Fit for phase development can allow you to shave half your cost and time for analytical development and batch release!
An interview with Dale Bennyhoff Sr. Director CMC with Velicept Therapeutics.
We have been hearing about fit for phase development for years. Please share how you think about fit for phase development?
Keep in mind that as leaders in biotech we are executing a series of experiments in an effort to determine if a compound will ultimately become safe and efficacious for an indication. To have confidence in the experiments we run and ensure patient safety, our analytical methods must deliver reliable results. We ensure quality and cost & time savings by eliminating/ streamlining validation preps and leveraging results for multiple validation attributes.
Why is implementing fit for phase important in the analytical space?
If you do not get this right, it will limit formulation shots on goal forcing you to choose the wrong phase 1/2 formulations, perhaps killing the program.
Often times analytical method development, validation and execution are done out of sight and out of mind by the vendor. However, those activities often sit on the critical path and can cost as much as 40% of the CMC development program. If method development and validation are not executed in a pragmatic way, burden to timeline and budget can be substantial.
How does a biotech company know they are getting fit for phase analytical development?
The first question to ask: Does the lab that will do your early phase work also do phase 3 and commercial work? If they do, this is a bad omen. The commercial mindset is to ensure validation meets ICH commercial standards. These labs also have a priority to release the commercial product over your development work.
What you should see is a method that was developed with scientifically sound controls that can establish sufficient accuracy, specificity and precision. In addition, your team should focus on the critical areas of risk for your product (for example genotoxic impurities, chiral forms etc.)
What is the best way to ensure you get fit for phase analytical development?
The key to realizing the benefits of this analytical strategy is your choice of manufacturer. I always ask a series of questions about their processes and timelines that make it abundantly clear if they are capable of working this way.
What questions do you ask?
“Do your early and late stage Quality Control labs share equipment?”
“Are your early and late stage labs separate or do they share personnel?”
A “yes” to either of these questions is a red flag. Scheduling equipment and people will take markedly longer in a late stage laboratory. Development products are almost always de-prioritized in comparison to a vendor’s Phase 3 & commercial products.
“Please show me your validation strategy for Phase 1/2 compounds as compared to a Phase 3.”
“Do you leverage validation sample preparations for multiple tests?”
A vendor with a fit-for-phase approach should be able to articulate the specific differences in validation study design for early and late stage products. Regulatory agencies understand that most development products will not be carried forward and therefore are more focused on ensuring safety and development of product and process knowledge. Typical areas of opportunity for efficiency are omission of intermediate precision and robustness and reducing points on the curve for linearity.
What is your typical turn-around time for method validation?
Fit-for-phase method validation should take between 4-6 weeks. This should be plenty of time to complete the key quality method validations (assay/impurities, dissolution etc.) Full ICH (commercial) method validation costs and timelines will be twice those of a fit for phase program and are unnecessary for an early phase asset.
This is an interview with Dale Bennyhoff Sr. Director CMC with Velicept Therapeutics. Velicept Therapeutics is a clinical stage life sciences company progressing solabegron for the treatment of overactive bladder. Dale has over 20 years CMC experience in both small and large molecules.
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