Masterstudiengang "Drug Regulatory Affairs"
Master-Thesis
Strategic ordination of the regulatory instruments for obtaining early market access in the EEA, USA and Canada of a novel anticancer drug ***
Anne Louise Kirkegaard (Abschlußjahr: 2006)
Language: English
As of November 2005 legal provisions for enabling an early market access to new and promising anticancer drugs exist in the EEA, US and Canada. The legal provisions in the three regions enable the grant of an early marketing authorisation where promising evidence on efficacy and safety is available and confirmatory data are still lacking. Due to these regulatory mechanisms patients suffering from cancer diseases will gain early market access to new anticancer medicines where an early evidence can be demonstrated based on a small amount of clinical data. Due to the severity of the diseases even an access only a few months earlier than would be the case with a normal marketing authorisation may save or ameliorate the lives of many cancer patients. This is the main argument for allowing a conditional marketing authorisation of a new medicinal product where the safety profile is not completely known and the efficacy not confirmed in a large patient population. At the same time an early return of investment is of interest for the pharmaceutical industry.
In the present thesis the various options of obtaining a marketing authorisation early in the development phase are addressed with special regard to the development of a novel anticancer drug. Main focus is on the new legal provisions for obtaining a conditional marketing authorisation in the EEA as compared to the already existing provisions for making use of a marketing authorisation under exceptional circumstances, compassionate use programmes, orphan drug regulations and obtaining an accelerated assessment. As similarities do exists to regulations in other regions, parallels to the US and Canadian legal systems are drawn.
With time the EEA conditional marketing authorisation will become a normal marketing authorisation as comprehensive data have been gained which is the main difference to the marketing authorisation under exceptional circumstances for which it cannot be expected that comprehensive data will ever become available, e.g. due to the rarity of the indication. Therefore, the marketing authorisation under exceptional circumstances does not enable early market access of new and promising therapies, it is a possibility for obtaining a marketing authorisation where data that will never become available are missing. The marketing authorisation under exceptional circumstances is an instrument enabling market access to therapies for which a marketing authorisation would otherwise not be granted.
In the US the accelerated approval is the equivalent to the EEA conditional marketing authorisation. The US accelerated approval can be granted to new drugs for serious or life-threatening illnesses where the clinical study design is based upon a surrogate endpoint or on an effect on a clinical endpoint other than survival or irreversible morbidity. Analogously, in Canada an approval under the notice of compliance with conditions policy may be granted for a drug product with promising evidence of clinical effectiveness providing it possesses an acceptable safety profile and is found to be of high quality. The EEA conditional marketing authorisation, the US accelerated approval and the Canadian notice of compliance with conditions all have in common that the marketing authorisation is granted earlier than a normal marketing authorisation based on promising evidence on efficacy and safety, where confirmatory data are still outstanding which are to be provided as a post-approval obligation.
There are many parallels in the regulatory mechanisms for enabling early market access to new important therapies - such as novel anticancer drugs between the EEA, US and Canada. The differences between the regulatory particulars in the different regions are less clear and these are probably mostly existent in the interpretation of the various terms at the different regulatory agencies. When looking at some of the most recent approvals of novel anticancer drugs in the three regions, it is clear that the regulatory authorities in the three regions are of a similar opinion when it comes to the clinical development programme as in all cases the same clinical endpoints in the pivotal studies have been accepted indicating that the same clinical studies were accepted in the three regions. However, when it comes to granting a full or conditional approval and/or priority review, the three authorities seem to differ greatly in their opinion on which data must be available in order for a full or conditional marketing authorisation to be granted as well as on which drugs are of priority. In this matter, naturally, also the different legal fundaments in the different regions and the different empowerment of the EMEA, the FDA and the Health Canada, respectively, play important roles. Although there is no guarantee that the EEA, the US and the Canadian authorities will issue the same or a similar advice to a certain question to the development programme of a new medicinal product, it is appropriate early in the development phase to discuss issues such as study design of the clinical studies, the possibility of applying adaptive clinical trial design and statistical methods to perform interim analysis of early results (e.g. Bayesian approach), the amount of clinical studies, the moment for submission of the marketing authorisation application as well as the possibility of a conditional marketing authorisation, marketing authorisation under exceptional circumstances and/or accelerated assessment/priority review with the competent authorities. This would lead to an overall better planning of the drug development phase, would likely avoid duplication of studies and allow for an accelerated preparation of the regulatory submission.
Despite disadvantages and problems seen with the various systems in the EEA, US and Canada, appropriate regulatory mechanisms for enabling early market access of novel anticancer drugs have now been established in the EEA, US and Canada. Surely, improvements are needed but since the fundaments now exist in all of these three regions, an important step has already been taken improving the regulatory environment for the development of new and better cancer therapies.
Pages: 52