Off-label use

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 29.10.2020

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Extension of the areas of application of a finished medicinal product without marketing authorisation in the procedure according to § 135 para. 1 SGB V.

General information
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  • It takes years from the first screening to the official approval of a new drug. In between are substance isolation, optimization, preclinical toxicology and phase I-IV clinical trials. Pharmaceutical companies are only able to offer the drug for application on patients once it has successfully undergone an approval procedure. The German Drug Law (AMG) and European guidelines regulate how and who checks the quality, safety and efficacy of drugs prior to their general application. High development costs, limited patent duration (15 years) and different market potentials lead to the fact that approval is preferably sought for large sales markets and widespread indications. For cost reasons, the manufacturer does not carry out an approval procedure for every possible indication. In addition, the inclusion of a new indication requires a complete new marketing authorisation under the German Medicines Act, which must be applied for by the manufacturer. For cost reasons, the manufacturer does not apply for marketing authorisation for every possible indication. A marketing authorisation covers, among other things, indication (disease, stage), dose, mode of administration, use in mono- or combination therapies and patient material.
  • The German Medicines Act does not prevent the physician from using a drug outside of the approval (off-label). The physician must therefore orient himself or herself to current professional standards. However, it is not clear who is liable for off-label use and who pays for it.

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  • The health insurance company is not obliged to provide benefits in the case of off-label use because neither the efficacy nor any risks have been tested for a new area of application according to the German Medicines Act (AMG). On the other hand, there is an obvious necessity in everyday medical practice to use drugs even when they are not covered by a marketing authorisation. In such cases, drug law does not contain a general prohibition of use for finished drugs outside the area of application defined by the marketing authorisation. Essential and proven effective therapies cannot be withheld from the patient. Therefore, an obligation of the health insurance funds to provide benefits in the case of off-label use should be considered under very strict conditions: it is a serious, i.e. life-threatening disease or a disease that permanently and permanently impairs the quality of life, for which no other therapy is available and for which there is a justified prospect that a successful treatment (curative or palliative) can be achieved with the preparation in question.
    • The latter is fulfilled if the extension of the marketing authorization has already been applied for and the results of a controlled phase III clinical trial (compared to standard or placebo) have been published and prove a clinically relevant efficacy or clinically relevant benefit with acceptable risks, or if findings obtained outside of a marketing authorization procedure have been published which permit reliable, scientifically verifiable statements about the quality and efficacy of the drug in the new area of application and on the basis of which there is consensus in the relevant professional circles about an anticipated benefit in the aforementioned sense.
    • If the above-mentioned prerequisites are met, the prescription of a drug according to § 15 Para. 1 of the Federal Master Contract Physicians/Replacement Funds is the sole responsibility of the SHI-accredited physician.
  • The liability of a manufacturer for a drug according to § 84 ff. AMG is not limited to the use for approved indications, but is based on "intended use". This also includes off-label prescriptions, provided that they are recommended, for example, in guidelines and the manufacturer does not expressly object to this. Otherwise, the physician is liable for off-label prescriptions that may lead to unforeseeable side effects. Patient education and good documentation are therefore essential for off-label prescriptions.
  • The use of off-label prescriptions for rare diseases ( orphan diseases) is legally particularly problematic.

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  1. Brunne V, Mertins G, Reimann G, Brockmeyer NH (2004) Off-label use in dermatological practice. The conflict between professional duty and legal requirements. dermatologist 55: 727-734
  2. Francke R, Hart D (2003) Off label use: Drug law, liability law, professional law and social law issues. Social jurisdiction 50: 653-664

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Orphan diseases;


Last updated on: 29.10.2020