1. Regulatory context
The Marketing Authorisation
Pharmaceutical companies wishing to bring a medicinal product in the market must obtain a Marketing Authorisation (MA), delivered by the concerned competent authority.
In order to obtain it, pharmaceutical companies must submit a Marketing Authorisation Application to the competent authority assessing it according to scientific criteria of quality, safety and efficacy. The MA application must describe:
- the manufacturing of the drug substance and the drug product (Quality)
- the non-clinical studies (Safety)
- the clinical studies (Efficacy)
This regulatory application must contain all the scientific data known concerning the medicine and reflect the manufacturing and control methods used to produce it.
These data must be in accordance with the regulatory requirements (ICH M4Q, M4S, M4E, and Volume 2 of the rules governing medicinal products in the European Union - Notice to Applicants).
The maintaining of the Marketing Authorisation
Once the initial MA application is accepted and the drug is marketed, the pharmaceutical company has to maintain the regulatory application up to date throughout the life cycle of the drug, via other submissions:
- Variations (Type IA, Type IB, Type II)
- Renewals
- Annual re-assessment
2. Le Common Technical Document (CTD)
The submission of the regulatory dossiers and the registration of the pharmaceutical drug was harmonised through an international regulatory process set up in 1990 by the ICH (International Conference on Harmonization).
ICH is constituted of the regulatory agencies, of three regions: the EMEA (European Medicines Agency) for Europe, the FDA (Food and Drug Administration) for USA and the MHLW (Ministry of Health, Labour and Welfare) for Japan.
ICH set up a harmonised structure of the drug application, the Common Technical Document (CTD), to facilitate the management of their creation, submission and life cycle. The main interest of this structure is that it is accepted and used by the EMEA, the FDA and the MHLW.
The CTD is divided in 5 modules:
- Module 1 : Administrative Information and Prescribing Information
- Module 2 : Common Technical Document Summaries
- Module 3 : Quality
- Module 4 : Nonclinical Study Reports
- Module 5 : Clinical Study Reports
Note: The 10 countries members of the ASEAN (Association of Southeast Asian Nations) use another structure, derived from the CTD, named ASEAN Common Technical Document (aCTD).
The increase of the use of computerised systems, within the pharmaceutical industry, brought the regulatory authorities to focus on the transition of the management of the documentation from paper to electronic format, in order to guarantee both, operational performance and the integrity of data, sensitive in a businees and regulatory point of view.
3. eCTD : electronic submission of regulatory applications
Developed by the ICH, with the aim of optimizing the interactions between pharmaceutical companies and regulatory authorities, the Electronic Common Technical Document (eCTD) is the electronic format of the pharmaceutical regulatory dossier, based on the structure of the CTD.
The eCTD is an interface for the transfer of regulatory information, in electronic format, between the pharmaceutical industry and the regulatory authorities. It facilitates the management of the creation, the review, the life cycle and the archiving of the regulatory submissions.
A submission dossier in eCTD format consists of:
- Regulatory documents in PDF format, ordered in directories and sub-directories numbered and organized into a hierarchy in accordance with the CTD structure
- XML files linking the documents and containing supplementary metadata
- Checksums for every file constituting the eCTD dossier
4. Non eCTD Electronic submission (NeeS)
The Non eCTD Electronic Submission (NeeS) is an electronic format of pharmaceutical regulatory dossier different from the eCTD, used by the member states of the European Community during the period of transition between CTD paper submission and eCTD electronic submission.
A submission dossier in the NeeS format consists only of files in PDF format, organized in directories and sub-directories following the CTD structure. Unlike the eCTD, the NeeS does not include XML files nor Checksums, and does not, thus, have the features of control, navigation and life management of the electronic applications of the eCTD.
The transition of the pharmaceutical regulatory dossiers to an electronic format is well enhanced today: the main regulatory authorities already require (FDA) or will, in a near future (EMEA), the use of this format.
The pharmaceutical industry has to comply with these new requirements by adapting the Electronic Document Management Systems, in order to be able to create and submit dossiers in this new format and, also, to manage the life cycle of the documents composing them.
ADN, and more specifically the RPMS (Regulatory Process Management Systems) team, helps you in the 3 following phases:
R3 Management
Risk management
- ADN assists you in the management of the Risk analysis related to the processes
- ADN supports you in the Management and preparation of the tests allowing the validation of the system and the reduction of the risks related to its use
- ADN assures the maintenance of the system in a validated status all along its life cycle
Requirement management
- Modelling of your processes and collection of the user needs, related to the submission of the marketing Authorisation submission, allowing the writing of the requirements
- System expertise: knowledge of the existing tools in the management the regulatory submissions and consulting of the suppliers:
- Liquent InSight Publisher (Thomson Reuters)
- EMC Documentum Submissions Manager for eCTD
- Ennov5 Dossier
- Datafarm eCTD Solutions
- Extedo eCTDmanager
- Image Solutions (ISI) eCTDXPress
- Lorenz DocuBridge
- GlobalSubmit REVIEW 2009
- PharmaReady eCTD Submissions Management
- Assistance in the choice of to system to be used according to your company organisation and to business and regulatory requirements
Regulatory management
- Regulatory Expertise related to the management of regulatory submissions (ICH M2 et M4, Volume 2-Notice to Applicants)
- Regulatory Expertise related to the validation of computerized systems, and more specifically the validation of the eCTD to be implemented (21 CFR Part 11, GAMP 5)
- Management of standard operating procedures and instructions allowing the use of a new system/tool and its insertion in your company processes
- Management of the documentation archiving
- Management of Audits: Assistance in the preparation of audits, Responses to audit requests, documentation search.
