Updated on: January 26, 2021
Updated by: Cathy Gatza, PhD, VP of Regulatory and Strategy
It is a story all too common: A drug product is developed, approved, and launched, only to flop in the marketplace. There are various reasons that such products underperform or fail, but frequently the cause is a lack of commercial strategy to help sponsors develop a roadmap to follow from the start through development, approval, and launch.
While a focus on FDA approval is important, a commercial strategy is imperative as well for overall success, and many drugs have failed on either or both counts. So how can sponsors get all their ducks in a row to prepare for a successful product, and how early should they start the process? The answer: Begin with the end in mind by creating and using a Target Product Profile (TPP) throughout the drug development journey.
To those still not convinced, consider the research performed by FDA-affiliated researchers that finds that using TPPs can reduce FDA review times. A well thought-out TPP can both save money in development costs and make money by getting a product to market faster. The market pays millions of dollars for priority review vouchers to achieve the same outcome: faster review times.
Camargo has long been an advocate of using TPPs to set the goals for development programs. A TPP is highly useful for a novel product, and it is critical for a drug improvement product that relies on, and distinguishes itself from, an existing product.
What Is a Target Product Profile?
The concept of a TPP arose in 1997 from a Clinical Development Working Group composed of representatives from the FDA and the pharmaceutical industry aiming to improve sponsor and FDA interactions in the drug development process. In a 2007 draft guidance called “Target Product Profile — A Strategic Development Process Tool,” the FDA defines a TPP as “a format for a summary of a drug development program described in terms of labeling concepts.”
There are several benefits of a TPP and the resulting improved dialogue:
- Minimized risk of late-stage drug development failures
- Increased probability that optimal safety and efficacy data will be available in a timely manner
- Improved labeling content
- Possibly decreased total time involved with drug development
- Targeted differentiation from previously approved products
As we have previously blogged, we view a TPP more broadly as a summary of the eventual drug-labeling concepts and the commercial product goals. It provides a focus for the development team and typically anticipates the expected and possible outcomes of the development program.
This process of building a TPP usually starts with a high-level concept of the drug product goal. The TPP is a fluid, dynamic document, and as more details become available throughout the development process, a more complete TPP evolves. Agreements with the Agency, the outcomes of any conducted studies, new proposed studies, relevant input from commercial or marketing assessments, and changes in the drug product itself should be reflected in the most up to date TPP.
The content of a TPP is organized into the sections of product labeling to demonstrate the sponsor’s goals for the final labeling. The sponsor’s proposed study designs can then be evaluated by the FDA in the context of whether the claims are achievable and whether the sponsor’s product development plan is the most efficient way of getting there.
What does a Dynamic and Customized TPP Look Like?
A TPP is dynamic and customized in terms of audience, time, goals, and product comparisons.
It is usually a good idea to maintain different versions of a TPP depending on the intended audience. For example, TPPs shared with the FDA may be restricted to the goals for the product labeling and planned studies, while internal versions may include a section on commercial goals and strategy.
Further, the TPP should be updated over time, throughout the drug development program, to demonstrate to the FDA both the progress in development for the new product (milestones reached) and the studies that have been proposed and completed.
A TPP does not commit a sponsor to a particular outcome. Instead, changes in the product goals over time can be highlighted in the TPP for discussion.
It may be useful to define the product in a TPP in comparison to other products. This is especially relevant for a drug improvement product, which must differentiate itself from other existing products to have commercial success. It may also be useful to list minimal and optimal product characteristics early in the development program to focus team discussions and provide target goals.
Other versions of the TPP may focus on quality considerations such as manufacturing goals and product-specific attributes from a patient perspective, as in Quality by Design TPPs. By mapping the product development plan with the ultimate goal in place, a sponsor makes it easier to identify those steps that can proceed concurrently, rather that consecutively, allowing substantial savings in the total time required for product development.
How Does a TPP Reduce the Likelihood of a Refuse-To-File and Cut Review Times?
A report published by researchers affiliated with the FDA found that products with a TPP enjoy shorter review times.
Of the 808 NDAs and BLAs approved between 2008 and 2015, only 87 (11%) used a TPP in their interactions with the FDA. Camargo’s own deeper analysis revealed that only 19.6% of approved BLAs, 14.2% of approved NDAs for novel products, and 6.4% of drug improvement approvals through the 505(b)(2) pathway used TPPs.
When comparing the submissions approved with a TPP against 353 control applications that did not use a TPP, the researchers found that applications without a TPP experienced significantly more Refuse-to File actions (15/353; 4.2%) compared with the programs that used a TPP (0; 0%).
The review time for the TPP group was also significantly shorter (median = 303 days) than that of the group without TPPs (333 days).
These figures only include approvals. Based on Camargo’s awareness of sponsors’ development programs and what can go wrong, we suspect that TPP usage is even lower among products that do not get approved, as issues preventing approval can be identified earlier in development with a TPP.
How Can Sponsors Use a TPP to Their Advantage?
In summary, sponsors should put together a basic TPP early in a product’s development, update it, and refer to it often. Given the need for early and efficient dialogue with the FDA when developing a product, a version should be shared with the Agency at each milestone meeting and with members of every internal department. Camargo includes a TPP as part of the tailored Pre-IND and Pre-NDA meeting package and strategic consulting we provide to clients.
But even earlier in a development program, we rely heavily on TPPs as part of the product ideation process. We begin with a preliminary TPP, which we refine during the product selection process to result in a working TPP. As a result, we “begin with the end in mind” and minimize product failures through thorough planning.
Contact us to find out how we can assist you in generating a custom TPP to meet your product goals or in crafting a product development plan.
Angela Drew, PhD
Product Ideation Consultant
Bob Kessler, PhD
Senior Director of Analytical Development