Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Implementation of an internal Standard Operating Procedure for the Preparation of Mutual Recognition Variations ***

Claudia Hettenkofer (Abschlußjahr: 2004)

Due to the growing amount of mutual recognition procedures and the resulting increase in mutual recognition variations, the idea was born to prepare a Standard Operating Procedure for the implementation of mutual recognition variations.

This Master-Thesis gives at first a short introduction to the subject of Standard Operating Procedures in general and the European variation system. Subsequently, after the introduction to the preparation of the SOP itself the result of this Master-Thesis the SOP 'Implementation of Mutual Recognition Variations' is presented.

Standard operating procedures are documents that contain general information and instructions on how to perform routine operations. The structure of SOPs is usually fixed in a separate SOP, where layout, structure, approval, introduction, distribution, updating, coding, revision and archiving is fixed - specific for the company. For the preparation of the subsequent SOP the company internal SOP "Issue, Approval and Administration of Standard Operating Procedures" was used as a basis, in which the preparation of SOPs, including formal aspects and structure, the approval, setting into force and distribution as well as the administration including archiving, revision and dealing with outdated SOPs is regulated. The second topic deals with mutual recognition variations. Briefly summarised, the Commission Regulation EC/1084/2003 classifies variations into three groups. Minor variations of type IA and type IB, major variations of type II and urgent safety restrictions. The focus of this paper lies on the standard variation procedures, i.e. type IA and IB notifications and type II variations. Urgent safety restrictions, which are interim changes to product information due to safety restrictions are not considered to be standard and have therefore been disregarded. Type IA and IB variations are notification procedures, which lie in the full responsibility of the RMS. Type IA variations (`tell and do procedure´) do not need to be evaluated in content in contrast to type IB notifications (`tell wait and do procedure´). Type II variations are approval procedures and are at first evaluated by the RMS who prepares the variation assessment report which shall be recognised by the CMS afterwards. The following table gives a brief overview of the variation system:

Procedure Timeframe Clockstop Overall duration incl. validation phase + clockstop
Type IA notification 14 days not possible 14 days
Type IB notification 30 days + 10 working days validation phase NMT 30 days 74 days
Type II approval standard: 90 days + 10 working days validation phase NMT 60 + 60 days 224 days

In order to be able to begin with the preparation of the present SOP Implementation of Mutual Recognition Variations it was necessary to become familiar with the above mentioned SOP for the preparation of SOPs. The main task was to get acquainted with the workflows and responsibilities in the course of the preparation of variation applications in which many parties are involved. These workflows had to be outlined, discussed with all parties and finally transcribed into the SOP-format. The final SOP, including all attachments, had been forwarded to all involved parties for their final comment and subsequently to the QA to be formally checked and finally approved. While completing this paper the SOP Implementation of Mutual Recognition Variations passes through the approval procedure and will be probably become effective in May 2004.

Pages: 51