“Compassionate use” is usually included in the respective national medicinal-products act. In Europe, the European Medicines Agency (EMA) provides recommendations through the Committee for Medicinal Products for Human Use (CHMP), but these do not create a legal framework. CUP are coordinated and implemented by Member States, which set their own rules and procedures (Article 83 of Regulation (EC) No 726/2004).
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Is granted for a group of (unnamed) patients
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Life-threatening, long-lasting, or severely debilitating conditions that cannot be satisfactorily treated with any currently approved drug
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Realistic probability of therapeutic benefit
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Patients should always be considered for inclusion in clinical trials before being offered CUP.
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Prior approval from the competent authority (e.g., EMA, FDA) is required. Medicinal product is included in an official list of currently running indicated-hardship programs.
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Already in a centralized marketing-authorization procedure or under clinical investigation (e.g., Germany: at least phase II clinical trial; USA: phase I clinical trial; Switzerland: no trial required).
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Product is manufactured according to the principles and guidelines of GMP.
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Inclusion and exclusion criteria must be stated, single patient or small-group use.
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Provided free of charge for use in patients in some countries.
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“Individual treatment trials” are ethically based on Article 37 of the Helsinki Declaration: “In the treatment of an individual patient, where proven interventions do not exist or other known interventions have been ineffective, the physician, after seeking expert advice, with informed consent from the patient or a legally authorized representative, may use an unproven intervention if in the physician’s judgement it offers hope of saving life, re-establishing health or alleviating suffering. This intervention should subsequently be made the object of research, designed to evaluate its safety and efficacy. In all cases, new information must be recorded and, where appropriate, made publicly available.” *
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Therapeutic trial always relates only to a specific/individual patient “Named Patient Use”
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Within the scope of the physician’s freedom of therapy, with the consent of the patient
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Life-threatening, long-lasting, or severely debilitating conditions that cannot be satisfactorily treated with any currently approved drug.
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No approval is required.
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Under the direct responsibility of the physician.
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Significantly higher standard of care in the physician’s approach (risk–benefit ratio, education).
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Case-by-case decision.
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Healing the individual patient is priority.
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No gain of knowledge in the sense of a research study.
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Drug/active ingredient, therapy plan, dosage, occurrence of undesirable effects and the general course of treatment are described in detail.
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In European law, notion of a magistral preparation (compounded-prescription-drug product in the US) is defined as “any medicinal product prepared in a pharmacy in accordance with a medical prescription for an individual patient” (Article 3 of Directive 2001/83 and Article 6 quarter). Today, there are no formal guidelines regarding the clinical use (e.g., medical indications, formulations, and posology) of magistral phage drugs.
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Pragmatic way to personalize patient treatments to specific needs and to make medications available that do not exist commercially.
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For a given individual, named patient, according to a prescription by a physician.
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Following the technical and scientific standards of the pharmaceutical art.
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APIs of magistral preparations must meet the requirements of the European Pharmacopoeia or of the national Pharmacopoeia. The relevant properties and qualities of the API should be defined in an internal monograph (prepared by the supplier).
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A certified laboratory performs external quality testing to evaluate the properties and quality of the API.
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For phage activity and bacterial-susceptibility testing, a “phagogram” is performed
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The phage API is then submitted to the hospital pharmacy for incorporation into magistral formulations.
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Magistral formulations should be delivered under the direct responsibility of a physician.
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