Navigating Global Pathways: Regulatory Approaches to Importing Unlicensed Medicines

Navigating Global Pathways: Regulatory Approaches to Importing Unlicensed Medicines

Introduction

In an increasingly interconnected world, the demand for timely access to innovative therapies has never been greater. Yet, for patients with rare diseases, life-threatening conditions, or unmet medical needs, approved treatment options may be limited—or entirely unavailable—in their home countries. In such cases, importing unlicensed medicines becomes a critical lifeline, offering hope where conventional regulatory pathways fall short.

The importation of unlicensed medicines is governed by a complex web of national regulations, ethical considerations, and logistical challenges. While the overarching goal remains consistent—ensuring patient safety and product quality—each jurisdiction takes a distinct approach to balancing access with oversight. From named patient programs in the UK and compassionate use schemes in the EU, to FDA expanded access provisions in the US and special access routes in Canada and Australia, the global landscape is as diverse as the patients it serves.

This article explores some of the regulatory frameworks that enable the legal importation of unlicensed medicines across key markets – from flexible to rigid frameworks, from low to high income countries. It examines the nuances of each system, highlights common challenges, similarities and divergence, and offers strategic insights for navigating these pathways effectively. Whether you're a regulatory affairs professional, a clinician, or a stakeholder in global health access, understanding these mechanisms is essential to bridging the gap between innovation and patient care.

EU:

France

France has arguably the most structured and comprehensive framework for access to unlicensed medicines, financed through social insurance, covering pre-marketing, post-marketing and pre-reimbursement phases. However there are still gaps remaining, as there is a strict eligibility criteria for products to be considered for unlicensed access in France, and these frameworks do not include post-trial access. Couple this with the mandatory collection of real-world data (RWD) and administrative complexity with protocols often required, and access can be delayed for patients.

• Early Access Authorisation (AAP) – grants access to “innovative” medicines before market approval, provided manufacturers commit to seeking authorisation.
• Compassionate Access (AAC) – permits HCPs to request unlicensed treatments for their individual patients.
• Direct Access – an experimental system to provide patients faster access to medicines recognised as “improving the patient treatment” but which are not eligible for early access post-marketing authorisation (AAP), which has restrictive criteria.

Italy

Italy has a well-structured framework for accessing unlicensed medicines, offering multiple pathways balancing patient needs with regulatory oversight. The Italian legislation covers all access gaps to maximise patient access for those with an unmet medical need. Despite reports of bureaucratic delays, AIFA’s turnaround on Compassionate Use submissions is consistently 15 calendar days, and USMAF’s customs clearance piece with the ‘nulla osta sanitario’ takes approximately 5 days. However, there are labelling requirements which can hold things up at program launch.

• Ministerial Decree 2017 – Allows compassionate use of unlicensed medicines, whether globally unlicensed, off-label or authorized abroad, for patients who lack other treatment options or are rolling out of a trial. The Sponsor must apply to AIFA in order to get the Compassionate Use Program launched first, and only then can Healthcare Professionals (HCPs) obtain the product through this mechanism. AIFA have 15 calendar days to raise a question or objection to the notification, after which this is a tacit approval. The product should be over-labelled in Italian with the additional phrase, “solo per uso compassionevole” included.
• Ministerial Decree 1997 – Governs supply of another country’s commercial pack, for an unmet medical need, permitting access to medicines licensed in other countries but unavailable in Italy. HCPs request MoH / customs approval to import.
• Law 648/1996 – Enables NHS-funded access to unlicensed medicines if no valid therapeutic alternative exists, covering medicines authorised abroad, in clinical trials, or used off-label. Only Italian HCPs can request a product be included on the 648 List.

Germany

Germany’s approach to unlicensed medicines import is very much aligned with EU standards, but it is rather a strict framework. The Medicines Act (Arzneimittelgesetz, AMG) does permit named patient access and cohort access.

