Why Managed Access Programs should be a key component of your strategy for Europe

Managed Access Programs (MAPs) provide patients with anticipated access to drugs before their full-fledged commercialization. As often seen in Europe, the situation is complex: on one hand, MAPs can refer to several different schemes within a country, on the other hand MAPs are regulated at country level, with almost as many situations as there are countries. Yet, MAPs are an integral part of a successful market entry strategy for Europe. How can you maximize your chances to implement a successful MAP that will help the patients in need and speed up your adoption by the medical community?

What are MAPs and why are they necessary?

While market authorization can now be granted at a European Level, “Pricing and Reimbursement” are still the prerogative of each Member State: in some countries, a drug can fall into the paradoxical state where it is approved and yet cannot be prescribed, for lack of reimbursement. To mitigate this problem, Managed Access Programs have emerged in most European countries.

MAPs are programs designed to accelerate patient access to new, efficacious drugs, in an ethical, compliant, and controlled way until they become fully marketed (approved, with price and reimbursement schemes in place). MAPs bridge the gaps that exist between clinical trials and commercially available drugs: they are usually set up once phase III results are known, and the marketing authorization has been filed, i.e. even before the marketing authorization is granted.

For the sake of clarity, MAPs in this article will be considered to be mostly Compassionate Use Programs, but be aware that the term “MAP” sometimes has a broader definition and could be used interchangeably with – or include – programs such as Early Access Programs, conditional approval, PriMe (Priority Medicine scheme) …

Even within a given country, MAPs could either concern individual patients or groups of patients. The first case is referred to as NPP for Named Patient Program, the second as Cohort Programs.

Who will benefit from a MAP?

The patients

Getting access to effective medicine when no other option is available: the benefit to the patient is obvious.

One way for patients to receive treatment early is to be included into clinical trials (e.g. Open label extension after the randomized phase of the pivotal trial), but not all patients are eligible to participate in the trials, which are protocol-driven and have stringent inclusion and exclusion criteria. Thus, MAPs are often the only option for patients who cannot wait for the drug to be commercialized and cannot enter clinical trials.

Furthermore, MAPs are validated by local authorities and the drug can only be distributed through well defined channels, reducing the risk for counterfeit drugs.

The physicians

For physicians, MAPs are extremely useful as well, because on top of the direct benefit it provides to their patients, it also allows them to better understand the drug and have their first hands on experience with a new drug.

It can also please the early adopters within the physician population, who, once convinced of the benefits the drugs bring to patients, can become the best brand advocates, whether to recommend to their colleagues or to intervene as experts during pricing and reimbursement negotiations.

The payers

Most compassionate use programs require the drug to be provided free of charge by the market authorization holder (MAH). Some named patient programs and the Autorisation Temporaire d’Utilisation in France (ATU, ‘Temporary Authorization for Use’) are the exception to the rule: the healthcare system would pay for the drug in this case.

The MAH still takes care of the pharmacovigilance (PV): this provides safety data from a larger population sample in a more “real-life” setting, which helps better assess the safety, tolerability, and Quality of Life aspect of the reimbursement and pricing negotiations.

The market authorization holder

Despite having to provide the drug for free in most cases and assuming the costs of PV, some associated benefits have been noticed as MAPs became more common:

  • Patient-centric company image: MAPs show the goodwill of the company towards patient needs, which helps strengthen the ties between the MAH, the medical community (both KOL and community prescribers) and the patient advocacy groups. Furthermore, it increases the likelihood that patients try the treatment offered through the MAP instead of others.
  • Spontaneous awareness: More physicians and patients will experience the benefits associated with the treatment, which will likely fuel discussion among patient groups. This increased spontaneous (i.e. non-promoted) awareness will more likely speed up the widespread medical adoption once the drug is commercialized. It is likely it has an impact on the 1st year market share[i] (a gain close to 1/3 in terms of market share was loosely associated with the implementation of a NPP in a small retrospective study).

However, one cannot stress enough that the primary goal of a compliant MAP should be to provide efficacious treatments to patients with unmet needs.

