Nitrogen Generators for the Pharmaceutical Industry
In the manufacture of medicines, nitrogen is what keeps oxygen away from the product: in the reactor, during transfer and drying, in the freeze dryer and in the pack. NITROBERG® generators produce that gas on your own site from compressed air, at grades from 97 % up to 99.999 %. This page works through what your processes actually need in purity, volume and continuity, before a model gets chosen.
What nitrogen does in pharmaceutical production
Nitrogen in a pharmaceutical plant is a process gas. It displaces oxygen and moisture wherever their presence would change the product: as a blanket over solvents and oxygen sensitive intermediates, as an inert atmosphere in reactors and dryers, as the purge that clears vessels and lines after cleaning, as the carrier that moves powders without an explosive atmosphere forming, as the backfill in vials before stoppering, and as the headspace in blisters and bottles. Gases administered to patients belong to a separate regulatory category with its own requirements, and they are not what this page is about.
What makes the supply question harder here than in most industries is not the volume. It is that the consumers are unlike each other. A reactor inerting duty draws steadily for hours. A purge cycle draws hard for minutes and then stops. A packaging line draws a small, constant trickle. The QC laboratory draws almost nothing and sets the highest purity on the site.
A nitrogen generator answers that by making the gas on site from compressed air. In a PSA system, compressed air flows through a bed of carbon molecular sieve that holds back oxygen, carbon dioxide and residual moisture much faster than it holds back nitrogen. Two beds alternate, one producing while the other regenerates at lower pressure, so the supply does not pause between cycles. The PSA nitrogen generator page describes the process step by step, and the carbon molecular sieve article explains why that one component sets the ceiling on purity.
Which nitrogen purity each pharmaceutical process needs
Purity on a pharmaceutical site is usually specified once, for everything, by whoever happened to have the most demanding process. That is the most expensive way to do it. The grades below are the ones normally used in practice. Treat them as a starting point and confirm them against your own validated process parameters, because the requirement moves with the product, the vessel and the purge strategy.
| Process | Typical grade | What the nitrogen does | Drives |
|---|---|---|---|
| Reactor inerting, API synthesis | 99.9 % to 99.99 % | Inert atmosphere over oxygen sensitive chemistry | Purity |
| Solvent storage and handling | 99.9 % | Blanket that holds the headspace below the limiting oxygen concentration | Volume |
| Purging vessels and lines after cleaning | 99.9 % | Removes residual air and moisture before the next batch | Volume |
| Drying and powder transfer | 99.9 % | Carrier and drying gas without an oxidising atmosphere | Volume |
| Lyophilisation, vial backfill before stoppering | 99.99 % and above | Inert headspace in the closed vial | Purity |
| Blister, bottle and pouch headspace | 99.9 % to 99.99 % | Displaces oxygen at the point of sealing | Volume |
| QC laboratory instruments | up to 99.999 % | Carrier, collision and evaporation gas | Purity |
Read the table by column rather than by row. The volume comes from blanketing, purging and packaging, which run constantly and are cheap to supply. The purity comes from one or two processes that will happily set the grade for the whole site if nobody separates them. Where a requirement is written as residual oxygen in the vessel rather than as a gas grade, the purge strategy carries as much weight as the gas itself: it is the number of exchanges that gets you to the ppm figure, not the label on the generator.
What higher purity costs you in compressed air
Every NITROBERG® size consumes a defined amount of compressed air per cubic metre of nitrogen it delivers. That ratio, the air factor, is the same across the range and depends only on the purity you set.
| Purity | 97 % | 98 % | 99 % | 99.5 % | 99.9 % | 99.99 % | 99.995 % | 99.999 % |
|---|---|---|---|---|---|---|---|---|
| Air factor | 2.3 | 2.3 | 2.6 | 2.9 | 3.4 | 4.6 | 5.2 | 6.4 |
Put a plant figure into it. A site drawing 60 Nm³/h for blanketing and purging needs around 204 Nm³/h of compressed air at 99.9 %. Specify 99.999 % across the site instead and the same 60 Nm³/h needs around 384 Nm³/h: close to twice the compressor, twice the electricity and twice the compressor room, for gas quality that blanketing cannot use. That is the whole argument for splitting the supply. Analytical instruments and vial backfill on a high purity line, blanketing and purging on their own cheaper one, each sized for what it does. The energy consumption article works through the running cost side of that decision.
