Following an initial Marketing Authorisation (MA), there are various post-authorisation procedures in place in order to maintain the licence or to incorporate any changes that are required. The three key procedures are:
Variations to an MA are required for a number of reasons; additional data or information on the product may become available or manufacturing changes may be necessary. These changes are implemented via a specific classification of variation procedures, depending on the complexity of the change, and are subject to the approval of the European Medicines Agency (EMA) or National Competent Authority (NCA). The classification of variations (type IAIN, type IA, type IB and type II variations, Extension of an MA, or Article 61(3) notification) determines the length of the variation procedure and the level of assessment that is required.
The EUDRAC team has extensive experience in writing and submitting variation procedures for a wide range of products; we provide support to our clients for:
An initial MA is valid for five years and then has to be renewed (Conditional MAs granted under Article 14(7) of Regulation (EC) No 726/2004 have to be renewed annually). The renewal application has specific documentation and submission requirements. The application undergoes a formal assessment procedure during which there may be an RFI before a renewal is granted.
EUDRAC regularly submits renewal applications for its clients and provides procedural and product writing support as well as advice on when an earlier renewal or a renewal with reduced clinical documentation might be an option for you.
An MA Transfer is the procedure by which the MA is transferred to a new MAH (this is a different person/legal entity). For licences granted via the Decentralised Procedure (DCP) or Mutual Recognition Procedure (MRP) such a transfer of ownership is granted nationally and the regulatory requirements and timelines are based on the national legislation in the Member States (MS). For licences granted via the Centralised Application Procedure (CAP), the transfer is granted via the EMA.
There are often consequential changes due to an MA Transfer. e.g. name change of the medicinal product, submission of the summary of the pharmacovigilance system of the new MAH; if these changes are subject to the variation regulations, they then have to be implemented by the relevant variation procedures.
EUDRAC has completed MA Transfers for many of its clients and has also prepared the subsequent variations so that they have been implemented with minimal disruption to the marketing of the product.
In order for efficient production and review of documents transmitted between Agencies, NCAs and the pharmaceutical industry, standardisation is required. The Common Technical Document (CTD) describes the organisation of modules, sections and documents to be used, by Marketing Authorisation Applicants and Holders, for a medicinal product for human use in each of the European Union (EU), Japan and the United States (US).
For every module of the CTD, EUDRAC has specialists and experienced writers, reviewers and publishers. We undertake the management, authoring, publishing and submission of a complete MAA; including any module adaptations for the US and other regions.
EUDRAC’s established review and tracking systems ensure the writing and publishing of the initial MAA and future responses and procedures are fully compliant and of exceptional quality.
Additional services include: gap analyses; package leaflet user testing co-ordination; artwork review and linguistic review.
Please see our Publishing page for more details.
Linguistic Review is the translation and review process for all new and updated Product Information (PI) that is required post-opinion for all products authorised by the centralised authorisation procedure. This is a standardised 25-day process, covering 25 European languages and is required for new Marketing Authorisation Application (MAA) and any variations to the Marketing Authorisation (MA) that affect the PI.
EUDRAC provides a specialist Linguistic Review Service for all types of MA procedures and has conducted over 150 different Linguistic Reviews.
As a company, we have developed specific systems and procedures in order to ensure that translations are provided accurately and efficiently. Our Labelling Team works with a Translation Team who is experienced and regularly trained in the QRD template and the many other requirements of QRD convention. We work closely with the EMA Product Lead, Member States and Company Affiliates throughout the procedure and provide the necessary advice and guidance required for more complex labelling. We also publish and submit the translations to the Member State (MS) and QRD group throughout the procedure.
EUDRAC works with a translation team who is trained to prepare swift and accurate translations according to the requirements of QRD convention. Our translators understand the tight timelines of the Linguistic Review procedure and the need to liaise with the client and the MS at the different stages of the procedure.
