Robust formulations are the backbone of successful biologic drug products — ensuring safety, efficacy, and stability throughout the product life cycle. Achieving this requires a unified strategy that integrates deep scientific knowledge, early-stage modeling, platform-based assessments (where appropriate), and process-aware development. With advanced in-silico tools, high-throughput screening platforms, and a collaborative, science-first approach, Coriolis Pharma helps drug developers design formulations that are not only resilient, but ready for the future.
Understanding the Dual Nature of Formulation Robustness
Robust formulations are defined by their ability to remain stable, safe, and effective throughout their intended shelf lives — typically 24 to 36 months at refrigerated conditions for biologics. Achieving this robustness is essential for long-term drug product success and requires a combination of both formulation and manufacturing robustness.
Formulation robustness refers to the ability of a drug product to maintain its critical quality attributes (CQAs) despite small, permissible variations in the formulation’s composition. It is achieved when a well-defined design space is established — one that accounts for allowable variability in factors like pH, excipients, and buffer concentrations while still ensuring stability and efficacy.
Manufacturing robustness, meanwhile, ensures that the drug product can be produced consistently at the desired quality level even when small fluctuations in critical process conditions occur. This aspect is evaluated and refined continuously throughout the development process, particularly during scale-up and technical transfer stages. It is closely linked to process understanding, as even minor deviations in filtration pressures, mixing rates, or temperatures can have significant impacts on product integrity and stability.
Together, formulation and manufacturing robustness underpin the reliability and performance of a drug product over time and across production scales. Because these attributes influence every stage of development — from preclinical formulation through commercial manufacturing — it is critical to approach robustness in a phase-appropriate way as a long-term strategy rather than a late-stage correction.
Laying the Groundwork with Knowledge and Collaboration
Developing a robust formulation begins with a deep understanding of the molecule and its intended clinical use — particularly the expected dosing levels and route of administration. These early insights inform the definition of the quality target product profile (QTPP), as well as the product’s CQAs, including their acceptable ranges, which serve as benchmarks for safety, efficacy, and stability. Establishing these parameters early requires comprehensive characterization of the molecule, a solid grasp of the manufacturing process, and the generation of high-quality stability data supported by tools like design of experiments (DoE) and accelerated stress studies.
However, scientific knowledge alone is not enough. Robust formulation development demands active collaboration among a wide range of stakeholders spanning formulation science, clinical development, manufacturing, and commercial strategy. Without this integrated approach, key requirements, such as a change from vial to prefilled syringe or the need for high-concentration formulations, may only emerge late in development, necessitating costly reformulations, additional bridging studies, and subsequent delays in regulatory approval.
Aligning around a clearly defined QTPP early in development is therefore critical. When formulation teams engage proactively with clinical and commercial experts, they are better equipped to anticipate future needs, reduce development risk, and avoid avoidable setbacks. In short, knowledge and collaboration are not just helpful; they are foundational to successful formulation design.
Accelerating Development Through Modeling and Platform Approaches
In today’s fast-paced drug development landscape, tools that enable earlier and more informed decision-making are critical. In formulation development, in-silico modeling plays a pivotal role by rapidly revealing key properties of drug candidates, such as isoelectric point, aggregation and self-interaction propensities, and potential degradation pathways. These insights help guide the selection of suitable excipients, pH ranges and buffer systems long before laboratory experiments begin.
At Coriolis Pharma, in-silico modeling is combined with platform-based high-throughput approaches for well-established modalities, such as monoclonal antibodies (mAbs), designed to streamline and accelerate formulation development from the late discovery phase onward. For example, our developability assessment combines predictive computational tools with empirical screening data to evaluate the most promising API candidates on the basis of their physico-chemical behavior. This information can be benchmarked against an internal database and compared to marketed products, enabling more confident decisions about which molecules to prioritize for formulation feasibility. In addition, a first judgment on the extent of formulation work required can be made and support the decision of choosing a fast-to-clinic platform formulation approach or perform systematic formulation screening.
