Managed access - Ex-US, understanding the regulations and key operational considerations

Managed Access Programs (MAPs) enable mechanisms for patients with unmet medical needs to get access to new medications outside of the clinical trial setting and well before marketing authorization and reimbursement in a patient's country. Also referred to as Expanded Access Programs and Early Access Programs, these programs are not limited to the USA; most countries around the world will have a defined approval process for a treating physician to apply for access to an unlicensed medicine. The challenge is that regulations, guidelines, and terminology will vary considerably from country to country, making it difficult to navigate and understand what is available and what is not. While the terminology can play a significant role in confusion, the good news is that the regulatory route usually falls into one of two available mechanisms: either a single patient by patient basis or, in some countries, a group or cohort of patients. The regulatory mechanism will be driven by whether the medicine is globally unlicensed or licensed in at least one market. The regulatory assessment and feasibility will be critical components of the initial planning phase of a MAP.

This article will explore the opportunities outside of the USA, how regulations by country can impact access strategies and other critical operational considerations.

What are the main opportunities/benefits for Pharmaceutical and Biotech companies?

• Expand global reach and meet the needs of patients suffering from serious life-threatening diseases who may not be able to access the product through a clinical trial or because it is not commercially available and reimbursed in their country
• Bridge the gap between approval and commercial availability/reimbursement delays
• Ensure a controlled and compliant supply chain and mitigate the risk of parallel importation
• Support the experience and education requirements for early adopter KOLs
• Leverage the MAP to collect real-world insight/evidence outside of the clinical trial
• Establish positive relationships with patient advocacy groups
• Use of medication via a MAP can increase HCP knowledge and experience of the product, which can impact the speed of uptake for suitable patients post commercial launch

Regulatory impact:

Most countries around the world have identified an approval process to allow for access to an unapproved medication to treat an unmet medical need, where no suitable alternatives are available. Clinigen has facilitated access and is familiar with the regulatory mechanism in over 130 countries. The regulations can be complex, as each country will have independent guidelines for how they will allow access or which route is available based on the licensed status of the medicine. Some countries may have more than one route available or a more defined process for access than others.

It's essential to first understand the two mechanisms available for access:

Single/Named Patient or a Group Cohort. Most countries will only offer the Single/Named Patient mechanism, while others will also offer a group approach. Within the countries that do offer the group approach, a handful will require this mechanism to be used for a product that is globally unlicensed but may have an alternative route of access for a product with a commercial launch somewhere.

(See Table 1 providing an overview of both approaches)

Assessing the regulatory routes and strategy early in the planning phase is a critical first step. Group/Cohort mechanisms generally have longer timelines for set-up, including protocol development, labelling, additional reporting for pharmacovigilance and local representation. A pharmaceutical company may also have a preference on the regulatory route based on their launch strategy in a particular country. France, for example.

In July of 2021, France released new guidelines for access to unlicensed medicines, which replaced the historical ATU mechanisms. While the objectives of the new regulation rework were to provide more consistency, simplicity and clarity, the guidelines are complex and require careful consideration and planning.

(See Table 2 for routes available – AC, AP1/AP2)

Consideration factors when including France in a MAP:

• The medicine must be compliant with the eligibility requirements (see Table 3)
• You can open access in France ahead of FDA and EMA approval under the Compassionate Access (AC) route or AP1 (if the intention is to file marketing authorization)
• AP2 dossier will be required after EMA approval to enable new patients to be enrolled in the MAP and the benefit of a temporary reimbursement until the official approval of the reimbursement dossier. In an AP2, as the product is already approved within the EU, the application is focused on a market access application and a collection of RWD
• AP1 and AP2 routes will have additional administrative requirements and longer timelines (i.e.: labelling, dossier preparation and submission, data collection and mandatory representation by a French exploitant Company)

Selecting the country scope for a Manages Access Program is a big decision for a pharmaceutical company, especially a company that is new to implementing these types of programs. Planning early and assessing the regulatory environment for countries in consideration is essential. It will help identify where an access route might not be available, where there may be a required mechanism with longer timelines and more administrative tasks, or where multiple mechanisms may be available, and decisions may dovetail with commercialization strategies. In all cases, the pharmaceutical company will have the control to select the countries entering into the program and when they will do so.

Other key operational considerations for Ex-US

• Defining the patient population and eligibility criteria
• Process flow for order management and medical review (if required)
• Preparation of protocol, submissions and timelines (for Group Cohort mechanisms)
• Ongoing communication with healthcare agencies
• Import permit support for requesting HCP (Single patient mechanism)
• Data collection requirements (required for French AP1/AP2 routes)
• Product presentation, labelling, qualified person certification and release (where applicable)
• Supply chain and logistics: restrictions in stock availability (e.g. In France, an AP2 approval will likely require a 'Shortage Management Plan'), frequency of shipments, import, wholesaler and VAT requirements in the country.
• Free of Charge (FOC) or Charged for supply
• If charged for, decision on price to be charged and if any rebate schemes exist In the identified countries
• Communication and training

MAPs - An integral part of every product strategy

Managed Access Programs enable patients to get access to a medicine they desperately need when it is not available through clinical trial or commercial channels. Demand for access can come from all over the world, and most countries will have a defined mechanism and regulatory route for importation. Planning early and considering a MAP as an integral part of a company's clinical and commercial development strategy could yield multiple long-term benefits.

Global Leader in Managed Access

Clinigen work with pharma companies to design and implement Managed Access Programs that meet the objectives of their clients and provide vital medicines to help treat patients. Our flexible approach and industry-leading experience mean that clients get the right solution – and patients get the right treatment. Having managed over 350 programs across 120+ countries, each new MAP receives the attention it deserves, regardless of company size or geography. Our global team of experts and local affiliates allows us to always stay up to date on changes in country-specific regulations, such as in France, giving our clients the most knowledgeable service possible.

We understand that country-specific regulations are complex, rapidly changing and can impact access strategies for your medicines. Contact us at contactMA@clinigengroup.com today to discuss how we can support your project.

Table 1 (27th of June 2022)

Table 2 (27th of June 2022)

Table 3 (27th of June 2022)

Author

Toni Williams is Business Development Director at Clinigen.

toni.williams@clinigengroup.com