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What are direct-access medicines ?

In France, medicines are classified into different categories according to the way they are delivered.

Medicines that present difficulties in use or risks in the event of inappropriate use can only be obtained on presentation of a prescription from a doctor, dentist or midwife. They are known as mandatory medical prescriptions (prescription médicale obligatoire). In particular, they appear on lists I or II of poisonous substances, or even on the list of narcotics. The Director General of the ANSM has recently inherited this competence from the Ministry of Health, within the framework of the law on the “acceleration and simplification of public action” (ASAP).

Medicines not subject to mandatory medical prescription may be advised by the pharmacist, requested by the patient or prescribed by the doctor and are known as Optional Medical Prescription (prescription médicale facultative).

Among the optional prescription medicines, only certain medicines can be placed in front of the counter (“Over The Counter” (OTC)) of the pharmacy in order to allow the patient to serve himself. They are called in various ways: “self-medication medicines“(médicament d’automédication), “officinal medicines” (médicament de médication officinale), “free access medicines” (médicament en libre accès) or “direct access medicines“(médicament en accès direct). This is only possible if all the eligibility criteria are met, including the fact that they are not reimbursable by the health insurance system.

The list of these medicines that can be presented for direct access in pharmacies is defined and evolves according to the decisions published on the ASNSM website after evaluation of the express requests from laboratories.

Which medicines are eligible for direct access?

The inclusion of a medicinal product on this list is done according to the criteria of article R.5121-203 of the Public Health Code in order to guarantee the safety and security of patients.

A direct access medicinal product must be able to be used without the intervention of a doctor for the diagnosis, initiation or monitoring of a treatment due to its therapeutic indication: the symptoms must be easily recognisable, and must not risk hiding a serious condition. In addition, the medicine must have an easy dosage, a short treatment duration, and a leaflet adapted to the language of the general public. A whole process of adapting the marketing authorisation must therefore be devised to change the status of a drug.

A medicine with a major contraindication or a significant risk of drug interactions, or a medicine intended for the paediatric population whose safety level is not sufficient for self-medication, would not be eligible for safety reasons.

How to apply for direct access to a medicine?

When applying to the ANSM for a change in marketing authorisation with a view to placing optional prescription medicines on the direct access list, the procedures for submitting applications for inclusion on the “officinal medicines” (Médicament de Médication Officinale) list differ depending on the active substance and the indication of the medicine. It is necessary to carefully examine whether the active substance or the fixed combination is already referenced in the list, and whether the targeted indication has been identified as being suitable for self-medication. The regulatory and clinical aspects should therefore be considered together.

The composition of the type II MA variation dossier depends on this analysis. In any case, the ANSM will examine a whole range of aspects, the most important of which is safety of use.



Article written by Laure DEAN, Regulatory and Pharmaceutical Affairs Advisor

France is known for its strict regulatory provisions when it comes to medicines. The exception will not be made for the framework of relations between industries and health professionals, now known in France as the LEA. (anti-gift law)

So who is LEA?

Before, we used to say “anti-corruption law”, “DMOS”, “anti-gifts law”… These terms are no longer used. This system, which will soon celebrate its 30th anniversary (we are getting on in years), has just been revamped and we now speak of the “Benefits Framework System” or the “Benefits Framework Law” (the famous LEA in French) because it is a set of texts and a real arsenal put in place since October, 1st 2020 so that the State can better control relations between the health industries in particular, and health professionals in the broadest sense of the term. It should be remembered that it has to be considered in a very distinct way from the system of transparency of links, which pursues the objectives of publicising the advantages procured and agreements made in order to inform the general public and avoid any conflict of interest.

As we have just said, this system is not recent. It is true that over the years it has been considerably strengthened since it now concerns all health products, whether reimbursable or not, and its scope of application has gradually been extended to health professionals, students and their associations. But, in fine, its fundamental principle has remained the same: we are faced with a genuine “anti-corruption” mechanism applicable to relations between companies that market health products, such as medicines or medical devices, or provide health services, and health professionals (doctors, but also all other health professionals as well as osteopaths, chiropractors and psychotherapists). The aim is to ensure that HCPs are guided only by medical considerations in their choice of prescribing a product or health service and to prevent conflicts of interest.

More concretely, the general principle is the following:

• Prohibition for companies to provide health services, producing or marketing health products to grant direct or indirect benefits, in kind or in cash; and

• Prohibition on health professionals, associations of health professionals and civil servants/public officials covered by the scheme from receiving such benefits.

It should be noted that these prohibitions are punishable under criminal law and that there is joint responsibility between the companies granting undue advantages and the beneficiaries of these advantages.

But let’s make it a little more complex… The LEA provides derogations from this principle of prohibition and subjects all authorised interactions (remuneration, hospitality in the context of professional, scientific or promotional events, participation in research activities, provision of services, sponsorship, donations) to prior control by the competent authorities, i.e. the medical professions’ council of order where they exist or the Regional Health Agency. However, one condition for the implementation of these derogations is the establishment of an agreement working as a contract which will then be submitted to the competent authorities. These derogations should not be confused with items excluded from the definition of a prohibited benefit, such as benefits in cash or in kind that relate to the exercise of the beneficiary’s profession and benefits of negligible value (e.g. impromptu meals, samples, books). It should be remembered that any benefit in excess of 10 euros must also be declared on https://www.transparence.sante.gouv.fr/ as part of the transparency of links.

Two submission regimes are possible: submission for declaration OR for authorisation.

To guide us in the choice of the applicable submission regime, threshold values have been published by decree. These values are then defined for each type of benefit provided. It now remains up to you to define the category in which your benefit falls…

If the benefits granted are below the thresholds, a declaration must be made 8 days before the benefit is granted, either on Idahe 2 or EPS. The benefit cannot be implemented before this deadline.

