The challenges of presenting to health authorities

A successful scientific presentation to the authorities is a major investment for a pharmaceutical group or a start-up. These meetings provide an opportunity to compare the scientific vision with the evaluators’ expectations, before development costs become prohibitive. The role of agencies such as the EMA or the ANSM is therefore to ensure patient safety whilst promoting medical innovation.

There are various types of regulatory meetings in Europe, ranging from Scientific Advice to pre-submission meetings. These discussions may also cover the Paediatric Investigation Plan (PIP) or the process of obtaining Orphan Drug Designation.

When it comes to cutting-edge therapies, it is useful to keep a close eye on approval timelines so that the overall market launch strategy can be adapted accordingly. Each meeting should therefore be seen as an opportunity to build a relationship of trust with the authorities.

Understanding the expectations of the regulatory agencies: EMA and ANSM

To succeed in this task, it is essential to adapt to the specific characteristics of each audience. Both the EMA and the ANSM have clear objectives: to validate the relevance of pharmaceutical, preclinical and clinical data and to ensure that the risk-benefit balance is favourable to the patient. The formats required are, therefore, strictly codified and must be based on scientific documentation of the highest quality.

Clarity and transparency are key when preparing technical documents and presentation slides. An effective presentation should not just look good. Above all, it must serve as factual evidence. Experts therefore expect complete consistency between the data presented in each visual and the substantive dossier already submitted. Any inconsistency can become a major sticking point and delay the product’s planned marketing process by several months. This rigour in presentation ensures a robust procedure for obtaining a Marketing Authorisation (MA).

The key steps to a successful presentation

Preparing and planning the presentation

Preparation is the first step towards success. It is essential to plan ahead for the meeting. To do this, drawing up a detailed reverse schedule helps to gather the relevant data, as well as to identify the most suitable in-house experts to contribute. This collaborative phase should result in the development of a clear message, in which every chart and every idea serves to support the main argument.

Team preparation and mastering the audition

Preparing the team is the second key step. It is not enough simply to have the data; you must also be able to present it confidently and manage the stress inherent in this type of hearing. Organising rehearsals that simulate the actual hearing helps to refine the language used and ensures that everyone in the group knows their role. A well-structured and consistent Q&A training session helps to answer the authorities’ most technical questions without hesitation.

D-Day session and strategic follow-up phase

On the day of the oral presentation, time management and a professional demeanour are crucial. At this stage, it is important to be factual and concise, and to maintain eye contact with the agency members to hold their attention. Finally, the follow-up after the presentation is all too often overlooked. However, it is essential to write a detailed report after the meeting. This is to analyse the agency’s feedback and adjust the development plan accordingly. This adjustment phase is critical, as it determines the project’s long-term viability. Regardless of the laboratory’s objective (national or European marketing), this stage finally confirms the prerequisites required to market a medicinal product in France and/or Europe.

A successful presentation does not end when the presentation is over. Follow-up is the stage that turns a verbal exchange into concrete regulatory decisions.

Mistakes to avoid when securing your project

One of the most common mistakes is to approach the agency with an unclear message or without having reached an internal consensus beforehand. If the company’s own experts cannot agree on the interpretation of a clinical result, the health authority will spot this immediately. This will seriously undermine its credibility. Similarly, providing unverified or incomplete data poses a significant risk and may slow down the consultation process with the agency and, ultimately, the approval of the medicinal product.

Underestimating the importance of communication and presentation is another common mistake. Even excellent scientific expertise risks not being fully appreciated if it is poorly presented. It is also important to pay attention to logistical matters, such as meeting submission deadlines and preparing supporting documents. The selection of service providers is a further risk factor.
Choosing the right partners for preclinical and clinical development ensures an unbroken data chain.

Finally, for drug candidates in the final stages of development, planning for post-marketing pharmacovigilance obligations in Europe must be considered from the dossier submission stage onwards.

The importance of expert support

Delivering a successful presentation to national or European agencies requires a thorough understanding of the subject matter and regulatory requirements. The company’s commitment to public health must be evident through flawless professional preparation. Seeking support from a regulatory affairs expert, such as Alhena Consult, is an invaluable service that can significantly improve your chances of success.

The impact of a favourable scientific opinion or a successful pre-submission is then measured in terms of time saved and faster market access. In addition to the approval of the main dossier, these meetings provide an opportunity to discuss specific schemes, such as early and compassionate access in France, in order to meet the needs of patients awaiting treatment. By managing every stage of the submission process effectively, the company is able to turn stringent regulatory constraints into genuine drivers of strategic development.

Sources

• ANSM (French National Agency for Medicines and Health Products Safety): framework for Scientific Advice and pre-submission meetings for the submission of Marketing Authorisation applications.
• EMA (European Medicines Agency): guidelines on interactions with the committees (CHMP/PRAC) under the Centralised Marketing Authorisation procedure.
• HAS (French National Authority for Health): guidelines on exceptional access schemes (early and compassionate access) in France.
• ICH (International Council for Harmonisation): international standards (M4) for the structure of technical and safety dossiers for healthcare products.

Regulatory anticipation to break the linearity of the timetable

Rapid market access depends above all on the company’s ability to stop viewing the stages sequentially and instead bring them together. Historically, Marketing Authorisation Applications (MAA) were only submitted once the clinical files had been completely closed. Today, industry leaders favour a proactive approach, consulting agencies as soon as pivotal studies are designed. The use of early access mechanisms is a major lever in this regard. In Europe, the European Medicines Agency’s (EMA) PRIME programme provides enhanced support and early dialogue, often paving the way for Accelerated Assessment. At the same time, in the United States, the FDA offers statuses such as Fast Track or Breakthrough Therapy, which can radically transform the submission timetable. It is also essential to understand the key differences in the approval of innovative therapies in order to choose the most favourable territory for a priority launch.

To save time, the aim is to reduce approval times through this accelerated assessment. In very specific contexts of public health emergencies or major unmet medical needs, the EMA may also authorise a “rolling review”. This mechanism, although less common outside of health crises, allows experts to evaluate quality modules and non-clinical data well before the results of the final clinical study are available. By anticipating the review of data in this way, this method makes it possible to obtain a scientific opinion much more quickly after the completion of phase III.

Industrial synchronisation: CMC at the service of marketing

The success of a therapy depends not only on its medical validation, but also on the laboratory’s ability to produce on a large scale according to the strictest standards. The CMC (Chemistry, Manufacturing and Controls) component often represents the insidious bottleneck of post-development. Anticipating industrial challenges means that the development of manufacturing processes must progress in tandem with clinical phases. The validation of sites and production lines must be initiated well before final authorisation is obtained. For innovative medicines, this step is critical. Particular attention must be paid to compliance manufacturing requirements. Even the slightest change in the process after clinical trials may require the company to prove bioequivalence, which would delay market launch by several months.

This forward planning also extends to logistics and raw materials. By securing stocks and anticipating packaging and labelling specific to the various European Union member countries, the healthcare industries ensure that the first launch units can be shipped as soon as the European Commission gives its approval. This reverse planning must incorporate all GMP (Good Manufacturing Practices) compliance requirements so that no inspection by the ANSM or any other national authority can block the product’s launch at the last minute.

