Key Considerations for Operationalizing an Expanded Access Program

While the COVID-19 pandemic brought many clinical trials around the world to a halt, it also spurred novel ways of reaching patients as the pharmaceutical industry pivoted quickly to re-think their clinical operations strategies. Advances in electronic consent, remote monitoring, telehealth, and direct-to-patient shipments are breaking down barriers to clinical trials, while also redefining the potential of the expanded access program.

Even before the pandemic put expanded access (and terms like compassionate use) in the spotlight, various legislative changes and patient-centric approaches have been accelerating support for the increased use of the expanded access program (EAP). Given the current momentum and the growing insights into how expanded access provides strategic value within drug development, it’s critical to understand what components are needed to successfully operationalize an expanded access program.

These components differ in certain areas from the traditional drug development process and bring various regulatory and operational complexities. Without the right knowledge, resources, processes, and tools, clinical and medical teams can be caught off guard by the specificities within an EAP.

Strategic Considerations for Expanded Access

Here are 10 key factors to consider (and how myTomorrows can help).

1. Why launch an Expanded Access Program?

Traditionally companies have utilized expanded access (EA) on the home stretch of commercial approval to bridge the gap between regulatory approval and commercialization. However, more companies have begun installing these programs earlier in development.

Companies that are developing targeted therapies with smaller clinical trials have been increasingly aware that EA programs may potentially be critical for patients with rare tumors, and diseases, as well as for patients who have exhausted standard treatments. The role of the expanded access program has become more strategic, involving clinical development and other company objectives simultaneously.

Engaging with an EA service provider that provides specific guidance and consultancy can help alleviate challenges, create more alignment, and ultimately develop a sound strategy to build a successful expanded access program.

2. Plan ahead and determine objectives

The first step is to determine the objectives and scope of the expanded access program. Establishing a structured, collaborative, and transparent process is needed to discuss market and product assumptions, as well as to assess clinical evidence and value drivers.

This strategy is heavily often dependent on the regulatory trajectory ahead. Although there are a lot of variables, it is key to align with various strategic internal stakeholders to capitalize on the opportunity an EAP can offer a pharmaceutical company.

If an EAP will be running in parallel with clinical trials, it is important to define the scope of the indication for the EAP and clearly specify inclusion and exclusion criteria. An EAP may be more inclusive than a clinical trial and may offer an opportunity for patients to access the drug who might be eligible for a clinical trial.

Several questions should be considered in advance:

• Will there be sufficient drug supply to support requests?
• How many patients may be involved?
• How frequently will requests from patients be received?
• Which geographic locations will be included?
• Will drugs be provided free of charge?

Moreover, it is important to determine whether a collection of Real-World Data could support some of the regulatory and payor objectives. This needs to be designed in a way that ensures the reliability and validity of this “observational” data.

myTomorrows has helped many leading pharmaceutical companies design successful EAPs, ranging from guidance on implementation and operational considerations to Real-World Data consultancy projects.

3. Physician engagement

A challenge of an expanded access program is the time and effort required of the treating physician. Physicians must be willing to be actively involved in the EA process and be willing to spend uncompensated time seeking access to an investigational drug.

Physicians are often hesitant to use an expanded access program because of the perceived time burden and complexity of helping a patient identify treatment options. Recognizing this, companies should adopt a physician-centric approach.

Physician-centric imperatives:

1. Capture requests on an unsolicited basis, preferably via a platform
2. Provide site management and support to alleviate burden (guidance throughout the process)
3. Install pragmatic safety and data collection mechanisms (if applicable)
4. Assist with providing ready-to-use templates and documentation for regulatory purposes

myTomorrows has an in-house team of medical doctors, patient navigators, and site managers that supports physicians, including helping with regulatory requirements to alleviate administrative burdens. The team helps create a physician information package and provides product training and educational sessions to ensure that the treating physician has access to all relevant information regarding the investigational drug.

4. Regulatory Pathways for Expanded Access

Though general EA guidelines are similar across the globe, each country has its own regulatory procedure/guidelines. Understanding and staying on top of country-specific requirements takes a lot of resources. Based on expected patient numbers, availability of trial sites, and other country-specific criteria, companies should decide whether they will develop single-patient or group access mechanisms.

It is valuable to have an EA service provider to assist with navigating the regulatory landscape, executing an EAP, and helping with the documentation required to get health authority approvals. It’s also useful to get guidance on additional data and regulatory requirements because companies may potentially cover these gaps proactively through a smartly structured expanded access program with real-world data collection.

At myTomorrows, each member of our regulatory team comes from the pharmaceutical industry and has specific global expertise in conducting EA programs and in-depth knowledge of drug development, as well as regulatory pathways and submissions.

5. Determine how an EAP fits your clinical development

Clinical trials are designed to collect the necessary safety and efficacy data needed for regulatory approval. An EAP may potentially supplement the clinical trial objectives as long as it does not deter or compete with clinical trial enrollment in any way. An expanded access program can thus work in parallel with clinical trials, addressing the needs of patients who are not eligible for a clinical trial.

Most companies do not have the resources to launch a trial in every country where patients reside. Launching an EAP can help facilitate access for those not living near a trial site and those potentially too sick to travel or in cases where trial sites do not welcome patients from other countries. Companies can also benefit by learning from patient groups that don’t meet the strict inclusion and exclusion, offering ways to incorporate additional data to potentially support labeling.

In addition, some patients who have participated in clinical trials may request access to an investigational drug for continued treatment (Post-Trial Access) after the trial ends. Lastly, companies need to consider how an expanded access program may provide a solution to the gap between regulatory approval and commercial launch.