Another valuable tool is the preformulation screening platform, which helps identify a formulation corridor and viable starting formulations that can be refined and optimized. For well-characterized modalities like mAbs, where there is an abundance of historical data, these platforms can often pinpoint ideal formulations quickly and cost-effectively. But even for novel or less understood molecules, prior experience can be leveraged to interpret results and guide formulation selection, despite greater uncertainty.
By combining in-silico modeling with high-throughput screening, Coriolis Pharma enables clients to rapidly narrow the formulation design space, reduce development risk, and minimize cost — all while accelerating progress toward clinical milestones.
Putting Formulations to the Test — Literally
Stability is a defining characteristic of a robust formulation. To ensure drug products remain safe and effective throughout their intended shelf life, stability studies must go well beyond testing under ideal storage conditions. For biologics, which are typically stored refrigerated or frozen, stability is also evaluated under accelerated conditions — commonly at 25 °C / 60% r.h. and 40 °C / 75% r.h. — to quickly assess degradation pathways and stress responses.
But stability is not only about shelf life of the final drug product. Drug products must also withstand real-world conditions encountered during manufacturing, transport, and patient use. Thus, during formulation development, a combination of relevant stress factors a product may be exposed to should be evaluated and tested. This includes mechanical stress, such as stirring, shaking and pumping, light stress, or freeze-thawing stress. Next to physical stress, sensitivity to selected chemical stress like stress by different pH or oxidative stress are often evaluated.
While a standard battery of tests — many outlined in ICH guidelines—is routinely applied, Coriolis Pharma complements these with customized stress studies tailored to the specific properties and requirements of each molecule and its QTPP. These may simulate unique manufacturing steps or anticipated distribution, as well as clinical scenarios. By replicating these stressors in controlled lab settings, formulation scientists can identify vulnerabilities early and design formulations that remain robust across every phase of the product life cycle.
Peptides on the Rise: Unique Formulation Challenges
One of the most significant trends in the pharmaceutical industry today is the surge in peptide-based therapeutics, particularly in the metabolic and weight-loss space, where several have quickly become blockbuster products.
Formulating peptides poses unique challenges distinct from those associated with larger biologics like mAbs. Peptides are prone to instabilities like oxidation, but via mechanisms that differ from those seen in larger proteins. In addition, solubility issues, aggregation, fibrillation, and gel formulation are common formulation challenges that a formulation scientist needs to tackle. Also, for many peptides, multi-dose formats are desired to enable simple and repeated at-home administration, which requires preservative addition to the formulation. These instabilities and challenges demand tailored formulation strategies, including different excipients and stress mitigation approaches.
Despite their smaller size, peptides can be surprisingly delicate. Their formulation requires careful balancing of stability, solubility, and manufacturability — particularly as industry pushes these therapies to market quickly. At Coriolis Pharma, growing experience in peptide formulation helps drug developers navigate these emerging complexities and build upon lessons learned from larger protein biologics.
Tailoring the Toolbox for Novel Modalities
As new therapeutic modalities continue to emerge, formulation scientists must strike a balance between leveraging existing knowledge and adapting to the unknown. For many protein-based drugs — including mAbs — development can begin with a well-established formulation toolbox informed by decades of research and prior experience. This platform-based approach draws from proven buffers, excipients, and pH ranges documented in internal data, marketed products, and recent scientific literature.
However, not all molecules fit neatly into this framework. Novel modalities, including multi-specific antibodies, fusion proteins, or antibody–drug conjugates, often behave unpredictably. In these cases, success depends on broader experimental screening to explore a wider range of formulation parameters, such as optimal pH, buffer systems, and excipient combinations.
The most effective path forward in these situations involves close collaboration between the drug developer and the contract research and development organization (CRDO). By combining the developer’s molecular insight with the CRDO’s formulation expertise, teams can rapidly iterate, troubleshoot, and refine strategies tailored to the molecule’s unique needs. At Coriolis Pharma, this iterative, collaborative process is central to solving complex formulation challenges for the next generation of biologics.