Operational cross-functionality to break down internal silos

Real acceleration cannot happen without seamless coordination between internal teams. Too often, the regulatory affairs, production, quality and market access departments work in isolation, only sharing information at the end of each stage. To increase efficiency, it is essential to establish a culture of collaboration from the middle of the clinical development process onwards. Early integration of the constraints of each profession makes it possible to identify risks before they become insurmountable obstacles. For example, involving pharmacovigilance experts from the outset of the marketing authorisation application process makes it possible to structure a robust risk management plan that will meet the expectations of the authorities without requiring multiple back-and-forth exchanges.

This cross-functional approach also makes it easier to anticipate post-marketing pharmacovigilance obligations. By forming a multidisciplinary launch team, the company ensures that its commercial strategy is consistent with scientific promises and regulatory realities. This synergy is all the more valuable when it comes to choosing the right partners.

Anticipating availability through the new early access framework

In France, the early access system represents an exceptional opportunity for innovative medicines. This system, which followed the major reform of ATUs (Temporary Use Authorisations) in France, makes it possible to make a treatment available to patients who have reached a therapeutic impasse. This can be done even before the marketing authorisation has been officially granted. Beyond the ethical aspect and the immediate benefit to public health, early access is a key strategic tool. It allows financial coverage by health insurance to begin much earlier and enables the collection of extremely valuable real-world data. This data will then support the assessment by the Transparency Commission of the Haute Autorité de Santé (HAS) during negotiations on price and reimbursement rates.

Mastering the mechanics of early access requires meticulous preparation. It is necessary to demonstrate that the drug offers real therapeutic progress and that its implementation is safe. This system bridges the gap between the end of research and full commercialisation, enabling a smooth transition to the common market.

Preparing the commercial ground and perception of value

While obtaining marketing authorisation is a unified European step, effective patient access to treatment depends on decision-making processes specific to each Member State. Pricing and reimbursement decisions remain a national competence, requiring specific applications to be submitted to each local health authority as soon as marketing authorisation is granted.

This crucial step must be prepared well in advance of the EMA’s opinion so as not to delay the availability of the treatment. This involves building a solid case demonstrating the therapeutic and medico-economic value of the product according to the specific requirements of each country. In France, for example, the dossier must demonstrate the medical benefit and the improvement in medical benefit in order to justify the cost of the treatment to the Ministry of Health and Social Security. Only a detailed understanding of how a drug is marketed allows the strategy to be adapted to the specific regulatory and economic characteristics of each territory.

Accelerating the arrival of a drug on the market is a high-precision exercise. There is no room for improvisation when managing key stages, making it strategically essential to rely on an expert partner. Alhena Consult supports you in transforming these challenges into opportunities for growth. Thanks to our operational support and expertise in regulatory affairs, we ensure that your strategy is consistent so that your innovations achieve their ultimate goal: treating patients effectively and quickly.

In this competitive environment, complete internalization of the value chain has become rare. Outsourcing is now an essential operational lever. Choosing the right partner goes beyond a simple customer-supplier relationship. It is above all a strategic decision that directly impacts data quality, meeting deadlines, and ultimately obtaining regulatory approval.

Understanding needs: from early stages to patient administration

Before entering into any collaboration, it is essential to precisely define the technical and regulatory requirements, which vary considerably depending on the stage of development.

The preclinical phase: proof of concept and safety profile

This stage marks the transition from fundamental research to human trials. Its objectives are to demonstrate proof of concept (efficacy) and assess the toxicity of the drug candidate. The partnership requirements here focus on cutting-edge scientific expertise: screening and selection of candidates, relevant animal models, and pharmacokinetic (ADME) and toxicology studies.

The clinical phase: methodological requirements and patient safety

From the start of phase I (first administration to humans) through to phase III, the challenges evolve. Beyond the scientific aspect, the priority extends to logistics, the protection of individuals and strict compliance with ethical and regulatory standards. This cycle does not end with the granting of authorisation: it continues with post-marketing pharmacovigilance.

Each of these phases requires specific skills and structures.

Identify key outsourcing stakeholders

The R&D services market is segmented. Distinguishing the roles of each partner is a prerequisite for building an effective project team.

CROs (Contract Research Organisations)

These are the central partners in outsourcing. A CRO can take on all or part of the operations.

• Preclinical CROs: these have the infrastructure and equipment necessary to conduct regulatory pharmacokinetic and toxicology tests.
• Clinical CROs: these orchestrate the operational implementation of trials: submission and obtaining approval for clinical trials, site selection, monitoring, data management and biostatistical analysis.

The choice between a global organisation (present in America, Europe and Asia) and a niche CRO (specialising in oncology or gene therapy, for example) will depend on the size of the trial and the resources allocated.

Specialised analytical laboratories

Some tests require specific expertise that generalist CROs do not always possess. This is the case for sample bioanalysis (pharmacokinetics/toxicology), the development of complex biomarkers, immunogenicity, and certain genomic analyses. These state-of-the-art laboratories are therefore essential for obtaining robust biological data.

Regulatory experts and consultants

Although they are not directly involved in experimental operations, their role is crucial. They anticipate the requirements of agencies (EMA, FDA) in order to prevent costly data from being rejected for non-compliance. A solid regulatory strategy then makes it possible to secure the process and reduce development time.

Patient associations and research centres

These stakeholders are essential, particularly in the field of rare diseases. Collaborating with an association at an early stage helps to optimise the protocol design to ensure its feasibility for patients and thus facilitate recruitment. Similarly, the selection of investigation centres (hospitals, networks such as Unicancer or research institutes) determines the speed of inclusion. In this regard, there are specific challenges, particularly for low-prevalence diseases.

Read our analyses on the development of medicines for rare diseases.

Selection criteria: prioritising long-term value

Selecting a service provider based solely on economic criteria represents a major risk. This can impact the viability of the marketing authorisation application. Here are the fundamental criteria to evaluate.

Technical expertise and therapeutic experience

Has the partner already conducted a similar trial? Do they have expertise in the specific biomarkers for your therapeutic area? A CRO with expertise in cardiology will not necessarily be effective for a vaccine or cell therapy.

Regulatory compliance: the distinction between GLP and GCP

Mastering this framework is crucial.

• In preclinical trials: it is important to note that not all studies require GLP (Good Laboratory Practice) certification. Exploratory discovery or early pharmacology studies may be conducted in a ‘non-GLP’ manner (with scientific rigour). However, pivotal safety studies (regulatory toxicology) must comply with GLP.
• In clinical trials: at this stage, compliance is mandatory. Compliance with GCP (Good Clinical Practice) is mandatory for all clinical research. To ensure the compliance of your future trials, it is essential to understand the requirements of the EMA (European Medicines Agency).

Communication and transparency

In a complex development project, unforeseen circumstances will inevitably arise. A reliable partner is one who immediately reports difficulties and proposes a corrective solution. Transparency regarding progress, deviations from protocol and budget management is a key indicator of trust.

Financial and operational stability

For a biotech company, ensuring the financial stability of its CRO throughout the entire Phase III trial is vital. Similarly, it is important to verify their IT capabilities and GDPR compliance (Health Data), issues that are increasingly monitored by the authorities.

The importance of centralised regulatory coordination

The multiplicity of stakeholders creates fragmentation that can hinder the project. This compartmentalised approach often leads to inconsistencies in the final dossier.

