Mitigating Risks in Early Access Programs: A Guide for Biotech Companies
Early Access Programs (EAPs) can offer a vital lifeline to patients suffering from life-threatening, long-lasting, or seriously debilitating illnesses, providing access to potentially life-saving drugs not yet licensed in their home countries. These programs extend hope to patients who are ineligible for clinical trials or need continued access post-trial, often being their only option in critical situations.
However, despite their significant benefits, launching an EAP comes with numerous risks that must be carefully mitigated. Before considering the launch of your program, it is essential to address potential adverse events, supply chain challenges, varying market guidelines across Europe and impacts on commercialization. Proactive planning and risk management are crucial to ensure the success and sustainability of an EAP.
The key risks and mitigation strategies
Adverse events
The most obvious risk an early access program can bring is the case of an adverse event, which could clearly jeopardize a future commercial launch.
Adverse event reporting is mandatory in all European markets. In most countries, liability rests with the treating physician, but in Germany, Sweden and Greece the manufacturer is responsible, while in France and the UK, authorities distinguish between quality and clinical use.
Therefore, it’s critical that before launching an EAP you ensure it is planned and delivered extremely carefully, particularly when it comes to being exacting over setting patient eligibility criteria.
Provide thorough training to all healthcare professionals involved in the EAP on proper use of the drug, its administration and adverse event reporting requirements. A pharmacovigilance system, including a patient registry, must be established, with all staff being made aware of how to properly adhere to the system in order to effectively collect, monitor, and analyze all safety data and adverse event reports in one place. Using emerging data that is easily accessible in the system will help you to continually assess the benefit-risk profile of the drug.
When rolling out an EAP, ensure all patients are well-informed about potential risks and the importance of reporting any adverse effects from the very start.
Supply chain issues
Early access programs often run in parallel to clinical trials, which has the potential to put both patient and product supply at risk. This tends to be a risk that can often be overlooked when launching an EAP.
In order to guarantee a secure supply of patients, you must establish mutually exclusive inclusion and exclusion criteria for both clinical trials and early access programs to ensure that the provision of unlicensed medicine is only considered after all viable treatment options are explored.
To help guarantee the supply of products, it’s crucial that any company planning on an EAP understands the level of unmet needs in their target markets and can project what future needs might look like with accurate forecasting. This includes agreeing on a definition of unmet need and deciding which types of patients and at what stage of disease progression the product should be offered.
There is no obligation on manufacturers to offer a product to any patient, but it can help to have this definition in place should a dispute arise. It’s also necessary to build an awareness of how suitable patients and treating clinicians will be identified and whether any access requests have previously been received.
Maintaining a safe stock of products could help to buffer against supply chain disruptions and ensure continuous availability of the drug for EAP participants, but may not always be possible.
Differing market guidelines across Europe
While the EMA can approve medication for use, each country in Europe is free to develop its own guidelines, regulations, and legislation, with many countries having developed their own national guidance around Compassionate Use Programs (CUPs). The complex European regulatory system for medicine, which includes specific regulations set in each country, needs to be understood by companies before launching an EAP there. For example, in the case of adverse event reporting it’s clear the regulations differ, as highlighted above.
One universal factor across all European countries is that unlicensed medicines can’t be promoted, so companies need to be very careful to demonstrate that any EAP is in response to an unsolicited request from clinicians.
To clearly provide evidence of an unsolicited request, it’s important that companies are transparent about strategic aims and why they want to run an EAP. Companies may want to run an EAP for reasons such as gathering more evidence of a product’s potential success or as part of an ethical strategy to improve access to orphan drugs.
EAPs often better reflect real-world use, as patients in these programs are more like the actual patients who will eventually use the drug. Through an EAP there’s the potential to gather a wealth of real-world data, particularly in Europe, which offers a diverse patient demographic, but this doesn’t necessarily lead directly to real-world evidence (RWE).
It’s important to decide what data needs to be captured and then understand how it will be used to develop RWE that can support the licensing and commercialization of the product. It can be helpful to appoint a specialist organization that can provide guidance and support on generating insight from data and ensure that all data capture and management meets the stringent European laws and regulations, such as the General Data Protection Regulation (GDPR).
Impacts on commercialization
It’s important that any organization thinking about launching an EAP also thinks ahead to its future commercial strategy.
Each stage of the product life cycle will need to be considered, including an understanding of whether any of the target territories require extended compassionate use support.
In some countries, it may be possible to charge a nominal fee for medications supplied through an NPP. However, this can set a precedent for future discussions around reimbursement and have an impact on product pricing in the longer term.
Patients, hospitals and national health insurance pick up the cost in most European countries, but in Austria, Greece and Spain they expect compassionate use products to be provided free of charge.
Healthcare financing in Europe is vastly different from that of the US, with most of Europe’s healthcare systems being state-funded. That said, real-world data from an EAP can be extremely valuable to supplement clinical trial data within a regulatory submission.
Similarly, poor patient adherence could lead to a misunderstanding of the product’s efficacy and impact on the success of commercialization. Patient expectations can also, understandably, be unrealistically high.
Additional costs need to be considered
EAPs can be extremely costly as most companies simply don’t have the internal expertise to run them. Therefore, many companies will turn to a specialist service provider to support the design and delivery of their EAP, particularly for guidance on generating insight from data and ensuring that all data captured and managed meets European laws and regulations and the regulations of the country itself. Even with additional support, running an EAP will likely tie up considerable internal resources.
For organizations that choose to engage with a third-party specialist to manage EAPs – which I would recommend – it’s still vitally important to understand who will be involved – internally and externally – and what the decision-making and governance processes will be. There may also be internal policies that will need amending or which are missing altogether, such as an early access policy.
Proactively addressing risks for a successful EAP launch
Ultimately, EAPs can be an attractive option for companies aiming to widen potentially lifesaving access to patients ineligible for a clinical trial or to continue access for those who have participated in a trial.
Patients suffering from rare diseases may gain access to much-needed treatments not yet licensed in their home countries through EAPs. Nevertheless, companies must be aware of how to navigate possible risks in EAPs to ensure a successful implementation.
Firstly, adverse events must be meticulously monitored and managed to protect patient safety and maintain the program’s integrity. Supply chain issues present another challenge, necessitating robust logistical planning to ensure consistent and reliable drug availability. Additionally, the complexity of market guidelines across Europe requires careful compliance to avoid regulatory issues.
Moreover, the impacts on commercialization and additional costs associated with EAPs must be thoroughly evaluated. These include not only direct expenses but also potential effects on market perception and future revenue streams.
With these factors in mind, I recommend companies proactively engage specialist service providers early in the discussion around EAPs. This approach can help organizations address the various risks and considerations, ensuring comprehensive planning and implementation. By doing so, companies can make informed decisions about whether an EAP is the right choice and how to address the associated challenges effectively.