Sterile drug formulation development involves a number of key decisions that can shape your entire strategy for clinical success or failure. The choices you make early about the formulation, sterilisation method, container type, and stability methods will affect everything from process design to scalability. If you don’t plan for these elements upfront with your CDMO (contract development and manufacturing organisation), you will run into delays and technical risks later.
Let’s walk through the key product considerations you need to think about.
One of the first questions to answer is whether you are developing a liquid or a powder formulation. That decision alone shapes your formulation strategy. Liquids might seem simpler, but they bring challenges with solubility, filtration, and long-term stability.
For powders, you’ll also need to think about how the product behaves once reconstituted. How fast does it dissolve? Is the solution stable after mixing? These are practical questions that affect your formulation design and how the product will be used in a clinical or commercial setting.
Aseptic processing vs. terminal sterilisation
Next, you need to decide between terminal sterilisation and aseptic processing. This is one of the most important decisions you’ll make, and it needs to happen early. It doesn’t just influence the formulation—it affects equipment, testing, regulatory requirements, and process complexity.
Terminal sterilisation, usually done with steam or radiation, is the preferred option when it’s feasible. It gives you the highest level of sterility assurance and is simpler to manage in manufacturing. But not all drug products can handle the conditions. Some APIs degrade under heat or moisture and others break down when exposed to radiation. Many biologics fall into this category, which rules out terminal sterilisation.
Terminal Sterilization vs Aseptic Processing
Aspect
Terminal Sterilization
Aseptic Processing
Process
- Sterilizes the final product in its container (e.g., autoclaving, steam, irradiation)
- Sterile components are assembled and filled under sterile conditions without final sterilization
Pros
- High assurance of sterility
- Generally simpler process control
- Often lower risk of contamination after sterilization
- Suitable for heat-sensitive or unstable products
- Enables complex formulations (e.g., biologics)
- Avoids degradation from sterilization methods
Cons
- Not suitable for heat- or radiation-sensitive products.
- Potential degradation of API or excipients
- May require specialized containers to withstand process
- Requires highly controlled environment and rigorous monitoring
- More complex and costly infrastructure
- Higher risk of contamination during filling
That’s when aseptic processing becomes essential. In this approach, each component, the drug, the container, and the equipment are sterilised separately. Then the filling happens under sterile conditions within an isolator. It’s more complex and carries a higher risk of contamination during fill-finish, which means stricter controls and more demanding validation work, like media fills and aseptic process simulations. But for sensitive molecules, there’s often no other option.
This decision has downstream impact. If you’re going with aseptic processing, your formulation must be sterile-filterable. It needs to withstand sterile hold times and perform reliably during filling. These are not things you can fix late in development, so make the call early.
Navigating the Sterile Fill Finish CDMO Landscape for Development & Manufacturing Success
Address filtration and line compatibility early
Once you’ve decided how you’re going to sterilise the product, you need to think about filtration and your process line. Is the formulation filterable? Will any of the excipients clog filters or cause pressure drops? Are there any risks of the API sticking to filter membranes?
You also need to consider what types of tubing and filter housings will be used. Some materials interact with the formulation, absorbing components or leaching into the product. Early filter and line compatibility testing helps you catch these issues before they become costly problems during manufacturing.
Container closure system considerations
The container closure system is another critical piece. Whether you’re using a vial, prefilled syringe, or another format, the container needs to be compatible with the formulation. That means no leachables or absorption risks. It also needs to withstand your chosen sterilisation method. If the product is light-sensitive or hygroscopic, the packaging must provide adequate protection.
You’ll also want to think ahead to dosing accuracy, delivery method, and user handling. These decisions feed directly into your clinical and commercial strategy.
Sterile formulation stability
Shelf life is a core consideration in sterile drug formulation development. Stability testing should begin early. You’ll need to assess both physical and chemical stability across different stress conditions.
Freeze–thaw studies show how the product handles temperature cycling, which is common during storage and shipping, especially for cold or frozen supply chains. Photo-stability testing reveals how sensitive the product is to light. Even low levels of UV or visible light can cause degradation in small molecules. Accelerated stability studies, where the product is stored at elevated temperature and humidity, help identify degradation pathways and predict long-term performance.
If you’re working with powders, you also need to assess how well the product holds up after reconstitution. Does it stay stable for the required period, or does it start to degrade or precipitate?
Navigating the Sterile Fill Finish CDMO Landscape for Development & Manufacturing Success
Aseptic spray drying
One area of rapid growth in sterile formulation is aseptic spray drying. It’s a technology that’s gaining attention because it solves a real problem—how to formulate sterile products when traditional sterilisation isn’t viable.
Aseptic spray drying lets you produce sterile dry powders without using heat or radiation. That’s a big advantage for APIs that are moisture or heat sensitive. It’s especially useful for biologics that can’t survive traditional sterilisation methods.
Why Use Aseptic Spray Drying?
When to Use Aseptic Spray Drying
- Preserves product sterility for injectable or inhaled biologics and small molecules
- Improves stability of sensitive APIs vs. liquid formulations
- Enables controlled particle engineering for specific morphology and size
- Removes need for cold chain by producing dry powder formats
- Scalable and continuous process with high batch reproducibility
- Flexible excipient use for improved solubility or
delivery
- When the API is heat- or moisture-sensitive
- When terminal sterilization is not feasible
- For inhalation therapies or injectables requiring dry powder form
- For biologics (e.g., monoclonal antibodies, peptides) needing enhanced shelf life
- In early development to explore alternate drug delivery formats
- When low dose precision and consistent particle properties are critical
The container closure system is another critical piece. Whether you’re using a vial, prefilled syringe, or another format, the container needs to be compatible with the formulation. That means no leachables or absorption risks. It also needs to withstand your chosen sterilisation method. If the product is light-sensitive or hygroscopic, the packaging must provide adequate protection.
You’ll also want to think ahead to dosing accuracy, delivery method, and user handling. These decisions feed directly into your clinical and commercial strategy.
Final thoughts
Sterile drug formulation development is full of decisions that ripple through the rest of the program. Choosing the right product format, sterilisation method, and process setup early will save time and avoid costly changes later.
Navigating the Sterile Fill Finish CDMO Landscape for Development & Manufacturing Success
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