Compassionate use program / Härtefallprogrammen is a protocolised cohort mechanism that allows compassionate use of unlicensed medicines for patients who lack other treatment options. If a product is globally unlicensed, this is the only pathway to allow access into Germany. However, the product must be in continued development or going through the Marketing Authorisation process somewhere. Sponsors must submit a compassionate use dossier to BfArM / PEI, which includes a protocol, informed consent forms, quality  documentation, application forms, and so on, to be submitted to BfArM (Bundesinstitut für Arzneimittel und Medizinprodukte) or the Paul-Ehrlich-Institut / PEI for biological products, ahead of the program launch, and the Sponsor must have an EU/EEA based representative. BfArM / PEI  will confirm within a period of 2 weeks from receipt whether the application is in accordance with the regulations and therefore valid. The Agency may request further information which would result in a clock stop. An additional 2 week Agency review is required following RFI response submission.

• Named patient import is permitted under Article 73.3 of the AMG, but BfArM / PEI do not take any responsibility for named patient supplies, this is the sole responsibility for the local HCP. The product must be in its original commercial livery from its country of origin, therefore globally unlicensed / clinical packs are not appropriate for named patient supply.

Once a product is  licensed in Germany, there is no further regulatory mechanism to allow for off-label post-trial supply, therefore a local commercial pack must be supplied or the trial must continue.

LATAM:

Brazil

Brazil’s system is considered fairly patient-centric for personal imports, as patients have the right to bring a lawsuit to the Brazilian government to gain access to an unlicensed product. But this can bring significant costs to patients and can be lengthy. However, in contrast to many low-and middle-income countries, Brazil has well established legal pathways overseen by its regulatory authority, ANVISA.

There are in fact several regulatory mechanisms through which to supply unlicensed medicinal products into Brazil as follows:

• Compassionate Use / Humanitarian Use programme (Uso compassivo) – this is a named patient import pathway, that a Healthcare Professional initiates. This is permitted for globally unlicensed medicines and medicines that have obtained a licence elsewhere, but is not appropriate for post-trial access or off-label use.
• Expanded Access Programme (Programa de Acesso Expandido) – this is a cohort mechanism, that requires the Sponsor Company or their local legal representative to make an up-front submission to ANVISA with a protocol for a predefined group of patients.
• Post-Study Supply Program (Fornecimento do Medicamento Pos Estudo) – as outlined above, this is a specially designed access pathway for patients who have participated in a clinical trial.
• Named Patient Access (NPA) / Personal Use – alluded to above, this is arguably the most empowering mechanism for patients, permitted under the Brazilian Constitution where a patient or their legal representative can apply under the patient’s right to gain access to an unlicensed medicine for an unmet medical need based on a physician’s prescription.

Brazil are also considered somewhat of the vanguard for post-trial access to patients continuing to derive clinical benefit after a trial concludes, as they released the pathway “Fornecimento do Medicamento Pos Estudo”, i.e. Post-Study Supply Program.

And whilst this is good news for patient access, the legislation dictates that once a clinical trial has concluded in Brazil, the product must be guaranteed for continuous free of charge access to patients who derived clinical benefit in the trial and continue to do so. This potentially means indefinite free of charge supply from the Sponsor to patients with a serious chronic condition, even if the product becomes licensed and commercially available and reimbursed in Brazil.

Therefore,  Sponsor Companies need to consider such obligations and implications when planning a clinical trial in Latin America, as other LATAM countries are following suit with such mandatory continued free access, e.g. Chile.

Argentina

A strong comparator to Brazil is Argentina, in that they have similarly structured but distinct regulatory approaches, and are also following suit when it comes to post-trial access obligations. Argentina is also arguably more flexible in emergencies than Brazil but the public sector access is decentralised via the Ministry of Health and provinces, as opposed to a national approach in Brazil.

Both Brazil and Argentina are among the most regulated LATAM markets, with other countries such as Peru, Colombia, and Chile following similar named patient regulatory pathways, but not as defined or rigid.

Like Brazil, Argentina has several regulatory mechanisms through which to supply unlicensed medicinal products, as  follows:

• Compassionate use -Régimen de Acceso de Excepción a Medicamentos no registrados, RAEM-NR (Regimen for Access to Non-registered Medicines by Exception) – this is a named patient import mechanism initiated by a Healthcare Professional. Globally unlicensed medicines cannot be supplied through this pathway, which restricts access to medicines that have obtained a licence somewhere in the world.
• Expanded Access Program (Programas de Acceso Expandido, PAE) – this is a cohort mechanism and is the appropriate route to import globally unlicensed medicinal products into Argentina. This route requires an up-front regulatory submission including a protocol, for a predefined group of patients and the product should be over-labelled. These steps add a level of regulatory complexity and additional time to set this up.
• Import of Medication/treatment and materials for post-study access – like Brazil, Argentina have carved out a specific route for patients who have participated in a clinical trial. The Sponsor Company should submit a protocolised application to ANMAT / DERM to set this up, approvals can take up to 6 weeks to obtain.