It is in this context that the support of a consulting firm with expertise in regulatory affairs guarantees overall consistency:

• Roadmap: support for establishing regulatory requirements and the type of studies to be conducted, consultation for scientific advice (when, how and where, depending on the stage of development, the type of molecule and the pathology).
• Strategic alignment: verifies that the protocols proposed by the CRO adequately address the scientific questions raised by the EMA or FDA.
• Smooth communication: liaises between the raw data from the laboratories and the drafting of the CTD (Common Technical Document)* modules.
• Compliance control: ensures that practices comply at all times with the requirements of agencies, in particular the EMA (Europe) and the FDA (US).
• Anticipation: prepares the final stages from the start of the trials.

* Standardised structure, agreed upon by international regulatory authorities, for the submission of marketing authorisation applications (MAAs).

To visualise the outcome of this work, understand the process for obtaining marketing authorisation (MA) for a new drug.

This coordination is also essential for preparing for the post-MA phase. The data collected during clinical trials form the basis of the future monitoring system. Inadequate management of safety data during the clinical phase will complicate the implementation of future obligations, particularly with regard to post-MA pharmacovigilance obligations.

Conclusion

The choice of partners for preclinical and clinical development requires in-depth analysis. The aim is to build a network of complementary skills capable of transforming scientific innovation into medical reality. Regulatory coordination therefore provides strategic direction for development. Without an integrated view of regulatory requirements, technical excellence alone does not guarantee market access. Alhena Consult positions itself at this critical interface to secure your choices and streamline the path of your innovation to patients.
Would you like to structure your development plan and secure your choice of service providers? Our experts are available to audit your strategy.

Establishing early dialogue with these authorities is therefore the solution to guaranteeing patient access to care while securing investments. When managed well, these interactions make it possible to align strategy with the expectations of evaluators. They therefore offer significant time savings and accelerate development.

Effective management of these exchanges is also a key lever for accelerating a drug’s market entry by securing regulatory milestones from the earliest phases of the project.

Understanding the role and scope of health agencies

In a globalised context, it is crucial to distinguish between the different stakeholders. While their common mission remains the protection of public health and the assessment of the benefit/risk ratio, their jurisdictions and operating methods differ.

The EMA and national regulatory agencies

The European Medicines Agency and national regulatory authorities coordinate the scientific evaluation of medicines developed for the European Union market. Its committees issue scientific opinions that are decisive for the authorisation of new medicines.

The FDA

In the United States, the Food and Drug Administration is the sole point of contact. It combines the roles of evaluator and decision-maker.

To better understand the nuances between these two giants, check out our analysis of their key differences.

The MHRA (Medicines and Healthcare products Regulatory Agency)

Since Brexit, the British agency has been operating independently. It remains an influential player, often pioneering innovation mechanisms.

Poor communication with these entities can have serious consequences: requests for additional clinical studies, suspension of trials, or even refusal of registration.

Different types of interactions: from concept to market

Opportunities for exchange vary depending on the stage of product maturity and the therapeutic area concerned.

Early stage interactions

Even before entering clinical trials, experimentation must be rigorously supervised. This is a critical phase in order to avoid taking the wrong direction during the preclinical development of a drug.

• In Europe (EMA): for highly innovative technologies or new methods, the ITF Briefing Meeting (Innovation Task Force) provides an informal discussion platform. Scientific Advice then provides a formal opinion on quality, preclinical or clinical development plans.
• Some European national agencies, such as those in the Netherlands, also offer early dialogue mechanisms, allowing for discussion with the authorities from the very early stages of development.
• In the United States (FDA): the informal equivalent for breakthrough innovations is often the INTERACT meeting. The key formal step is the Pre-IND Meeting (Investigational New Drug), which is essential before launching the first human trials across the Atlantic.

During clinical development

Once trials have begun, dialogue must remain fluid. Key moments include End-of-Phase Meetings (particularly at the end of phase II in the United States). These are crucial for validating the design of future pivotal phase III studies and securing investment. However, interim discussions may be necessary during the study. These interactions help to avoid deviations and reduce development time.

In addition, the EMA, through Scientific Advice, offers structured support for clinical development and supports project leaders throughout the drug development cycle.

Pre-MA (Pre-submission) interactions

Just before submission, pre-submission meetings and follow-up meetings are held to ensure that the format of the dossier is compliant. This is the time to check that the dossier is appropriate for the marketing authorisation (MA) process.

Post-authorisation: a continuous cycle

Product lifecycle management requires regular interaction to ensure that new safety requirements are implemented. After authorisation, the relationship continues through periodic safety update reports (PSURs), marketing authorisation variations for new indications, and regulatory on-site inspections. Compliance remains a priority in order to scrupulously meet post-marketing pharmacovigilance requirements.

Best practices for successful interactions

A meeting with an agency cannot be improvised. It is a high-stakes exercise that requires meticulous preparation.

Define a clear regulatory strategy

You should never approach a health agency without a precise battle plan. The interaction should aim to validate a specific approach. It is therefore essential to anticipate the authorities’ questions. But you should also prepare the exact objectives of the meeting and define the key messages to be conveyed in advance. This strategic preparation will help you avoid distractions.

Building a credible case

Data quality and clinical consistency are paramount. A clear narrative and transparent information reinforce the credibility of the application, especially with regard to compliance requirements.

Prepare the internal team

Effective preparation involves reviewing likely questions and aligning positions. Assigning roles during the meeting ensures a professional image.

Manage the meeting professionally

Establishing effective communication helps build trust. The aim is to encourage dialogue to facilitate data validation through clear and substantiated responses.

Making effective use of feedback

It is essential to analyse recommendations and update the development plan. In the case of rare diseases, among others, this ability to adapt is vital.

Why seek support from a specialist partner?

The process of coordinating with the authorities requires expert resources in order to avoid common pitfalls. The support of a specialist partner provides cross-functional expertise:

• Multi-agency expertise: having a global vision makes it possible to harmonise the often divergent requirements of the EMA and the FDA.
• Knowledge of ‘unwritten rules’: beyond the letter of the law, experience of past interactions provides an understanding of the implicit expectations of assessors and current trends.
• File structuring: an expert consultant knows how to present arguments to maximise their impact and reduce the risk of blocking questions. This is particularly relevant when navigating complex frameworks such as clinical trials.
• Support during meetings and post-meeting follow-up: the presence of expert consultants during direct discussions with agencies helps to moderate debates and ensure that technical responses are formulated in the best possible way.
• Reduced risk of additional requests: expert advice helps to anticipate sticking points in order to avoid requests for additional studies and secure approval deadlines.
• Comprehensive operational support: from medical expertise to pharmacovigilance management, the use of specialist consultants enables continuous improvement of the dossier and contributes significantly to the success of the marketing authorization.

Conclusion

The relationship with health agencies is a common thread that runs through the entire life cycle of a medicine. It is not a mere administrative formality, but a demanding collaboration which, when mastered, becomes a catalyst for success.

Identifying the right moment to communicate. Preparing a flawless dossier. Demonstrating professionalism during exchanges. All these steps are the pillars of a winning strategy.

Surrounding yourself with experts who can decipher regulatory expectations and coordinate these interactions is often the most profitable decision for your development. Alhena Consult positions itself as your strategic partner to ensure this link with agencies, providing you with the operational support and regulatory expertise you need to successfully navigate each step.

