Masterstudiengang "Drug Regulatory Affairs"
Master-Thesis
Package Leaflets: Testing and harmonisation in relation to the overall business process in regulatory procedures - An example of the impact of changing regulatory requirements ***
Dr. Susanne Sommer (Abschlußjahr: 2007)
Language: English
The present thesis describes the impact of two new European obligations on the business processes of pharmaceutical companies as well as on package leaflets (PLs).
Package leaflets in Europe have several roles to fulfil:
- They are part of the Marketing Authorisation (MA) for medicinal products, as well as of the finished package for distribution. According to Directive 2001/83/EC as amended Art 59 they are in general an obligatory part of the medicinal product, with detailed requirements on their content, and are directed to the user, in most cases the patient.
- The information PLs provide to the patient are meant to enable him to make his own benefit-risk assessment and agree to the therapy based on his pharmaceutical informed-consent.
- In conjunction with other product information texts the PL protects the Marketing Authorisation Holder (MAH) against liability issues.
Due to the New Medicines Legislation (NML), particularly Directive 2004/27/EC, PLs have to satisfy two further compulsory aspects:
- They need to be tested in order to ensure their usability and the reports on these tests have to be provided to the competent authorities.
- PLs of decentralised procedures have to be commonly agreed upon by all parties concerned, as it is the case for Summaries of Product Characteristics (SPCs).
The first of the preceding compulsory aspects represents a new obligation. In addition, both aspects also apply retroactively to established MRP products, which is extremely onerous for the pharmaceutical companies.
Pharmaceutical companies have had to develop and implement new processes. In particular, they have to
- make decisions on PL-testing methods and selection of Contract Research Organisations (CROs) in the case of out-sourcing.
- budget for additional funds and personnel.
- acquire knowledge about PL harmonisation and PL-testing.
- integrate the concomitant regulatory procedures into the life cycle of MAs.
The firms involved seek a process which minimizes costs in time and money while satisfying the requirements of regulatory authorities. Towards this end most companies choose the Diagnostic Leaflet Testing method which originated from the Communication Research Institute of Australia (CRIA) as the archetype. Its major advantage is its readiness for use, its acknowledgement by European Competent Authorities (CAs), and the availability of CROs that offer this method as a service. Alternate methods are being developed, but mostly at the national level.
Beyond the costs of developing a PL, there are considerable costs in making it suitable for use across the European Union (EU). Additional time and expenditures (CROs, translations, fees) amount to approximately 100,000 - 200,000 per retroactively harmonised and tested MRP-PL with about 14 countries involved. Knowledge of PL harmonisation and PL-testing increases constantly through hands-on experience, intensive communication with CROs and feedback from authorities during various procedures. It becomes evident that CAs are not prepared any better for the new obligations than the MAHs and generally prefer to come back to established national attitudes. Overall, the new obligations tend to delay the start of regulatory procedures, particularly in the case of established MRPs, as relevant documentation must be available on Day0.
PLs change. Based on the Directive 92/27/EEC applicable throughout Europe, the anticipation for national PLs of established MRP products was that they would not differ in content but only in language. However, with new Quality Review of Documents (QRD)-templates for decentralised procedures in place and the need for harmonisation, it became obvious that national approaches by companies and CAs differ from country to country. By means of an analysis of PLs from two established MRP products this thesis makes an attempt to categorize these attitudes and provide explanations for CAs comments during procedures.
As far as the editorial interests of PLs are concerned, there are still many outstanding issues. PL-design, font size, pictograms, and the use of colour are a matter of considerable debate. Due to the lack of approved, obligatory, EU-wide demands, only some cautious approaches are being undertaken to use these effective tools in PLs. The adoption of ready to use pictograms is proposed in this thesis.
The last part of this thesis considers the perhaps most promising developments on the horizon for providing more patient-friendly PLs. Such developments involve patient-tailored PLs that meet all of the following requirements: full disclosure, avoidance of liability issues, and being understood by patients. Interestingly enough, the actual way to these patient-tailored PLs would lead back to the initial purpose of a PL, which is, to be a tool for improving doctor/pharmacist-patient communication rather than as a replacement for this dialogue.
Pages: 85,
Annexes: pages : 20