Navigating CMC challenges in NBE and therapeutic antibody development

Published: 11-Sep-2023

Insights by Dr Thomas Flad, Senior Director of Solutions & Innovation at ProtaGene, as he poses solutions to the difficulty matching analytical resources with analytical demands

In April 2021, the FDA approved the 100th monoclonal antibody as a therapeutic entity, a milestone that took 35 years to reach. As of the fall of 2022, the FDA has approved 162 antibody therapies, and approval momentum continues to accelerate.

Classical IgG-based monoclonal antibodies (mAbs) are by far the most mature protein-based therapeutic modality, with a projected global compound annual growth rate of over 10% until 2030. However, newer antibody therapeutic constructs, like bispecific antibodies, antibody fragments, radiolabeled antibodies, and antibody conjugates, are gaining importance and are projected to experience compound annual growth rates as high as 44%.

So what does all this growth mean for innovator organisations? While these are exciting times for antibody drug development, there are challenges, many of which fall on the shoulders of analytics teams.

Logically, most innovators align their analytical resources to account for several expected failures in Phase I and II trials

Specifically, as I look across ProtaGene’s client base and the industry at large, I see common challenges—grappling with unpredictable and inconsistent analytical demands, cost management concerns, and the occasional need for highly specialised analytical expertise, which is not always possessed by the in-house team. These demands are further exasperated by escalating pressures to shorten time-to-market. I’ve shared some of my experiences and observations related to these matters and would love to hear your thoughts and explore these and other challenges together.

Difficulty matching analytical resources with analytical demands

Analytics are essential at every stage of antibody development, and demands increase as a molecule moves into later phases of development. However, a complication that nearly all innovators face is that almost 90% of therapeutics in development fail to reach the market. Unfortunately, failures often occur in human clinical trials after expending reasonable analytical resources.

Logically, most innovators align their analytical resources to account for several expected failures in Phase I and II trials. However, sometimes more investigational drug products than planned succeed and move to Phase III. While this is a good problem, it is challenging because analytical demands are much higher as the development organisation prepares for Biologics License Application (BLA) filing. Analytical team resources become highly strained, and bottlenecks commonly result in costly delays.

Analytical departments can also be simply under-resourced, risking the development team’s ability to fill and move their development pipeline adequately—posing a clear risk to the long-term financial health of the overall biopharmaceutical organisation. On the other hand, over-resourcing the analytical department risks eroding corporate profitability as personnel and other fixed costs sit idle or are under-utilised during lulls.

Platform utilisation makes outsourcing classical format mAbs with the right partner highly plannable and efficient

In short, my experience working with many development organisations points to analytical resource needs rarely being accurately predictable and certainly not constant. Therefore, an increasing number of innovator organisations see the value in a collaborative analytical partner that can seamlessly integrate with their in-house analytical team, allowing the organisation to quickly scale up or scale down analytical resources to address the reality of unpredictable analytical resource demands.

Cost and profitability management

On the surface, work performed by an external analytical department is more expensive than that of an in-house team. Simple calculations will reflect a higher hourly or per assay rate when ProtaGene or any other external analytical partner conducts work.

However, a biologics organisation’s highest costs are an insufficient development pipeline or delays reaching the market. While often less significant than market delays, the costs of insufficiently or unevenly utilised laboratories, instrumentation, and personnel cut into the organisation’s bottom line.

Clients also know that our team is ready and able to collaborate as challenges arise or fill in when highly specialised knowledge is required

As previously stated, the analytical demands of most biopharmaceutical organisations are not constant and can be difficult to predict. Volatile needs in many functional areas are best served in collaboration with an external partner allowing the innovator organisation to throttle resources up and down appropriately and cost-effectively. In short, your analytical partner’s slightly higher hourly rate is a bargain compared to stalled market entry or bloated fixed costs.

Additive scientific support, expertise, and efficiency

Highly skilled and experienced analytical experts populate the analytical teams of most innovator organisations. However, as antibody therapeutic modalities become increasingly complex, innovator teams commonly have small gaps in specialised knowledge that can be collaboratively filled by ProtaGene experts, avoiding the need for additional innovator hires to address what often is a short-term need.

Additionally, ProtaGene’s teams of experts have worked on many programmes and molecules. They are excellent collaborators when our innovator clients reach various development crossroads and need seasoned advice to navigate more nuanced development issues.

Finally, because ProtaGene works on many products, we have the experience to collaborate on challenging problems and the platform resources to efficiently manage analytical programmes for more established drug products, like mAbs and mAb variants.

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Make room for your internal team to prioritise their innovative NBEs

Innovative mAb developers often have classical mAbs (such as IgG1, 2, or 4) and sophisticated, newly engineered bi- or multi-specific proprietary formats in their candidate pipelines. Though even development candidates based on the classical mAb format often need specialised expertise, the majority of analytical assays, in particular at early clinical stages, leverage platform methods.

Platform utilisation makes outsourcing classical format mAbs with the right partner highly plannable and efficient. By collaborating with an experienced partner capable of applying the entire platform method panel for such mAb candidates, significant in-house resources can be prioritised for developing more complex innovative molecules.

Buying confidence and cost-efficiency

Ultimately, our clients are buying confidence and/or cost-efficiency. Skilled ProtaGene Molecule Managers take ownership of client programmes and provide confidence in the integrity of our analytical data, our ability to support regulatory filings, and our ability to manage projects on time and on budget. Clients also know that our team is ready and able to collaborate as challenges arise or fill in when highly specialised knowledge is required.

Our new biologic entity development partners frequently express that our approach to providing complete analytical solutions for an entire candidate offers both reliability and flexibility. They value our team’s dedication to accomplishing their development objectives rather than just executing individual assays—a significant point of distinction when I look across the field contract research organisations serving the industry.

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