Operation Neptune:
Preparation Phase
Deliverables, timeline and processes. In that order! It is the secret for a successful European Launch.
In the previous article1 we mentioned the importance of retro-planning in the design of the EU Business Case & Operating Model: start with the end and reverse-engineer the launch process.
This is how it looks from a calendar planning perspective:
Once the target launch date is realistically determined, the next step is to outline the teams’ structure and the sequence of their involvement during the preparation and launch phase. The image below displays the teams involved in the process, arranged in chronological order of deliverables and milestones.
1. Commercial Operations
The Metamorphosis: The Commercial Readiness is the chrysalis that will transform your company.
The transition from a clinical stage company to a commercial company is a challenge in it-self. It is even more true when considering the complexity of the European market from a foreign perspective.
This is why “The Key to Success Lies in Advanced Preparation”1.
The first step in establishing local capabilities is recruiting a General Manager and a vital partner: the PMO. Both roles must have the relevant strategic commercial experience for the target markets and therapeutic area.
💡 Tip: companies often delay proceeding to the next phases until R&D results are known aiming to reduce risks and costs. However, this approach often has the opposite effect. An effective way to optimize resources, gain local expertise, and balance risks and costs is to hire contractors, such as the PMO.
From the project’s early stages, the Managing Director and the PMO will assist the company in meeting timelines and milestones. They provide guidance to the global HQ resources of the company, manage the interdependencies between various functional teams, and monitor the launch efforts.
This pair works simultaneously to establish the European presence and launch the new therapy.
The Commercial Team usual milestones:
Market landscaping
Healthcare professionals segments
- Identify and select the key healthcare professionals who will be involved in administering, prescribing, or recommending the new therapy. It’s a crucial part of the market analysis and strategy development for launching a new pharmaceutical product.
Sales strategy
Sales force sizing & hiring
Commercial operations
Country rollouts
2. Medical Affairs
Silence, science is talking.
The Medical Affairs Team serves as a link between Research & Development (R&D), Commercial/Marketing, Market Access, Health Economy and Regulatory Teams. Additionally, it is responsible for managing external scientific engagements.
In an age of scientific and digital rapid advances, Medical Affairs’s objective is to identify opportunities for to improve patients journey, diagnostics, treatment and follow-up, while facilitating optimal science-driven dialogue and ensure alignment of common objectives to enhance patient outcomes.
The roles and responsibilities in Medical Affairs Teams depends highly on the organization. In this chapter, we will focus on the function with an Inside-Out and Outside-In approaches at the affiliate level for pre-launch activities.
The Medical Affairs Team represents the interests of patient communities in the development and provision of innovative solutions that address societal value issues. Medical Affairs Team collaborates with HCPs to identify the most relevant patient populations who may benefit from innovative medicines and treatments in a safe and effective way.
Customer-centric “Inside-Out” & “Outside-In” Principles
| Inside-Out | Outside-In |
|---|---|
| Internal value reaches the right customer at the right time. | Engaging with the relevant stakeholders to understand the external environment and develop strategic plans. |
| Engagements of HCPs in clinical trials. | Medical and clinical insights collection to understand external needs and develop optimal company strategies and action plans that are relevant for patients or society |
| Ensure patient access to new, innovative medicines in liaison with national payer entities with submission of HTA dossier and negotiation | Explore Private-Public partnerships opportunities to leverage the creation of sustainable healthcare solutions. |
| Customer-and patient-centric communication of scientific data, disease awareness, or product related information using multiple means of communication. | Develop meaningful solutions for patients and societies by incorporating their insights in the development phase, thus promoting patient-centricity. |
“Inside-Out” & “Outside-In” principles primary deliverable is to translate and contextualise the results of clinical trials to the relevant stakeholders in the healthcare ecosystem such as HTA and Payers through RWE data generation.
Pre-launch deliverables
- Inside-Out
- Country selected and investigator sites active in global clinical trials
- Evidence gap analysis; plan and execute medical evidence generation projects including publication and dissemination planning
- Development of the clinical dossier for the HTA submission
- Internal medical education of cross-functional teams
- Outside-In
- Clinical Landscape, Standard of Care mapping
- Key External Experts (KEE) and Key Opinion Leaders (KOLs) mapping and engagement plan
- Building Awareness & collect external insights around the Therapeutic Area and company product:
- Introductory meetings with KEEs
- Disease Insight Visits (DIVs)
- Patient Advocacy Groups (PAGs)
- Scientific & Advisory Board meetings
- Participation in medical, research and clinical congresses, consultancy meetings, publications, and many more…
- Collaborate with external stakeholders to develop educational scientific meetings and forums, preceptorship events (educational & observational)
👉🏽 What is Patient-Centricity in healthcare?
- Understanding Patient Needs.
- Incorporating Patient Perspectives.
- Tailoring Healthcare Solutions.
- Empowering Patients.
- Ensuring Access and Affordability.
- Continuity of Care.
Medical Affairs is the "Central Nervous System" of the Preparation Phase
During pre-launch phase, the Medical Affairs plays a pivotal role to coordinate and regulate all stakeholders internally and externally.