Orphan drug designation: criteria and procedure

The “orphan” designation is the first hurdle to overcome. It does not equate to marketing authorization, but it is the key that unlocks access to incentives.

Strict eligibility criteria

For a product to obtain this designation from the Committee for Orphan Medicinal Products (COMP) and the European Commission, the sponsor must prove:

• Prevalence: the condition must affect no more than 5 in 10,000 people in the EU.
• Severe condition: the condition must be life-threatening or cause chronic serious disability.
• No alternative or significant benefit: if an authorized treatment already exists, the new drug must offer a “significant benefit” to patients.

The application dossier submitted to the EMA

The application is evaluated by the EMA’s Committee for Orphan Medicinal Products (COMP). This dossier requires absolute scientific rigor, combining bibliographic data and preliminary results. The schedule is strict: once the application has been administratively validated, the procedure lasts 90 days.

Interactions with the COMP (questions/answers, oral hearings) are frequent and decisive. The possibility of requesting a meeting/teleconference prior to submission is also strongly recommended: the EMA strongly encourages sponsors to request this meeting as it allows for an initial regulatory assessment of the application and provides advice on possible improvements to the application that will be submitted.

Validation steps and average timeframes

Once the evaluation is done, the COMP gives its opinion. If it’s positive, the European Commission then has 30 days to approve the decision and add the product to the Community list of orphan designations.

Regulatory and financial benefits

Once designation has been obtained, the benefits are tangible:

• 10-year marketing exclusivity after marketing authorization;
• Protocol assistance: scientific advice at reduced cost or free of charge;
• Reduction in administrative fees charged by the EMA;
• Access to specific funding for European research.

Regulatory stages of development

The development of an orphan drug does not follow a conventional straight line. The scarcity of available data means that each stage must be optimized.

Preclinical and clinical: adapting to rarity

From the preclinical development stage of a drug, it is necessary to anticipate the transition to human trials. In the clinical phase, the small number of patients affected makes large randomized trials difficult. The EMA therefore encourages innovative study designs. It is therefore crucial to be aware of the EMA’s requirements for clinical trials so as not to invalidate years of research with a protocol that does not comply with European regulatory standards.

Strategic interactions with the EMA

To ensure a smooth process, dialogue with agencies is based on several key mechanisms:

• Scientific Advice: a major risk mitigation tool. It allows developers to submit questions to the agency regarding quality development.
• Protocol Assistance: a version of Scientific Advice dedicated to orphan drugs. It allows the relevance of planned studies to be validated with the EMA.
• PRIME (PRIority MEdicines) program: if the drug meets a major unmet medical need, it can benefit from enhanced support and accelerated assessment.

Documents to prepare and recommendations for each phase

Regulatory success depends largely on anticipating the documentation required, which acts as validation milestones.

• Early phase (ODD designation dossier): this stage requires the compilation of a solid scientific argument proving medical plausibility and compliance with prevalence criteria.
• Preclinical and clinical development; protocol assistance, PRIME if applicable.
• Clinical development: even for a rare disease, a PIP (Pediatric Investigation Plan) must be submitted to the EMA, usually after the first pharmacokinetic studies. If the disease only affects children, the EMA may also request that the PIP be submitted at the end of the preclinical phase before clinical studies begin.
• Marketing authorization application: the final dossier (Common Technical Document¹) compiles all the modules.

Evaluation and authorization procedures (MA)

Unlike conventional medicines, which can sometimes go through national procedures, orphan drugs must follow the centralized procedure with the EMA. A single MA opens the doors to all 27 EU countries.

Assessment by the CHMP and COMP

The MA application is reviewed by the CHMP (Committee for Medicinal Products for Human Use) for a benefit/risk assessment. At the same time, the COMP reassesses whether the orphan designation criteria are still met at the time of authorization. These committees rely on internal expert groups for in-depth data analysis.

To understand the complexity of the application, it is useful to refer to the basics: how to obtain marketing authorization (MA) for a new drug.

Conditional marketing authorization and exceptional circumstances

In the field of rare diseases, waiting for complete data is not always ethical or possible. Conditional marketing authorization therefore allows approval based on less complete data, if the benefit of immediate availability outweighs the risk inherent in the lack of data. Marketing authorization under exceptional circumstances applies when the rarity of the disease makes it impossible to obtain complete data, even in the long term.

These procedures have a direct impact on the EMA’s approval times for new drugs, which can be shortened to speed up access to care.

Post-authorization monitoring and obligations

Obtaining marketing authorization does not mark the end of regulatory oversight. For orphan drugs, monitoring is even more rigorous.

Pharmacovigilance and risk management

Any uncertainties accepted at the time of marketing authorization must be resolved after the drug is placed on the market. The Risk Management Plan (RMP) is therefore particularly detailed. Laboratories must strictly comply with post-marketing pharmacovigilance obligations in Europe. These often include post-authorization safety studies (PASS) or patient registries².

Reassessment of orphan status

The granting of orphan status confers on the holder ten years of market exclusivity from the date of marketing authorization. However, this exclusivity may be lifted after five years if the COMP considers that the drug has become sufficiently profitable to cover all research and development investments.

The “orphan” designation may also be reassessed at any time if the initial conditions are no longer met, particularly in the event of a change in the prevalence of the disease, or if the significant benefit of the product is called into question.

The arrival of a competing drug does not automatically result in the loss of exclusivity, unless it is demonstrated that it provides a superior clinical benefit or that the existing drug no longer meets medical needs.

The role of expert regulatory support

Developing an orphan drug is a race against time. Every regulatory error results in months of delay, or even refusal of approval. The complexity of the dossiers, the specific nature of the arguments to be provided for “significant benefit,” and the management of interactions with EMA require a 360° view.

Alhena Consult supports biotech companies and pharmaceutical laboratories. We help transform scientific innovation into regulatory success. We do this in several ways:

• Strategic structuring: analysis of eligibility for orphan designation and drafting of a well-argued dossier for the COMP.
• Interactions with agencies: preparation and support during Scientific Advice or Protocol Assistance (PIP) meetings.
• Operational drafting: handling of regulatory modules (CTD) for marketing authorization applications.
• Post-marketing authorization support: pharmacovigilance management and maintenance of authorizations.

In a sector where regulations evolve as quickly as science, surrounding yourself with experts allows you to secure your most valuable asset: time to market.

Are you developing a molecule for a rare disease? Do you want to secure orphan status for your drug? Contact Alhena Consult for an audit of your regulatory strategy.

¹ Common Technical Document (CTD): internationally standardized mandatory format used to submit a Marketing Authorization Application.

² Specific obligation required in the Risk Management Plan (RMP) to collect, over the long term and in real-world settings, the safety and effectiveness data that were lacking at the time of Marketing Authorization.

During this phase, the mechanism of action of the drug candidate is validated, and its safety (toxicity) and activity in the body are evaluated. A preliminary pharmacokinetic and pharmacodynamic profile is then established. All of this data is then used as a basis for calculating, with safety margins, the initial dose and route of administration for the first clinical study in humans.

Definition and objectives of preclinical development

Preclinical studies mark the first stage in the life cycle of a drug. Conducted on non-human systems (cell models followed by animal models), these studies identify the drug’s efficacy, mechanism of action, adverse effects, toxic doses, and target organs. They therefore include the analysis of pharmacodynamics, pharmacokinetics (ADME), and toxicology, in accordance with GLP requirements and ICH¹ guidelines. Preclinical development is essential for compiling the regulatory dossier for the clinical trial application (CTA) and the marketing authorization application.