EUDRAC undertakes Linguistic Review Procedures for the complete spectrum of regulatory procedures; we often work at very short notice and always meet the prescribed timelines. We have developed systems and procedures for all types of Linguistic Review, which ensure that translations are always produced accurately and efficiently. EUDRAC routinely conducts Regulatory Intelligence updates and so is immediately aware of any changes in the requirements of the procedure.
EUDRAC also produces translations for associated Educational Materials and other regulatory documents.
In order for efficient production and review of documents transmitted between agencies, national competent authorities (NCA) and the pharmaceutical industry, standardisation is required. The Common Technical Document describes the organisation of modules, sections and documents to be used, by Marketing Authorisation Applicants and Holders, for a medicinal product for human use in each of the European Union, Japan and the United States.
EUDRAC has a full Publishing Service for all regulatory and PV procedures; we also manage electronic submissions to NCA and the EMA.
EUDRAC continuously conducts Linguistic Review Procedures for our clients; for many of them, we do this as part of the full Labelling Service that we provide for them over their product lifecycle.
EUDRAC routinely undertakes the entire Linguistic Review Procedure on behalf of our clients and so publishes the final Day 25 translations as appear on the EMA website; we have developed software applications to apply the specific formatting requirements to all word and pdf documents.
The EMA working group on Quality Review of Documents (QRD) has developed and published specific templates for the Product Information. These are updated on a regular basis with the purpose of maximising linguistic accuracy and clarity of the information and scientific terminology contained within the PI.
The EUDRAC Labelling team has a very high level of expertise in dealing with the linguistic requirements of the Product Information. Our translators are highly trained on the requirements of QRD convention. EUDRAC performs a Regulatory Intelligence Service so is always aware of any updates that are required for the Linguistic Review Procedure.
The Product Information (PI) is the core document on the medicinal product for the physician and the patient. It is a pivotal part of the Marketing Authorisation (MA) and defines all Labelling, Educational Material, Advertising and Prescribing Information on the product. During the lifecycle of a medicine, any changes required to the MA are implemented via different regulatory procedures and many of these will affect the PI, which has to be updated as part of the procedure.
Packaging Review includes the check of the labelling for packaging materials to make absolutely sure that it contains all required details for accurate identification, storage and delivery of the medicinal product. In addition, the package leaflet provides patients/users with important information on application and safety of the medicine. During the lifecycle of a medicinal product, any changes to the MA or safety information and changes in the legal requirements may affect the packaging, which has to be revised accordingly.
We manage packaging review processes in compliance with the client’s procedures and liaise with the client’s team members who are responsible for medical information and packaging release.
After a Marketing Authorisation (MA) has been granted, the Marketing Authorisation Holder (MAH) is responsible for maintaining the dossier and keeping it up to date. Updates may be required in relation to any new legislation or guidelines that are published and also any new information and data that become available on the product, as well as any changes that are made to the manufacturing process.
EUDRAC has the capabilities to manage the complete range of your post-authorisation CMC and Quality activities across our offices (in UK, France and Germany). EUDRAC Consultants have worked on a wealth of post-approval CMC projects, from assessment of manufacturing site change controls for regulatory impact to project management of complex technology transfers such as the switch to a new finished product manufacturing site. We have experience with 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 are equally comfortable dealing with small molecules or complex biological drug substances and will ensure that your project is assigned to the Consultant with the most appropriate expertise.
A key area in which our expertise is beneficial is in providing a link between the manufacturing site and the MA. EUDRAC accomplishes this through the assessment of manufacturing site change controls for any regulatory impact and providing advice on new regulatory requirements. We then provide advice to our clients on a suitable regulatory strategy to implement any necessary changes to the dossier. We go on to author the updated sections of the dossier and finally publish and submit them via the appropriate regulatory procedure.
