Masterstudiengang "Drug Regulatory Affairs"

Language: English

In keeping with efforts to rationalise and harmonise the regulations of medicinal products the ICH has developed standardised specifications for the Common Technical Document (CTD) and the electronic version of that the eCTD. The eCTD standard describes a message format and protocol for transferring submission documents and processing instructions to an agency system. The eCTD standard provides a mechanism to record all interaction between industry and agencies in a way that highlights changes between multiple submissions. This lifecycle view of the submission is achieved through the use of the so-called XML format. The XML format describes each document in the submission. Additionally, it provides instructions to the receiving system allowing the management of data, which describe the submission. Based on the XML format additional specifications have been developed by various regions for content within the eCTD standard. Often these replace unstructured document files (e.g. pdf, -doc, -rtf.) with highly structured XML documents exemplified by the FDAs Study Tagging File or Europe`s electronic Application Form as well as labelling initiatives such as the FDAs Structured Product Labelling and EMEAs Product Information Management. This trend can be seen as the continuous extension of the eCTD standard making the submitted information more granular and more manageable by automated systems. This generally improves the quality and efficiency of the regulatory review process.

The eCTD standard is now in Step 5 of the ICH process implementation by the national competent authorities. The Member States are progressing with implementation of the eCTD standard at quite different rates. Therefore, the eCTD readiness and experience to date varies dramatically by country within the EU. Only a minority of European national competent authorities already accept or plan to accept electronic-only submission of marketing authorisation applications by the end of 2008. In contrast, the majority of the national competent authorities still require paper based dossiers due to national archival law or due to the fact that the necessary electronic work flows are not in place. As per November 2007, 23 Member States still need to implement legally binding requirements covering completely electronic-only submission of marketing authorisation applications of all types - initial, variation and renewal, so that no additional paper copies are needed.

Nevertheless, more and more Member States are moving into the eCTD standard. Full adoption of the eCTD standard is targeted by the end of year 2009. Unfortunately, some national competent authorities have followed an aggressive e-submission/eCTD implementation schedule and have already succeeded in having legislation changed to permit electronic-only submissions. However, these are not necessarily eCTDs. Currently, electronic submission based on the eCTD standards represents only a minor fraction of all electronic submissions within the EU. As detour to the eCTD standard national competent authorities such as MHRA (UK) and DGMP (Belgium) have implemented various national requirements representing no standard, but in fact individual procedures and acceptance criteria resulting from their bespoke e-submission processing system that accepts a variety of electronic submission types. Therefore, submitting and managing an eCTD - especially in support of marketing authorisation applications following the MRP or DCP might be a regulatory minefield. To successfully navigate these waters applicants need to know what the eCTD standard is capable of providing, how sequences should be related, how much hypertext linking is desirable, and when to replace, delete, append and submit new files. In this connection it should be noted that harmonised best practice guidance for how to do eCTDs for MRP/DCP submissions is currently under development.

Due to the flexibility of the EU Module 1 specification all administrative and prescribing information that is common to all Member States can be submitted to all Concerned Member States and the Reference Member State within one sequence. Also all country specific information of Module 1 including “additional data” can be incorporated in one single sequence for all Member States. On the other hand, the current version of the eCTD standard is not able to provide:

The solution for these shortcomings of the eCTD standard might be the new standard for electronic submission called Regulated Product Submission. The Regulated Product Submission standard is the American answer to European eCTD. Health Level Seven (HL7), a standard organisation similar to the International Organisation for Standardisation (ISO), has initiated it. The Regulated Product Submission standard creates a regulated product submission message based on XML including meta data, which is general enough to handle all regulated products and which contains enough information to allow regulators to support structured review. It is intended that the Regulated Product Submission standard will be used worldwide for regulated products, including but not limited to foods, medical devices, human and veterinary medicinal products. The Regulated Product Submission standard allows for document lifecycle, reuse of documents across applications, product/submission management, submission lifecycle, computer aided review, visibility into product/submission, and regional/product differences. Therefore, the Regulated Product Submission standard might overcome the difficulties especially in support of marketing authorisation applications following the MRP or DCP in Europe based on the current eCTD standard.
All in all, electronic submission standards in the pharmaceutical industry have made significant progress in the last years, with both industry and regulatory bodies acknowledging the benefits. It can only be anticipated that these standards will continue to evolve and new standards will be proposed. Nevertheless, any standard should be designed with one ultimate goal providing safe and effective healthcare to patients.