leaders

NGS is set to revolutionise drug testing and release by replacing methods that have been in use for over 25 years. This marks a significant leap forward.

Likewise, to fully leverage these advancements, we must remain open to evaluating new technologies while collaborating with regulators to ensure they meet—if not exceed—the quality of traditional methods. Innovation should be embraced in manufacturing, testing and drug release, prioritising safety and accessibility for as many patients as possible.

Speed is essential in advanced therapies, where drug stability is a critical factor. However, this does not mean we cannot integrate cutting-edge solutions to enhance efficiency and reliability. I encourage everyone to keep an open mind, explore emerging technologies and embrace innovations that will enable us to develop better, safer and more effective treatments, particularly for unmet medical needs.