In order for efficient production and review of the many documents that are transmitted between Agencies, National Competent Authorities and the Pharmaceutical Industry stakeholders, standardisation is required for writing and publishing. The Common Technical Document (CTD) describes the required content, format and organisation of a Marketing Authorisation Application (MAA) for a medicinal production in the EU. The submission of the CTD also has specific requirements.
How can we help?
EUDRAC provides support for its clients at every stage of the MAA; we write, review and submit all the modules required for the different application types. We oversee the complete procedure for many of our clients and continue to manage the MAA throughout the assessment phase until the authorisation is complete.
For every module of the CTD, EUDRAC has specialist and experienced writers, reviewers and publishers. We undertake the management, authoring, publishing and submission of a complete MAA; including any adaptations of modules written originally for the US and other regions.
EUDRAC’s established review and tracking systems ensures that the writing and publishing of the initial MAA and subsequent responses and procedures are accurate, complete and fully compliant.
Additional services include: Gap Analyses, Package Leaflet User Testing, Educational Materials, provision of Artwork and Braille and management of the Linguistic Review Procedure (including translations).
Clinical trials cannot be legally performed within a region without the authorisation of the trial by the regulators of the region. In the European Economic Area (EEA), the trial must be authorised by the national competent authority (NCA) and Ethics Committee (EC) for the region where the clinical trial is to take place.
Further information can be found here.
EUDRAC writes, reviews, publishes and submits clinical trial documentation for all stages of clinical trials (including Clinical Trial Applications, Annual Reports, Pharmacovigilance Reporting & Clinical Study Reports).
The electronic common technical document (eCTD) is a standardised interface and international specification for the pharmaceutical industry to transfer regulatory information, developed by the International Conference on Harmonisation (ICH).
The Common European Submission Portal (CESP) is a system that provides a simple and secure mechanism of exchange of information between the industry and regulatory authorities.
The purpose of the system is to:
EUDRAC has many successful years of publishing and submitting documents to competent authorities and the Agency. The publishing team has knowledge of the most up to date submission systems and has developed a rugged publishing process; including technologies to aid and consistency check the process.
About 30 million people living in the European Union (EU) suffer from a rare disease. The orphan drug designation programme helps facilitate the development and authorisation of medicines for rare diseases. Sponsors of designated ‘orphan medicines’ can benefit from a number of incentives which include:
In order for a product to qualify for orphan designation it must meet this criteria:
EUDRAC is involved in the development of a range of Orphan Drugs; we assist our clients with protocol assistance, clinical trial applications and HTA assessments. For a number of our clients we are the Regulatory representative for the Company.
EUDRAC write, submit and support ODD applications for our clients; we are also responsible for Annual Reports of the Orphan Drug Development (EU & US).
The link between manufacturing site operations and regulatory affairs is critical in the life cycle of the product. Ensuring that the correct information is included accurately and is both well written and correctly published has a significant impact during product development, assessment of the marketing authorisation application and in the post-authorisation phase.
We help to link manufacturing and regulatory functions by authoring specific technical reports or dossier sections. Many in our CMC team have prior experience gained via research and development roles in industry prior to a career in Regulatory Affairs.
The CMC team provides the necessary technical expertise to our clients to review raw data and reports and then extract the critical information needed to address the key regulatory requirements for the medicinal product. It also has the experience to know how to position this information within the relevant CMC modules. The team has prepared complete Module 3 sections for its clients from a variety of manufacturing site documentation including pharmaceutical development reports, process validation summaries and analytical method summaries and validation reports.
The preparation and submission of a Marketing Authorisation Application (MAA) is a detailed and lengthy process. Therefore, prior to embarking on the preparation of an MAA, it is important to organise, plan and develop a strategy to deal with the large volume of documents that are needed. Undertaking a gap analysis very early in the process ensures that any potential issues with both the draft dossier and the proposed submission strategy are highlighted.
EUDRAC provides support for its clients’ MAAs at both a strategic and operational level. We provide services for our clients at the point of their specific needs; we can fully project manage the MAA procedure or provide customised support to a client’s existing regulatory team.
Our team members all have at least 10 years experience in the different fields of Regulatory Affairs and Project Planning and we have assisted our clients with successful MAAs gained through the Centralised, Decentralised, Mutual Recognition and National Procedures. We produce detailed project plans which are customised to our clients’ development programme and we ensure full transparency at every stage of the MAA procedure.
The MAA procedure requires that accurate and complete responses are prepared and submitted according to strict timetables.
