Each of these three options has advantages and disadvantages, which you and your team will need to weigh when selecting the right approach for your product. Some drug developers may also test two or more options in parallel, choosing the final strategy at a later stage to launch their product. But no matter how you decide to approach this step, you need to start the evaluation and implementation processes as early as possible.
Reformulation: The best option, but often difficult to achieve
For any injectable medication, the optimal stability profile is for the drug product to be stable at room temperature in liquid form. This simplifies and de-risks numerous dimensions of the product’s clinical and commercial lifecycle, including shipping, storage, and expansion into markets with less developed infrastructure.
So, why not reformulate any drug substance with stability limits? Reformulation is a time-consuming and cost-intensive approach, which offers no guarantee of success. It can be an indefinite process that may or may not result in a new formula that delivers reliable stability characteristics – and that adds considerable risk to this approach.
If you are unable to reformulate, there are two other proven options. These approaches also require investment and present their own logistic considerations to work through – but they do deliver predictable stability outcomes for a wide range of injectable drug products.
Freezing: Cost-efficient, but logistically complex and often not applicable
A frozen formulation – if possible – is a familiar method of protecting the integrity of an injectable drug product – one that’s often preferred by drug developers seeking a quick, effective path to the clinic or market. It’s well-established in most regulatory frameworks, and relatively cost-effective – especially compared with an open-ended commitment to reformulation and the relatively cost-intensive process of developing a lyophilization cycle.
But freezing your product also has drawbacks. Not all molecules are suitable to this approach; some are simply too fragile to withstand the multiple freeze-thaw cycles during manufacture. Frozen formulations also require access to a consistent, effective cold chain – a logistically demanding requirement that can complicate distribution channels and limit availability of your product in markets with less-developed infrastructure.
A cold chain can be a major operational complexity for even the most in-demand products. Before committing to a frozen formulation, carefully consider how much of a barrier this requirement may be in the target markets for your product.
Lyophilization: A significant investment in securing long-term stability
The third stability strategy many drug developers consider is lyophilization: transforming the drug substance into a freeze-dried powder that’s stable at room temperature, and that can be reconstituted as needed.
Like freezing, this method is also effective, proven, and well-established in global regulatory frameworks. Lyophilization, however, is a significantly more complex process that requires additional investment, planning, and lead time to implement successfully:
Operationally, a lyophilization step can’t simply be ‘bolted on’ to your manufacturing processes. Freeze-drying to the standards reflected by cGMP requires a dedicated, customized cycle which must be fully integrated into your aseptic filling process.
Naturally, these steps add development and manufacturing costs to your product, as well as time to your project plans. These need to be factored in as early as possible for best success.
This investment can pay dividends. Lyophilized products typically have a desirable, predictable stability profile, which can be achieved with an approach that balances the consistent success of freezing with the lasting integrity that reformulation seeks to achieve.