How to size a nitrogen generator for a pharmaceutical plant
List the consumers, not the plant
Take a figure per consumer: reactor, dryer, packaging line, transfer system, laboratory. Then separate the ones that draw continuously from the ones that draw in bursts. A purge cycle is a peak, not a running load, and a system sized on the sum of all peaks is a system nobody needed.
Set the purity from the process, not from the site
Take the most demanding requirement on the list, then ask whether it belongs on the same supply as everything else. Where the specification is written as residual oxygen in the vessel, confirm what that means for the gas grade before it turns into a site wide number.
Decide the buffer and reserve concept
A batch that cannot be interrupted changes the sizing before any model is chosen. The nitrogen vessel carries a buffer, and how large it has to be follows from the longest interruption your process can absorb. The reserve supply strategy is defined together with the system design and the requirements that apply at your site.
Check the compressed air, quantity and quality
Flow times air factor gives the demand. Quality counts as much as volume and is the part that gets forgotten: oil carry-over and residual moisture shorten the life of the carbon molecular sieve, so an undersized dryer costs more over five years than a slightly undersized compressor. NITROBERG® expects compressed air to ISO 8573-1:2010 Class 1.4.1 at 7 bar(g).
Need sizing for your application?
You do not need a full data set to start. Tell us roughly what you use today and we will say whether on-site generation is worth a closer look for your operation. If you already have flow, purity and operating hours to hand, send them and you get a sizing proposal back.
Documenting nitrogen quality in a GMP environment
With delivered gas, quality arrives as a certificate attached to a delivery, and the record behind it belongs to somebody else. With on-site generation the record is yours, and it is continuous rather than per delivery. Residual oxygen in the product stream is measured while the plant runs, so a drift shows up as an alarm during the batch instead of as a question afterwards. Most operators find that the stronger position. It does, however, move work forward into the design stage.
That work is worth naming, because none of it is answered by a generator specification. Where do the sampling and measuring points sit, and are they at the point of use or only at the generator? What is monitored continuously, and what is checked periodically? How is the pipework routed so that dead legs and low points do not undo what the generator delivers? What has to be qualified, and what documentation does that qualification need? Verifying gas quality at the point of use is the operator’s responsibility, and every one of these questions is cheaper to settle before the pipework goes in than after. Bring the documentation requirement into the sizing conversation and the measuring points can be designed in from the start.
On-site nitrogen compared with cylinders and bulk liquid supply
Cylinders and a bulk liquid tank both deliver purity, and both charge for time rather than for gas. Rental runs through quiet weeks, evaporation losses run overnight, contracts carry price escalation clauses, cylinder handling ties up people in a building where clean space is expensive, and the delivery schedule that decides when the tank is full is not one you control. On-site generation replaces that with an investment and an electricity bill. For many of the plants we have supplied, the payback against liquid-gas supply has fallen within two to three years. Whether it does for you depends on your consumption profile and your electricity price, so that calculation is worth running together rather than taking a rule of thumb.
Purity you configure and monitor
The generator is set to the grade your processes need rather than to the highest one available, and residual oxygen is measured continuously in the gas it delivers. A drift shows up as an alarm, not on a certificate that arrives with the next delivery.
Standard wear parts
Filters and consumables are off-the-shelf items from the open market. There is no proprietary parts programme waiting after the purchase, and it is worth asking every supplier you compare where their filters come from.
Capacity that follows the site
The NITROBERG® range runs from 1.2 to 1,709.1 Nm³/h across 18 sizes, so the same technology covers a single packaging line, a filling suite and a full production building. Capacity is added as lines are added.
Direct access to engineering
Sizing and documentation questions go to the people who design the machines, not to a call centre. Delivery, commissioning and service come from one source within the BERG Group. Warranty runs three years as standard and up to five years with a service contract.
