Medicinal gasses - questions and answers
Must all the contents from cylinders returned by a user be destroyed?
In principle, a medicinal gas may not be dispensed to a user if the gas has previously been returned to the retailer by a different user.
However, the changes made in December 2007 to the Executive Order on Medicinal Gases have opened up for the possibility to redispense a gas which has been returned by a different user.
Gases may only be redispensed if:
- the gas is a mono-component gas,
- the gas has not exceeded its shelf life and the user can use it in time,
- the gas was originally dispensed to the user from the retailer or pharmacy it later was returned to,
- the gas also meets the current quality standards.
Cf. section 18(1) of the Executive Order on Medicinal Gases.
Section 18(2) stipulates that redispensing is also subject to the retailer and the pharmacist having a written procedure for receiving and redispensing the returned medicinal gases to ensure that the conditions in section 18(1) are met.
Retailers and pharmacies must keep documentation on receipt and redispensing of medicinal gases. The documentation must be available to the Danish Medicines Agency for five years.
The retailer and pharmacy must also ensure that returned medicinal gases are stored separately from other gases until the retailer and pharmacy have examined the gases and determined that the conditions in section 18(1) are met.
If a returned medicinal gas does not meet the conditions for redispensing, the retailer or pharmacy must destroy the gas safely. Alternatively, the gas can be returned to the manufacturer or distributor for destruction.
Is it legal to fill a cryogenic tank at a patient?
A company which has a retail authorisation is permitted to fill cryogenic tanks for home use at a user’s/patient’s home as well as at the company’s own address. However, under the condition that there is a filling procedure which a person is qualified to perform, and which ensures that there is absolutely no doubt of which batch that is in the user’s/patient’s tank.
The batch number is necessary in the event of withdrawal.
What are the requirements if a hospital is to take delivery of prescription-only medicinal gases?
The hospital department concerned must be authorised pursuant to section 39 of the Danish Medicines Act, or the associated hospital pharmacy (which by definition holds a section 39 authorisation) must take delivery of medicinal gases. Otherwise, a doctor must fill out an order form for each vessel of gas to a patient, or vessel to use in the hospital department.
When is a medicinal gas which is defined as a medicinal product required to be available only on prescription?
This is definitively assessed in connection with the assessment of a marketing authorisation application for the medicinal gas concerned.
In deciding which medicinal products are to be prescription-only, it is considered very carefully whether the medicinal products may present direct or indirect health risks. Even when taken in recommended doses without the supervision of a doctor, they present a direct or indirect health risk because they often and on a large scale are used incorrectly, contain substances or products which effects or side effects are necessary to monitor, or which need to be given parenterally (injected or the like).
If the gas is prescription only, it can only be dispensed to a user if a doctor, dentist or veterinarian has written a prescription for the gas and if the required information in the order form is available.
What is an order form?
An order form corresponds to a prescription or a requisition and must be provided if the medicinal gas (medicinal product) is a prescription-only medicine.
See sections 13 and 14 in the executive order on medicinal gases for information on details to be stated in the order form.
Who may sell medicinal gases to a patient/user?
Only companies with an authorisation for retail distribution or a pharmacy may sell directly to the user.
Who are considered 'users' in retail sale?
A user is a person/company/hospital department not authorised pursuant to section 39 of the Danish Medicines Act.
Pharmacies/hospital pharmacies have by definition an authorisation pursuant to section 39 of the Danish Medicines Act even though the authorisation does not exist on paper.
Do the same rules apply to hospitals as to the industry?
YES, the rules for industrial manufacturing of medicinal gases also apply to hospitals’ manufacturing. Hospitals which manufacture medicinal gases must therefore have an authorisation in accordance with section 39 of the Danish Medicines Act and meet the requirements in the appertaining executive orders including GMP, cf. executive order on the manufacture and import of medicinal products and intermediate products.
After receipt at the storage facility (tanks or cylinders), distribution of medicinal gases within the hospital will not be subject to the Danish Medicines Agency’s control.
Who is required to have an authorisation for retail sale of medicinal gases?
The company which physically handles medicinal gases for distribution to consumers/patients/hospital departments must have an authorisation for retail sale.
If a company (contract giver) has a contract with another company (contract acceptor) about being responsible for storage facilities, receipt and distribution of medicinal gases to users, the contract acceptor must have an authorisation for retail sale.
How is it ensured that the manufacturing and distribution chains of medicinal gases are authorised?
In wholesale, the sender/seller is responsible for ensuring that the receiver/buyer is authorised pursuant to section 39 of the Danish Medicines Act.
In retail sale, the user is not required to have an authorisation.
What requires authorisation after 31 December 2007?
Manufacture of medicinal gases requires a manufacturer’s authorisation (cf. section 39(1) or (2) of the Danish Medicines Act), be the gases manufactured in Denmark, the EU or a third country.
Distribution of medicinal gases requires a distributor’s authorisation (cf. section 39(1) of the Danish Medicines Act). A distributor may further distribute gases manufactured and released in another EU country.
Sale/storage of medicinal gases intended for sale/distribution directly to the consumer/patient requires an authorisation for retail sale (cf. section 4 of executive order no. 1318 of 27 November 2007 on medicinal gases).
How must medicinal gases be packaged?