Please note: this article does not detail the clinical phases that follow the preclinical phase. However, it is important to note that the design of the first study in humans, particularly the choice of dose, route, and frequency of administration, is determined by the preclinical results of toxicology and pharmacokinetics. Similarly, the toxicology program continues in parallel with clinical development to monitor long-term safety.

The main stages of preclinical development

The preclinical phase comprises a series of pharmacological and toxicological studies conducted in a progressive manner.

In vitro studies (pharmacology and screening)

Tests conducted on cells or biochemical models confirm the targeted mechanism of action. They then enable promising candidate molecules to be quickly identified. This phase therefore provides early pharmaceutical proof of concept before progressing to more complex trials.

In vivo studies (efficacy and toxicology)

The selected candidates are then tested on animals to assess both efficacy and systemic toxicity. These experiments provide a preliminary safety profile: acute toxicity (single dose), subchronic and chronic toxicity (repeated doses), and reproductive toxicity.

Pharmacokinetics (ADME)

The fate of the drug in the body is then studied (Absorption, Distribution, Metabolism, Excretion). This step measures blood concentration over time, identifies metabolites, and evaluates how the compound is eliminated. It therefore defines, in particular, the appropriate route of administration and frequency in humans.

Pharmacodynamics

During this phase, the dose-response relationship is quantified using dose-response curves and parameters such as the median effective dose (efficacy threshold) and median lethal dose (toxicity threshold). It then validates the activity of the active ingredient at the cellular and organic levels.

Toxicology and safety pharmacology

These specific tests detect any potential adverse effects on vital systems. “Safety pharmacology studies” evaluate, for example, the effects of the candidate at doses higher than therapeutic doses on heart rate, blood pressure, brain function, etc. They follow the principles of the ICH S7A “Core Battery” and must meet GLP² (Good Laboratory Practice) standards.

Specificities according to molecule type

The preclinical study plan varies depending on the nature of the candidate: small chemical molecules, biological molecules, or cell therapy or gene therapy drugs. Biological drugs, for example, require immunogenicity and binding stability testing. Gene therapies involve biodistribution and targeted genotoxicity studies. Additional recommendations are provided depending on the type of therapeutic entity, according to specific regulatory guidelines (EMA for Europe, FDA for the United States).

Preparation of the regulatory dossier

All preclinical results must be compiled in the regulatory development dossier. As part of a clinical trial application, data from preclinical studies are included in the Investigational Medicinal Product Dossier (IMPD) and/or summarized in the investigator’s brochure for a clinical trial application dossier. These elements are then included in the Common Technical Document (CTD), particularly modules 2 (syntheses) and 4 (non-clinical reports) for the marketing authorization application (MAA).

These detailed preclinical data are required by all health authorities in Europe and the United States. This is required even before clinical trials begin. To this end, it must comply with international standards (ICH guidelines). It must also demonstrate that the drug candidate is reasonably safe for initial testing in humans. This same data will be included in the marketing authorization application (MAA).

Challenges and issues in preclinical development

Several challenges arise during preclinical development.

Long duration and high cost

Preclinical development involves complex studies (in vitro, in vivo, toxicology, pharmacokinetics) over several years. Conducting these studies in accordance with GLP requires significant technical and financial resources. These early investments, with no guarantee of success, further increase the overall cost of drug development.

See also: Reducing drug development time

Very high failure rate

More than 90% of drug candidates fail during development. According to a Forbes study cited by PharmAnalyses, the failure rate for candidates is as high as 95%.

Strict regulatory constraints

Studies must comply with numerous standards. To this end, they follow a testing program tailored to each therapeutic indication. The required reports, which must be comprehensive and traceable, significantly increase the regulatory burden.

Ethical constraints related to animal testing

Animal testing, which is essential for preclinical studies, raises major ethical issues. Regulations therefore impose strict protocols, governed by GLP. Alternative approaches (organoids, organs on chips) are being developed in parallel to limit the use of animals.

Prediction limitations and health risks

Certain adverse effects remain difficult to detect in the preclinical phase. This structural risk therefore often requires a margin of safety (safety doses) to be built in. It also requires the continued collection of safety data (pharmacovigilance) well after the preclinical phase, when the drug is used in clinical trials.

Conclusion

Despite these limitations, preclinical development remains essential for the creation of safe and effective drugs. It serves not only to rule out dangerous candidates as early as possible, but also to deepen understanding of the drug. This must be done before taking the risk of administering it to humans for the first time.

¹ ICH (International Council for Harmonization) is an international organization that develops harmonized guidelines to ensure the quality, safety, and efficacy of drugs in the world’s major regulatory markets.
² GLP (Good Laboratory Practice) refers to an international regulatory framework that guarantees the quality, traceability, and reliability of non-clinical studies submitted to health authorities.

Sources:

• Pharmacomedicale: “Drug development and monitoring”
• Interpharma: “Preclinical phase”
• Leem: “Preclinical development or initial evaluation”
• Inserm: “Drug development: from test tube to pharmacy”

This article explores the regulatory framework, the main challenges encountered, and the solutions being implemented to advance research and facilitate access to appropriate therapies.

Definition and key data

A rare disease is a condition that affects a small number of people and requires specialized care. In France, there are approximately 7,000 rare diseases, affecting more than 3 million patients, or nearly 4.5% of the population. Half of these diseases appear before the age of 5 and are responsible for around 10% of deaths between the ages of 1 and 5.

Nearly 80% of rare diseases are genetic in origin. In half of all cases, they cause motor, sensory, or intellectual impairment, and in 9% of cases, total loss of independence.

The term “orphan disease” applies to rare diseases for which there is no effective treatment.

Challenges in developing drugs for rare diseases

Small population size and methodological difficulties

The small number of patients affected by a rare disease is a major obstacle to research. It limits scientific visibility, access to funding, and the ability to conduct robust clinical trials. Prevalence of sometimes fewer than a few hundred cases complicates identification and inclusion. Clinical heterogeneity and the lack of data on natural history hinder the definition of relevant endpoints and weaken protocols.

The methodology of clinical trials is often based on small sample sizes, which limits the scope of the results and increases uncertainty about efficacy in real-world conditions.

Patient-specific issues and limitations of clinical trials

Many rare diseases affect children, which impose specific constraints in terms of ethics, protocols, and appropriate formulations. Clinical trials conducted on small populations do not always allow for the prediction of long-term effects or real-world efficacy at the time of Marketing Authorization. These methodological limitations complicate development and slow down access to treatments. They also undermine the economic attractiveness of the field, as companies have to bear high costs for an uncertain return on investment. This situation justifies the use of specific regulatory and financial support.

Role of stakeholders and need for collaboration

Approximately 61% of clinical trials are sponsored by the pharmaceutical industry, compared to 39% by non-commercial stakeholders, mainly academic institutions. Basic research provides scientific foundations, while companies are responsible for clinical and regulatory development. However, for many rare diseases, the knowledge base remains insufficient, which limits investment. Furthermore, information remains fragmented across different institutions, reducing its usefulness to stakeholders.

These constraints make structured collaboration between researchers, clinicians, patients, funders, and authorities essential. The combination of multidisciplinary skills is a prerequisite for advancing the development of orphan drugs.

