OEL Surprises and Solutions for Flexible Isolators


Natural laws affect us daily in unanticipated ways. Conventionally, OEL’s are established for solid drug substances and process intermediates.


However, compounds have finite vapor pressures which increase with temperature. OEL banding commonly reference μg/m3 and more recently ng/m3 (a human cell has a mass of ~1 ng). As materials manipulations continue to effect genetic changes the probability of exposure bands invoking picogram (10-9 g approaching DNA fragment mass range) and femtogram (10-15 g - HIV-1 virus mass range) may become commonplace.

Materials vapor pressures affect everything we do on a daily basis:

  • That expensive gemstone that you or your partner wears is losing value daily as carbon on those brilliant facets is evaporating continuously, albeit minutely when measured in the femto- and atto- gram range. Likewise gold, silver, and platinum continually evaporate.
  • The two cylindrical pillars commissioned by the International Union of Pure and Applied Chemistry (IUPAC) of ultra-pure silicon representing the international kilogram have unintentionally been losing mass since they were first created because of silicon vapor pressure at normal temperature and pressure. To maintain the integrity of the international kilogram the ingots are now stored under a vapor pressure-controlled regimen.
  • A client utilized field validation as a standard procedure when measuring materials airborne concentrations. Similarly, their facility wide statistically random settling plates (measuring materials deposition) routinely used a known spike validation technique. For an intermediate considered to be potent (OEL of 0.2 μg/m3) a 1 μg settling plate spike was not detectable after 30 days of exposure, while spiking at 10 μg resulted in repeated recovery of only 9 μg. A review of the preceding 3 years of air sampling also revealed constant loss of 0.15 μg in the over 80 sample sets, resulting in only 85% recovery due to air-stripping, i.e. a loss of 75% of the OEL concentration during sampling.
    • Above, a detailed analysis of the laboratory and production practices revealed that the early FabOhio Inc. design using an air-purifying filter in a passive pressure mode had achieved the desired worker protection, albeit vapor containment was not the anticipated purpose.
    • FabOhio Inc., was able to help by providing a glovebag fitted with air purifying filters based on this experience learned since 1993 with our earliest pharmaceutical company flexible isolators.
  • Review of materials vapor pressure can reveal improved delivery of drug doses through chilled milling to decrease particle size, resulting in a higher surface area/unit mass (surface area is proportional to the cubic function of the radius). This can lead to better drug uptake since vapors penetrate membranes faster than liquid or solid forms for workers and patients. Flexible isolators can support the required enhanced containment protection for the API during handling.
  • During a toxicology review to establish the OEL of a purchased starting material it was agreed to establish 0.2 μg/m3. Unfortunately, the vapor pressure of the material exceeded the proposed OEL 3,000 fold. This required further toxicological review.

As ever more potent drugs are developed, failure to establish OEL’s for materials existing in both the solid and vapor phase can put materials handling into unusual containment strategies. FabOhio Inc. has successfully overcome such challenges since our earliest days of potent compound manufacture.

If you suspect or observe failure to control your workers' target exposures, Contact Us at FabOhio Inc. for assistance. We have over 120 man years of collective experience in contained handling of solids, liquids, vapors, and radioactive materials in collaboration with our clients.

Written by Brian Ward, PhD, CSci, CChem, FRSC

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