Linking the experimental process to the design controls defined by FDA can help ensure an effective and efficient new product development effort, as well as a competitive market advantage.

Perry Parendo

FDA guidelines exist for two key purposes. First, to ensure a product performs as expected, and second, to ensure that products can deliver the therapy required to treat the patient condition.

The tests to provide this evidence are the final confirmation tests and part of the validation effort. Prior to taking this final exam it is wise to do your homework. Failure to perform appropriate characterization testing can disrupt development schedules with validation delays, and create big questions in the minds at FDA. The following are examples of "experiments gone wrong" that could have been avoided with proper test planning and set up.

Smart Design Inputs

The only way to know a test is successful is to know that you have met the product requirements. It is far too common to fail a validation and find out the original product requirements (FDA calls this Design Inputs) were not correct. Changing requirements to pass a validation is heavily frowned upon by FDA.

The solution? Ensure you spend the time up front to understand the source of requirements. Do a quick confirmation test prior to final validation to ensure critical-to-therapy requirements are going to pass. The consequences are either a long story to explain sloppy requirements development, or a redesign to pass an unnecessary specification that is not benefiting the patient.

Firm Design Freeze

Definitive proof of meeting requirements is required for validation. New functions need to be evaluated during characterization, and the earlier, the better.

On one project, an electrical instability was determined after design freeze. Additional components were needed to address this issue. The consequences? A new component needed to be sourced through procurement. This component needed manufacturing evaluation for process compatibility. The circuit board layout needed to be changed, making prior process characterization work suspect. It changed the testing fixture and test process.

Even though only one design requirement was being reviewed, nearly every manufacturing step was being questioned. The solution here is performing design characterization work early and in depth. Going beyond the design freeze led to a need for reworking and a risk of failing the validation.

Start the Clock

Every company faces the rush to FDA submission. Validating a design that needs further changes prior to market launch creates a quandary. Do we start the clock, knowing that many questions will need to be resolved? Or do we delay our submission and clean up the design to a level we plan to release?

My preference is to clean up the design first. Ultimately, this saves FDA review effort and will likely speed the final approval date. Companies need to focus on what gets approval fastest, not how to get something in front of FDA fastest.

One implantable project was able to get FDA approval a year faster than a competitor. Our focus was on a clear and compelling story, and it showed in the questions we received and our ability to address those questions within 24 hours. Think about starting the clock for acceptance of your application. The consequence can be endless questions from FDA as they find holes in your story.

Questions to Answer

Validation testing needs to be done to answer expected and potential questions from FDA. Did we include enough depth in our characterization testing? Did we make assumptions that we are certain of and have proof of? Is there a use condition that has been ignored or overlooked?

Using Design of Experiment methods can ensure the ability to cover a wide range of input variables, as well as customer use conditions. Seeing this comprehensive testing builds confidence with FDA, compared to a test that tries to slip through with minimum effort to attempt to reduce the validation schedule. The consequence here is delays during FDA review. They are likely to dig deeper in all areas when they do not get a positive first impression.

Do Your Homework

When we are not clear about our requirements, do not understand or acknowledge project risks (different than product risks), or have a comprehensive test strategy, we are destined to create a situation where the project can go off the tracks. Linking your experimental process to the design controls defined by FDA can help you ensure an effective and efficient new product development effort.

Done right, it can create a competitive advantage in product performance and in overall speed to market.

Perry Parendo is the founder and president of Perry's Solutions, Inc., a consultancy focused on Design of Experiment methods and new product development.

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