formulation-for-novel-biologics
Bringing a novel biologic to market is a complex journey, where formulation can determine success or failure. This guide offers a straightforward look at biologic formulation challenges and how to achieve a stable, effective, and commercially viable product. Read on to master your CMC strategy.
Menu
Formulation for Novel Biologics: A Practical Guide for CMC Leaders
FAQ
1. Current Situation
2. Typical Market Trends
3. Current Challenges and How They Are Solved
4. How Leukocare Can Support These Challenges
5. Value Provided to Customers
Formulation for Novel Biologics: A Practical Guide for CMC Leaders
As a Director in CMC or Drug Product Development, you know that bringing a novel biologic to market is a complex journey. Formulation is a critical piece of this puzzle, one that can determine the success or failure of a promising molecule. This article offers a straightforward look at the current state of biologic formulation, its challenges, and how a collaborative approach can lead to a stable, effective, and commercially viable product.
1. Current Situation
The biologics market is growing rapidly, with a projected value of over $719 billion by 2030.[1]This growth is fueled by the potential of new modalities like monoclonal antibodies (mAbs), viral vectors, and RNA-based therapies to treat complex diseases.[2]However, these molecules are inherently complex and sensitive. Their large size and intricate structures make them prone to physical and chemical degradation, such as aggregation and oxidation.[3, 4],
This instability presents significant hurdles for formulation development.[5]Ensuring a biologic remains safe, stable, and potent from manufacturing to patient administration is a primary concern.[6], Many companies, particularly small to mid-sized biotechs, are turning to outsourcing to manage these complexities.[8, 9], A 2022 survey noted that nearly 87% of respondents outsourced some biopharmaceutical manufacturing.[10]This allows them to access specialized knowledge and technology without the large capital investment required for in-house capabilities.[11, 12, 13, 32, 33],
2. Typical Market Trends
Several key trends are shaping the biologic formulation landscape:
High-Concentration Formulations: To improve patient convenience and allow for subcutaneous self-administration, there's a strong push toward developing high-concentration protein formulations (HCPFs), often exceeding 100 mg/mL.[14, 15, 16]This reduces the injection volume but introduces challenges like increased viscosity and a higher tendency for protein aggregation.[14, 16]
Advanced Delivery Systems: Innovation isn't just in the formulation itself but also in how it's delivered. Prefilled syringes and auto-injectors are becoming more common to improve dose accuracy and ease of use for patients.,
New Modalities, New Rules: The rise of viral vectors for gene therapies and lipid nanoparticles (LNPs) for RNA delivery introduces entirely new formulation challenges.[19, 20], These are not traditional protein formulations and require different approaches to ensure stability and successful delivery to the target cells.[21, 22, 23],
Predictive Modeling and AI: To accelerate development and de-risk projects, companies are increasingly using computational tools. Predictive models, often powered by AI and machine learning, can help forecast a molecule's behavior and optimize formulation parameters with less experimental work.[3, 17, 25, 26, 28]This data-driven approach allows for more informed decision-making early in the process.[29, 30],
Outsourcing as a Strategic Partnership: The relationship with contract development and manufacturing organizations (CDMOs) is evolving from a simple fee-for-service to a more strategic partnership.[31, 9], Biotechs are looking for CDMOs that can provide not just capacity, but also deep scientific and regulatory guidance throughout the development lifecycle.[12, 32, 33],
3. Current Challenges and How They Are Solved
As a CMC leader, you're likely familiar with these persistent challenges:
Ensuring Stability: Biologics are sensitive to their environment.[20, 35]Stresses from temperature changes, pH shifts, and mechanical forces during manufacturing and shipping can cause them to degrade.[5]
Solution: A thorough understanding of the molecule's unique properties is the starting point. This involves extensive characterization to identify potential liabilities.[28]Formulation scientists then use a combination of pH optimization, buffer selection, and specific excipients like surfactants and sugars to protect the molecule.[14, 16], Lyophilization (freeze-drying) is another common strategy to improve long-term stability, especially for sensitive molecules.[17, 25, 3],
Managing High Viscosity: As protein concentrations increase for subcutaneous delivery, so does the viscosity of the solution, making it difficult to manufacture and inject.[14, 16]
Solution: This is often tackled by carefully selecting excipients, such as certain amino acids or salts, that can disrupt protein-protein interactions and lower viscosity.[15]Optimizing the pH of the formulation can also play a significant role.[15]In some cases, advanced delivery devices are designed to handle more viscous solutions.[16]
Navigating CMC and Regulatory Hurdles: The chemistry, manufacturing, and controls (CMC) section of a regulatory submission is complex and heavily scrutinized.[6, 37, 38]Incomplete or inconsistent data can lead to significant delays.[38, 6]
Solution: Early and proactive planning is key.[38, 6]A well-defined CMC strategy that aligns with regulatory expectations from the start can prevent issues down the line.[6, 39, 41], This involves phase-appropriate development, where the level of detail and validation increases as the project moves through clinical trials.[39, 41], Partnering with a CDMO that has a strong regulatory track record can provide invaluable guidance.[32]
The Need for Speed vs. Thoroughness: For many biologics targeting serious conditions, the pressure to accelerate development is intense.[6]However, taking shortcuts in formulation development can lead to problems later.
