Any medicinal gas with a pharmacological effect, as stated in Article 1 of the Medicines Act, and classified as a medicinal product in accordance with Article 1 of Directive 2001/83 (65/65) EC must be authorised before they are allowed on the market.
The product to be authorised should always meet the definition stated in Article 1 of the Dutch Medicines Act, specifically: “Any substance (gas) or any mixture of substances (mixture of gases) intended to be administered, used for or presented in any way as appropriate for:
- curing or preventing disease, deficiencies, wounds or pain in humans
- making medical diagnoses in humans, or
- restoring, improving or otherwise modifying physiological functions in humans by exerting a pharmacological, immunological or metabolic effect.”
Evaluation criteria medicinal gas dossier
The MEB uses two European Directives in its assessment of the chemical-pharmaceutical dossier for applications for medicinal gases:
- EMA Note for guidance on medicinal gases, pharmaceutical documentation, CPMP/QWP/1719/00
- Manufacture of Medicinal Gases; Annex 6; European Commision guide to GMP
In addition, the MEB and the marketing authorisation holders have agreements in place on core SmPCs and core labelling texts.
Final product to be authorised
A Qualified Person (QP) assigned by the manufacturer/marketing authorisation holder should at any time be able to guarantee the quality of the gas. This applies to both:
- gases supplied in final containers ready to for use by patients and to
- gases delivered and stored at third parties (care facilities and homecare companies) in storage tanks
In all cases, the delivered product must be subject to a release procedure.
Transfer of released bulk gases into a storage tank at a care facility or medical homecare company may only occur if this process has been validated as intended in GMP guideline Annex 6.
Dossier requirements relating to distribution
The delivery of bulk gases in mobile delivery tanks or stationary storage tanks to care institutions or medical homecare companies should be described in detail in the authorisation dossier and falls fully under the manufacturer’s responsibility. Documentation should be available demonstrating that there will be no mixing between the bulk gas in question and any gases originating from other manufacturers in the storage tanks intended for the bulk gas. The authorisation dossier should also state who the owners are of such storage tanks and who is responsible for the soundness of these tanks.
Subsequent distribution or dispensing of medicinal gases by third parties constitutes no part of the dossier to be assessed and authorised by the MEB.
Dossier requirements relating to the use of medicinal gases
The assessment of the risk/efficacy ratio and the authorisation as a medicinal product focus on the product’s (recommended) use. It is very important that this use is accurately described.
If the medicinal gas does not have pharmacological action, but only delivers a mechanical or a physical effect, the gas is considered a medical device. Examples of such gases are gases used for insufflation of the abdominal wall, liquid nitrogen for wart removal, aerosol delivery using an air-jet nebuliser, and so on. Such uses do not form part of an authorisation dossier.
The Note for guidance on medicinal gases addresses homecare containers. The MEB interprets the "homecare containers" listed herein as:
"packages filled by the patient themselves or by a homecare company intended for use by patients in an extramural environment."
This filling process cannot fall under the responsibility of the manufacturer and therefore, authorisation of such homecare containers is not possible.
Authorisation as a medicinal product is also not possible for homecare containers with a generator/concentrator. Gases administered to patients from these containers are not produced by a pharmaceutical manufacturer. After all, this gas is concentrated in the homecare container from atmospheric air at the home of the patient.
The above-mentioned policy was established on 23 December 2009.
In consultation with the Health and Youth Care Inspectorate (IGJ), it is decided that (starting 1 October 2010) manufacturers of medicinal gases, especially medicinal gas supplied in bulk to care institutions and facilitatory companies, must have submitted an application dossier to the MEB.