The EUDRAC team has significant practical and regulatory experience that enables us to distil the critical issues from the questions raised during an MAA and identify effective strategies for responses. EUDRAC has developed its own templates for responses that many clients choose to use. We also have a document and publishing tracker to ensure the status of the overall response is immediately apparent to all team members.
The Pharmacovigilance Risk Assessment Committee (PRAC) often requires Marketing Authorisation Holders to develop Educational Materials for patients and/or Healthcare Professionals to minimise potential risks with new medicines. These are required to be agreed with each National Competent Authority (NCA) before launch of the product in that country.
EUDRAC manages the Regulatory Approval of these materials with the different NCAs throughout Europe; we have Partners in all European countries. We understand the process and timelines required in each country and can recommend strategies to minimise frequent updates of the Educational Materials and therefore the need for re-submission to the NCAs.
A medicine can be authorised in Europe through different Regulatory Procedures i.e. Centralised, Decentralised, Mutual Recognition or National Procedure.
Some medicines have a “mandatory” requirement to be authorised via the Centralised Procedure (managed by the EMA) e.g. oncology products; others may request eligibility to this procedure if they meet the criteria required for authorisation under the “optional” scope. A single pan-European Marketing Authorisation is obtained through this procedure which is valid in all EU Member States.
The Decentralised procedure requires the medicine to be submitted to the Regulatory Agencies in the markets that are of interest to the Applicant. One NCA takes the lead in the assessment of the Application and is known as the Reference Member State (RMS); the other Agencies, known as Concerned Member States (CMS), subsequently review the Assessment Report of the RMS. At the end of the procedure, a separate National Marketing Authorisation is issued by each of the Member States.
The Mutual Recognition Procedure is used when the medicinal product is already authorised in a Member State (the Reference Member State) and the Applicant wishes to expand this authorisation to other Member States.
The National Procedure should only be used if the Applicant intends only to market the product in one country.
The EUDRAC team has supported a large number of its clients with all of these MAA procedures; it has also worked with a number of different NCA who have acted as Rapporteurs or Reference Member States for these MAAs. Eudrac can also assist its clients directly or with the support of its local Partners by managing the final national steps of MRP/DCP procedures prior to issue of the national authorisations by the different NCAs throughout Europe.
Some products must follow the Centralised Procedure and others must follow the Decentralised or Mutual Recognition Procedures; however a number of products could choose either route.
Where there is a choice of procedure, we work with our clients to understand their commercial goals and the strength of the regulatory data package. We will then provide them with advice on the different options available and the relevant pros and cons of each one; we will also describe regulatory precedent and experience with different Member States.
After the appropriate data exclusivity period has passed, generic and hybrid products can be commercialised by referencing the data of the innovator product. Topical products, e.g. many ophthalmic and dermatology formulations, are not considered as pure generics because systemic bioequivalence studies cannot be conducted. These products are, therefore, considered as hybrid products and must demonstrate similar physical-chemical properties to the reference innovator product to avoid the need for additional clinical studies.
EUDRAC has registered many generic and hybrid products. For hybrid applications. We provide advice to our clients on the physical‑chemical studies required to avoid the need for additional clinical studies. We also provide advice on the appropriate reference product for hybrid and generic applications.
In the European Union (EU), a Paediatric Investigation Plan (PIP) is a development plan aimed at ensuring the necessary data are obtained through clinical studies in children to support the marketing authorisation of a medicine for children.
All Marketing Authorisation Applications (MAA) for all drug types are required to include the results of studies described in the PIP, unless there is a specific exemption due to a deferral or waiver. This is also true for Marketing Authorisation Holders (MAH) who want to add a new indication, pharmaceutical form or route of administration.
Development of drugs for the paediatric population is an important consideration to be undertaken at an early stage in drug development. It is important to note that EU regulators require the PIP to be submitted soon after Phase 1 studies are completed.
EUDRAC advises, writes and submits full Paediatric Investigation Plans for its clients. We also submit PIP modifications and provide Chemistry, Manufacturing and Control (CMC) support for new paediatric formulations, and regulatory advice on the paediatric clinical trial requirements for an MAA.
EUDRAC is involved in the project management of successful Marketing Authorisation Applications (MAAs) for medicinal products authorised via the Centralised, Decentralised and Mutual Recognition Procedures. An accurate and well-written Module 3 is needed in order to meet the strict criteria required in Europe for Chemistry, Manufacturing, Controls (CMC) and Quality.
How can we help?