JAPAC:

China

China enforces strict controls on the importation of unlicensed medicines, and does not allow much access from outside of China, therefore remaining one of the most restrictive markets for unlicensed medicine importation. There are limited legal pathways and high enforcement .

For the majority of China, the option for NMPA to grant import authorisation for a patient with an unmet medical need has conditions that are not being met with the majority of MAPs experienced, such as:

• The legal source of drugs for hospitals is only from NMPA-qualified drug manufacturers in China.
• Hospitals are not permitted to import on a named patient basis by other providers.
• Drug must be approved in the country of origin.

However, there are some exceptions to this rule with the introduction of “pilot zones” or “free trade zones”, the first of which was introduced in Hainan BoAo Lecheng region, off of mainland China.

China has now established 5 pilot zones:

• Hainan BoAo Lecheng
• Guangdong-Hong Kong-Macao Greater Bay Area
• Shanghai Lingang
• Tianjin
• Beijing

Each pilot zone does work slightly differently, but they all require a commercial pack from somewhere in the world, therefore it cannot be for a globally unlicensed product or clinical pack presentation, which causes limitations.

Furthermore, patients tend to have to stay in the pilot zone where they obtained treatment, as it is not always possible to travel with the unlicensed treatment around China.

Operational fees such as the pilot zone government fee and local distributor fees are fairly high, so it’s a fairly expensive option for patients, on top of the travel / accommodation in the pilot zone if they are not already located there.

Australia

One of the most flexible systems in the JAPAC region, Australia allows for unmet medical needs to be addressed via their Special Access Scheme (SAS).

The TGA caters for several different scenarios for patients with unmet medical needs.

The SAS has 3 categories:

Category A: Life-threatening conditions requiring immediate treatment and requires a retrospective notification from the HCP to the TGA up to 28 days after the treatment begins.

Category B: Non-life-threatening but medically necessary and must be approved for import by the TGA.

Category C: Pre-approved medicines for specific indications with streamlined notification and must be approved for import by the TGA.

There is a further mechanism, known as the Authorised Prescriber Scheme which enables medical practitioners to prescribe unapproved medicines to specific patient groups, and also requires TGA approval and ethics committee endorsement.

India

Classed as a lower-middle income country, India has a clear framework in place known as Import of Unlicensed Medicines for Personal Use.

India recently updated its import regulations for unlicensed medicines to enhance compliance, safety, and quality control.

Amongst other changes that this update brought about, any new or unapproved products imported into India must comply with New Drugs and Clinical Trials Rules 2019, as well as the Drugs and Cosmetics Act 1940 and the Drugs Rules 1945. This means that for access to a globally unlicensed product, this falls under clinical trial regulations, hence it is not handled by an unlicensed access mechanism, instead pushing this kind of access through a trial, and if no trial is running in India, there is little hope for Indian patients to gain access to such a product until it has received its first approval globally.

Applications for import for personal use require a lot of information and documentation, some of which needs to be locally notarised, which can cause delays in patient treatment.

Conclusion

As healthcare systems strive to meet the evolving needs of patients, the importation of unlicensed medicines remains a vital—yet complex—mechanism for delivering timely treatment. While regulatory pathways differ across jurisdictions, they share a common purpose: to provide access to potentially life-saving therapies when no approved alternatives exist.

Navigating these pathways demands more than regulatory knowledge; it requires strategic foresight, ethical sensitivity, and cross-functional collaboration. Regulatory professionals play a pivotal role in ensuring that unlicensed medicines are supplied compliantly and with full transparency. Good planning, based on full understanding of the regulations, ensures that patients will get the product they desperately need without unnecessary delays

In an era of accelerated innovation and global health challenges, harmonising regulatory approaches and fostering international dialogue will be key to improving access while safeguarding public health. By understanding and respecting the nuances of each system, stakeholders can better serve patients, uphold regulatory integrity, and contribute to a more responsive and equitable healthcare ecosystem.

If you have any questions, please reach out to Regulatory@clinigengroup.com