6. Drug supply, labeling, and packaging requirements

An expanded access program presents unique packaging challenges as it is designed to provide patients with investigational drugs that aren’t commercially available. EAP orders and batches may be very small and may be infrequent or unpredictable. As such, requests are often time-sensitive, and distribution logistics can be complex. In addition, manual activities such as relabeling or repackaging, may be needed to fulfill requests from clinical inventory (surplus).

Pharmaceutical companies should make sure there is enough drug supply available to meet the demand from both clinical trials and EA programs.

Packaging and labeling requirements can vary by country, so companies must meet country-specific packaging/labeling, documentation, and distribution and importation requirements.

Packaging for EAP combines features from both clinical and commercial packaging. These needs are often infrequent, can be complex, may involve the use of manual assembly, and must often support patient compliance.

In close coordination with the pharmaceutical company, myTomorrows offers strategic advice on (re)labeling and (re)packaging services and guidance to adhere to country-specific requirements. As myTomorrows works in line with the compliance-driven GMP (Good Manufacturing Practices) standards, this enables us to deliver and meet the highest industry standards, as well as deal with case-specific and emergency cases.

7. Availability of internal resources

It is important to determine the clinical development priorities for the internal Medical Affairs, Clinical, Regulatory, Quality, Pharmacovigilance, Supply, and Legal resources. They need to be aligned on the value, challenges, and solutions down the road. A key consideration is whether the company is able to set up, handle, and manage EA requests diligently. Is there general awareness of the benefits within a company for expanded access, or is there limited flexibility beyond the clinical research mindset?

Having the right regulatory and operational expertise available in-house is essential to program success, and the lack thereof is an important indicator that a clinical research-focused organization may need the support of an external service provider.

Partnering with the right EA service provider pulls the best practices and experience, whilst supporting EA specificities needed to launch and deliver the strategic program goals. myTomorrows offers companies a way to outsource EAP management — reducing the need for staffing or infrastructure and tapping into in-depth expertise for this niche area within drug development.

8. Patient support

Seeking an investigational drug through EA is a time-consuming and complex undertaking for a patient who is seriously ill and already has faced substantial medical challenges. A considerable burden also falls on physicians who are faced with their patients’ questions about such drugs and how to navigate the process of accessing them.

myTomorrows supports patients (and their physicians) with a unique model. Our team of Patient Navigators, who have medical backgrounds and are supervised by our physicians, support patients every step of the way — from searching for pre-approval treatment options to explaining how eligibility criteria work. Our Patient Navigators — who are fluent in seven languages — are skilled communicators who specialize in efficiently and effectively explaining complicated medical concepts to patients.

Our Treatment Search and our patient portal make it easy for patients to search for clinical trials and upload their medical records for our team to review to verify their eligibility for clinical trials.

This model can be tailored to support pharmaceutical companies that are lightly staffed at the medical affairs level or have other clinical development priorities. Designing an optimal process that meets the needs of both the patients and the pharmaceutical company provides an effective EA solution.

9. Meeting reporting requirements

Companies need to be aware of the local reporting obligations when supplying an investigational drug under an expanded access program.

EA service providers should facilitate the collection and processing of safety events as needed for regulatory requirements. In addition, industry-standard aggregated safety reports such as Periodic Safety Update Reports (PSUR) and Development Safety Update Reports (DSUR) need to be submitted as part of your EAP. In some cases, these reports can be combined with reports that are produced for your clinical trials or marketing authorizations, but this does require time and resources. Since physicians are not paid to report safety events, assistance is always welcome to increase the quality of safety data.

Regulators understand the context of the safety events and have been increasingly vocal in assuaging companies’ fears that adverse events could negatively affect regulatory approvals. myTomorrows has extensive expertise in helping companies with adverse event reporting.

In addition, myTomorrows can help write program summaries, including patients treated, indications treated, physicians who requested the drugs, and a supply overview. The program summaries are typically more relevant to cohort programs. Each service provider should be able to quickly produce such data, especially in unforeseen matters (e.g., a product recall).

10. Expanded Access Awareness

Making treating physicians and their patients aware of the availability of an expanded access program can enhance its success.

The 21st Century Cures Act was passed in 2016 in response to patients and their physicians voicing frustration about the cumbersome process of requesting investigational new drugs. This law requires companies to make their EAPs publicly available upon either the initiation of a phase 2/3 trial or after the drug has received breakthrough or fast-track designation (whichever occurs first).

Companies should think about developing a solid EA policy that shares criteria that will be used to evaluate requests and explain how and when companies intend to respond.

A compliant awareness strategy should go beyond publishing a press release or a listing on trial registries. In addition, compliant disease awareness programs can help educate patients and inform them of all treatment options.

Conclusion

In recent years, the industry has acknowledged the increased company, physician, and patient needs and requirements for establishing an effective expanded access program. This has resulted in a shift from supply-only focused solutions to more “comprehensive approaches” that can support both clinical development and medical governance objectives.

Understanding the patient’s needs and allowing for the right amount of physician-centricity may offer an improved uptake and quality of an overall expanded access program, especially when data collection and other insights need to be gained to position the value of these programs more strategically.

EA management is at the core of myTomorrows. We combine this expertise with an industry-leading platform for physicians, patients, and BioPharma. This offers increased compliance, traceability and workflow solutions that address key pain points within the management of these complex programs.

myTomorrows HCP portal is now part of the myTomorrows platform. Take a look at the services and features of myTomorrows for Healthcare Professionals.