Designing Formulations with Scale-Up in Mind
As drug products move from the lab bench to commercial manufacturing, robust formulations must translate seamlessly into scalable processes. For biologics, final drug product manufacturing typically includes ultrafiltration/diafiltration (TFF) to achieve the desired concentration in the target buffer, followed by sterile filtration and filling into the primary packaging material (PPM) — be it a vial, cartridge, or prefilled syringe.
To ensure that this transition is smooth, formulation scientists must understand the technical requirements and constraints of downstream manufacturing. Early and ongoing collaboration between formulation teams, drug developers, and contract manufacturing organizations (CMOs) is essential. This cross-functional alignment ensures that formulations are not only stable and effective but also compatible with the equipment, process parameters, and quality expectations of commercial production.
Scaled-down process models are critical tools in this effort. At Coriolis Pharma, miniaturized TFF systems are used to replicate key process parameters, such as membrane load, pressure, and flow rate, enabling translatable insights into large-scale performance. Similarly, for formulations requiring freeze-drying, Coriolis Pharma leverages both small-scale lyophilizers and in-silico lyophilization process modeling to simulate full-scale behavior and reduce risks during the technical transfer to the drug product CMO.
By incorporating manufacturing realities into formulation development from the outset, Coriolis Pharma helps clients avoid surprises at scale, streamline technical transfer, and accelerate their path to clinical and commercial milestones.
The Coriolis Approach: Science-Driven, Platform-Enabled, Client-Focused
The strategies outlined here reflect the formulation development philosophy at Coriolis Pharma — one grounded in scientific rigor, technological innovation, and collaborative partnership. Every formulation project is designed not only to deliver a robust, stable product, but to do so with speed, efficiency, and adaptability.
At the core of this approach is a dedicated Science & Technology team that actively develops and integrates in-silico modeling tools in alignment with real-world project needs. These tools are used in tandem with high-throughput screening and empirical testing to refine formulation design and de-risk early decision-making.
Client interaction at Coriolis Pharma goes far beyond project management. Each program is supported by a scientific advisor and scientific reviewer who are both technically involved and directly engaged with the client team. This model ensures that every decision is grounded in deep scientific understanding and supported by a shared strategic vision. Experienced formulation scientists and analytical experts from Coriolis Pharma also engage directly with their counterparts at the client, enabling eye-level collaboration that accelerates development and improves outcomes.
Some platform approaches developed for mAbs, such as preformulation screening and developability assessments, can be adapted to some of the novel modalities, further increasing efficiency and reducing time to clinic. These tools, paired with Coriolis’ data benchmarking and formulation expertise, provide a strong foundation for both large pharmaceutical clients with complex pipelines, as well as emerging biotech companies operating under leaner constraints.
Ultimately, Coriolis’ integrated and collaborative model is designed to help all drug developers — regardless of size or stage — establish optimal formulations quickly, reach key milestones with confidence, and accelerate the journey to first-in-human studies and beyond.
Looking Ahead: Preparing for the Future of Formulation Science
The biopharmaceutical industry is in constant evolution. Every day brings new challenges, whether through emerging modalities, evolving regulatory expectations, novel packaging systems, or cutting-edge manufacturing technologies. While the exact shape of future demands may be difficult to predict, they are both inevitable and exciting to anticipate.
Coriolis Pharma is well-positioned to meet these challenges head-on. With a strong foundation in computational modeling, high-throughput formulation screening, and a collaborative, science-first culture, Coriolis Pharma continues to expand its capabilities and knowledge base in lockstep with the industry’s most pressing needs.
As the field advances, technologies like artificial intelligence will be better understood as suitable tools for how formulations are designed, assessed, and optimized. Coriolis Pharma is actively exploring these possibilities, reinforcing its commitment to staying at the forefront of formulation science — not just for today’s drug products, but for the therapies of tomorrow.