Time and again, we see a case of a drug being developed, approved, and launched, only to flop in the marketplace. There are varying reasons for these market launch failures, but one reason, reliably, is the lack of commercial strategy to use as a roadmap from the start through development, approval, and launch.
While a focus on FDA approval is important, a commercial strategy is imperative for overall success.
Over the years, Camargo has seen many drugs fail on either or both counts. So how can you get all of your ducks in a row to prepare for a successful product, and how early should you start this process? The answer: begin with the end in mind by creating and using a Target Product Profile (TPP).
If you are still not convinced, consider the recent research performed by FDA-affiliated researchers that finds that using a TPP can reduce your review time 1. A well thought-out TPP can save you money in development costs, and make you money by getting your 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 a TPP to set the goals for a development program. While a TPP is highly useful for a new molecular entity, it is critical for a 505(b)(2) product that relies on, and distinguishes itself, from an existing product.
Yet which applications are least likely to include a TPP? Our analysis has found that it is products approved via the 505(b)(2) pathway.
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 industry aiming to improve Sponsor and FDA interactions in the drug development process. In a 2007 Draft Guidance Target Product Profile — A Strategic Development Process Tool, the FDA defines a TPP as “a format for a summary of a drug development program described in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.”
The benefits of a TPP and the resulting improved dialogue are listed as:
- minimized risk of late-stage drug development failures
- increased probability that optimal safety and efficacy data are available in a timely manner
- improved labeling content, and
- possibly decreased total time involved with drug development
As we have previously blogged here and here, 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 target product profile typically starts with a high-level concept of the drug product goal. Then throughout the development process, as more details become available, a more complete target product profile evolves.
The content of the 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 if the development program is the most efficient way of getting there.
The Dynamic and Customized TPP
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, the TPP shared with the FDA may be restricted to the goals for the product labeling and planned studies, while the company version/s may include a section on commercial goals and strategy.
Further, the TPP is updated over time to demonstrate to the FDA 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 another product(s). This is especially relevant for a 505(b)(2) product, which must differentiate itself from other existing products in order to have success. Or it may be useful to list minimal and optimal product characteristics early in the development program to focus team discussions.
Other versions of the TPP may focus on quality aspects, including manufacturing goals, and product-specific attributes from a patient perspective, such as in Quality by Design TPPs. By mapping your development plan with the ultimate goal in place, it becomes easier to identify those steps that can proceed concurrently, rather that consecutively, allowing substantial savings in the total time required for product development.
Using a TPP Reduces Likelihood of Refuse-To-File and Cuts Review Time
A recent analysis performed by researchers affiliated with the FDA found that products with a TPP enjoy shorter review times1.
The researchers found that of 808 new drug and biologic applications, NDAs and BLAs respectively, approved from 2008 – 2015 only 87 (11%) used a TPP in their interactions with the FDA.
The researchers went on to compare the approved products with a TPP to 353 control applications that did not use a TPP. Products without a TPP experience significantly more Refuse-to File actions (15; 4.2%) compared with the TPP products (0; 0%).
The review time for the TPP group was significantly shorter (median = 303 days) than that of the group without TPPs (333 days).
The time from IND opening to application submission/approval was not different between the groups, yet the authors noted a high number of extreme outliers in the control group. Additionally, it was noted that TPPs are often ineffectively used as they are introduced too late in the development process.
These figures only include approvals. Based on Camargo’s awareness of Sponsor development programs and what can go wrong, we suspect that TPP usage is even lower among products that don’t get approved, as issues preventing approval can be identified earlier in development with a TPP.
TPPs Are Least Frequent in 505(b)(2) Applications
The researchers noted that TPPs are underused: only 87 of 808 approved applications between 2008 and 2015 (11%) used a TPP in the development process.
Camargo’s own analysis finds that of the approved applications during this period, TPP use was lowest among 505(b)(2) applications: only 6.4% of 505(b)(2) approvals used TPPs compared with 14.2% of 505(b)(1) NDAs and 19.6% of BLAs.
Given the complexities of 505(b)(2) applications and the need for early and efficient dialogue with FDA, this is a missed opportunity.
How to Use a TPP to Your Advantage
In summary, put together a basic TPP early in a products development, update it, and refer to it often. Share a version of it with the FDA at each milestone meeting, and with members of each department of your company.
Camargo includes a TPP as part of the tailored Pre-IND and Pre-NDA meeting package strategic consulting we provide to clients.
But even earlier in a development program, we rely heavily on TPPs as part of our Product Ideation process. We begin with a preliminary TPP and refine this during the product selection process to result in a working TPP. We encourage the notion of “beginning with the goal in mind.” And we recognize the importance of minimizing product failures through thorough planning.
If you would like assistance in generating a custom TPP to meet your product goals, or need advice on your drug/device development program, contact us.
Angela Drew, PhD, Product Ideation Consultant, Camargo Pharmaceutical Services
Bob Kessler, PhD, Senior Director of Analytical Development, Camargo Pharmaceutical Services
1Breder, C.D., Du, W., Tyndall, A. (2017) What’s the Regulatory Value of a Target product Profile? Trends in Biotechnology 35, 576 – 579.