The European regulatory framework

An incentive framework to encourage innovation

In order to support the development of drugs for rare diseases, the European Union introduced Orphan Drug Designation (ODD) in 2000. This applies when the prevalence is less than 5 per 10,000 inhabitants and the disease is serious or debilitating.

This designation provides access to several benefits: ten years of market exclusivity, tax reductions, subsidies, and free scientific advice. The EMA also offers the PRIME procedure, which facilitates early exchanges with the authorities. Finally, Marketing Authorization Applications (MAAs) may benefit from accelerated assessment or result in conditional Marketing Authorization or Marketing Authorization under exceptional circumstances, when not all clinical data can be provided.

Persistent constraints and the need for monitoring

While these measures speed up access to treatment, they do not remove regulatory requirements in terms of benefit/risk. Orphan drugs must demonstrate sufficient efficacy and safety despite sometimes limited clinical data. The authorities therefore impose enhanced risk management plans, post-authorization monitoring and, in some cases, additional real-world studies.

These constraints are intended to compensate for the uncertainties associated with small sample sizes and the difficulty of predicting efficacy in real-world conditions. Furthermore, the regulatory framework remains complex for project leaders, who must adapt their development strategy to the specific characteristics of each disease. This complexity justifies the need for specialized regulatory support, capable of anticipating the expectations of agencies, optimizing the choice of procedures, and securing interactions with health authorities.

Collaborative initiatives and the role of patients

Beyond the regulatory framework, the European Union has set up several collaborative programs designed to strengthen research and pool resources.

Among them, the European Joint Program on Rare Diseases (EJP RD) promotes the transition from basic research to clinical application, while the European Reference Networks (ERN) bring together more than 900 specialized units in 26 member states.

The ERICA consortium coordinates the clinical research activities of the ERNs, and infrastructures such as EATRIS and ECRIN support preclinical development and multinational trials.

Platforms such as Orphanet centralize knowledge and facilitate access to information, while the IRDiRC and EURORDIS strengthen international cooperation and the voice of patients.

These initiatives demonstrate the importance of a collective approach to overcoming data fragmentation and optimizing the development of orphan drugs.

Available solutions and levers

Natural History Studies (NHS)

Natural History Studies (NHS) describe the progression of a disease throughout the patient’s life in the absence of treatment. They trace the different phases of the disease, from the pre-symptomatic period to the advanced stages, and incorporate genetic, clinical, and environmental variables.

They play an essential role in rare diseases, enabling the characterization of phenotypes, the identification of patient subgroups, and the definition of appropriate endpoints for clinical trials. However, conducting these studies remains complex due to the small number of patients available and the dispersion of data.

Patient registries

Patient registries complement these studies by collecting clinical and epidemiological information in a structured manner. There are currently more than 700 rare disease registries in Europe (Orphanet). These tools facilitate recruitment for clinical trials, enable post-treatment follow-up, and document phenotypic variability and genotype-phenotype correlations.

They are therefore an essential tool for meeting regulatory requirements and strengthening research by providing a consistent and usable database at the European level.

The importance of strategic and regulatory support

The development of treatments for rare diseases relies on appropriate organization. Collaboration with patient associations provides essential data on disease progression, unmet needs, and therapeutic priorities, which can be incorporated into the design of clinical trials.

Early identification of reliable biomarkers is also crucial to understanding the disease, refining patient stratification, and guiding therapeutic strategies.

Finally, setting up a multidisciplinary team combining researchers, regulatory experts, market access specialists, and patient representatives helps to enhance the quality of development and optimize interactions with health authorities.

Conclusion

Rare diseases collectively affect millions of patients but lack therapeutic solutions. The constraints associated with low prevalence and lack of data are mitigated by a specific regulatory framework, including Orphan Drug Designation and accelerated procedures.

The use of registries, Natural History Studies, and international collaborations is now the preferred route for advancing research and accelerating the availability of treatments.

This article outlines the conditions that must be met for a promotional campaign to comply with the regulation.

Applicable regulatory framework

In France, advertising for human medicines is defined in Article L.5122-1 of the Public Health Code (“CSP: Code de la Santé Publique”) as any form of information, solicitation, or incentive aimed at promoting the prescription, dispensing, sale, or consumption of these medicines. Certain strictly informative exchanges are excluded, such as non-promotional correspondence or information on changes in packaging or pharmacovigilance.

Advertising must not be misleading or harmful to public health. It must comply with the data validated in the Marketing Authorization (MA), the recommendations of the ANSM and those of the Haute Autorité de Santé (HAS), and present the drug objectively, promoting its proper use (Article L.5122-2 CSP).

Promotional materials must comply with the summary of product characteristics (SmPC) and clearly indicate, where applicable, the nature of the medicinal product, its conditions of use, and warnings (Article R.5122-1 CSP). Specific rules apply to homeopathic and traditional herbal medicinal products, with mandatory information set out in Article R.5121-146 CSP.

All advertising for a medicinal product, whether aimed at the general public or healthcare professionals, requires prior authorization (known as an advertising visa) issued by the French National Agency for Medicines and Health Products Safety (ANSM), valid for a fixed period (two years).

All the rules applicable to advertising are set out in Articles L.5122-1 to L.5122-16 of the Public Health Code.

Role of the exploitant in promotion

The company marketing a medicinal product in France is responsible for promoting that medicinal product. In accordance with Article R.5122-2 of the Public Health Code, the exploitant must have a department responsible for advertising, under the supervision of the Chief Pharmaceutical Officer (“Pharmacien Responsable”). The latter ensures compliance with all regulatory provisions applicable to the advertising of medicinal products, in particular the scientific validity of the information disseminated.

The company is also required to keep a copy of each advertisement issued, accompanied by a sheet specifying:

• The recipients of the message;
• The method of dissemination;
• The date of first dissemination;

These documents must be archived for three years from the date of last distribution and made available to the French National Agency for Medicines and Health Products Safety (ANSM) in the event of an inspection.

Advertising aimed at the general public

In France, advertising of medicines to the general public (GP) is strictly regulated. It is only permitted in the cases provided for in Article L.5122-6 of the Public Health Code, in particular for medicines that are not subject to mandatory medical prescription, provided that they are not reimbursed by health insurance and do not present a particular risk to public health.

When permitted, advertising to the general public (GP) must comply with several substantive and formal requirements, as defined in Articles R.5122-3 to R.5122-8 of the Public Health Code.

Mandatory information

The promotional message must be clearly identifiable as such and the medicinal product must be presented as a health product. It must include:

• The name of the medicinal product and its common name;
• The information necessary for the proper use of the medicinal product;
• An explicit invitation to read the instructions for use or the information on the packaging carefully;
• A warning message, a reference to the pharmacist’s advice, and an invitation to consult a doctor if symptoms persist;
• For generic medicines: a statement indicating that they are generic, where applicable, accompanied by the name of the reference product and a reminder of the precautions associated with excipients with known effects.

Adaptations are provided for radio advertising: certain information, such as the common name, is only required if the medicinal product contains a maximum of two active ingredients.

