The EU non-prescription market represented 14.5% of total pharmaceutical sales in 2009, equating to 26,062 million Euros (source AESGP). Estimated figures for 2010 are that the EU market will account for 36% of the global non-prescription market (1). This market deserves consideration for established prescription products in the EU Community and can be accessed via a process of ‘switching’ legal status, either at a national or European level. Several articles have highlighted the impact on the business of switching a product to non-prescription status and the growth of the OTC market (2, 3). This article will outline the structured approach used by NDA’s dedicated Switch Team to assess the multiple facets to be explored, when considering a change in legal status of a product.
The categorisation of a product is determined according to national criteria. These national categories drive whether the product can be advertised to the patient, reimbursed and whether they are available only via a pharmacist or freely available for self-selection by the patient. There are differences across the EU Member States in categorisation of non-prescription medicines and the impact of these differences should be assessed taking into account the target markets of interest for non-prescription EU sales, for example in France and Italy, the Regulatory Agency may prohibit advertising of certain self-medication products.
For a product approved via the EU Centralised procedure, the legal status is defined at a high level at time of approval, e.g. for the product alli ‘medicinal product not subject to medical prescription’. However, the appropriate national categories are still applied e.g. alli is sold as a P or Pharmacy product in the UK.
SWITCH DRIVERS AND CLIMATE
The interest of the Pharmaceutical Company in consideration of a switch in legal status may be driven by the desire to expand their product portfolio, as an end of patent life strategy or to reach a potentially wider patient population for conditions which are undiagnosed or untreated in a considerable percentage of the total patient population. There is also the potential for an additional 1 year’s data exclusivity if new significant data are generated to support the switch application. The type of data which could trigger the additional data exclusivity is defined in the EU switch guideline (4) and includes ‘significant pre-clinical / clinical studies, new dosage strengths/indications/ pharmaceutical form or Actual use studies which support safety and efficacy in the non-prescription setting.
In terms of the switch climate and receptiveness of Regulatory Agencies to switch applications, this is again very Member State specific. Public Health needs and cost savings to National Health Authorities if products are switched, facilitate a positive switch environment in some EU countries. The UK stands out as being particularly proactive in encouraging switch considerations and has worked with other key stakeholders to produce a list of possible therapeutic areas and medicines that could be switched (5).
Appropriate self-medication is also in the interest of the patient, since it leads to easier availability of treatments for self-diagnosable conditions and saves time (and money) needed for a visit to a physician to obtain a prescription. Identification of key EU and national patient organisations covering the relevant therapeutic area, who could help in providing the patient’s perspective on the proposed OTC development, also forms part of the assessment.
Finally, the role of the pharmacist needs to be considered, since they can be critical in successful use of a non-prescription medicine. Depending on the product concerned, pharmacists may be called on to establish a patient’s suitability to receive the product via a structured questionnaire or ‘screening’ type questions.
MECHANISMS FOR SWITCH
There are multiple regulatory pathways available for switching legal status depending on the initial route of approval, i.e. national or European basis. Legal status of an existing licence can be changed by submitting a variation or a new application may be filed. It is also possible to file a pan- EU application via the Centralised procedure on the basis of ‘interest of patient health at community level’. An assessment considers the pros and cons of the different regulatory strategies.
The EU switch guideline referenced above is pivotal to consideration of switch suitability. It must be demonstrated in the switch application that the product does not meet any of the criteria below:
“Medicinal products shall be subject to medical prescription where they:
are likely to present a danger either directly or indirectly, even when used correctly, if utilized without medical supervision, or
are frequently and to a very wide extent used incorrectly, and as a result are likely to present a direct or indirect danger to human health, or
contain substances or preparations thereof, the activity and/or adverse reactions of which require further investigation, or
are normally prescribed by a doctor to be administered parenterally.”
The Clinical section of the NDA assessment therefore provides a detailed analysis of whether any of the above criteria would be triggered, by consideration of the safety and efficacy profile of the product together with an assessment of the current approved labelling. Potential posology options for the OTC product are proposed. A detailed review of existing competitor products in specific EU countries is also part of the assessment. This has been useful to provide details of switch precedents and compare potential labelling of the proposed switch product with existing competitors.
The Regulatory assessment, in addition to description of potential regulatory filing options , also reviews precedents or concerns raised previously by Agencies, impact of on-going product commitments and the impact of multiple presentations or duplicate licences on the Regulatory pathway. Critical issues for discussion with Agencies are identified.
NDA SWITCH ASSESSMENT EXPERIENCE
Since national legal basis categories and switch procedures have such an impact on switch consideration, the core NDA Switch Team works with consultants in all major EU countries to ensure that the switch assessment provides this national focus in addition to the overall assessment.
The NDA Switch Team has combined experience of working on over 60 OTC switch assessments or switch applications to agencies, for multi-national pharmaceutical companies, in a variety of therapeutic areas including Central Nervous system, Genito-urinary and Cardiovascular.