high-throughput-screening-for-bsab-formulations
Bispecific antibodies offer immense therapeutic promise but bring unique stability and manufacturing hurdles. Getting the formulation right early is fundamental to success. Discover how high-throughput screening can de-risk your bsAb development program.
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Current Situation
Typical Market Trends
Current Challenges and How They Are Solved
How Leukocare Can Support These Challenges [16]
Value Provided to Customers
FAQ
The Formulation Puzzle: Using High-Throughput Screening to De-Risk Bispecific Antibodies
For any Director of CMC or Drug Product Development, the path to bringing a new biologic to the clinic is paved with calculated risks. With bispecific antibodies (bsAbs), that path has a few more turns. These complex molecules offer tremendous therapeutic promise, but their intricate structures also present unique stability and manufacturing hurdles. Getting the formulation right, early on, isn't just a "nice to have," it's fundamental to a successful development program.
This is where high-throughput screening (HTS) comes into play. It's not about testing more for the sake of it, but about testing smarter to find the precise conditions that will keep your bsAb stable, safe, and effective from the lab bench to the patient.
Current Situation
The excitement around bispecific antibodies is palpable. The global market is projected to grow at a staggering rate, with some estimates suggesting a CAGR of over 40% between 2025 and 2032. We're seeing a wave of these molecules in clinical trials, targeting everything from cancers to autoimmune diseases.
Unlike traditional monoclonal antibodies (mAbs), bsAbs are engineered to bind to two different targets [1, 3]. This dual functionality is their therapeutic superpower, but it's also the source of their complexity [5, 8]. Their engineered formats, which deviate from the natural antibody structure, often come with a higher risk of stability issues. Problems like aggregation, fragmentation, and solubility are not just technical footnotes; they are major obstacles that can derail a program [6, 9]. [5, 6, 8, 9]
Typical Market Trends
The drive for innovation is matched only by the pressure for speed. Fast-track designations and the need to get to IND/BLA as quickly as possible are the new normal. We also see a rise in virtual and small biotech companies with lean teams and outsourced operations. These groups need partners who can act as an extension of their team, providing not just data but strategic guidance.
At the same time, large pharma companies are tackling new and challenging modalities where they may not have deep in-house experience. They need specialized support to navigate the uncertainties of a new molecule type without getting stuck in early development [19, 7]. This combination of speed, complexity, and specialized needs defines the current landscape. The market is also seeing a surge in investment and innovation, particularly in oncology, with AI and machine learning beginning to play a larger role in drug development. [1, 3]
Current Challenges and How They Are Solved
For anyone in drug product development, the challenges of bsAbs are familiar, but amplified.
Stability and Aggregation: BsAbs are often less stable than their mAb counterparts. They can be more prone to aggregation, where molecules clump together, which can impact efficacy and create safety concerns [6, 9]. The unique structures can also lead to fragmentation or other chemical modifications [5, 8]. Finding the right formulation to prevent this is a delicate balancing act.
Manufacturing and Purification: The complexity of bsAbs, often involving multiple polypeptide chains, makes manufacturing a significant challenge. Product-related impurities, such as half-antibodies, can be difficult to separate from the final product, adding another layer of difficulty to purification.
Finding the Right Conditions, Fast [8]: Traditional formulation development is often a slow, iterative process. With bsAbs, the experimental space of potential buffers, pH levels, and excipients is vast. There's often not enough time or material to test every possibility sequentially.
High-throughput screening (HTS) is the standard answer to this challenge. HTS platforms use automation and microplates to test hundreds or even thousands of formulation conditions in parallel. This allows development teams to quickly screen a wide range of excipients, like buffers, salts, amino acids, and surfactants, to find the optimal conditions for stability [11, 12]. By stressing the molecule under various conditions (e.g., temperature, agitation) and using sensitive analytical techniques, HTS can rapidly identify promising formulation candidates and flag potential liabilities early in development [13, 14, 15].