Prohibited statements

Under no circumstances may the content include elements that could mislead the public, discourage them from consulting a healthcare professional, or promote inappropriate use. In particular, it is prohibited to:

• Portray medical consultation or surgery as unnecessary.
• Suggest that the drug has no adverse effects or that it is equal to or superior to another treatment.
• Present the use of the drug as necessary to improve normal health, or implying that failure to treat could alter it (except for certain vaccination campaigns).
• Address children primarily or exclusively.
• Refer to recommendations from scientists, healthcare professionals, or public figures that may encourage consumption.
• Equate the medicinal product with food, cosmetics, or any other consumer product.
• Exaggerate the medicinal product ‘s effectiveness or use misleading representations of the human body.
• Refer to testimonials of recovery or the granting of Marketing Authorization as proof of effectiveness.
• Offer material benefits (gifts, bonuses, objects) linked to the purchase or use of the medicinal product.

Failure to comply with these rules exposes the exploitant to administrative or criminal penalties.

Advertising aimed at healthcare professionals

Advertising for medicines aimed at healthcare professionals is subject to strict requirements, both in terms of content and form. It is only authorized for medicinal products that have been granted Marketing Authorization (MA), in accordance with the conditions set out in that authorization.

In accordance with Article L.5122-9 of the Public Health Code, prior approval from the ANSM is required for any advertising aimed at professionals authorized to prescribe, dispense, or administer a medicinal product. This approval is granted for a maximum period of 2 years. It may be suspended or withdrawn by the agency in the event of a breach of regulatory requirements.

Mandatory information and substantive requirements

The information provided must be accurate, up-to-date, verifiable, and sufficiently comprehensive to enable healthcare professionals to form an informed opinion on the therapeutic value of the medicinal product.

Article R.5122-8 specifies that advertising must include at least the following information:

• Name of the medicinal product;
• Name and address of the exploitant;
• Pharmaceutical form;
• Qualitative and quantitative composition (active substances and essential excipients);
• Marketing Authorization or registration numbers;
• Pharmacological properties;
• Therapeutic indications and contraindications;
• Posology and method of administration;
• Adverse effects, drug interactions, warnings, and precautions for use;
• Classification of the drug in terms of prescription and dispensing;
• Information on reimbursement or approval for local authorities;
• Retail price (if applicable) and daily treatment cost;
• Specific information for generic drugs.

Each material must also mention the date of creation or last revision of the advertisement.

Focus on medical visits

The dissemination of promotional information during medical visits is governed by a charter regulating the practices of medical representatives. This charter aims to guarantee the quality, objectivity, and compliance of the information provided to professionals, and to strengthen the role of medical representatives in promoting the proper use of medicines.

For vaccines, advertising aimed at healthcare professionals must include the full recommendations of the HAS (Haute Autorité de Santé), without referring to other documents.

Regulating medicinal product advertising: a strict regulatory requirement

Advertising a medicinal product in accordance with French regulations requires a thorough understanding of the Public Health Code and constant vigilance regarding changes in practices regulated by the ANSM.

With extensive experience in advertising control, Alhena Consult supports pharmaceutical companies at each stage of their campaigns. From detailed analysis of documents to drafting materials and approval requests, our expertise ensures rigorous, secure communication that complies with the strictest regulatory standards.

Promotional campaigns: regulatory requirements and support from Alhena Consult

Advertising for medicines in France is subject to strict regulations defined by the Public Health Code, with specific requirements depending on the nature of the product, its target audience (general public or healthcare professionals), and its regulatory status. Each campaign requires prior verification of applicable standards, full compliance with the Marketing Authorization and the opinion of the Haute Autorité de Santé (HAS), and the inclusion of mandatory information. This ultimately enables the exploitant to obtain approval from the ANSM.

Alhena Consult supports pharmaceutical companies throughout this process, from the regulatory analysis phase to the drafting of promotional materials and the management of authorization requests. Thanks to its in-depth expertise in regulatory affairs and communication under regulatory constraints, Alhena guarantees the security of the messages disseminated, while ensuring their scientific consistency and alignment with ANSM requirements. This integrated approach optimizes approval times and limits the risk of rejection in a context of increased regulatory oversight.

For a complete overview of market access procedures, find out how to market a drug in France (centralized Marketing Authorization and other cases).

Further reading:

Strategies to reduce drug development time
What are the EMA requirements for clinical trials?
Requirements for compliant manufacturing of biotechnological products

What is pharmacovigilance?

Pharmacovigilance is the science and set of activities aimed at monitoring, evaluating, preventing, and managing the risks of adverse effects related to the use of medicines. It is applied continuously, before and after medicines are marketed, and is a central part of monitoring the safety of treatments.

Its main objective is to detect and evaluate any adverse effects, whether they occur:

• in the context of use in accordance with the Marketing Authorization,
• or in other situations: overdose, misuse, abuse, medication errors, etc.

The pharmacovigilance system is based on:

• The reporting of adverse effects by healthcare professionals, manufacturers, and also patients and their associations;
• The collection, analysis, and evaluation of safety information;
• The conduct of additional studies or specific work on the safety of medicines when necessary;
• The implementation of corrective or preventive actions to reduce risks.

In Europe, these activities are governed by a set of regulations and directives, supplemented by Good Pharmacovigilance Practices (GVP) defined by the European Medicines Agency (EMA). In France, these activities are also defined in the Public Health Code and supplemented by local Good Pharmacovigilance Practices. They involve various stakeholders: health authorities, regional pharmacovigilance centers, exploitant laboratories, healthcare professionals, and patients.

Why is pharmacovigilance important after obtaining Marketing Authorization?

Marketing Authorization does not mean that monitoring of a drug stops. Marketing Authorization holders must ensure continuous monitoring of safety data, in particular by reporting adverse effects to their drugs to the EMA via the European EudraVigilance system, which is mandatory under EU regulations.

This ongoing vigilance makes it possible to detect unknown or rare signals in real-world conditions and to continuously reassess the benefit/risk balance.

In the event of a proven risk, public health measures may be implemented, such as changes to indications, restrictions on use, or withdrawal of the drug from the market. Post-authorization studies (PASS/PAES) are often required to confirm a safety profile or measure the effectiveness of risk management measures.

Regulatory framework for pharmacovigilance in Europe

The European Union’s pharmacovigilance system monitors the safety of medicines marketed in Europe. This system, which has been in place for several years, has evolved over time to adapt to current practices and needs.

The European Commission revised this system with new regulations adopted by the European Parliament and the Council in December 2010, which came into force in July 2012. The European Medicines Agency (EMA) and EU Member States are responsible for its implementation.

This European regulation strengthens the existing system, making it more robust and transparent, to improve patient safety through better detection, assessment, understanding, and prevention of adverse effects or other problems related to medicines.

Major changes include:

• The obligation for local authorities to set up a national web portal enabling patients to report adverse effects directly.
• The broadening of the definition of adverse effect to include reactions related to misuse, medication errors, abuse, or occupational exposure.
• The harmonization at European level of the concept of “additional monitoring” for medicinal products, particularly for new active substances and biological medicinal products.
• The publication of certain data from the European EudraVigilance database, accessible to the public and healthcare professionals via www.adrreports.eu.

