Key Steps to Commercialization Readiness in Europe

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The steps to commercialization readiness are complex, multi-faceted and often left too late in the launch strategy of a pharmaceutical product.

This can be particularly problematic in Europe, where the diversity of national legislation can make supply chain logistics very challenging. Among the issues faced, particularly for non-European Union (EU) countries, are defining the product’s logistics, identifying stakeholders who will be involved in the supply chain in Europe and ensuring that all these individuals are ready to assume their roles soon after the product’s approval (marketing authorization [MA]) with the relevant licenses and quality technical agreements in place.

Depending on the complexity of the storage and transportation conditions of the product and the number of stakeholders envisaged for the supply chain, experience shows that preparing all these steps can take up to two years for quality assurance, commercial and supply chain departments. In addition, while the EU has harmonized wholesale distribution regulations and introduced good manufacturing and good distribution practices in the pharmaceutical legislation (Directive 2001/83/EC and Directive 2003/94/EC and Guidelines 2013/C 343/01 (1-3), respectively), which have helped patients to access medicines faster, there are still different post-approval requirements in each EU Member State, and in the United Kingdom (UK) and Switzerland.

Among these differences, the importation, distribution and release of medicines in the EU, UK and Switzerland still present specificities requiring national authorizations to permit these activities. Moreover, in our experience, getting the necessary licenses to ensure an efficient supply chain in all targeted territories requires significant preparation.

Adopting a Systematic Approach

Before starting the commercialization journey, it is important to map out a short-, medium- and long-term strategy that considers the countries where the product should be launched and when. Knowing this will prevent early missteps that require costly and complex changes (for example, identifying the EU site of importation and establishing the EU supply chain with appropriate low-market licenses).

From experience, it is advisable to start coordinating commercialization steps before a product's late-stage development is completed — ideally when there is enough data to give companies greater confidence in a successful marketing authorization approval by regulators.

One of the first considerations should be ensuring the product can be supplied to the patient once it has been authorized since a common source of frustration is challenges with the supply chain. In addition, the European Medicines Agency (EMA), through its Medicines Shortages Steering Committee and some EU agencies, has placed an emphasis on addressing supply chain vulnerabilities and measures to avoid shortages of medicines (4).

Companies entering the European market can also struggle with deciding where to set up their EU headquarters or marketing authorization holder (MAH) and how best to weigh financial and strategic considerations. Key to that decision is having all the necessary stakeholders and partners in place to support the marketed product, including pharmacovigilance, regulatory and medical information professionals, and quality management and compliance. Quality management and compliance can support the identification of compliant supply chains and risk assess supply chain challenges.

To determine the right approach, it is important to consider local regulations, economic considerations and the company’s objectives. The following questions deserve a comprehensive analysis:

• Which countries is the company targeting for commercialization?
• Where is the product likely to be manufactured and how will that impact the supply chain as well as import licenses?
• Has the company identified a local partner, or does it plan to apply for an appropriate license authorizing it to manufacture or import, distribute/commercialize the product?

Need for a ‘Commercialization License’

Obtaining a MA for a medicinal product is, of course, a critical prerequisite before placing a product on the market. Still, the MAH must also ensure that batch testing and release of the product are managed properly by authorized sites. Depending on where the bulk/finished product has been partially or fully manufactured in the EU/European Economic Area or a third country, the importation and qualified persons (QP) batch certification can be complex, and the MAH must ensure that all importation/batch certification sites hold a Manufacturing and Importation Authorization (MIA) (5).

Besides, the MAH must identify and select distributors supplying the product to targeted EU markets and retail pharmacies and hospitals. These distributors must hold a Wholesale Distribution Authorization (WDA) defined in the EU Regulation (6).

Some EU countries, e.g., France or Germany, also require a national WDA on top of the European WDA granted to distributors for the commercialization of medicinal products. These national WDAs are also delivered by national competent authorities that certify that the WDA holder meets good distribution practices (GDP) requirements (7). WDAs are directly placed under the supervision of a Responsible Person (RP) who is the authorities’ single point of contact for most, if not all, matters related to the commercialization of the product, and RPs are named on the license.

Understanding Country Specifics

One of the most complex countries in Europe from a commercialization perspective is likely France, which expects very rigorous oversight of product distribution and lifecycle management. On the other hand, France has put in place attractive early access programs that offer the hope of faster revenues compared to other EU markets which experience has shown to have a less attractive legislative framework in this regard or have lengthy price and reimbursement procedures (which can also be the case in France) (8).

Companies seeking to market their products in France must have an "exploitant" authorization, which is defined under the French Public Health Code as the organization responsible for drug “exploitation,” i.e., commercialization under the responsibility of an RP (9-10). The exploitant can be a separate entity from the MAH, which can be based anywhere in the EU. Exploitation, in this context, refers to any activity that applies to commercializing medicinal products in France (including quality management and compliance with pharmaceutical legislation, pharmacovigilance activities, market batch release, etc.).

While the definition of the exploitant is not included in the European regulations, it is highly advisable that a company seeking to market a medicinal product in France should hold an exploitant status locally or partner with a consultancy in France to manage the exploitant requirements since many exploitation activities require native French speakers with deep knowledge of the French regulation and specific local requirements.

Since its exit from the EU, the UK has also brought additional commercialization complexities. A national WDA is also mandatory for any company that supplies medicinal products to the UK market. WDAs are issued by the national competent authority, the Medicines and Healthcare Products Regulatory Agency. In addition, the role of Responsible Person import (RPi), unique to the UK, has been introduced. The RPi is responsible for confirming QP certification and overseeing products imported into Great Britain from countries on the Approved Country for Import list (initially, this refers to countries in the EEA).

As in France, Germany, the UK and Switzerland, there is also a need for a national WDA (11). In addition, companies looking to commercialize their products in Switzerland must have a local entity to even apply for marketing authorization (given that Swissmedic, the national competent authority, does not recognize EU approvals) (12). This is because Swissmedic requires a Responsible Person based in Switzerland who can quickly access the site in case any issues with a product need to be resolved diligently.

To obtain a WDA from Swissmedic, the request must be carried out by a company legally established in Switzerland, for which an RP also based in the country has been nominated to supervise quality assurance (QA) activities and maintain the Quality Management System. The RP is also in charge of releasing batches for the Swiss market and is the ‘QA voice’ in contact with Swissmedic and the concerned Cantonal Inspectorate.

Indeed, given that Switzerland is a federation of states (the Cantons), there are also Cantonal considerations in Switzerland, with some regulations being federal, and others Cantonal, which our experience shows add further complexities for companies seeking to set up a local presence and commercialize their pharmaceutical products in the country. Cantonal inspectorates conduct regular inspections, on behalf of Swissmedic, and the MAH must ensure all their procedures and an effective quality management system are in operation under the close supervision of a Responsible Person named on the WDA (13).

Conclusion: Preparing for Commercialization Complexities

Understanding the complexity of supplying medicines within European markets, establishing local/regional entities and the associated licenses required does create commercialization challenges for non-EU companies. However, early planning and a well-executed commercialization strategy enable companies to navigate these important markets better and expand the reach of their products.