David Shoemaker, PhD, SVP R&D, has over 25 years of experience in pharmaceutical product development. He has served as a Program Leader or Advisor for multi-disciplinary program teams and has been involved with ensuring products meet regulatory standards at all stages of the development process.
A recent study by the MIT Sloan School of Management determined only 14 percent of clinical studies succeed, indicating there is room for vast improvement in the pharmaceutical industry’s ability to develop needed therapeutics more efficiently1. Inasmuch as the clinical develop program for a product comprises several to dozens of clinical studies to achieve marketing approval, chances are that one or more studies will fail during development. Coincidentally, this success rate of 14 percent approximates the age-old estimate that 10 to 20 percent of products that enter human studies make it to the market2,3. However, an eventual failure rate of 80 to 90 percent for products entering Phase 1 speaks to more than simply clinical study failure rate. The failure rate indicates an overall development process shortcoming that begins during the preclinical stage and destines product development programs for failure. This is due in part to the fact that companies are in many cases not doing the correct clinical study on an efficient path to marketing a needed therapeutic product. They do not possess a road map for success.
As a contract research organization who works extensively with late stage development companies collaborating on the preparation of their marketing applications, Rho continually observes product sponsors who fail during late stage development due to preventable missteps with their product development program. We are always buoyed by starting a new relationship with a company who has taken the time to prepare a Target Product Profile (TPP) because we know we have a client who understands the importance that prescribing information and market position play in the ultimate approval of a product by the regulatory authorities and the commensurate successful market capture. Simply achieving marketing approval is not the goal. The goal is to provide a useful therapy that will meet the needs of patients, physicians, and payers and hopefully advance current therapeutic options. The TPP provides a road map for development of a product, laying out all the key development performance criteria that the investigational product must meet in order to ultimately become the useful therapy the sponsor wants it to be; failure to meet any of these key criteria means the investigational product will not succeed as a useful marketed product and development should be abandoned or somehow re-engineered.
The crafting of a TPP is enabled by a detailed understanding of not only the disease and its associated market, but also unmet patient, physician and payer needs. The goal posts for each of the stakeholders need to be determined by identifying the minimal and the optimal characteristics for a variety of TPP elements. The major criteria to meet patients’ needs reside primarily in efficacy and safety elements, but satisfying dosage, route of administration, and specific patient reported outcomes also must be considered. Obviously physicians’ primary needs will be met if the patients are satisfied but there may be additional considerations regarding route of administration as well as ease and efficiency of therapy. Payer value is derived from beneficial differentiation of efficacy and safety but there may also be differential market forces to consider based on geographical regions (e.g., free market, US; clinical effectiveness, France and Germany; cost effectiveness, UK and Canada). If it becomes clear at any point in development that you will fail to meet the minimal criteria for your product to satisfy any one of these stakeholders’ regulatory or commercial requirements, a company is well advised to abandon development. Also, it is simply common sense for companies to identify their principal competitive product on the market as well as potential competitive products in development prior beginning their development program in earnest. A comprehensive TPP should contain all of these elements.
The organization of the TPP is understandably varied across the industry with some people using the US Prescribing Information as a template and others adopting the European Summary of Product Characteristics. The FDA even issued guidance back in 2007 advocating the use of the US Prescribing Information organization (https://www.fda.gov/media/72566/download). The advantages of these strategies include the fact that you are effectively preparing your US annotated package insert during your development plan. These documents help both with minimizing and focusing development activities and organizing your marketing application, and they are in a format optimal for discussions with regulators. However, a complete TPP should still include an independent payer assessment that is of no interest to regulators. Other companies prefer more general categories than are found in product labeling such as efficacy, safety, payer value, dosage, indication, population and juxtapose these elements with the attributes of their target competitive product for a more commercially oriented TPP. This allows one to easily see when your product comes up short against a competitor thereby rendering a course correction or a No Go decision.
By focusing both the developmental and marketing goals in the TPP at the preclinical stage a company is able to build a commercial differentiation strategy into their early development plan. Preclinical studies are a lot less expensive to conduct than clinical studies and hypotheses can be tested versus competitive products efficiently. These preclinical experiments may or may not lead to earlier examination of active comparator studies in the clinic. However, it will most certainly enforce the understanding that validating a novel mechanism of action is less important than clinical differentiation from a competitive product. These experiments may allow a company to distinguish between competitors and identify the key competitive product to compete against. Demonstrating proof of concept in no way guarantees profit on return, so it is imperative that companies explore pharmacodynamic activity versus competitive products in their preclinical development programs.
A common reason small or inexperienced companies do not prepare a TPP is the proposed cost and amount of time that must be devoted to its preparation. Companies with an exit strategy at proof of concept or prior to phase 3 often claim the cost is not justifiable. However, the value created by a well-run development program that checks all the boxes for an intelligent investor is worth much more than the cost invested in the preparation of the TPP. Investment firms and big pharma are primarily looking for investments where the risks have been minimized and a program that has been conducted efficiently focusing on the ultimate appropriate indication and patient population while examining carefully the commercial landscape holds enormous value.
Perhaps the greatest value of the TPP is as a communication tool. The ultimate goal of the development program is shared clearly and continually with all the company disciplines, e.g., clinical, preclinical, chemistry manufacturing and controls, regulatory, and marketing. The TPP is also able to be used as an external communication tool that facilitates interactions with regulatory authorities, investors, and the media. The document can be used to help structure regulatory and investor briefing documents as well as press releases. The TPP’s additional use as a communication tool is as an educational document for new team members whether they are within the company or at regulatory authorities.
The bottom line is, you must prepare a TPP early and revise it continually during development if you wish to bring a successful therapeutic to market to advance patient treatment or you are left relying on nothing more than good fortune.
1 Wong, C.H, Siah, K.W., and Lo, A.W. Biostatistics. 2019; 20(2): 273 – 286.