Across our offices (in UK, France and Germany), the EUDRAC CMC team works on a wide range of different dosage forms, encompassing immediate and modified release tablets and capsules, oral solutions, transdermal patches, sterile ophthalmic and auricular formulations, topical aerosols and solutions for intravenous administration. We have CMC experts with a high level of experience in both small molecules and complex biological drug substances and so provide a wide range of appropriate expertise.
EUDRAC adopts a specific, tailored approach to each client’s MAA submission based upon the level of support required; we work on product development in the pre-authorisation phase, throughout the MA approval procedure and on launch and post‑authorisation activities. For many clients, we also provide project management services to coordinate product development activities at different manufacturing sites and oversee development timelines and objectives. The success of this approach has led us to become a key part of many of our clients’ Regulatory CMC function.
Irrespective of the stage of development of a client’s project, EUDRAC recommends completion of a gap analysis; this highlights any potential issues with both the draft dossier and the proposed submission strategy. This is particularly helpful when regional differences exist. our CMC team has completed numerous reviews of US New Drug Applications (NDA) to inform clients on the different requirements for an EU MAA and it has significant experience for many different procedures.
Any issues identified during a gap analysis which require remediation can be considered as part of the overall regulatory strategy. In terms of project management, this approach can also highlight potential questions which may be raised during assessment of the MAA and allow for a response and any necessary study or data to be planned in advance. When reviewing the dossier, we also consider updates that could minimise post-approval regulatory submissions.
Ensuring that the correct information is presented concisely and in the most appropriate dossier sections is critical to facilitate validation of the MAA; it also facilitates the location of information for the regulatory reviewers during the assessment procedure.
EUDRAC authors all modules required for the drug substance and drug product sections of the dossier – including expert reports – and has prepared these sections with information from a variety of sources including manufacturing site documentation, an existing IMPD and a non-EU application such as an NDA. We also have significant experience in updating an authorised EU marketing authorisation for a repeat-use application via the Decentralised or Mutual-Recognition procedures.
Despite extensive international harmonisation of the requirements for regulatory submissions, there remains significant regional divergence for specific content. EUDRAC has a regulatory intelligence service to ensure that our CMC team is always aware of the latest European and national requirements as well as future developments that may apply throughout a product’s lifecycle. Through awareness of these requirements, the CMC modules are written to ensure compliance with current regulations, but also with consideration of those that will be implemented in the future.
The link between manufacturing site operations and regulatory affairs functions is critical during product development and remains so in the post-authorisation phase. The regulatory impact of manufacturing site documentation or change controls has to be assessed and a summary of key information presented in a suitable format in the submission dossier.
We help to link manufacturing and regulatory functions by authoring specific technical reports or dossier sections. Many in our CMC team have prior experience gained via research and development roles in industry prior to a career in Regulatory Affairs.
The CMC team provide the necessary technical expertise to our clients to review raw data and reports and then extract the critical information needed to address the key regulatory requirements for the medicinal product. It also has the experience to know how to position this information within the relevant CMC modules. The team has prepared complete Module 3 sections for its clients from a variety of manufacturing site documentation including pharmaceutical development reports, process validation summaries and analytical method summaries and validation reports.
Following the submission of the initial Marketing Authorisation Applications (MAA) for a medicinal product, the Product Information (PI) continues to evolve throughout its authorisation and marketing. It is reflected in the Packaging, Prescribing Information, Educational and Promotional Materials as well as National Formularies and Product Databases.
The EU has strict requirements for both the content and format of the PI, as well as the procedures in which it is updated.
EUDRAC has an experienced Labelling Team who is involved in the development and writing of the PI for new Marketing Authorisations, as well as in the review of mock‑ups and other post-marketing documentation which are based on the PI. We have Partners in all EU countries so we can perform translations and implement national requirements.
The Product Information (PI) should be a document that provides the necessary information to healthcare professionals and patients via the Summary of Product Characteristics (SmPC) and the package leaflet respectively. The package leaflet must also undergo testing with a representative group of potential users and a report prepared for submission to the regulatory agency. The use of clear, patient-friendly text and good design/layout is the aim for the development of package leaflets. The Product Information (PI) will be amended many times during the MAA procedure and good version control is critical. The Product Information also contains the ‘labelling’ section which covers primary and secondary packaging in the MAA e.g. a blister/label and the outer carton. The text in this section must be transposed into artwork mock-ups of the finished packaging.
EUDRAC has both the scientific and regulatory expertise to write high quality product information for use by healthcare professionals and the patient/carer. We also provide guidance in the artwork preparation of the primary and secondary packaging based on experience with regulatory agencies. We have qualified a vendor for performing user testing of the package leaflet ensuring a smooth assessment of the report by regulatory agencies.