By Mitch Valdmanis, Product Manager

Continuing our series on the subtle, but important aspects of RIVA’s operation, I would like to turn our attention to the matter of managing gas pressure inside of drug vials as liquid and gas are drawn out or injected in.

Vial stoppers are designed to seal the contents of the vial even after being punctured, but when it comes to the pressure inside of the vial, stoppers are a bit like Goldilocks – they don’t like the pressure too high or too low; the pressure needs to be just right for stoppers to function properly. In general, the pressure in a vial should be kept slightly below the ambient air pressure to prevent the contents of the vial from leaking out, though for most vials there is a range of pressures that are acceptable. Below, I’ll refer to this as the “golden range.”

Too High

When vial pressure is too high, the liquid (drug) can leak out of the vial. This should be avoided for multiple reasons: waste of the drug itself, errors in doses drawn from the vial, and perhaps most critically, cross-contamination concerns if the leaked drug spills onto inventory intended for different doses.

The most common cause of high pressure is reconstitution of powder drug vials. As diluent is put into the vial, there is less space for the gas, so the pressure increases. Inject enough liquid without controlling for the pressure in the vial and the pressure gets too high, potentially leaking drug or spraying an aerosolized mixture of air and drug into the compounding chamber.

Another, less obvious cause of high pressure is geography. Consider two compounding sites: one on a coast at sea level and one at a high altitude in the mountains. If, in absolute terms, the pressure in the vial starts at standard atmospheric pressure, then drawing a small dose at the coastal location is likely to leave the pressure within the golden range. At the mountainous location, however, the pressure in the vial, though unchanged in absolute terms, may be near 20% higher relative to the local atmospheric pressure. Performing that same small draw straight from the vial may leave the vial at a pressure that is still above atmospheric – outside of the golden range – but now with a hole in the stopper through which the drug can leak.

Too Low

Low pressure in a vial is the result of pulling drug out of the vial without replacing the volume it had been taking up with air. As the limited amount of gas in the vial expands to fill up the whole volume, its pressure can potentially get extremely low.

The problems with the pressure in the vial getting too low are more subtle, but can still cause serious problems. The pressure in the vial could potentially get so low while drawing a dose as to (temporarily) physically deform the syringe. The barrel of the syringe may flex inwards, and the rubber on the end of the plunger can bulge inwards as well. All of this takes up volume in the syringe intended for the drug. Once the needle tip is exposed to ambient pressure again, the syringe returns to its normal shape, but the volume it had been consuming is now filled with air instead of the intended drug, so the dose is too low.

The other problem with pressure too low is air leaking into the vial. At first blush this may seem like it’s not a problem; it’s getting the pressure closer to the golden range, after all. However, if we were trying to manage the low pressure by, say, injecting additional air into the vial, but not expecting air to leak into the vial on its own, then we might end up injecting too much air, resulting in the vial pressure getting too high again.

Managing Vial Pressure

Pharmacy technicians are used to managing vial pressures by injecting and withdrawing air from vials as they perform compounding operations. The pharmaceutical consumables industry has also offered several products for managing vial pressure, such as vented needles for vial reconstitution and vented closed system transfer devices for hazardous chemicals. Such pressure management solutions add additional complexity to the compounding process and additional costs for every dose prepared. When preparing hundreds of doses per day, the costs of these additional consumables can quickly add up.

RIVA automatically manages vial pressures using the same types of syringes and needles it uses for all other fluid transfers without the need of any additional consumables, reducing the burden on pharmacy technicians preparing inventory and reducing the costs for preparing doses.

Mitigating Risks

No matter which means of vial pressure management are employed, there will always remain some risk of drug leaking from the vial. Syringe needles or fluid transfer devices may not be applied properly or may fail; vial stoppers vary in quality, perhaps a vial has a particularly poor quality stopper that starts to leak easily; or perhaps the manufacturer has changed their production process (or location) and vials now arrive at substantially higher pressures than previously.

For these reasons, it is critical that other mitigations against the risks of fluid leaks are in place. Such mitigations include laminar airflow to prevent the spread of aerosolized drug, and ensuring that all fluid transfers take place away from other inventory and consumables. In particular, fluid transfers should not be performed directly above other inventory items. Pharmacy staff members are taught this when learning proper aseptic handling techniques, but it is also an important factor when considering a pharmacy automation solution.