Three Routes to Pre-Licensing Access: Compassionate Use, NPP and Off-Label Use

For innovative medicines whose Turkish entry is delayed in global launch sequences, pre-licensing access routes are strategically vital for both patients and companies. There is a direct line between a patient hearing "not available in our country" and a company's launch-sequencing decision; the mechanisms that fill the gap are instruments with legal boundaries that demand careful management. This article compares the three core mechanisms in Turkish practice — compassionate (early) use, named-patient programmes (NPP) and off-label use — and builds the strategic frame from the company's perspective.

The frame: why does "pre-licensing access" exist as a problem?

Global companies build launch sequences around commercial potential, regulatory readiness and supply planning. Türkiye, owing to its FX and pricing dynamics, may not feature in the first wave for some products; yet the disease burden and clinical need can be urgent. The state's responsibility, under Law No. 1262, is to secure patients' access to medicines; the company's responsibility is to consciously design under which status and conditions its product reaches Turkish patients. The three mechanisms are that design toolbox.

1. The compassionate (early) access programme

Run under TİTCK regulations, the programme applies to patients with serious or acute, life-threatening diseases who have failed — or cannot be treated with — licensed products and standard therapies in Türkiye, and who cannot be enrolled in regulated clinical trials. The core logic: a medicine not licensed in Türkiye, but licensed abroad or in development, is supplied free of charge for humanitarian reasons by the developing/supplying company.

Critical steps in the programme's operation: the physician's written assumption of responsibility for enrolling the patient, notification of patients to the Agency, and monitored import and distribution processes. From the company's perspective the programme means two things. First, goodwill supply and experience: real-world data and clinical experience accumulate in small patient groups and can feed the future licensing and reimbursement files. Second, a status that must not mix with commerce: the programme rests on free supply; confusing it with commercial expectations creates both legal and reputational risk. Application processes, patient-file compliance and reporting duties require defined internal ownership (typically medical affairs).

2. Named-patient programmes (NPP)

NPP is the mechanism by which products not licensed in Türkiye but approved by major regulators (FDA, EMA, etc.) are imported and supplied for specific patients, by physician prescription. It differs from compassionate use in that the product is approved and the supply runs through a more structured, company-managed process. The critical point is that the alternative reimbursement framework can also apply to NPP products: a payment construction is possible even before licensing; through a negotiated agreement with the Institution, the company can secure coverage of supply costs.

NPP's value for companies operates on three levels: (1) market learning — data on the Turkish patient pool, physician profile and treatment practice; (2) a launch bridge — clinical relationships and patient records built during NPP prepare fast post-launch penetration; (3) evidence generation — real-world data feeds the local-evidence section of the future reimbursement file. In return, the operational load is real: import procedures, patient-level tracking, pharmacovigilance reporting and Agency notifications must run regularly.

3. Off-label use

The SUT can bring off-label use into reimbursement coverage (Annex-2/C) under defined conditions; oncology is where the practice concentrates. The mechanism: use of a licensed medicine outside its licensed indication can be reimbursed conditional on scientific justification and Institution approval. List entry involves the opinion of the relevant medical discipline, literature support and file evaluation.

The strategic caution for companies is the mechanism's position. Off-label use can give patients access to a product in an indication that is not yet licensed there; but it must not substitute for licensed use. When off-label supply starts to look like "cheap access" that pre-empts a licensing application, the company's long-term market access and pricing dynamics suffer; the sound approach is to define off-label use as a transition-period tool run in parallel with the licensing process. A second caution is promotion law: promoting off-label use means communication outside the approved indication and, under the Turkish Promotion Regulation, cannot be directed at physicians, dentists or SMMs (Satış Mesul Müdürleri — responsible sales managers).

Comparing the three mechanisms

The bridge from early access to licensing: data continuity

The strategic value of the chosen route lies in the continuity of the data it produces. Patient data collected during compassionate use and NPP should be structured so it can serve the local-evidence section of the post-licensing reimbursement file: patient follow-up forms, progression records, resource use and adverse-event data become the inputs of future model adaptation. Because the early-access period feels "temporary", data discipline loosens; yet one of the strongest pages of a reimbursement file is "your product's real-world experience in Turkish patients" — and that experience begins during early access.

The global-company perspective: putting Türkiye higher in the sequence

The existence of early-access mechanisms is an argument that improves Türkiye's position in global launch sequencing. The scenario to present to headquarters: "Structured access is possible in Türkiye even pre-licensing (NPP + alternative payment); early entry produces patient-level data and accelerates post-launch penetration." The argument carries only if the local team operates the mechanisms correctly and can present the resulting data to headquarters. Otherwise Türkiye remains stuck in the profile of "entered late, recovered slowly".