NITROBERG® sizes for pharmaceutical duty
The sizes below cover the band most pharmaceutical installations fall into, shown at the three grades that matter here. Smaller duties sit further down the range: the NITROBERG® 500 delivers 1.2 Nm³/h at 99.999 %, which is enough for a single filling line or a laboratory bench.
| Model | N₂ at 99.9 % | N₂ at 99.99 % | N₂ at 99.999 % |
|---|---|---|---|
| NITROBERG® 1000 | 34.4 Nm³/h | 18.5 Nm³/h | 10.1 Nm³/h |
| NITROBERG® 1100 | 45.1 Nm³/h | 24.2 Nm³/h | 13.2 Nm³/h |
| NITROBERG® 1200 | 55.8 Nm³/h | 29.9 Nm³/h | 16.3 Nm³/h |
| NITROBERG® 1300 | 78.7 Nm³/h | 42.2 Nm³/h | 23.0 Nm³/h |
| NITROBERG® 1400 | 109.9 Nm³/h | 59.0 Nm³/h | 32.2 Nm³/h |
Note what the columns do to each other. The machine that delivers 55.8 Nm³/h at 99.9 % delivers 16.3 Nm³/h at grade 5.0. Specify a whole site at the grade one instrument needs and you buy three machines where one would have done. Above these sizes the range continues to 1,709.1 Nm³/h, which is the territory of a site supplying several buildings from one source. Applicable NITROBERG® pressure equipment is conformity assessed under PED 2014/68/EU within the certified scope. Engineering and manufacturing are Made in Germany.
Where a site has no suitable compressed air network, the nitrogen generation package combines generator, air generation, treatment, storage and control in one pre-assembled unit, in plug-and-play configurations for NITROBERG® 500 to 900. Pharmaceutical nitrogen is one of several application areas that share this technology: instrument supply in the QC laboratory is covered on the laboratory page, and intermediate and fine chemical production on the chemical applications page.
FAQ: nitrogen generators for pharmaceutical manufacturing
NITROBERG® PSA generators are configured between 97 % and 99.999 %. At 99.999 %, which corresponds to quality grade 5.0, residual oxygen is 10 ppm or lower. Purity is a configuration decision taken when the system is sized rather than a fixed property of the machine, so it is worth basing it on the processes you actually run. Higher grades cost noticeably more to produce, because the compressed air needed per cubic metre of nitrogen rises with the purity you set.
No. Nitrogen used in pharmaceutical manufacturing is an industrial process gas. It inerts, blankets, purges and dries during production, transfer and packaging, and it is not administered to a patient. Gases administered to patients belong to a separate regulatory category with its own requirements, and that is not what these systems address. If your specification calls for a defined gas quality beyond the grades described here, raise it at the enquiry stage so the requirement is on the table before anything is sized.
The generator produces the gas. The quality record is built around it, and that is the operator’s responsibility. In practice it means deciding where sampling and measuring points sit, what is monitored continuously and what is checked periodically, how the pipework avoids dead legs and low points, and what has to be qualified and documented. Those decisions cost far less before installation than after, so the documentation requirement belongs in the sizing conversation rather than in commissioning.
The nitrogen vessel holds a buffer, which covers short interruptions and gives time to react. How large that buffer needs to be follows from the longest interruption your process can absorb, and that is a question worth answering before a model is chosen rather than after. Beyond the buffer, a reserve supply remains part of a sensible plan. The reserve strategy is defined together with the system design and the requirements that apply at your site.
The generator runs on compressed air, and the amount depends on the purity you choose: multiply your nitrogen demand by the air factor, which runs from 2.3 at 97 % to 6.4 at grade 5.0. Air quality matters as much as quantity, because oil carry-over and residual moisture shorten the life of the carbon molecular sieve. NITROBERG® expects compressed air to ISO 8573-1:2010 Class 1.4.1 at 7 bar(g). Where a site has no suitable network, the skid-mounted package brings its own air generation and treatment.
It can, and the question is whether it should. A shared supply runs at the purity of its most demanding consumer, so blanketing and purging would run at laboratory grade and pay the compressed air that goes with it. Where the laboratory needs 99.999 % and production does not, a separate high purity line for the instruments is usually cheaper than lifting the whole site to that grade. The laboratory page covers the instrument side in detail.
No. The wear parts are standard components rather than a proprietary programme, which keeps the running cost open to competition: filters can be sourced where you want and service offers can be compared. Over the service life of the machine that usually weighs more than the difference in purchase price. Warranty runs three years as standard and up to five years in combination with a service contract.