Solution: Predictive modeling and high-throughput screening platforms can accelerate the process by allowing for the rapid evaluation of many formulation conditions with minimal material.[42]This allows development teams to focus on the most promising candidates, saving time and resources without sacrificing rigor.[26]
4. How Leukocare Can Support These Challenges
At Leukocare, we understand these challenges because we work with them every day. Our approach is built on a foundation of deep scientific understanding and a collaborative spirit. We act as a strategic partner, not just a service provider.
Our technology platform combines advanced analytics with AI-powered predictive modeling. This allows us to rapidly screen and identify optimal formulation conditions that ensure stability and functionality for a wide range of modalities, from mAbs to viral vectors and LNPs. We focus on creating formulations that are not only stable but also tailored to the specific delivery requirements of the product, whether it's a high-concentration subcutaneous injection or a complex gene therapy.
For companies facing the build-versus-buy dilemma, we offer a third option: partnership. We integrate with your team, providing the specialized formulation expertise that might be missing in-house. This allows you to stay focused on your core mission of drug discovery and clinical development while we handle the complexities of creating a robust and commercially viable drug product.
5. Value Provided to Customers
Working with a dedicated formulation partner like Leukocare provides tangible value for CMC and drug product leaders:
De-risking Development: Our data-driven approach helps identify potential formulation issues early, reducing the risk of costly late-stage failures.
Accelerated Timelines: By using predictive modeling and rational design, we can shorten the formulation development process, helping you get to the clinic faster.
Material Sparing: Our methods are designed to work with small amounts of material, which is particularly valuable for early-stage projects where the drug substance is precious.
A Clear Path to Commercialization: We design formulations with the end in mind, considering manufacturability, scalability, and regulatory requirements from day one.
A True Partner: We provide clear communication, proactive solutions, and a deep understanding of the pressures you face. We become an extension of your team, dedicated to the success of your project.
FAQ
Q1: What is the most critical first step in biologic formulation development?
The most critical first step is a deep characterization of the molecule. Understanding its unique physicochemical properties and potential instabilities is essential for designing a successful formulation strategy.[28]
Q2: How early should we start thinking about formulation?
You should start thinking about formulation as early as possible, ideally during lead candidate selection.[6, 38]Early formulation work can help identify molecules with better developability profiles and set the project up for long-term success.
Q3: Can a single platform formulation work for all biologics?
While platform approaches can be a useful starting point, especially for similar molecules like mAbs, a one-size-fits-all solution is impractical.[43]Each biologic is unique and typically requires a tailored formulation to ensure optimal stability and performance.[6]
Q4: What's the biggest formulation challenge with new modalities like viral vectors or RNA?
For viral vectors, the main challenge is maintaining the integrity of the viral capsid and preventing aggregation to ensure infectivity.[22]For RNA therapies delivered via lipid nanoparticles (LNPs), the key is designing a formulation that both protects the fragile RNA molecule and facilitates its effective delivery into the target cells.[20, 35],
Q5: How does outsourcing formulation development impact our internal team's workload?
Partnering with a specialized CDMO should reduce your internal team's workload by offloading the complex and time-consuming tasks of formulation screening, stability studies, and analytical development. This frees up your team to focus on overall project strategy, clinical planning, and other core activities.
