Table 1 Implementation of NPPs in the Netherlands, Belgium and France

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National legislation

Article 3.17 of the Dutch Regulation concerning Medicines Act (Regeling Geneesmiddelenwet)

Article 6 quarter §1, 1° of the law on medicinal products of 25/03/1964, revised on 01.05.2006 and its Royal Decree dated 14/12/2006 (Art. 102 and 105).

Article L.5121-12 a of the French Public Health Code

Jurisdiction

Health Care Inspectorate (IGZ)

FAMHP (Federal Agency for Medicines and Health Products)

ANSM (French National Agency for Medicines and Health Products Safety; under the supervision of the Ministry of Health).

Legal entities that can apply for an NPP

-Manufacturers

The licence-holder as defined in Art 74 of the Royal Decree dated 14/12/2006.

Request of the prescribing physician submitted to ANSM by a pharmacist at the healthcare institution.

-Wholesalers

-Pharmacists

-Dispensing general practitioners

The applicant must be domiciled or have a registered office in the Netherlands.

Application

Application must be accompanied by documents to enable assessment of safety, therapeutic rationale and (non-) substitutability of the product. The first application must be accompanied by a declaration signed by the prescribing medical doctor in which the doctor agrees to be fully responsible and to accept the risks of prescribing an unlicensed medicinal product.

Authorisation for importation, distribution and delivery of unauthorised medicinal products is obtained through an unsolicited request (medical statement) from a healthcare professional for use in a particular patient. The initiation and conduct of the treatment falls under the full responsibility of the treating physician.

A ‘nominative’ ATU is issued for a named patient, and upon the request and responsibility of the prescribing physician. The request form is accompanied by a prescription, the patient’s clinical history and a justification for using the drug, and is submitted by the hospital pharmacist. ANSM must authorise the ATU for each patient and reserves the right to modify or discontinue the ATU at any time.

Entity that can supply the drug

Manufacturers , wholesalers, pharmacists, dispensing general practitioners

The licence-holder as defined in Art 74 of the Royal Decree dated 14/12/2006 at the request of a pharmacist based on a prescription for a properly defined patient.

Only hospital pharmacists may supply the medicinal product subject to an ATU.

Pharmacovigilance

Entity demanding pharmacovigilance

The Inspectorate

The Belgian Centre for Pharmacovigilance for medicines for Human use (BCPH), which is part of the FAMHP.

ANSM

Patient follow-up and data collection

The Inspectorate asks suppliers to report annually the number of patients treated with the specified unregistered product

Unspecified

ANSM requires a medicinal product dossier beforehand from the pharmaceutical company in order to establish a predefined protocol for therapeutic use (PTU), specifying the conditions for use, patient follow-up and the collection of efficacy and safety data.

Reporting adverse events

Adverse reactions suspected to be related to the medicinal product must be reported to the Inspectorate by the treating physician (specified in the doctor’s declaration)

Adverse reactions suspected to be related to the medicinal product must be reported to BCPH by the treating physician (specified in the doctor’s declaration).

Any physician, pharmacist, dentist or midwife observing a serious or unexpected adverse reaction that could be due to the medicinal product with an ATU should notify the regional pharmacovigilance centre (CRPV) to which the reporter is geographically linked with or the addressee indicated in the PTU, which in turn conveys the information to ANSM.

Who gathers pharmacovigilance data

A manufacturer, wholesaler or pharmacist who has been granted permission to supply an unregistered product is required to record all reported side effects (Art 3.17), which should be reported to the Inspectorate

The Belgian Centre for Pharmacovigilance for medicines for Human use (BCPH) is responsible for the coordination of various tasks related to pharmacovigilance. No further details (website page under construction)

As defined in the PTU, although mostly Regional Pharmacovigilance Centres (CRPV) collect and assess the information and transmit it to ANSM. The ATU may be suspended or withdrawn by the Director General of ANSM for public health reasons.