Marketing Authorisation Process
The regulatory process
The regulatory process is in place to ensure that only drugs that are effective and are safe are approved. When evaluating whether a drug is effective, regulators take into account whether the drug leads to a clear benefit for the patients, what are its side effects and what the severity of the disease is (i.e. what happens when patients are not treated?). Based on this information, they will make a ‘benefit/risk’ analysis, taking the severity of the disease into account, where the positive effects of the drug (e.g. less symptoms, slower disease progression) are balanced against the side effects of the drug.
Different type of marketing authorization
In Europe approval for drugs for rare diseases is centralized via the European medicine agency (EMA). There are different types of marketing authorization that provide access to the EU marketing and are available for companies or academia developing new drugs to apply for. A full marketing authorization is the standard type, which requires a comprehensive amount of information on clinical benefit and safety for the drug in question. For rare diseases it can be difficult to obtain “the standard“ amount of data due to the limited patient numbers.
Conditional marketing authorization is a mechanism for drugs that treat severe and/or rare, life threatening diseases for which no appropriate treatment is available. For this type of authorization the amount of information needed at the time of approval must be sufficient to allow the regulators to perform a benefit/risk analysis and conclude that the benefits outweigh the risks, but these data could be less than “the standard”. For conditional approval, the additional data that would be required for full marketing authorization can be collected AFTER the approval has been obtained. The approval is conditional on the basis of the collection of further data and the benefit/risk balance is re-evaluated on a yearly basis. Once all the required additional data have been gathered, the drug can receive full marketing authorization (provided the benefit/risk evaluation is still positive). The legal basis of this approach allows for drugs to be taken off the market if the evaluation of additional data reveals that the benefit/risk ratio is no longer positive.
For rare, debilitating and life-threatening diseases, EMA set up a pilot program on adaptive licencing and are currently exploring the adaptive pathways concept further. This is a process where a drug is authorized early for a restricted group of patients (e.g. a certain age range, or disease stage) based on data that show strong trends for clinical benefit in the absence of safety issues. When additional information is obtained in additional groups (e.g. another age range or disease stage), the licensing can become wider.
For very rare diseases, where comprehensive data will never be available, marketing under exceptional circumstances can be used. This is restricted to situations where it is impossible to acquire information in clinical trials to use the other models for marketing authorization (e.g. due to a very limited patient populations). Here, yearly evaluation of the benefit/risk ratio will be done (like with conditional marketing authorization).
Patients can gain early access to drugs that have not yet obtained marketing authorization through compassionate use programs. This mechanism only applies to drugs that are in the development stage or subject of a marketing authorization procedure. Regulations for compassionate use differ per country (e.g. who is responsible, who reimburses the costs and how adverse events and/or efficacy are measured). Compassionate use can only be provided if there is a reason to believe the drug in question would be beneficial to a group of patients not included in the ongoing clinical trial to test the safety and efficacy of the drug. Once marketing authorization is obtained in EU countries, compassionate use is no longer an option in these countries.
Content provided by COST Action from the COST Action BM1207 funded meeting on translational and regulatory challenges for exon skipping therapies