Diversity of schemes across Europe

The diversity of programs available in France (FR), Germany (DE), Italy (IT), Spain (ES) & the United Kingdom (UK) illustrates the complexity of setting up a European MAP for a newly approved drug:

Absence of global EU framework: Within the scope of Article 83 of Regulation (EC) No 726/2004, the EMA provides recommendation through the Committee for Medicinal Products for Human Use (CHMP), but does not create a single legal framework.

There are 5 different authorities to coordinate:

  • Agence nationale de sécurité du médicament et des produits de santé (ANSM, FR)
  • Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM, DE) & Paul-Ehrlich-Institute (PEI, DE)
  • Agenzia Italiana del Farmaco (AIFA, IT)
  • Agencia Española de Medicamentos y Productos Sanitarios (AEMPS, ES)
  • Medicines and Healthcare Products Regulatory Agency (MHRA, UK)

Diversity in program types: Cohort programs only (DE), Named Patient Program only (UK) or both cohort and NPP available (FR, ES, IT).


European MAPs are more complex than their US counterpart, with no centralized approach (yet). However, and despite their non-negligible cost, they provide benefits for all stakeholders within the healthcare ecosystem, including the market authorization holder. Thus, MAPs are an integral part of strategy to foster fast adoption by the medical community but require careful planning to reach their goals while keeping expenditure under control.

Cepton Strategies will be attending the JP Morgan conference in January. We would be delighted to discuss these points with you in detail and address your concerns for the European market. Please click here for more information and to get in touch.

[i] A.K. Bates, Journal of Medical Marketing (2008) 8, 319 – 324

11 things innovative healthcare firms must know when planning to launch in Europe

1.      EMA and FDA do not have the same requirements when evaluating a registration file. Anticipate the design of your phase 2 and 3 clinical trials to account of these differences.

2.      Every European country has a specific healthcare system, with variations of reimbursement procedures and requirements (timing, dossier, price). Reimbursement decisions will be made by a combination of regional and national committees: national has precedence in some countries like France but regions can be the main decision-makers in other countries like Germany or Italy, despite using guidelines issued by national committees.

3.      Medical practices are rather homogeneous across Europe. There is generally a European Expert Society for each therapeutic area, gathering members of national societies. Therefore, practitioners usually follow the same guidelines, published by these European Expert Societies.

4.      There are numerous patient advocacy groups and associations, organized at the regional, national, and pan-national level. In some disease areas, such as AIDS, these groups can be quite influential. This is true both in the US and the EU, and it is normal for groups focused on the same areas to exist on both continents.

5.      The registration procedure (CE mark) for medical devices and diagnostics is more simple and straightforward than in the US, but reimbursement is country-dependent and may be quite slow (up to several years). However, regulations are changing, and the registration process will become more demanding for Class 2b and 3 devices. Read more here.

6.      For diagnostics, there is no such thing in Europe as the LDT status allowing quick commercialization on a limited scope through CLIA labs.

7.      Depending on disease areas, your commercial model will be different across countries. You will generally have to be more payor-centered in Northern Europe and more physician-centered in Southern Europe, with several countries such as Germany standing in-between.

8.      All European payors will demand comparative trial data with the standard of care. This will have tremendous implications on your trial design and must be anticipated.

9.      HEOR studies may be quite useful in some countries but not relevant in others due to different funding processes and stakeholders, or different evaluation methodologies at national level. For example, France’s HAS does not fully recognize QUALYs as a valid outcome measure.

10.   Private health insurance companies have little influence over the reimbursement process of most drugs and devices. They usually follow the decisions of the National Healthcare System.

11.   For most drugs, a certain launch sequence has to be followed in order to maximize reimbursement prices. You must start with countries with fast processes and high historical prices, and end with low-price and/or slow countries such as Italy, Spain or Eastern European countries.

The future of IVDs: important regulatory changes will soon redistribute the cards in the EU

With the new European in vitro Diagnosis Device Regulation (IVDR), published in May 2017 [1], but fully in place in 2022, the rules will change for IVD players in Europe. American companies will feel more at home due to the system becoming aligned with that in the US, in addition to having the possibility to replicate processes used in their operations. Although European firms not accustomed to the US market will be starting from scratch, US companies will need new protocols to ensure efficient operations in Europe in order to develop a competitive advantage, and may benefit from specific European support, particularly to go through the reimbursement process.

