Simulated workplace protection factor study of powered air-purifying and supplied air respirators.

A study protocol was developed to obtain simulated workplace protection factor (SWPF) data for eleven models of powered air-purifying respirators (PAPRs) and supplied-air respirators (SAR) with hoods and helmets. Respirators were tested in a chamber that allowed the simulation of 12 exercises, including 2 exercises of interest to the pharmaceutical industry. Each respirator was tested by 12 volunteers, and a total of 144 sets of test results were obtained for each device. The testing protocol allowed SWPFs up to 250,000 to be measured (limit of quantification). Median SWPFs for all respirators, except one SAR, were at or above this reporting limit. Lower fifth percentiles were above 100,000, except for one SAR previously noted. An assigned protection factor (APF) was estimated for each respirator by dividing the lower fifth percentile by a safety factor of 25. APFs ranged from 6000-10,000 for PAPRs (including one loose-fitting PAPR) and 3400-10,000 for SARs, with one exception. This SAR had a lower fifth percentile of less than 20 and an estimated APF of 1. Results indicated that most respirators tested could provide a high degree of protection for workers, although one National Institute for Occupational Safety and Health-approved SAR provided minimal, if any, protection. Direct testing in a simulated workplace seems the only method that will assure employers of choosing an adequate SAR. This may be true for other classes of respirators. Furthermore, the historical approach of establishing APFs for classes of respirators, rather than individual models, may not provide adequate protection to the wearer. This is also a serious problem for regulatory agencies seeking to promulgate respirator standard provisions such as APFs for classes of respirators.

Setting health-based residue limits for contaminants in pharmaceuticals and medical devices.

A procedure for determining health-based residue limits for impurities in drug substances and medical devices is described. The procedure is based upon the concept of setting residue limits that correspond to the intended usage of the drug or device, i.e., short-term use, prolonged use, and/or lifetime use. Data pertaining to chemical and physical properties, occurrence and use, biodisposition, pharmacology, toxicology, and effects in people are used. After evaluation of these data, acceptable daily intake (ADI) values are derived using a safety margin approach for short-term and prolonged exposure limits. The safety margin approach combines the use of safety factors and professional judgment. ADI values for lifetime exposure are calculated using the safety margin approach for noncarcinogens and for some carcinogens, and they are calculated using risk assessment procedures that provide ADI values corresponding to no more than a 1 in 10,000 excess lifetime cancer risk based upon maximum likelihood risk levels for other carcinogens. A weight-of-evidence test determines the use of each approach. Finally, ADI values from relevant routes and endpoints are compared and a residue limit or residue limits are estimated. The standard is expressed in terms of maximum dose per exposure period and/or dose per day and is applicable to medical products intended for short-term use, for prolonged use, and/or for lifetime use as a major clinical indications dictate.

Internal wall losses of pharmaceutical dusts during closed-face, 37-mm polystyrene cassette sampling.

A current practice for the determination of personal exposures to dusts involves the aspiration of known quantities of air through membrane filters held in 37-mm plastic cassettes. Samples are collected with the cassettes in the closed-face configuration. A major negative bias error has been identified with this sampling procedure for low-level pharmaceutical dusts. For the pharmaceuticals studied, on average, 62% of the active dust collected in each sample was found on the inside surface of the cassette top. Only 22% of the total active ingredient of the dust was found on the filters. The remaining 16% was found on the inside of the cassette bottoms; electrostatic attraction appears to be the reason that pharmaceutical dusts adhere to the inside surface of the cassette. Adherence to the inside surfaces of the polystyrene cassette occurs without regard to the type of material used to seal the two-piece cassette together. The use of shrink wrap versus plastic tape versus using no sealing material had no effect on where or how much of the active ingredient was found on the inside cassette surfaces. Because very little active ingredient was identified in backup cassettes, it is hypothesized that the active ingredient found on the inside of the bottom portion of the cassettes (past the filter and support pad) got there by falling off the filter during filter removal from the cassette prior to analysis. To eliminate both of these errors, an internal cassette extraction procedure was developed that (1) negates the error caused by static charging and (2) eliminates the need for opening the cassettes prior to analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Development and validation of a protocol for field validation of passive dosimeters for ethylene oxide excursion limit monitoring.