Hands-on, Medical Affairs must also have observing and listening skills to explore all opportunities.
Competence in digital health solutions, artificial intelligence, and machine learning algorithms are crucial. Data science skills to identify and address evidence gaps in treatment traditions will be increasingly important to improve trial designs, including recruitment of more diverse patients, and addresses regulators’ requirements in terms of Real-world data (RWD) and Real-world evidence (RWE) data.
3. Regulatory Requirements
All roads lead to Rome: One Objective, different ways.
The European market is particularly attractive for companies developing therapies for conditions designated by the EMA as having “high and unmet need”. These are typically referred to as “orphan” diseases. In addition, an orphan product has to demonstrate that it brings exceptional therapeutic advancement.
A quick look at the Regulatory system in the EU
The European medicines regulatory system consists of about 50 regulatory authorities from 30 EEA countries, the European Commission, and EMA. This unique network is supported by over 4,000 Europe-wide experts, ensuring top-quality scientific advice.
EMA and Member States collaborate and share expertise in assessing new medicines, monitoring their safety, and responding to public health emergencies. They also exchange information regarding medicine regulation, clinical trials oversight, and inspections of manufacturers and practice compliance.
Patients and healthcare professionals are part of EMA’s scientific committees, Emergency Task Force, and Medicine Shortages Steering Group, contributing to scientific advice and advisory groups.
Marketing Authorisations procedures
Several options exist for filing a new drug Marketing Authorization (MA) application in the EU.
One path, if eligible, the therapy can undergo the EMA centralized process for a single marketing authorization in all EU countries. This marketing authorization is granted following the scientific assessment of the application by the relevant committees of the EMA.
While the Marketing Authorization is important, numerous additional national regulatory activities in EU member states are still required before the drug’s commercial launch.
The table below shows the four different types of procedures to apply for MA in Europe:
| Pathway | Description | Advantages | Disadvantages |
|---|---|---|---|
| Centralized | Requires a single marketing authorization for all EU member states. | Streamlined and uniform approval process across the EU. | Limited flexibility for tailoring products to specific markets. |
| Decentralized | Involves multiple EU member states and requires a mutual recognition procedure. | Access to multiple markets and flexibility in navigating different regulatory requirements. | Longer approval process due to involvement of multiple member states. |
| Mutual Recognition | Allows for recognition of a marketing authorization granted by one EU member state in other member states. | Reduction in the need for separate approvals and broader market access. | Limited control over the approval process in each member state. |
| National | Requires separate marketing authorizations for each individual EU member state. | Tailoring products to meet specific country requirements. | Increased complexity and cost due to separate approvals for each member state. |
The pathway depends on the medicinal product and its current registration status. For example, developers of Advanced Therapies Medicinal Products (ATMPs) might consider France, Spain, and Italy as entry points. They can take advantage of Early Access Programs (EAPs), which allow exceptional use of drugs before obtaining Marketing Authorization. These three countries were pioneers in Early Access Programs.
It’s important to note that the choice between the EMA and EU National Health Agencies depends on various factors, including the company’s strategic goals, target market, and resources. Each option has its own advantages and considerations, and companies should carefully evaluate their specific circumstances before making a decision.
💡 Contact us for further information on advantages and disadvantages of each pathway including cost savings and investment incentives offered by the member states.
Usually following the Centralized Pathway, the entry route into the EU involves targeting the four largest countries in terms of pharmaceutical spending (the EU big-4): Germany, France, Spain, and Italy. Obtaining reimbursement in one of these countries often facilitates entry into the remaining EU countries.
💡 The European drug approval process is one of the most obvious differences between US, China and Japan governing bodies. In Europe, due to the multiple pathways, it is key to have a regulatory strategy matching with the marketing expectations, taking into consideration the regulatory constraints as well as planning future geographical roll-outs.
The Regulatory Team usual milestones in addition to the Regulatory Requirements:
- PoC for EMA and Dossier Development, submission, Q&A and follow up
- Quality Management Systems
- Pharmacovigilance
- Quality Training
The Regulatory Team is also accountable for the milestones below in cooperation with Manufacturing and Supply Chain Teams:
- Manufacturing and Importation Authorization procedure
- Wholesale Distribution License
4. Market Access
Get the right Price, for the right Patients, at the right Time.
In the EU, every member state has its own priorities to set pricing of medicinal products. Each member state has its own way of organising its health systems, as well as its tax and Social Security systems, which cover the cost of medicines that patients can access.
Understanding the payer requirements, and how the reimbursement and funding system work in each market, is critical for how you develop your product, what price you can get, for which patients it will be reimbursed and when it will be accessible to them.
Value propositions, payer research, evidence gap analysis, and health economic models are important tools to support commercial decision-making as well as the clinical development program.
It’s essential to get the right price, for the right patients, at the right time when launching a new product.
"Price is what you pay. Value is what you get." - Warren Buffett
By conducting payer research, companies can identify the payer’s value drivers and obtain insights into the payer’s decision-making process. Evidence gap analysis can help identify the gaps in the clinical trial evidence being collected that need to be filled to meet payer requirements.