The ethics and accountability frame

The most sensitive area in early-access programmes is the distribution of responsibility. The physician's written assumption of responsibility, the company's supply and notification duties, the Agency's supervisory role and the patient's informed consent — the four actors' roles must be clarified in writing. Pharmacovigilance obligations run regardless of product status; adverse-event reports, distribution records and patient tracking should be retained as evidence that may be requested in inspection scenarios.

Company strategy: the sequencing frame

1. Map patient need: quantify the Turkish patient pool, unmet need and current treatment gaps.
2. Sequence the mechanisms: compassionate use, NPP or accelerated licensing? Compare each on cost, data, liability and time.
3. Design the licensing bridge: run the chosen route with a data-collection plan that produces inputs for the future licensing and reimbursement files.
4. Payment construction: test the applicability of the alternative reimbursement framework to NPP with the Institution early.
5. Compliance architecture: consolidate notifications, records and pharmacovigilance under single ownership; teach the team the boundaries of promotion law.

The decision tree: which mechanism fits which product?

Selection among the three mechanisms can run on a four-question tree. Q1: Is the product approved by major regulators? If no (in development), the only option is compassionate use. If yes, proceed. Q2: Is a Turkish licensing filing planned, and when? If within 12 months, consider accelerated licensing with an NPP bridge instead of compassionate use; with a distant horizon, NPP becomes the primary mechanism. Q3: Is the patient population defined and traceable? A defined, registrable population (reference centres, patient registries) is the precondition for NPP and future outcomes-based payment; a scattered, undefined population makes NPP operationally heavy. Q4: Is a payment construction with the payer possible? Where budget impact is high, combining NPP with the alternative reimbursement framework strengthens access. The tree's output is an access route map: which mechanism, when, for which patient group, under which payment construction — and what data each step will produce for the licensing dossier.

Comparing the operational load

In selection, operational load — not cost — is decisive. In compassionate use the load is intense but steady: few patients, heavy documentation, periodic notification. In NPP the load is continuous: per-patient import procedures, customs-regulatory cycles, patient tracking, pharmacovigilance and stock management — beyond ~50 patients these processes demand systems, not email traffic. In off-label use the load sits with the payer: list-entry dossier, scientific justification and diagnosis/year-based reporting; the company tracks usage data and guards ethical boundaries. These differences require a choice that accounts for team capacity and existing systems: the right mechanism is the one you can operate.

Compliance risks: three critical areas

1. Promotion boundaries: during early access the product is unlicensed or off-label; promotion to HCPs is prohibited. The line between medical information and promotion must be protected by written procedures and a content-approval chain.
2. Pharmacovigilance continuity: adverse-event reporting is independent of product status; in compassionate-use and NPP processes the reporting chain (physician → company → agency) must be defined upfront, with lot-level distribution records.
3. Data use and consent: for early-access data to serve future files, patient consent must be broad and explicit from the start; consent texts should be designed together with KVKK/GDPR and ethics-committee requirements.

A scenario: the first year of an NPP programme

Imagine a global company deciding on NPP for an approved product unlicensed in Türkiye for a rare disease. Q1: agency notifications, import procedures, protocols with 3-4 reference centres, design of patient consent and follow-up forms. Q2: first patient entries; activation of the registry backbone (minimum data set: diagnosis, baseline, response, resource use); pharmacovigilance training. Q3: data-quality control; the first interim report to headquarters — "X patients in Türkiye, Y response profile" — the first local evidence for the launch file. Q4: the payer conversation under the alternative payment framework; the precursor data package for the licensing filing. In one year the programme produces not merely product supply but the backbone of the post-licensing file — that is precisely what makes early access strategic.

A glossary: the language of early access

The field's terminology invites confusion; the core distinctions: Compassionate use: free supply of an unlicensed product; applied under different legal frames in the EU and Türkiye with the same logic. Named-patient programme (NPP): named-patient supply of an approved product; a non-commercial, prescription-based process. Expanded access: broad access programmes outside clinical trials; in US practice, a close relative of compassionate use. Early access programme: the umbrella of institutional pre-licensing access; content varies by country (France's early-access schemes are an example). Off-label: use of a licensed product outside the approved indication; can be linked to reimbursement. Access: the product's physical availability — a process concept distinct from availability. Diagnostic odyssey: the journey to diagnosis; the clinical counterpart of the early-access agenda. Registry: structured follow-up producing data from the early-access period. Clarifying this glossary within teams prevents misunderstandings in communication with agencies and centres — confusing compassionate use and NPP in internal reporting, in particular, raises compliance risk for hybrid programmes.

