2. Module 1 region specific
Module 1 contains region-specific administrative and product information. The EU has developed its own version of Module 1. The EU eCTD Module 1 Specification has been updated to reflect clarifications and the updated version 3.0.4 is approved and should be used from April 2021.
The module contains the following elements:
1.0 Cover letter.
1.1 Comprehensive table of contents.
1.2 Application form.
1.3 Product information documents.
1.4 Information about the experts.
1.5 Specific requirements for different types of applications (if required).
1.6 An Environmental risk assessment.
1.7 Information relating to orphan market exclusivity (if required).
1.8 Information relating to pharmacovigilance.
1.9 Information relating to clinical trials (if required).
1.10 Information relating to paediatrics.
Regulatory Affairs (RA) professionals are responsible for advising on, collating and reviewing the elements before submission.
In addition, other items such as answers to regulatory questions, rationale for variations and renewal documentation could also be included in Module 1.
1.1 Comprehensive table of contents
(In eCTD the XML backbone acts as a table of contents)
1.2 Application form
The application form (1.2), contains administrative data, information about the type of application and submission procedure, extensive basic information about the medicine or medical device, a summary of the pharmacovigilance system, and all companies involved in manufacturing or in clinical trials (contract companies, CROs).
In addition, it is stated whether scientific advice was sought prior to the submission. The advice will be included to facilitate the work of the assessors. Seeking scientific advice is helpful for the applicant when planning various steps of the development process. The success rate is much higher for submissions when scientific advice has been sought and adhered to. From 2008 to 2012, approximately 85% of such applications were approved. For those not adhering to the advice, the success rate was only of approximately 40%.
Of note: As from 01/01/2016, use of electronic application forms for all procedures is mandatory. The Application form presently applicable is “Medicinal Products for Human Use, VOLUME 2B, Module 1.2: Administrative information Application form September 2021 (Rev. 15)” (see also below 4.2. Electronic Application Forms (eAF))
1.3 Product information
Product information (1.3) refers to the summary of product characteristics (SmPC), a detailed document for healthcare professionals, the labelling (outer and immediate packaging) and the package leaflet (PL), formerly called patient information leaflet (PIL). based on the mandatory format and lay-out (see “QRD template” on the EMA Website). The SmPC and PL must be written to be easily understood by a lay person. The applicant must demonstrate the required consultation with target patient groups, often referred to as ‘user testing’ and predominantly using a so-called ‘readability test’. Likewise, information that will appear in Braille on the printed outer packaging material should be mentioned. (See also the “Guideline on the Readability of the Labelling and Package Leaflet of Medicinal Products for Human Use”)
1.4 Information about the experts
Experts in each field should write the summaries and overviews in Module 2 and provide detailed reports of the documents and particulars which constitute Modules 3, 4 and 5. Each of the experts should provide a curriculum vitae (CV) in section 1.4. Furthermore, they must sign a declaration that they have followed the rules of the applicable directive when creating the summaries.
1.5 Specific requirements for different types of applications
Section 1.5 should indicate the “legal basis” of the application – the corresponding Article of Directive 2001/83/EC such as applications of type: “full”, “generic”, “hybrid”, “similar biologic”, well established use”, “fixed combination”, “conditional”, “under exceptional circumstances”, etc.
1.6 An Environmental risk assessment
All active substances in medicines may potentially be of risk to the environment, as they or their metabolites will ultimately end up in the environment. Therefore, the pharmaceutical company needs to address these problems in the application in section 1.6 and ask what could be the problems for the environment in the use, storage, and disposal of the medicine.
1.7 Orphan market exclusivity
If the medicine is for treatment of an orphan or rare disease, specific information is needed in section 1.7. The new medicine may have received orphan designation. Another medicine on the market may already have market exclusivity for the same indication. In this case a new medicine may only be approved under special conditions, i.e. during the market exclusivity period similar medicines will not be granted a marketing authorisation for the same therapeutic indication. An exemption exists if the MAH for the orphan product approved first gives consent, is unable to supply sufficient quantity of the medicine, or the second applicant demonstrates that although ‘similar’, the medicine is ‘clinically superior’ to the already authorised orphan medicine.
In section 1.8 the applicant should describe the pharmacovigilance and risk management systems. These elements are important. The applicant needs to demonstrate that surveillance of adverse reactions and potential risks are in place.
1.9 Clinical trials
Clinical trials performed in the EU need to follow a specific set of regulatory and ethical requirements. In many cases, some of the clinical trials are performed outside the EU. In such cases, the applicant should include in section 1.9 a statement that those trials also respect EU requirements.
1.10 Information relating to paediatrics
All new medicines need to be considered for the paediatric population in the EU (Regulation (EC) No 1901/2006 (‘paediatric regulation’). In general, they should be tested in children. However, a waiver for this requirement may be granted if the disease is seen only in elderly people or other adults, or the new medicine is likely to be ineffective or unsafe in part or all of the paediatric population. If a waiver is not possible, the pharmaceutical company must produce a plan for testing in children, a Paediatric Investigation Plan (PIP). If the activities (usually clinical trials) under the PIP cannot be completed in an adequate time a deferral can be granted in which case the PIP can be delayed. In section 1.10 a copy of the waiver or of the decision on the PIP should be included.