Health economic models can help estimate the product’s cost-effectiveness and demonstrate its value to payers. Value propositions, value dossiers and value messages help articulate the product’s value to payers and other stakeholders in a coherent, evidence-based story.
Value Identification
Market access landscape/analogue assessments
Payer research/advisory boards
Early health economic modelling
Early value proposition
Price assessment/commercial opportunityValue Generation
Value Generation
Evidence gap analysis/evidence generation plan
Literature reviews
Input to clinical trial (payer) endpoints
Statistical analysis plan/treatment comparison
Value message testing
Value Communication
Global value story and dossier
Global health economic model
Global pricing strategy and launch sequence
Internal launch preparation
Health Technology Assessment (HTA) submission
By utilizing these tools, companies can make informed commercial decisions, optimize their product’s pricing and reimbursement, and ensure that their product reaches the right patients at the right time.
Without Evidence, Data is nothing
By involving market access early on, it will support the demonstration of the added value of the drug compared to the standard of care. It will also gather compelling evidence on how the new medicine/therapy improves the standard of care and contributes positively to public health and finances.
Until the adoption of an harmonized approach to Health Technology Assessment (HTA)2 in 2025, this approach will facilitate the work of local HTA bodies and payers in assessing the quality and benefit/risk ratio of a drug.
The Market Access Team usual milestones are:
- Global price corridor
- Reimbursement dossiers development and submission
- PAYER negociations
- RWE strategy development, rollout and data collection
5. Corporate Services
The best science can’t be orphan from great support.
Great science is, and always will be, the primary focus of successful biopharmas. This said, achieving operational efficiency in corporate services is vital for the long-term success.
Establishing an « European Home »
It isn’t about merely setting up a physical presence. It’s about creating an organisation aligned with the operational needs and cultural values of the company.
The ideal location depends on a multitude of factors, from the availability of a skilled workforce and operational costs to cultural and linguistic compatibility. Europe offers a rich landscape of potential hubs for biopharmas, each with its unique advantages and challenges.
Setting up in Europe also means navigating diverse regulatory landscapes, intellectual property considerations, operations setup, and go-to-market strategies. Regulatory and market authorisations vary by country, and this can impact aspects ranging from GxP authorisations to recycling rules on waste.
Intellectual Property rights and the evolution of Financial and IP policies also need careful consideration. Operations setup depend on factors like the Marketing Authorisation Holder’s location, supply chain and distribution models and authorisations, indirect taxes, and cyber security. Each of these aspects requires careful planning and execution.
Supply Chain Challenges
Global disruptions risks make essential for companies to secure multi-sourcing capabilities and an agile procurement function.
The supply chain function has to be smart, responsive, and able to balance the need to increase safety stock on critical products without compromising working capital.
Understanding the entire logistics process of importing drugs, storing them in a central location, and ensuring their safe and rapid delivery is crucial, especially for orphan drug supply, given its low volume and often-urgent delivery requirements.
Finance, Tax and Intellectual Property
In the financial domain, companies are dealing with rising interests, increasing energy costs and higher working capital. This environment requires accuracy in forecasting and digital tools capable of handling financial and non-financial data.
Finance and Tax teams are also key stakeholders for financing options and support for due-diligence processes in technology and research collaborations, M&A, and IPO-readiness, as well as licensing deals.
Mandatory tax transparency policies are also impacting intercompany transactions3 which have to be carefully considered in the Arms Length Agreements3.
Environmental, Social and Governance (ESG)
Transitioning to more sustainable ways of producing medicines, reducing waste and greenhouse gas emissions, maintaining diversity in clinical trials and company leadership, and integrating ESG goals as part of corporate strategy boosts reputation, employee retention and patients perception.
Information Technology
Cyber threats, manage data storage and access efficiently and securely, and ensure regulatory compliance under GDPR regulations are some of the challenges to take.
Implementation of digital technologies are challenging due to factors like data complexity and heterogeneity, regulatory compliance, talent and skill gaps, legacy IT systems, and the cost and ROI of implementing new technology.
6. Conclusion
Launching a new therapy in Europe involves a complex process that requires meticulous planning and execution across various critical areas and involve many cross-functional work and teams.
Professionals who have worked on such projects often feel immense pride and satisfaction.
Furthermore, companies that successfully reach this milestone often see increased success.
Last but not least, more patients benefit from cures for life-threatening diseases.
Disclaimer
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While the information contained in this publication has been obtained from sources believed to be reliable, LSS disclaims all warranties as to the accuracy, completeness, or adequacy of such information. It is crucial for readers to exercise their own judgment and discretion when using this publication as a resource.
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In conclusion, the access and use of this publication is at your own risk.
Rui Teixeira, OPERATION OVERLORD.
The Key to Success Lies in Advanced Preparation
Regulation (EU) 2021/2282 en EU LEX on health technology assessment (HTAR).
This regulation is part of the Pharmaceutical Strategy for Europe and has already demonstrated several successes. The regulation came into force in January 2022 and will be mandatory for all EU members starting from January 2025.
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