The cost accounting of early access: visible and invisible

The cost picture of early-access decisions reads in three layers. Visible cost: product cost in free-supply programmes; supply, logistics and import processes in NPP; and in both, pharmacovigilance and registry infrastructure investment. Semi-visible cost: team time — the effort regulatory, medical and market access teams devote to programme management, growing linearly with patient numbers. Invisible cost/benefit: opportunity cost (the same effort redirected to the licensing dossier) versus the local data generated, centre relationships and payer familiarity. Decision analysis prices the three together: with few patients, free supply's visible cost is low and data value high; with larger populations, NPP's operational cost is sustainable only when a payment construction exists. The right question is not "should we do early access" but "in which model, at what scale, with which data objective".

The ethical frame: between patient benefit and evidence generation

Three foci organise the ethics of early-access programmes. First, selection fairness: who enters the programme? Criteria (disease severity, absence of alternatives, exclusion from trials) must be written in advance and their application documented; selection left to physician or company discretion creates legal and ethical risk alike. Second, the quality of consent: the patient must receive an intelligible account of the "experimental/approved but unlicensed in Türkiye" status, known and unknown risks, and data use; consent is a process of understanding, not a signature. Third, expectation management: early access is no guarantee of cure; managing the burden of hope in families is part of the programme's field leg. In well-designed programmes these three foci are worked through with ethics committees and disease associations. A programme with a strong ethical frame is also the most defensible programme before the payer.

Step by step: establishing an NPP programme

Construction proceeds in ten steps. Step 1 — Portfolio and patient-need analysis: which product, which indication, estimated patient count, current treatment gap. Step 2 — Global approval and resourcing: headquarters' programme approval, product allocation, budget. Step 3 — Local legal-frame check: import procedures, Agency notification duties, ethics-committee requirements. Step 4 — Centre network: protocols with 2-5 reference centres; patient intake and follow-up rules. Step 5 — Process documents: physician application form, patient consent text, supply and distribution records, pharmacovigilance procedure. Step 6 — Systems: patient-registry infrastructure (minimum data set), stock and logistics tracking. Step 7 — Training: programme procedures and reporting chain for centre physicians and nurses. Step 8 — Pilot: process rehearsal with the first 5-10 patients; removing bottlenecks. Step 9 — Scaling: planned growth of centres and patients; regular data-quality control. Step 10 — Exit/licensing bridge: the programme's transformation with the licensing filing — structuring the data into the file. These ten steps show NPP is not a supply transaction but an evidence and access programme.

The minimum data set: what to collect during early access?

An early-access period run without data is wasted; the minimum set has four blocks. Block 1 — Patient definition: age, sex, diagnosis and age at diagnosis, genetic/mutation information where available, prior therapies. Block 2 — Baseline measurements: disease-severity indicators (disease-specific scores), functional status, comorbidities. Block 3 — Treatment and response: administration schedule, dose changes, response assessments (at protocol-defined times), adverse events. Block 4 — Resource use: hospitalisations, outpatient visits, laboratory/imaging, medications — the cost inputs of future model adaptation. Three design rules: few but consistent fields (forms must stay fillable), measurement times fixed by protocol (response data must stay comparable), and KVKK-compliant consent covering data use. Data collected under these rules becomes, at programme's end, not an "activity report" but the product's first local evidence file in Türkiye.

Sources and key takeaways

Core sources: TİTCK arrangements (compassionate early-access programme, import procedures); the SUT (off-label annexes); the Alternative Reimbursement Regulation (NPP payment); Law No. 1262. Recommended monitoring: TİTCK announcements (programme procedure), SGK lists (Annex-2/C movements), NGO agendas (patient-need signals). Our key takeaways: (1) the three mechanisms are branches of one decision tree, selected by product status and population; (2) NPP combined with the alternative-payment framework enables pre-licensing payment; (3) minimum-data-set collection during early access becomes the launch file's first local evidence; (4) build the compliance triangle (promotion boundary, pharmacovigilance, consent) upfront; (5) the early-access strategy is itself the argument that moves Türkiye up the global launch sequence.

Conclusion

The three routes of pre-licensing access offer different balances of speed, cost, data and control; the right choice must fit the product's clinical urgency, company resources and Türkiye strategy. From early-access analysis and publication support to NPP construction, from strategic sequencing to the post-licensing reimbursement bridge, we stand with you through our Reimbursement Application service. For a detailed assessment, reach out.