Unlicensed Medicines Drug Development Stage and Manufacturer Types

Intuition suggests that a large pharmaceutical company and a small biotechnology firm would run access programs in very different ways, but in practice the stage a product has reached usually determines the available routes before the size of its manufacturer does.

Across the unlicensed medicines and managed access programs market, four development stages create demand: pre-approval medicines, post-approval and pre-launch medicines, market withdrawal alternatives and discontinued product supply programs.

A product that has not been authorised anywhere can only be supplied through compassionate use, expanded access or similar routes, which carry the strictest conditions. A product already authorised elsewhere has more options, including named patient supply and early access.

A product that has been authorised locally but not yet launched sits in a narrow window in which supply is controlled by the manufacturer's launch plan, and a product that has left the market sits in a different situation again, where hospitals are seeking continuity.

Each stage also defines the regulator's position. Before approval, the regulator is considering whether to allow supply of an investigational product, whereas after approval it is concerned with ensuring that supply outside the authorised channel is controlled and reported.

Manufacturer size still matters, but mainly for capacity. A large company may run the program with its own regulatory, medical affairs and logistics teams, while a smaller one has to decide which of these functions to build and which to buy from a provider.

The two factors interact. A small developer at the pre-approval stage faces the most constrained route and the fewest internal resources, which is why it is the profile most likely to seek an outside partner for its first program.

For hospitals and health systems, the development stage helps predict how long a product will be available through an access route, since pre-approval supply is expected to end at launch or a negative regulatory decision and withdrawal supply may continue for years.

This page describes market structure and categories of supplier only. It does not assess the effectiveness or safety of any medicine and it gives no clinical, prescribing or patient-eligibility guidance.

Pre-Approval Medicines

Pre-approval medicines are products that have not received marketing authorisation anywhere in the relevant region, or that are still in clinical development. Supply of these products outside a trial is the most closely controlled form of unlicensed access.

The usual routes are compassionate use and expanded access programs, and in some cases early access programs where the regulator has set up a framework for products with a pending application.

Manufacturer agreement is essential. Unlike a licensed product that a physician can seek from a distributor, a pre-approval product is available only if the developer decides to supply it, and that decision is shaped by development strategy, supply capacity and regulatory advice.

Sponsors weigh several considerations before opening a program. These include how supply of the product outside a trial may affect recruitment to ongoing studies, how much product can be spared from the development supply, and whether the regulatory conditions can be met in the countries concerned.

Manufacturing capacity is often the binding constraint. For products made in small batches, such as cell therapies and some biologics, the quantity available for a program may be limited to a small number of patients at any one time.

Safety reporting is a core obligation. The sponsor must collect and report adverse events from program patients and may use that information in its regulatory submissions, which makes pharmacovigilance capability a central requirement of any pre-approval program.

Documentation requirements are extensive. Each request typically requires a statement of need, confirmation that no authorised alternative is suitable, evidence of regulatory or ethics approval and import documentation where the product crosses a border.

Pre-approval programs are time-limited by nature. They end when the product is authorised and launched in the relevant country, when the sponsor discontinues development, or when a regulator withdraws permission, and good program design allows for each of these endings.

Post-Approval/Pre-Launch Medicines, Market Withdrawal Alternatives and Discontinued Product Supply Programs

Three further stages follow authorisation, and each creates a different kind of demand. Post-approval and pre-launch medicines are authorised products that are not yet commercially available in a particular country.

The interval between authorisation and commercial launch can be long. Pricing and reimbursement negotiations, supply chain preparation and distributor appointments all take time, and during that period hospitals may request product through named patient or early access routes.

Which product categories and therapeutic areas are involved depends on the pipeline and on where the product has been authorised, with oncology and rare disease therapies appearing frequently in the post-approval and pre-launch window.

Market withdrawal alternatives address a different need. When a licensed product leaves a market, whether for commercial or manufacturing reasons, hospitals that relied on it need either the same product from abroad or a suitable alternative, and they often use import routes to obtain either.

Discontinued product supply programs are the organised version of this response. A manufacturer, or a third party that has taken over a product, may continue to supply a medicine to patients who still need it after the product has formally been withdrawn from sale.

These programs can run for a long time. Because patients who remain on a discontinued product need continuity, a supply program may continue for years, which makes reliable manufacturing and storage important.

For third-party providers, withdrawal and discontinuation programs can be a steady source of work. Taking over supply of a legacy product requires regulatory knowledge, inventory management and the ability to maintain product quality documentation over a long period.

Pricing in these stages is typically agreed between the supplier and each buyer rather than set by a regulator, and arrangements vary by country, product and buyer type, which is one reason why the details are not reproduced in this overview.

Global, Specialty and Biotechnology Manufacturer Types

Manufacturers of unlicensed and managed access products fall into five types, and the first three are global pharmaceutical companies, specialty pharmaceutical companies and biotechnology companies.

Global pharmaceutical companies have the broadest portfolios and the largest internal teams. They commonly operate their own early access and managed access programs for major products and may appoint partners for specific countries or functions.

Their programs are usually integrated with global regulatory and medical affairs strategy. A decision to open a program is tied to the launch plan, and the program is managed alongside the commercial rollout of the product.

Specialty pharmaceutical companies focus on narrower therapeutic areas or product types. They often have deep expertise in particular fields but fewer geographic subsidiaries, and they may rely on partners to cover countries where they have no presence.

Biotechnology companies are typically smaller and development-focused. Many have a single product or a small pipeline, and a first access program may be their first experience of supplying patients outside a trial.

The make-or-buy choice differs by type. A global company may keep the program in-house for strategic products while outsourcing for smaller markets, while a biotechnology company more often outsources the whole operation to a provider with an established network.

Capacity to handle regulatory complexity also differs. Global companies maintain regulatory affairs teams in many countries, whereas smaller firms depend on consultants and service providers for country-specific submissions.

Each type also has a different relationship with hospitals. Large companies have established commercial relationships, specialty companies often know the key centres in their field, and biotechnology firms may be unknown to many of the hospitals that request their product.

Rare Disease and Cell and Gene Therapy Developers

The remaining two manufacturer types are rare disease developers and cell and gene therapy developers. They are the groups for which access programs are most closely tied to the business model.

Rare disease developers work on conditions with small patient populations spread across many countries. A product for such a condition may have only a few hundred or a few thousand patients worldwide, so supply through access programs is often the first, and sometimes the only, form of availability in many markets.

Because commercial launch in every country is rarely justified, these developers often plan long-running access programs in countries where they do not intend to seek authorisation, or where authorisation will come much later than in their main markets.

Many of these developers work with companies that specialise in rare disease access to run programs in countries where they have no regulatory or logistics presence of their own.

Cell and gene therapy developers face a related but more demanding situation. Their products are often complex to make, may be produced for individual patients and need specialised handling, so supply to a new country needs qualified centres and carefully controlled logistics.

Both groups tend to be small organisations by headcount, even where the products have significant development funding. They typically have limited commercial infrastructure and rely on partnerships for the operational side of access.

For these developers, access programs can also serve strategic purposes. They allow the company to build relationships with treatment centres and physicians ahead of launch and to gather practical experience of how the product will be supplied commercially.

The demand from these groups is a main reason for growth in outsourced access program management, because the combination of small organisations, complex products and many countries is difficult to handle without external capability.