Non-Registered Products

Conditions for compassionate and emergency treatments in Israel

On 5 November 2006, the director general of the Israeli Ministry of Health (MoH) issued a guideline setting out the conditions for the specific use of medicinal products in cases of compassionate treatment and emergency treatment in a medical institution. The guideline includes definitions, the details relating to approval of these types of medicinal products and the reporting requirements. The provisions of this guideline also apply (with the appropriate changes) to the use of non-registered medical devices and instruments.

Definitions

The guideline defines “compassionate treatment” as treatment with a medicinal product, which is not registered in any country, administered to a patient suffering from a serious disease or a disease that may cause a significant disability. Such a treatment cannot be adequately undertaken with a medicinal product registered and approved for marketing in Israel, or in any other country, and it cannot be included in the framework of a clinical trial. A compassionate treatment requires prior approval by the MoH.

The term “emergency treatment” is defined as treatment with a medicinal product not registered in any country, administered to a patient exposed to an immediate hazard to his life, or an immediate risk for loss, or irreversible disability, of an organ. Such a treatment cannot be adequately undertaken with a medicinal product registered and approved for marketing in Israel or in any other country, and due to the urgent need, there is not enough time to obtain approval thereof from the MoH.

The “Drug Committee” is an internal committee appointed by the director of the medical institution, to review and recommend the medicinal products to be used in the institution.

Compassionate Treatment

The approval is granted subject to compliance with the following conditions:

· the treatment complies with the aforementioned definition of “compassionate treatment”;

· when, in the opinion of the treating physician, the benefit of the treatment outweighs the risk inherent therein;

· the application refers to an individual treatment (generally speaking, a treatment in the framework of a clinical trial is preferred to a compassionate treatment);

· the responsibility for the treatment lies with the treating physician and with the director of the medical institution in which the treatment is provided, despite the approval granted by the MoH for such treatment;

· the treatment was approved by the chairman of the institutional Helsinki Committee, the chairman of the Drug Committee, the director of the pharmaceutical services, and the medical director of the institution;

· the medicinal product should be available to the patient throughout the treatment, as determined by the treating physician; and

· the treating physician is committed to follow up the treatment and report on the outcome, including adverse reactions, to the MoH.

The medical institution shall submit the application for the treatment to the Pharmaceutical Administration of the MoH, on the special form intended for such purpose, signed by the treating physician, the chairman of the Helsinki Committee, the chairman of the drug committee, the director of the pharmaceutical services, and the medical director of the institution.

The following should be added to the application form:

· the medical history of the patient, the diagnosis, the state of the disease, and the reactions to previous treatments;

· the follow-up and checking of the effect of the use of the medicinal product including the adverse reactions observed;

· the informed consent form of the patient or his/her representative; and

· the existing scientific literature supporting the treatment.

Emergency Treatment

The approval is granted subject to compliance with the following conditions:

· the treatment complies with the aforementioned definition of “emergency treatment”;

· when, in the opinion of the treating physician, the benefit of the treatment outweighs the risk inherent therein;

· the responsibility for the treatment lies with the treating physician and with the director of the medical institution in which the treatment is provided;

· due to the urgency, the treatment was approved, at least, by the chairman of the Helsinki Committee and the medical director of the institution;

· the medicinal product should be available to the patient throughout the treatment, as determined by the treating physician; and

· the treating physician is committed to follow up the treatment and report on the outcome, including adverse reactions, to the MoH.

The medical institution shall report on an emergency treatment, to the Pharmaceutical Administration, within three working days from the start of the treatment. The report shall include the following:

· the medical history of the patient, the diagnosis, the state of the disease, and the reactions to previous treatments;

· details of the treatment and reasons for it;

· the follow-up and checking of the effect of the use of the medicinal product including the adverse reactions observed;

· the informed consent form of the patient or his/her representative, if feasible;

· the approval of the chairman of the Helsinki Committee, the chairman of the Drug Committee, the director of the pharmaceutical services, and the medical director of the institution; and

· the existing scientific literature supporting the treatment.

Reporting and other requirements

Following finalisation of the compassionate or emergency treatment, a report must be submitted by the medical institution to the Pharmaceutical Administration on the results of the treatment, its efficacy and the adverse reactions observed.

Note: In the event that the director of the medical institution realises that the medicinal product, used according to this guideline, may endanger the health of patients, he is entitled to forbid its importation, marketing and use thereof, as appropriate.

Background

According to Article 47A(b) of the Pharmacists' Ordinance (New Version) - 1981, a person shall not manufacture, market or provide instructions for the use of a medicinal product unless such product has been duly registered and in accordance with the licence terms and with the provisions of the aforementioned ordinance.

Exemption, however, has been granted, as per Article 29 of the Pharmacists' Regulations (Products) - 1986 and all subsequent amendments to date concerning the use of medicinal products imported into, or manufactured in Israel, which are not listed in the National Drug Register^1,2.

In April 1988, the MoH issued a guideline setting out the conditions and the procedure required for the approval for use of a non-registered medicinal product in a medical institution, subject to Article 29³.

ISAAC SETTON

References

1. The Regulatory Affairs Journal, 2001, 12(1), 22

2. The Regulatory Affairs Journal, 2002, 13(2), 139

3. The Regulatory Affairs Journal, 1988, 9(8), 557-560

Disclaimer: All parts appearing in this publication, which constitute a translation from the official Hebrew version of the relevant circular issued by the Ministry of Health in November 2006, are unofficial, non-binding translations. The only valid and binding text is the official Hebrew version.