Best Practices for Maintaining Laboratory Freeze Dryers

Brandoch Cook, PhD, is a freelance scientific writer. He can be reached at: [email protected].

There are two axioms of laboratory equipment maintenance. One is to incorporate regularly scheduled maintenance into standard operating procedures. The second is to avoid extra maintenance whenever possible through planning, equipment checks, and appropriate use. For freeze dryers, before considering maintenance schedules, one should assess the full range of products that will be freeze-dried, in what volume and frequency, and their associated eutectic points or collapse temperatures. The consequent selection of instrumentation will often obviate any necessity for unscheduled maintenance and repair for a significant portion of the instrument's expected lifespan.

Keeping in mind optimal differences between condenser and eutectic temperatures, using vapor pressure over ice as guidance, lab managers should make purchases based on the most challenging sample that will be collected, factoring in requirements for solvents, acids, lowest setpoints, and whether final products will be symmetrical and crystalline or amorphous and glassy. From there, users should pay close attention to every integral part, and adhere to a scheduled maintenance program at periodic intervals.

In a proper freeze-drying process, the freezing itself must be complete before beginning the thermodynamic process of pulling moisture out of a sample. This is a two-step procedure consisting of sublimation, followed by desorption to first vaporize ice and then eliminate bound water molecules. The vacuum pump has the most influence on ultimate yield and reproducibility. If the vacuum is functioning properly, products should be recovered in predictable amounts at desired pressures and temperatures. For benchtop manifold freeze dryers with external flasks rather than integrated shelves, this is additionally dependent on clean and scratch-free glassware, which can otherwise implode under strong vacuum. Properly freeze-dried products should attain long shelf lives and allow easy reconstitution using water or their cognate solvents.

The most common malfunction that impedes success is a loss of vacuum pressure. Most benchtop systems use rotary vane, oil-sealed vacuum pumps. Oil leaks compromise function, and can be mitigated by changing the oil at regular intervals, usually at least once every 2,000 hours of use, or when the oil becomes visibly cloudy or discolored. Some larger systems use dry scroll pumps, and some use a combination of the two, especially for acid- and solvent-based drying. Freeze dryers can be modified after-market with the addition of carbon solvent, soda acid, or dry ice traps to protect vacuum pumps and customize application. The lack of oil lubrication reduces regular maintenance, although scrolls require replacement about every 40,000 hours, and entire faulty pump systems must sometimes be rebuilt.

Additional instrumentation, particularly temperature and pressure sensors, should be periodically calibrated, with calibration intervals adapted to whether a freeze dryer is used for research purposes or is GMP-certified. Some sensors can be calibrated to zero degrees using a crushed ice bath; others must be calibrated electronically. Vacuum sensors can be checked with a dry and empty system and a setpoint of zero millitorr, and assessed for whether dual Pirani and capacitance gauges co-correspond. Alternatively, vacuum transfer standards can serve as accurate calibrators. Mechanical and refrigeration systems should be assessed through regular function tests or standard recipe dry runs. Condensers, chambers, and shelving should be cleaned after every run, and doubly checked before initiating any new runs. Additionally, chambers and surfaces must be neutralized with pH buffers following acid-based freeze-dry cycles.

As with any expensive laboratory instrument, regularly scheduled maintenance of freeze dryers translates to long-term low maintenance and limited downtime. Paying particular attention to maintaining vacuum pumps optimizes function, consistency, and lifespan.