Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Due diligence of R&D projects - A guideline for evaluating regulatory aspects ***

Alice Ebel (Abschlußjahr: 2009)

Language: English

The licensing of research and development products, as a common business strategy in the pharmaceutical industry, allows collaborators to progress the development of the drug up to marketing. Reasons stretch from 1) limited resources of the licensor; 2) different development focuses of the licensor (rather research than development); 3) seeking alliances with partners with manufacturing capability; 4) exploiting different field(s) of application; or 5) the licensors lack of commercial capability.

Once the wish of licensing in a product has been expressed, the licensing goal should be clearly identified. This should include the acceptability of the potential drug by competent authorities, its scientific value, its market and development potential, its fit to the licensees product portfolio and its overall value for the company. The due diligence process which is necessary to assess the net present value and the risk/benefit profile of a drug in question should focus on whether these licensing goals can be met.

This thesis combines the detailed regulatory and scientific risk/benefit assessment of drug candidates with the evaluation of their market potential and market risks. This assessment work, which is performed by the close interaction of scientific (technical, preclinical and clinical), quality, regulatory and marketing experts, is best coordinated by a regulatory expert and provides the basis for the analysis for the final decision on whether or not the drug should be licensed in or not.
The regulatory expert should lead this assessment with his expertise on the legal requirements regarding the development of the drug. A close assessment of the feedback gained from authority interactions (e.g. national scientific advices, hearings during clinical trial applications, pre-IND or end-of-Phase-II meetings in the US, or even failed MAA procedures) reveals the acceptability of the generated data and proposed development by the authorities and identifies issues which still need to be addressed prior to filing a MAA and might constitute a project risk which needs to be factored in into the risk/benefit assessment of the project.
The scientific assessment of the drug candidate is best initiated by comprehending the status quo of the respective development areas (CMC, preclinical and clinical). Summaries of the work performed are often available in regulatory required documents such as the IB, IMPD or the IND (depending on their stage of development). The completeness of such summaries should be assessed to ensure that no unfavourable data is concealed.

By assessing which rules, regulations and guidelines apply to the development of the drug in question, the value of the development work already performed by the licensor as well as the work still required to bring the drug to market in the target indication can be assessed. This evaluation should not only be reduced to a technical gap-analysis, but also the scientific aspects of the drug should be taken into account. By assessing the results of the work performed, factors which might contribute to the project being unsuccessful, need to be identified. Such factors could be safety risks inherent in the production process (e.g. inconsistent process; impure or unstable drug) or the physiological effects of the drug detected in either animal or human studies (e.g. toxicity, carcinogenicity or pharmacological side-effects), or even the insufficiency or lack of efficacy. Hence, the scientific risk/benefit profile should be carefully evaluated and be taken into account when identifying the additional work which is necessary to bring the drug to market. The risk/benefit assessment should however also include an evaluation as to which further potential the drug candidate may have in other indications.
In parallel to this scientific and regulatory assessment of the product in question, the marketing expert needs to assess the competitive market. This is best done by defining the targeted SmPC (with the help of the scientific and regulatory experts) and should include the identification of available competitive products (either in development or already on the market) and the impact they could have on the development (e.g. timelines or study designs) and market share of the product. The potential revenues should be estimated, also taking into consideration the costs of licensing the product (milestone and royalty payments).

The regulatory expert in support of the scientific and marketing experts should establish a project plan for the recommended further development of the drug, taking all risks, potentials and impacting factors into considerations. Possible legal provisions for either a faster way to market for drugs which address high medical needs (e.g. EU: conditional or accelerated approval or approval under exceptional circumstances; US: accelerated approval, fast track status or priority designation), or to reduce development costs (e.g. SME status awarded by the EMEA) should be considered.

In summary, all considerations made by the close interaction of the experts in the due diligence process should serve as an all encompassing basis for a detailed decision analysis using the methods described. This elaborate evaluation delivers a sound decision on whether a product is worth while to be licensed in or.

Pages: 32; Appendices: 3, pages: 4