Depending on the agreed delivery to the customer, medicinal gases can be contained in:
- Gas tankers/stationary cryogenic storage tanks
- Gas cylinders
- Transportable cryogenic tanks
May a manufacturer of medicinal products charge payment when a product is dispensed in accordance with a granted compassionate use permit for its use?
YES, because dispensing the product must not be free of charge.
Is it possible to apply for a compassionate use permit for a medicinal gas?
YES, it is possible to apply for a compassionate use permit pursuant to section 29 of the Danish Medicines Act, according to which, the Danish Medicines Agency can in certain cases and after application authorise sale or dispensing of medicinal products not covered by a marketing authorisation or not marketed in Denmark.
However, compassionate use permits can only be granted if the medicinal product concerned cannot be replaced by a medicinal product already available in Denmark, and if there are therapeutic grounds for choosing a medicinal product not marketed in Denmark.
When a compassionate use permit is granted, terms may be attached to the permit, and the Danish Medicines Agency can withdraw the permit if the stipulated terms are not met, or if severe side effects or serious problems arise relating to the quality, safety or efficacy of the medicinal product.
How will the Danish Medicines Agency assess a marketing authorisation application for a medicinal gas if the application is submitted via the mutual recognition procedure with a different reference member state than Denmark?
The Danish Medicines Agency will assess the application in the same way as any other MRP case. In connection with the granting of a marketing authorisation after ended procedure, a dispensing group for the medicinal gas concerned will be determined.
Will the Danish Medicines Agency collectively assess the marketing authorisation applications concerning the same medicinal gases to ensure that the products are not on the market with different dispensing groups?
Dispensing groups are generally determined in connection with the granting of a marketing authorisation for a medicinal product.
However, in December 2007, the Danish Medicines Agency assessed the submitted applications concerning medicinal gases to determine which dispensing groups the various medicinal gases should belong under. We did so to ensure the same assessment for identical products, which was also important to list the individual medicinal products in Medicine Prices (Medicinpriser).
Consequently, marketing authorisation applications submitted to the Danish Medicines Agency before 31 December 2007 were included in Medicine Prices on 1 January 2008 under the allocated dispensing group.
The Danish Medicines Agency will not necessarily perform a collective assessment, but regarding dispensing groups, later authorisations of medicinal gases will be placed in the same dispensing group as already authorised identical gases.
What is the assessment time for approval of an application for marketing authorisation?
For medicinal gases, see the Danish Medicines Agency’s website area about assessment times for handling applications for marketing authorisation. Read more about authorisation of medicinal products.
How are variations handled in terms of applications, e.g. if an authorised gas is added to a different holder?
Such variations must be applied for in accordance with the Variations Regulation. Whether an application is type IA, IB or II depends on the content and character of the variation. For more information, see the Variations Regulation no. 1234/2008 of 24 November 2008.
How is the shelf life of a medicinal gas determined?
Documentation on the medicinal gas' shelf life must be attached to the application for marketing authorisation for a medicinal gas. Both the gas and the holder will be included in the complete assessment of the shelf life. If the product is stable, it can receive a shelf life of up to five years.
How are devices for concentrating oxygen classified?
Portable devices designed to be at a patient’s bedside to concentrate oxygen are medical devices, and therefore not covered by the rules on medicinal gasses.
How are veterinary gases assessed?
The gases will be assessed as medicinal products in the same way as gases for human use.
Is a gas used for cryosurgery (e.g. in connection with wart removal and cellular changes) a medicinal product?
NO, because gases for this purpose cannot be ascribed a pharmacological effect.
However, the gas will be considered a medical device, and must therefore be CE marked.
Is laughing gas a medicinal product?
Laughing gas (nitrous oxide) will always be considered a medicinal product like all other anaesthesia gases, because it has a pharmacological effect.
Is oxygen a medicinal product?
YES, if the oxygen is used:
- to prevent or treat oxygen deficiency (hypoxia), e.g. in connection with anaesthesia, intensive therapy, resuscitation etc.
- for hyperbaric oxygen therapy e.g. in treatment of decompression sickness, smoke poisoning, gangrene, fractures, wound healing etc.
NO, if oxygen is e.g. used:
- by smoke-helmeted firemen or divers.
- for minimal access surgery (laparoscopic surgery).
- in oxygen bars at e.g. nightclubs.
Which gases are not medicinal products?
Gases which are used to sustain a condition are not considered medicinal gases, e.g. air to help severely injured persons in breathing, oxygen mixtures for smoke-helmeted firemen, and oxygen mixtures for divers during normal diving and ascent.
Gases marketed as medical devices, e.g. for minimal access surgery (laparoscopic surgery), cf. the European Commission’s guidelines MEDDEV 2. 1/3 rev. 2.
Gases used for calibration of devices used at hospitals etc.
Gases used as oxygen for welding, nitrogen for inert welding, food packaging, cooling of environmental chambers, etc.
When is a gas covered by the medicinal product definition and thereby a medicinal gas/medicinal product?
When the gas is either:
- claimed to be useful for prevention or treatment of disease, or
- the gas has a pharmacological, immunological or metabolic effect, or it is used to make a medical diagnosis.
Note that the two definitions are individual and comply with the interpretation of section 2 in the Danish Medicines Act.