Nitrogen

Drug? Device? Industrial?

It is sometimes confusing how to determine if nitrogen is a drug, device or industrial product. Let’s consider several case studies for nitrogen applications:

Drug Manufacturing Operations   Medical Drug
Gaseous and liquid nitrogen is often used in pharmaceutical companies to provide purges for piping and reactor vessels. Even if there are no chemical reactions between the drug and the nitrogen, this nitrogen clearly has contact with the drug and/or the process. Nitrogen in this case must be medical. The nitrogen in this case is classified as a drug: Nitrogen, NF.

Purges in Hospital Piping for Maintenance   Medical Drug
Maintenance personnel and piping contractors must purge out the oxygen in hospital piping before they begin welding/soldering operations. Again, after the work is complete, the piping must be cleaned for medical use. Even though there is no prescription, this is clearly a legitimate medical use of the nitrogen: Nitrogen, NF.

Cryosurgery Applications   Medical Drug
Cryosurgery is a process for freezing and killing abnormal cells (warts, tumors, cancer and some precancerous or non-cancerous conditions). Cryosurgery can be used both inside the body and on the skin. The low temperature from liquid nitrogen causes a small cryogenic burn. This damages the tissue and eventually the cryogenic tissue damage is repaired with healthy tissue. The liquid nitrogen can be directly applied to the tissue, or it can be circulated through tubing in contact with the diseased tissue.

This would seem to be a “medical device” application for liquid nitrogen. In the past, there was some ambiguity in correspondence from both the drug and device centers in the FDA about this application for liquid nitrogen. The current understanding is that liquid nitrogen for cryosurgery applications may be a device, but it can be treated by the manufacturer as if it is a drug.

Cryosurgery nitrogen is often delivered to the physician in small, open-mouthed dewars (approximately 20 to 30 liters). These dewars are sometimes filled at the doctor’s office from portable cryogenic containers. This presents some compliance challenges to the company making the delivery.

Since the product is delivered in open mouthed dewars, it is not feasible to sample or conduct the typical USP/NF testing on the product. The open-mouthed dewars must be filled from a qualified source. If the dewars are being filled from the bulk tank at the plant, the bulk tank must be qualified as Nitrogen, NF. If the dewars are being filled from a portable cryogenic container, that portable cryogenic container must be qualified as Nitrogen, NF.

Nitrogen, NF testing includes an assay (purity), odor test, carbon monoxide test and an identity test. The bulk tank and portable cryogenic container must have been filled, tested and released according to Current Good Manufacturing Practices by a registered drug manufacturing firm.

The small, open-mouthed dewar should be labeled with a Liquid Nitrogen, NF label. A lot number should also be applied to the dewar.

Cryopreservation of Bull Semen   Industrial
The liquid nitrogen used as the refrigerant in cryo-freezing bull semen tissues is actually an industrial application. No special FDA requirements currently apply to liquid nitrogen used in this application.

Gases and Welding Distributors Association
Meet the Author
GAWDA’s FDA & Medical Gases Consultant Thomas L. Badstubner is president of AsteRisk LLC in Blackstone, Massachusetts. Members can reach him at 508-883-0927 or at tom.badstubner@asterisk-inc.com.