An exposure and analysis protocol is described for the field validation of passive dosimeters for ethylene oxide (EtO) excursion limit monitoring. The protocol calls for the use of a field exposure chamber with concurrent sampling using Tedlar air-sampling bags. The bags are analyzed immediately after sampling by gas chromatography with flame ionization detection (GC-FID). The chamber design allows all monitors to be exposed for the exact same time in the field. The sampling and analysis procedure not only determines the actual concentration of EtO present during the monitor's exposure but estimates if concentrations of EtO vary from point to point in the monitor array during the exposure. In chamber operation, the accuracy of the standard generator used to calibrate the GC-FID was independently verified in the field by the standard additions method. The sampling bias of the sampling train was determined to be -3.5% in the 2.4 ppm to 14.3 ppm concentration range. To estimate the stability of collected EtO samples in Tedlar bags, the rate of EtO loss in the bags was determined to be 0.011 ppm/hr at 2.57 ppm and 0.066 ppm/hr at 8.07 ppm. Sampling bias of the passive methods by additional EtO exposure of the monitors in the closed chamber after sampling and during purging was determined to be +1.5%. The Tedlar bag sampling method with subsequent GC-FID determination demonstrated a coefficient of variation of 1.8% at 2.43 ppm.

Field validation of three passive dosimeters for excursion limit monitoring of ethylene oxide.

The Occupational Safety and Health Administration (OSHA) set a 5-ppm excursion limit (EL) for ethylene oxide (EtO) in April 1988. Both active and passive sampling methods have been proposed for monitoring workers against this new standard. Passive dosimetry has considerable advantages over active sampling for monitoring short-term exposures to EtO, including reduced sampling and analysis complexity, increased chemical stability, and reduced cost. The major disadvantage of these passive methods is their questionable ability to meet the OSHA requirement for the test result to fall within +/- 35% of the "true" result with 95% confidence at the EL over a 15-min sampling period. A field validation study was performed to estimate the accuracy of three EtO EL passive dosimeters: 3M 3550/3551, Crystal Diagnostics AirScan, and Assay Technology EO CHEM CHIP. Area samples were taken at four unique concentration areas within a hospital products sterilization facility. A specially designed field exposure chamber was used to expose 12 dosimeters of each type concurrently at each sampling location while concurrently collecting six Tedlar bag samples from locations surrounding the dosimeter array. The Tedlar bag samples were analyzed on-site by gas chromatography with flame ionization detection (GC-FID). To enhance the strength of this validation study, manufacturers of the dosimeters were requested to take part in the investigation. Their input was used during the design of the exposure chamber and study protocol and in the interpretation of the results. Two of the three dosimeter types were analyzed by the investigators.(ABSTRACT TRUNCATED AT 250 WORDS)

Laboratory and field validation of a JXC charcoal sampling and analytical method for monitoring short-term exposures to ethylene oxide.

A sampling and analytical method for the measurement of ethylene oxide (EtO) short-term exposure limits (STEL) was validated under both laboratory and field conditions. These studies were designed to examine the method against both the Occupational Safety and Health Administration (OSHA) EtO permissible exposure limit (PEL) method requirements and the National Institute for Occupational Safety and Health (NIOSH) industrial hygiene method validation criteria. The method's pooled accuracy was shown to be within both OSHA requirements and NIOSH guidelines. The EtO was collected on a JXC charcoal tube at a sample flow rate of 100 mL/min for 15 min. The samples were shipped on dry ice and were stored in a freezer until analyzed. The EtO was desorbed by carbon disulfide and the eluent was analyzed by gas chromatography with flame ionization detection (GC-FID). The desorption efficiency of EtO from JXC charcoal tubes was determined to be 84% over the 15-min time-weighted average concentrations: 2.5, 5.0 and 10 ppm EtO. The method limit of detection was determined to be 1.0 ppm. The coefficient of variation of the combined sampling and analytical method was 5.7%. A -7% method bias was calculated. Field validation of the method included data from a portable GC-FID for the determination of method bias. Results of the field validation study over the concentration range of 2.4 ppm to 19.9 ppm generated a field precision of 8.1% with an absolute bias of 3.9%. The method accuracy was determined to be +/- 20%.(ABSTRACT TRUNCATED AT 250 WORDS)