The current European directives are more manufacturer-friendly than the US regulation

In the current “In Vitro Diagnostic Medical Devices Directive” (IVDD). There are four list-based categories. In the EU, manufacturers have to follow the EC’s IVDD and will have to comply with the IVDR by 2022. The current requirements address the design, production, labelling, and instructions for use. Depending on the technical specificities and indication, an IVD belongs to one of the four categories specified in the classification (General, Self-test, List B, and List A). [2]

With the current IVDD, 80% of the IVDs are self-declared. Even though there are four categories, with the current IVDD 80% of the IVDs belong to the Class I category, and so, do not need a Notified Body, making it simpler and cheaper to go through the EU regulatory pathway. [3]

The US was the only country, until now, to take patient safety into consideration, and is the most regulated one for IVDs

FDA classification is divided into three categories based on risk. It is the risk and the level of control necessary to provide reasonable assurance of the safety and effectiveness of the device that will determine its category, unlike the aforementioned list based approach of the IVDD. Depending on its risk, the device belongs to one of the three (and not four as in the EU) following categories:

In addition to classification, the FDA enforces the Clinical Laboratory Improvement Amendments (CLIA). A categorization based on the technical competence required by the user is made by the FDA (scoring of 1, 2, or 3). For example, a test that is cleared by the FDA for home use would receive a CLIA-waiver (score 1) because it requires minimum competence from the user. Whereas the Centers for Medicare & Medicaid Services (CMS) enforces the CLIA in the locations where the tests are performed, which means it controls the laboratories. [3] [4].

The IVDR brings about a convergence of the US and EU classification of IVDs, which are now both risk-based approaches

The new regulation is risk-based as the FDA, and Notified Bodies will have more products to control and power than ever before. Now, there are four categories from low to high risk (A, B, C, and D). Class D refers to IVDs dealing with high public health and high personal risk, and degressively, class A being low personal and low public health risk, and therefore the only category to be self-declared. As a result of these changes, Notified Bodies will have to assess more products than before: 80% of IVDs’ manufacturers will need them. Other new measures include clinical performance studies, the Unique Device Identification (UDI) and post-market safety surveillance. [5] [6]

An opportunity for US companies to expand into Europe

This new regulation will give a competitive advantage to companies used to the US market. It will lead to the implementation of new manufacturing processes and post-market surveillance systems in addition to an increase in legal costs (Notified Bodies’ related fees) and so on. The level of time and investment needed in designing, implementing, and managing these new processes will force companies to build more robust business cases. But for companies already competing in the US market, the internal regulatory resources, the quality assurance measures, and the clinical evidence they adopt for the FDA will be useful in their applications for CE marking. Therefore, they will not feel the impact of the changes in the same way EU companies do, thus the cards will be extensively redistributed amongst the competitors on the European market.

The different reimbursement systems in Europe stay a challenge for US manufacturers, harmonization is coming

The new IVDR regulation will quicken reimbursement processes. Despite the CE marking process for IVD products being previously quick and rather straightforward, reimbursement was slow, complex, and highly country-dependant. The new IVDR regulation, however, requires much higher levels of clinical evidence. This is exactly what payers in Europe demand to grant reimbursement. It is therefore to be expected, paradoxically, that the new IVDR regulation will speed up reimbursement processes in most EU countries. [7]

Cepton Strategies will be attending the JP Morgan conference in January. Please click here for more information.

1 – European Commission website – Regulatory framework – “The new Regulations on medical device” – 15 November 2017

2 – BSI: an In Vitro Diagnostics Notified Body – “A guide to the In Vitro Diagnostic Directive” – 2012

3 – European Observatory on Health Systems and Policies – “Ensuring innovation in diagnostics for bacterial infection” – 2015

4 – FDA website – Medical Device

5 – Lloyd’s Register LRQA – “In Vitro Diagnostic Device Regulation (IVDR)” – 2017

6 – BSI: an In Vitro Diagnostics Notified Body – “IVD Regulation What you need to know” – 5 may 2017

7 – CEPTON Strategies’ article – “European medical device reform: the changes to expect for class IIb and class III medical devices” 2017