formulation-design-for-subcutaneous-injection-products
Moving biologics from IV to SC offers huge patient benefits but brings complex formulation challenges. Leaders in drug product development face tough spots in creating stable and effective subcutaneous injection products. Dive into this practical guide to navigate the latest trends and smart strategies.
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Formulation Design for Subcutaneous Products: A Practical Guide
FAQ
1. What's Happening Now
2. What Trends We're Seeing
3. Challenges and Solutions
4. How Leukocare Can Help
5. How We Add Value for Customers
Formulation Design for Subcutaneous Products: A Practical Guide
Moving biologics from IV to SC isn't just a technical adjustment; it's about making treatments more patient-friendly. For leaders in drug product development, this shift offers exciting chances but also brings some big formulation headaches. This article dives into what's happening right now, the tough spots, and smart ways to create stable and effective subcutaneous injection products.
1. What's Happening Now
The main reason for SC delivery is to improve patients' lives. Being able to self-administer at home means fewer trips to the hospital, which is a huge plus for people with long-term conditions. Recent research showed patients really prefer SC over IV, mostly because it's so convenient.[1, 3] Because patients prefer it and it could save money, many companies are making SC formulations a top goal.[4, 5]
You can see this change happening in the market, which is expected to get much bigger. The worldwide market for subcutaneous drug delivery devices is set to jump from over $33 billion in 2024 to almost $70 billion by 2034.[6, 7] More chronic diseases and a growing list of biologic drugs are driving this growth.[8, 9]
2. What Trends We're Seeing
Here are a few key trends shaping how SC formulations are developed today:
High-Concentration Formulations: Often, you need high-concentration products to get the right dose into a small volume (usually under 2 mL).[10, 22, 31] That's especially true for monoclonal antibodies (mAbs), where doses can be 150 mg or more.[10, 22, 31] A big focus is making stable, injectable formulations at concentrations over 100 mg/mL. Want to know more? Check out our article on Subcutaneous High-Concentration Biologics: Navigating the Formulation Triangle.
Larger Injection Volumes: Even though smaller volumes are usually better, the industry is looking at how to deliver bigger amounts subcutaneously. Devices like on-body injectors can give doses from 2 mL to over 10 mL over a longer time, which is a good option for molecules that are hard to concentrate.[12, 13, 14, 15]
Drug-Device Combination Products: The formulation and the delivery device are more and more being developed together.[16, 17] Autoinjectors and pre-filled syringes need to be built to handle specific properties of the formulation, like how thick it is, so patients can give themselves the dose right and comfortably.[15]
3. Challenges and Solutions
Creating a high-concentration biologic for SC delivery comes with its own set of technical headaches. As a drug product leader, you probably know these challenges all too well.
High Viscosity: This is probably the biggest problem. As you cram more protein in, it gets thicker, making it tough to make, process, and inject.[18, 19, 26, 27, 28] If it's too thick, you'll need a lot of force to inject it, which can hurt and might even stop people from being able to give themselves the shot.[18, 26] The aim is usually to keep it thinner than 20-25 mPa·s.[22, 32] We usually manage this by tweaking the formulation's pH and salt levels or by adding special excipients that thin it out, like arginine, salts, or amino acids.[18, 22, 23, 24, 26, 32] Sometimes, mixing excipients works better than using just one.[23, 24]
Stability and Aggregation: When proteins are highly concentrated, they're more likely to clump together, which can mess with how well the drug works and raise safety worries like immune reactions.[10, 19, 22, 27, 28, 31] The formulation needs to stop both physical and chemical breakdown for the entire shelf life of the product. We tackle this by carefully picking stabilizers like sugars (sucrose, trehalose) and surfactants (polysorbates), and finding the best buffer system. For a closer look at picking excipients, check out our post on How to Select Excipients for Stable bsAb Formulations, it gives you more context.[18, 26]
Immunogenicity: There's always a worry that the body will fight against the therapeutic protein with an immune response.[19, 25, 27, 28, 29] Ingredients in the formulation and protein clumps can add to this risk.[25, 27, 29] A good formulation keeps proteins from clumping and protects their original structure, which is crucial for reducing risks.
Delivery Volume and Injection Pain: The space under the skin can only comfortably hold a small amount of liquid.[10, 22, 31, 32] Go over that limit, and it can cause pain and reactions at the injection site.[31] Besides the amount of liquid, things like pH and osmolality of the formulation can also make injections painful.[22, 32] Getting these factors right is a super important part of designing the formulation.
4. How Leukocare Can Help
Tackling these formulation challenges well means using a systematic, data-focused approach. At Leukocare, we partner with you to make this process less risky and faster. We base our approach on advanced analytics and predictive modeling to create formulations that are stable, work well, and are easy for patients.
We combine high-throughput screening and computer analysis to quickly explore many different formulation options. This helps us find the best mix of pH, buffers, and excipients to tackle issues like high viscosity and clumping. Our data-focused way goes beyond just trying things out; it gives us solid reasons for our formulation choices.
When things get complicated, our machine learning helps predict how stable a formulation will be and guides us in choosing excipients. This is super helpful for new types of drugs or proteins that are tough to formulate when old methods don't quite cut it. This ability to predict helps us spot good candidates early, which saves a lot of time and materials. You can learn more about this in our article on de-risking biologic formulation with ML-guided excipient selection.
5. How We Add Value for Customers
Teaming up with a specialized formulation partner directly benefits your development program. The aim is to create a strong formulation that helps you sail through regulatory approval and succeed in the market. Here are some of the main perks:
Accelerated Timelines: By using predictive models and data, we can cut down formulation development time, helping you hit tough deadlines and get to the clinic faster.
Reduced Risk: Our organized approach spots and reduces potential formulation risks early on. This gives you a stronger data package and a better CMC story when talking to investors and regulatory bodies.
A True Partner: We act like an extra part of your team. For mid-size biotechs who already have partners, we can jump in to solve tricky, specific problems. For bigger pharma companies working on new types of drugs, we act as a thought partner, offering specialized knowledge and data to help with internal decisions.
Our goal is to deliver a formulation that is not just stable, but also manufacturable, compatible with the chosen delivery device, and well-tolerated by patients.
FAQ
Q1: How do you manage the high viscosity of a >150 mg/mL mAb formulation?
Handling high viscosity takes a few different approaches. First, we pick the right buffer system to get the electrostatic interactions just right. Then, we test a bunch of excipients that reduce thickness, like amino acids and salts, to find what works best for your molecule. Our data-focused methods help us find excipient combinations that work even better together to reduce thickness and keep things stable long-term.
Q2: What is the best way to ensure stability for a product intended for an auto-injector?
For auto-injector products, the formulation needs to be tough enough to handle the stress of injection and any temperature changes. We do stress tests that copy these conditions, like shaking and freeze-thaw cycles, to pick the most stable formulation. Choosing the right surfactants and other stabilizers is key to stop clumping and make sure the product stays safe and works well throughout its shelf life.
Q3: How early in development should we focus on subcutaneous formulation?
It's best to start thinking about subcutaneous formulation when you're picking your lead drug candidate. Checking properties like thickness and how likely it is to clump early on can help you pick a molecule that's more likely to work well in a high-concentration formulation. Sorting these things out early can save you from big delays and wasted money later in development.
Q4: How does your AI platform speed up the formulation process?
Our AI and machine learning tools speed up formulation development by predicting how stable different formulation mixes will be. Instead of testing thousands of options by hand, our models look at data from a few early experiments to find the most promising formulation areas. This means we can focus our lab efforts on the candidates most likely to succeed, making the development much quicker.
