Developing Botulinum Toxin Drugs: Unexpected Challenges

The development of a new botulinum toxin (BT) drug is a major project associated with numerous challenges. Obvious ones include financing, manufacturing, registration and marketing. They will not be covered here. We want to cover challenges, which may be unexpected, but still will be crucial to the success of the development project. Potency is the most important critical quality attribute (CQA) of BT drugs. It is based on biological assays and the manufacturers’ internal reference standards. Clinical experience shows that the potency labelling of BT drugs is not directly comparable. As long as external reference standards do not exist, comparative data on the potency labelling should be provided for all new BT drugs. Idiosyncratic potency labelling will hinder the clinical use and the positioning of a new BT drug in the market. Therapeutic profiles are also a CQA. They describe efficacy and safety of BT drugs. They may be influenced by various molecular differences amongst the different BT types and BT subtypes. Therapeutic profiles can only partly be explored in animal experiments. As extrapolation to a human therapeutic use is problematic, human pilot studies would be helpful. Immunogenicity is another pivotal CQA. It can best be described by the specific biological activity (SBA). In the absence of animal models, the SBA of new BT drugs should be determined to predict immunogenicity, before post-registration studies become available to allow analysis of large number of patients over prolonged periods of exposure. Manufacturers of new BT drugs will make product claims, usually as unique selling points. These claims will be scrutinised by the medical community and challenged by the FDA. If they can’t be substantiated by robust scientific data, they will not be accepted for the registration documents. Undelivered promises may jeopardise the success of the development project.