A well written Module 3 containing information on Chemistry, Manufacturing, Controls (CMC) and Quality can offer significant benefits in the post-authorisation phase of the product lifecycle. A key area is a potential reduction in the number of CMC changes that have a regulatory impact; these changes can arise from diverse sources such as manufacturing sites and active ingredient, excipient or packaging suppliers.
If the implementation of post-approval CMC changes is not well-managed it can adversely impact on commercial supplies. Updates to CMC sections of the dossier can also result in changes to other areas of the dossier such as the product information and an appreciation of these aspects is an important point to be aware of when assessing CMC Changes and defining a strategy for implementation.
Changes to medicinal products in the EU are introduced via the relevant variation procedure. These changes are subject to the approval of the EMA or the competent authority of the Member State(s) concerned and are classified in different categories (type IAIN, type IA, type IB and type II variation, extension of a marketing authorisation or Article 61(3) notification), depending on the level of risk to public health and the impact on the quality, safety and efficacy of the medicinal product concerned
The EUDRAC team has a broad experience in the management of post-approval changes such as variations and can provide you with regulatory, procedural and technical support:
EUDRAC’s regulatory intelligence service serves to ensure that our Consultants are aware of the latest changes to regulatory guidelines of relevance to your submission. This will provide you with a dossier fit for submission today and with future changes considered throughout, to minimise the potential regulatory impact of future changes.
Ensuring regulatory compliance and uninterrupted commercial supplies is critical for any company. One of the most frequently observed problems, particularly for established products, is a divergence between actual manufacturing site practices and the registered details contained in the CMC section of the CTD dossier. Examples of this include deviations in the method of manufacture, analytical test methods and specification limits applied to excipients or the active substance. These can be caused by updates in compendial monographs, changes introduced by suppliers, a poorly written CMC section of the dossier, or not ensuring regulatory commitments are fulfilled.
Completion of a gap analysis can be undertaken by EUDRAC to compare the currently registered dossier against technical documentation from the manufacturing, packaging and QC testing sites.
The EUDRAC CMC team can identify any differences between the different information sources. We will then confirm if these discrepancies have any regulatory impact and propose a remediation strategy to ensure that changes are implemented at a site level to ensure compliance. If this is not possible, we will propose a regulatory submission strategy to update the dossier in line with current practices. When reviewing the dossier, we also take the opportunity to propose additional updates to minimise further post-approval regulatory submissions. EUDRAC has a Regulatory Intelligence Service to monitor and communicate all regulatory changes to our team and to our clients.
The link between manufacturing site operations and regulatory affairs functions is crucial during product development and of equal importance in the post-authorisation phase. It is often necessary to review manufacturing site documentation or change controls, assess the regulatory impact and to extract a summary of the key information into a format suitable for regulatory submission.
We can help to link manufacturing and regulatory functions by providing a service authoring specific technical reports or dossier sections. Many of our Consultants have prior experience gained via research and development roles in industry prior to a career in Regulatory Affairs.
We can provide the necessary technical expertise required to review raw data or reports and extract critical information, together with the knowledge of relevant regulatory guidelines in order to summarise the information in a format ready for submission. We have previously prepared complete Module 3 dossier sections from manufacturing site documentation and some specific examples are pharmaceutical development reports, process validation summaries and analytical method summaries or validation reports.
The promotion of a medicinal product starts usually with the initial press release following its Marketing Authorisation (MA). Promotional material and activities are strictly regulated in all EU countries and the rules and requirements vary from country to country, e.g. some countries require that the material is reviewed by the National Competent Authority (NCA) before it is used. Most promotional material needs to include Prescribing Information which also has to comply with specific requirements.
Educational materials for the patient and physician are often required as additional risk minimisation measures to ensure the medicinal product is used correctly and safely. They must be clearly distinguished from promotional material. Educational materials and their distribution also need to be approved by the NCA.
EUDRAC currently assists its clients to review and provide advice on both Promotional and Educational Materials for their products. We have Partners in all EU countries to prepare translations, implement local requirements and facilitate NCA review when this is required.