Challenges and good practices for staying compliant

Non-compliance in pharmacovigilance can compromise patient safety, which is the primary goal of post-marketing surveillance. It can also result in financial penalties and severe regulatory measures ranging from restrictions on use to changes to the summary of product characteristics (SmPC), or even suspension or withdrawal of the Marketing Authorization. Finally, these breaches can also have repercussions on scientific credibility and the trust placed in the laboratory by authorities and healthcare professionals. To remain compliant, Marketing Authorization holders must:

• Establish and maintain precise procedures covering, in particular, the collection, analysis, and transmission of safety data.
• Regularly train their teams to ensure that processes are mastered and procedures are properly applied.
• Plan regular internal audits to assess the effectiveness of the pharmacovigilance system and detect weaknesses before an inspection;
• Continuously monitor regulatory developments at European and national level to anticipate new obligations;
• Integrate pharmacovigilance into the overall governance of the company, considering it as a strategic lever and not a regulatory requirement.

Post-marketing pharmacovigilance is an essential requirement for ensuring patient safety. It requires continuous monitoring, rigorous processes, and constant adaptation to European regulatory requirements.

See also:

• Early access and compassionate use: making a drug available when not authorized in France
• How to market a drug in France? Centralized Marketing Authorization and other cases

In this article, we detail the key steps to be taken after Marketing Authorization to ensure rapid and compliant access to the French market.

Marketing Authorization: essential but not sufficient

Before a drug can be marketed in France, it must have Marketing Authorization, issued either at the national level by the ANSM or at the European level by the European Medicines Agency (EMA). The EMA is responsible for the centralized procedure, which is mandatory for certain classes of drugs (e.g., biotechnologies or treatments for cancers or orphan diseases) and optional for others (e.g., when the drug represents a therapeutic innovation).

Drugs may also be authorized through other European procedures, such as mutual recognition or decentralized procedures, coordinated between several Member States.

When a medicine needs to be made available more quickly because it meets an unmet medical need, Marketing Authorization may be conditional. This type of MA is used in particular for serious, rare, or life-threatening conditions where a potential therapeutic benefit has been demonstrated despite the lack of comprehensive clinical data. These marketing authorizations, supervised by the EMA, are subject to strict post-marketing obligations.

However, regardless of the procedure followed, Marketing Authorization is only the first step. Once authorization has been obtained, the holder must still complete several steps to actually place the product on the French market.

NB: This article applies mainly to drugs that have obtained centralized Marketing Authorization, but the principles are similar for national or decentralized Marketing Authorizations, with some variations in procedure depending on the competent authority (EMA or ANSM).

Appointment of a local exploitant for marketing

In France, a drug cannot be marketed without the appointment of an exploitant laboratory, as required by the Public Health Code. The exploitant is not necessarily the holder of the Marketing Authorization, but must be established on French territory. It acts as the official contact for the ANSM for all operations related to the manufacture and marketing of the drug.

Beyond this regulatory role, the exploitant is responsible for the proper execution of a number of essential activities, including:

• Advertising to healthcare professionals, in compliance with the legislative framework in force.
• Wholesale or free transfer, according to the channels defined by the regulations.
• The dissemination of reliable medical information to healthcare professionals and/or patients.
• The implementation of an operational pharmacovigilance system that complies with post-marketing authorization requirements.
• Batch tracking, including traceability and management of batch recalls if necessary.
• Storage activities, ensuring that the medicinal product is stored under optimal temperature and safety conditions.

The exploitant is also responsible for submitting the drug marketing declaration form to the health authorities (ANSM), which is essential for officially launching the drug on the French market. Its role is therefore strategic, regulatory, and operational, at the heart of the drug marketing system in France.

See also: What are the EMA’s timelines for the standard and accelerated procedures?

Regulatory and administrative procedures

Once the exploitant has been designated by the Marketing Authorization holder and the declaration form has been submitted to the ANSM, several administrative steps must be completed before the product can be placed on the market. These include packaging validation: the commercial packaging of the medicinal product (box, package leaflet, label) must comply with the information approved in the Marketing Authorization dossier. Any subsequent change in presentation or modification of the packaging wording must be subject to a regulatory variation, to be submitted to the ANSM or the EMA, depending on the type of Marketing Authorization.

These variations are classified according to their impact: type IA for minor changes with no clinical consequences, type IB for moderate changes requiring review, and type II for major changes likely to affect the quality, safety, or efficacy of the drug. Marketing with the new packaging can only take place after final validation by the Chief Pharmaceutical Officer of the exploitant site.

Other steps may also be necessary: validation of prices and conditions of prescription and dispensing, particularly if the drug is intended to be covered by health insurance (see next section), as well as information or promotion of drugs to healthcare professionals, regulated by regulations on drug advertising. Materials such as brochures or product datasheets may then be distributed under the responsibility of the exploitant.

See also: How to manage regulatory variations of a Marketing Authorisation (MA)?

Pricing for market access

For drugs intended to be covered by health insurance (Social Security reimbursement), access to the French market involves a two-step process: medical-economic evaluation and price negotiation. Two key bodies are involved:

• The HAS (Haute Autorité de Santé), via the “Commission de la Transparence”, evaluates the medical service provided (“SMR: Service Medical Rendu”) and the improvement in medical service provided (“ASMR: Amélioration du Service Médical Rendu”) of the drug. This evaluation influences the level of reimbursement (or coverage).
• The CEPS (Comité Economique des Produits de Santé), which negotiates the sale price of the drug with the pharmaceutical company.

Logistics and post-marketing obligations

Once the product has been authorized for sale, other considerations must be anticipated to ensure compliant, safe, and sustainable marketing.

Distribution

The distribution of medicinal products for human use must comply with Good Distribution Practices (GDP) as defined by the guidelines of November 5, 2013 (2013/C 343/01). These GDPs aim to ensure that the quality and integrity of products are preserved throughout the supply chain. They require that medicinal products be distributed only by establishments holding wholesale distribution authorization and that they be delivered only to authorized persons or entities, in particular retail pharmacies or hospital pharmacies.

The supply chain must allow for complete traceability, with a documented system ensuring the identification of each product movement. Medicines must be stored, transported, and handled under appropriate conditions to prevent any deterioration, including temperature control, packaging integrity, and protection against contamination.

An effective system for managing complaints, returns, product recalls, or the identification of counterfeit medicines must also be in place. All operations must be carried out under the responsibility of a qualified person (in France, the Chief Pharmaceutical Officer) and be subject to comprehensive documentation to enable regulatory audits and inspections.

Pharmacovigilance

Marketing Authorization requires the monitoring of adverse effects through an operational pharmacovigilance system, for which the exploitant is responsible locally. The data collected is sent to the Marketing Authorization holder, who updates the safety information on the drugs described in various documents intended for healthcare professionals and patients (such as risk management plans (RMPs), Summary of Product Characteristic (SmPC) and leaflet for the patient.

Regulatory monitoring

Periodic safety update reports (PSURs), post-marketing surveillance studies (particularly in the case of conditional MAs), and summary reports on the efficacy and safety of drugs must be submitted to the authorities. In addition, any change to the drug or its conditions of use (e.g., new indication or change in dosage) requires a variation application to be submitted to the ANSM or EMA, depending on the type of initial procedure.

Conclusion

Obtaining Marketing Authorization is a crucial step, but it is only the beginning of the journey toward commercializing a drug in France. From choosing an exploitant to submitting applications to the ANSM, including pricing requests and compliance with post-marketing obligations, each step must be carefully planned in advance.
A thorough understanding of the French regulatory framework, combined with strategic and operational support, is essential to ensure rapid, secure, and compliant access to the French market.

See also: Strategies to reduce drug development time