How Leukocare Can Support These Challenges [16]
While HTS is a powerful tool, it's how you use it that matters. At Leukocare, we see formulation development not just as a screening exercise, but as a data-driven strategy. We build on the foundation of HTS with an approach that integrates predictive modeling and deep expertise to solve the specific challenges our clients face.
For the fast-track biotech leader under pressure to get to BLA, our AI-enhanced platform moves beyond simple screening. We use predictive models to forecast long-term stability from short-term data, helping to design a formulation that is scientifically sound and built for regulatory success. This provides the data-driven confidence needed to move quickly without taking unnecessary risks [17, 23].
For a small biotech with no internal drug product team, we act as that team. We provide clear communication and structured processes that align with investor and regulatory needs. It's about proactive partnership. We think ahead to reduce the internal workload and build a robust CMC story that gives investors confidence.
When a mid-size biotech hits a bottleneck with an existing partner or a tricky new modality, we can step in to solve a specific problem. We can tackle a niche challenge like lyostability or provide overflow capacity. Our "pilot first, scale second" approach allows companies to test our capabilities on a defined project, building trust before committing to a larger partnership.
For the large pharma company tackling a new modality, we provide the specific insights needed to move forward. We don't offer generic, templated solutions. Instead, we provide deep technical know-how on vectors, ADCs, and other complex molecules, supported by tailored materials and workshops. We act as a sparring partner, helping internal teams build confidence and make sound decisions.
Value Provided to Customers
Our goal is to provide more than just a formulation. We provide confidence and a clear path forward.
De-risking Development: By identifying and solving potential stability issues early, we help de-risk the entire development program. A stable formulation is the bedrock of a successful biologic.
Accelerating Timelines: Our data-driven, high-throughput approach provides answers in weeks, not months. This helps our clients meet aggressive timelines for IND and BLA filings.
Data-Driven Decision Making: We provide clear, actionable data that supports internal decision-making and builds a strong case for regulators and investors.
A True Partnership: We work as an extension of your team. Whether you're a virtual company or a large pharma organization, we adapt to your needs, providing the right level of support and collaboration.
The journey of a bispecific antibody is complex, but the formulation challenges are solvable. With the right strategy, one that combines high-throughput screening with predictive intelligence and a collaborative spirit, we can navigate the complexities and help bring these promising therapies to the patients who need them.
FAQ
1. How early should we start thinking about bsAb formulation?
Ideally, as soon as a lead candidate is identified. Early developability and pre-formulation assessments can uncover potential liabilities before significant resources are committed. This allows for a more informed selection of the best possible molecule to move forward [19, 7].
2. How does AI actually improve formulation screening?
AI and machine learning models can analyze vast datasets to identify patterns that predict stability. For instance, models can use data from short-term stress studies to predict long-term shelf-life with a high degree of accuracy, a process that would normally take years [20, 21, 22]. This allows for a more intelligent design of experiments, focusing on the formulation space most likely to yield a stable and effective product [17, 23].
3. If we already have a lead buffer, can you work with that?
Absolutely. We can start from an existing lead or conduct a broad screen from scratch. Often, a client will have a platform formulation they prefer to start with. We can use our systems to optimize that formulation or run a parallel screen to see if a non-platform buffer might offer superior stability for a particularly challenging molecule.
4. How do you ensure your formulation work translates to our CDMO?
We see ourselves as a partner in the entire CMC ecosystem. We generate a comprehensive data package with a clear rationale for the chosen formulation. This package is designed to be easily transferred to a CDMO to ensure a smooth transition into GMP manufacturing. We can also provide ongoing support during tech transfer to help troubleshoot any issues that may arise.
5. What makes bsAb formulation different from standard mAb formulation?
The main difference is complexity. The engineered nature of bsAbs means they often have unique instability profiles that aren't seen in standard mAbs. They can be more susceptible to aggregation, have lower solubility, or be more sensitive to specific excipients [6, 9]. This requires a more tailored and in-depth screening and characterization process to ensure a robust final product [24, 25].