If the benefits granted are above the thresholds, an application for authorisation must be made at least two months before implementation. At the end of the two months, the competent authority will issue a binding decision, not an opinion.

To sum up :

Few innovations have been published since the new system was introduced on October 1st 2020, but the day-to-day implementation of the system raises a large number of questions of interpretation. ATESSIA can assist you in setting up and adapting your processes to comply with this system.



Article written by Floriane LUCY, Regulatory & Pharmacist Affairs Advisor

On Wednesday 11 May 2022, our 4th Lunchwork of the year took place on the theme of nitrosamine impurities for which the regulatory deadlines are fast approaching. This event, organised around lunchtime and accessible free of charge to our ATESSIA INTELLIGENCE subscribers, brought together 70 participants from French and international pharmaceutical companies.

On this occasion, Lorraine BALIN, Senior Consultant for Regulatory and Pharmaceutical Affairs and Christelle PETIT, Director and Consultant for Pharmaceutical Affairs at ATESSIA respectively presented an overview of the European regulatory news on nitrosamines and led constructive exchanges with the participants

After a presentation of the root causes of the formation of nitrosamine impurities in medicines, the chronology of events relating to nitrosamines on a global scale from 2018 to the present day, the actions initiated in France and in Europe and their implementation methods, the impacts on the European Pharmacopoeia and CEPs, it was mainly the concrete management of a project to analyse and mitigate the risk of nitrosamines in chemical and biological medicines (new or already registered in Europe) and traditional herbal medicines (new only) that was discussed. The discussions were based on concrete cases (feedback from ANSM), from ATESSIA’s experience.

Our speakers recalled that knowledge of nitrosamine impurities was constantly evolving and insisted on the need to regularly monitor the texts issued by the health authorities on this subject, in order to take into account any new root cause of formation identified and any limit applicable to a specific nitrosamine defined by the authorities on the basis of safety data. Indeed, since 2018, health authorities have implemented various action plans in order to protect patients’ health, including a worldwide batch recall for medicines containing nitrosamines above the defined acceptable daily intake limit.

Tout en soulignant que les exigences en terme d’évaluation du risque de présence de nitrosamines ne s’appliquaient pas à ce stade aux spécialités radiopharmaceutiques, il a été rappelé que les médicaments traditionnels à base de plantes déjà enregistrés et les médicaments homéopathiques pourraient être intégrés ultérieurement dans le champ des spécialités concernées, en fonction de l’expérience acquise.

At the time of this lunchwork, pharmaceutical companies are involved in the conduct of step 2 (confirmatory testing: identification and quantification of nitrosamines actually present in the medicinal product) of the process of analysis and mitigation of the risk of the presence of nitrosamines in medicinal products of chemical and biological origin, and even for some of them in the conduct of step 3 (updating of marketing authorisations after prior validation of the control strategy by the authorities, for example : submission of a variation modifying the control specifications of the medicinal product) of this same process for medicinal products of chemical origin for which a common deadline of 26 September 2022 has been set in Europe. An additional period of time is granted for biological medicinal products (1 July 2023) for the completion of step 2 and 3.

Pending further clarification from the ANSM regarding the filing of variations to the marketing authorisation dossier, marketing authorisation holders are invited to communicate the results of the confirmatory tests and their proposals for a control strategy sufficiently in advance and to prepare their variations now so as to comply with the deadlines set to comply with the conclusions of the summary procedure according to Art5(3) of the CHMP on 26 September 2019.

ATESSIA assists its clients in the preparation, drafting and filing of variations to their marketing authorisations.


Article written by Isabelle MOUVAULT, Pharmaceutical Affairs Advisor

On Wednesday April 20, 2022, our 3rd Lunchwork of the year took place. On the occasion of this lunchtime event, accessible free of charge to our ATESSIA INTELLIGENCE subscribers and having gathered more than 70 participants from many pharmaceutical companies and DM manufacturers, we had the pleasure to welcome the LEXCASE for a presentation dedicated to the new French Quality Charter of professional practices for reimbursable products and services.

Diane BANDON-TOURRET, Associate Lawyer, Victoire STORKSEN, Lawyer, and Lucie CLOUIN-MOTHE, Director of Operations of ATESSIA, gave an update on the new obligations, the stakes and what has still to be precised, in the management of this major turning point for the practices applied to the marketing of reimbursable products and services in France, especially medical devices.

After a review of the origins of the system, the history of the difficult negotiations between the various stakeholders, and the establishment of the legal framework, the speakers discussed the current status of the work of drafting the certification guide and the timeframe for implementation.

While stressing that all the texts are not yet available and that many things remain unclear, the speakers detailed the scope, the operators and products concerned and excluded, the semantic analysis and the definition of terms and of the different roles according to the new Charter, as well as the possible financial penalties.

Although it is possible to draw parallels with the Charter applicable to medicines in France, the two systems are clearly different in many respects. This observation can be made in many areas, such as the rules for organizing visits, the for ethics and for distributing samples. In this context, the simultaneous management of two Charters, with sometimes contradictory injunctions or additional restrictive terms, is likely to become a challenge for the companies that will be subject to both systems, beyond possible inequities between competitors who, due to their product portfolios, would not be subject to the equivalent requirements.

While waiting for more details, one thing to remember is that the Charter already applies, and even if many actions can only be undertaken once the entire system has been clarified and the certification guide is not yet available, there are already applicable measures! ATESSIA can assist you in setting up and adapting your processes to comply with these new standards.

Article written by Raphaël DAUVERGNE, Regulatory and Pharmaceutical Affairs Advisor