A Veterinary Managed Access Program (VMAP) is an umbrella term used to describe a regulated framework that allows eligible approved patients with serious or life-threatening diseases or conditions who cannot participate in clinical trials, have no available or satisfactory alternative treatment options in their country access to unapproved, unlicensed or commercially unavailable drugs or biologic treatments in their country. Diseases or conditions that are not treated and may become serious, or life-threatening fall into this framework.

VMAPs encompass several types of country specific regulated access routes that often include:

• Compassionate Use Programs (CUP): Allows patients who have exhausted all available [HM2.1]treatment options for individual or groups of patients*

• Named Patient Programs (NPP): Provide access to treatment options for individual patients

• Emergency Access: Allows patient access to an unapproved, unlicensed or commercially unavailable drugs or biologic product when needed immediately for a serious or life-threatening disease or condition

• Expanded Access Programs (EAP): Expanded Access Programs (EAPs)—often called compassionate use, early access, or pre-approval access are formal programs often protocol driven for individual or groups of patients

* Regulated access terminology and requirements is defined by country (refer to the list of definitions

Eligibility typically includes:

• Inability to enroll in an ongoing clinical trial (e.g., due to geographic limitations or not meeting trial criteria).

• Patients with serious or life-threatening diseases or conditions who have no available or satisfactory alternative treatment options in their country

• No comparable or satisfactory alternative treatment options

• The potential benefits of treatment must outweigh the risks, as determined by the veterinarian.

• The treatment is typically in active clinical development or under review for marketing authorization.

The process varies by country, but generally:

• A qualified veterinarian requests access on behalf of the patient.

• The request includes details about the treatment, patient, patient’s medical, treatment history and justification.

• A formal request is submitted to the relevant Health Authority for approval to access or to import an unlicensed treatment

VMAPs are governed by strict regulatory and ethical guidelines to ensure patient safety:

• Access must not impede clinical trial enrolment or compromise ongoing clinical trials.

• The decision to provide access is primarily based on the veterinarian’s justification of potential benefit patients will receive from treatment.

• Data collection (if required) is not a prerequisite for access but may be used to understand real-world outcomes.

• Compliance with local regulations is critical.

Key differences include:

• Purpose: VMAPs focus on providing treatment, not research, though some data collection may occur. Clinical trials aim to generate efficacy and safety data.

• Inclusion Criteria: VMAPs often have less stringent inclusion/exclusion criteria compared to clinical trials.

• Recruitment: Recruitment in VMAPs are passive, while clinical trials have active recruitment.

• Regulatory Oversight: VMAPs follow specific regulatory pathways for unapproved medicines, while clinical trials follow strict protocols for research.

The variety of names (e.g., Compassionate Use, Expanded Access, Named Patient, etc.) reflects differences in national regulations and processes. Each country has its own legal framework, and terms are often used interchangeably in practice, though they may have distinct meanings. For example, in the US, “Expanded Access” is a formal FDA term, while in Europe, “Early Access” or “Compassionate Use” may apply. Harmonization efforts are ongoing but challenging due to diverse regulatory systems.

Yes, real-world data (RWD) collected from MAPs can provide insights into treatment use outside of clinical trials in diverse patient populations. While not a primary source, such data may support clinical trial data in regulatory decisions, especially for rare diseases or one-time therapies. Companies like Novartis have developed guidance for prospective data collection at product resupply to assess patient benefits, though this is not mandatory for access.

• For Patients: VMAPs provide early access to potentially life-saving treatments when no other options exist, offering hope and potential therapeutic benefits.

• For Sponsors:

1. VMAPs provide veterinarians experience with a new treatment

2. Build relationships with veterinarians and regulators

3. Enhance launch preparedness

4. Provide real-world data to support full approval of a conditionally approved drug or biologic and may inform further development

5. Fulfill country-specific ethical obligations for continued treatment of patients in need.

Challenges include:

• Regulatory Variability: Differing national regulations create complexity, especially in Europe, where each country has its own framework.

• Logistical Issues: Managing supply chains, labeling, and administration of complex drugs or biologics (e.g., cell therapies) can be difficult.

• Administrative Burden: Initiating and managing MAPs requires significant resources and coordination.

• Ethical Dilemmas: Sponsors must balance providing access with ensuring clinical trial completion required to support regulatory approval.

MAPs are typically temporary and end once a medicine receives regulatory approval and is commercially available in a country. Patients may then transition to sustainable local access pathways (e.g., commercial availability or reimbursement programs) as per local regulations.

• United States: The FDA oversees Expanded Access Programs, which include individual and cohort access, with strict protocols. Compassionate Use is an informal term.

• Europe: The EMA provides the regulatory framework, but each Member State implements its own laws.

• Other Regions: Requirements vary, with some countries allowing only drugs and biologics having received at least one approval in another country (e.g. US or other countries with similar stringent regulatory processes) or mandating continued access post-clinical trial.

Processes and timelines vary by country and regulatory route used.

Veterinarians are responsible for collecting and reporting adverse events according to country specific regulations and/or program requirements. At the time of ordering, veterinarians are required to sign a declaration acknowledging that they will follow the applicable reporting requirements in their country and notify the manufacturer using the information provided on the respective adverse event reporting form or as instructed for a specific program.