Target Product Profile:
Starting with patients in mind
Rob Don, DNDi Project Manager
By the time a new drug reaches a patient it has to be able to cure the disease safely, with few side-effects. To be truly effective it has also to satisfy many others criteria. These may include an attractive formulation to ensure that children comply with their treatment, or robustness suitable for transport and storage in tropical conditions.
During drug discovery, which is the very start of the R&D process, researchers can too often become so involved with the interaction between drug molecules and targets associated with the disease that they forget critical features of the final product. A Target Product Profile (TPP) keeps research focused on the endgame a medicine for a patient.
A common format for the TPP is a “package insert” which contains all of the information necessary for a medical practitioner to effectively prescribe the drug. At DNDi, additional features include low cost of manufacture to make the drug more affordable to patients and governments, and robustness suited to the extremes of climate that our drugs will encounter.
The TPP provides a statement of intent very early on in the drug’s development programme. It starts as a description of an ‘ideal’ drug, and changes over the development process as limitations in the potential drug emerge. Because the TPP reflects the final product, it is a useful tool to assess whether these limitations are acceptable. If they are, development of the drug continues; if not, it is back to the drawing board for a new potential drug.
Good knowledge of patient needs is essential to a credible TPP. It is necessary to solicit input from health-care workers, patients, health regulators and policy-makers in disease-endemic countries that are the final destination for the drug. Their inclusion in the early stages of the decision-making process ensures that their needs are reflected in the final product.
Used properly, the TPP can play a central role in the entire drug discovery and development process. This role includes (1) effective optimisation of drug candidates (2) decision-making within an organisation, (3) design of clinical research strategies, and (4) constructive communication with regulatory authorities.
1. Effective optimisation: At the very early and high-risk end of drug discovery drug screening and lead optimisation a TPP can provide an objective method to decide whether the drug should be allowed to go through the development process. It takes the emotion and subjectiveness out of hard decisions that have to be made. The description of what the final drug needs to be creates a ‘decision matrix’ of specific assessments (manufacture and kinetics, efficacy and safety).
At the screening stage, the matrix asks simple questions such as: Is the molecule drug-like? Does it kill the parasite? Is it likely to yield a product which will be cheap enough? As the compounds are refined, the matrix becomes more discriminating and asks whether the drug candidate works in complex models of disease and if it has an acceptable safety profile etc.
2. Decision-making: Within the organisation the TPP provides an objective, shared understanding of each drug development programme and facilitates rapid orientation for new personnel.
3. Planning the clinical development strategy: With knowledge of the final drug product, the complete clinical trial programme needed to generate the data necessary to support registration can be designed. Manufacturing and formulation issues can be addressed well in advance. This shortens development time and delivers new medicines to patients faster.
4. Constructive communications: A well-written TPP can serve as an excellent briefing document for meetings with regulators.
It is a multidisciplinary tool and includes detailed information about drug manufacture, safety, pharmacokinetics, pharmacodynamics, and statistics. The regulatory agency can thus assess the development strategy for a product and provide accurate advice on whether the strategy will satisfy all necessary requirements for registration.
Published by Drugs for Neglected Diseases Initiative - 1 Place St Gervais 1201 Geneva Switzerland
Editor: Jaya Banerji - Tel: +41 22 906 9230 - Fax: +41 22 906 9231 - www.dndi.org