Using Surrogate Testing to Determine Selection and Performance of Contained Dust Collection Systems

The proper selection and operation of contained dust collection equipment is critical to pharmaceutical plants for a host of reasons, from environmental requirements and employee health and safety to production cleanliness and efficiency. The use of surrogate testing is a valuable tool in ensuring that contained dust collectors are meeting the requirments for containment relating to the hazards associated with the materials being processed and any applicable good manufacturing practice.

What is surrogate testing and why is it necessary? Historically, no performance data existed on contained dust collection systems until they were already installed. Surrogate testing offers a way to provide meaningful performance information prior to installation, to help pharmaceutical entities determine if the equipment will meet required guidelines and standards for a specific project. Surrogate testing involves the use of a substitute or surrogate compound to simulate an Active Pharmaceutical Ingredient (API) for verifying the effectiveness of dust containment options for handling hazardous materials. Test conditions are designed to mimic workplace operations as closely as possible without incurring the expense or health concerns of handling the actual API. This case study describes how a pharmaceutical manufacturer, who shall be referred to as the "customer," dust collection equipment supplier, and a certified independent laboratory together employed surrogate testing to validate performance of a planned dust collection system that would serve a new manufacturing area.

The Role of Surrogate Testing
In selecting dust collection equipment for pharmaceutical applications, it is critical to understand the toxicological properties of the material to be captured, i.e., the potent, toxic or allergenic properties of the compound as it relates to personnel exposure. This determines the Occupational Exposure Limit (OEL), a value specific to each individual API. The OEL is defined as the amount of material determined to be the maximum air concentration, expressed as Time Weighted Averge (TWA), to which a healthy worker can be safely exposed for an 8-hour shift, 40-hour work week, without potentially suffering adverse health effects. This value is typically expressed in micrograms per cubic meter of air (µg/m³).

In most cases, some level of isolation and containment is required, due to the fact that the pharmaceutical dust is hazardous and cannot be released into the surrounding environment. There are several benefits to conducting a surrogate test program, but the most noteworthy is the ability to verify effectiveness of isolation and containment equipment. Surrogate testing makes it possible to verify at different points in the evaluation and purchasing process whether the contained dust collection equipment is performing as needed for the project. This is accomplished by manipulating the test compound to simulate workplace operations and performing air and surface sampling during the operational manipulations.

Testing can be performed on equipment handling an API with unknown toxicological properties, as in this case study example, or for verification of existing systems. Surrogate testing also can be performed during Factory Acceptance Testing (FAT), again as illustrated in this case study, and/or Site Acceptance Testing (SAT) after equipment has been purchased to ensure proper performance once installed. By validating equipment performance during the engineering phases of a project, pharmaceutical manufacturers stand to reduce costs while also reducing risk.

Figure 1. Dust collection equipment used in the surrogate test.

The equipment selected for evaluation by the customer was a cartridge-type contained system designed for high efficiency collection of dry dusts. This equipment is suited to a variety of pharmaceutical dust collection applications including tablet presses, coating machines, fluid bed drying, spray drying, blending, granulation, central vacuum systems, and general room ventilation. The equipment to be tested contained four cartridge filters rated at 99.999 percent efficiency (MERV 16) on 0.5 micron particles and larger with the capability to handle risk-based category 3, 4, and 5 compounds with OELs less than 1.0 µg/m³ for an 8-hour time weighted average.

Any point of potential exposure to hazardous dust must be enclosed and maintained so the dust collector was equipped with soft-walled, safe-change containment technology for both the filter cartridges inside the collector and the discharge system underneath. The filter cartridges utilized the Bag-In Bag-Out (BIBO) technology with two cartridges removed per bag. The discharge system utilized continuous liner technology to contain the dust that would be released from the cartridges to the angled hopper below during automatic pulse-cleaning.

The surrogate testing commissioned by the customer was a Factory Acceptance Test (FAT) to verify performance. It was conducted with the idea that if the equipment did not function as expected, it would be easier to address modifications at the factory rather than at the customer site. The supplier's stated claim was that the equipment would perform at or below the standard threshold limit of 1.0 µg/m³ for a TWA.

There were three possible outcomes to the surrogate testing depending on the equipment's measured capability to meet this desired containment threshold:

1. If results met or exceeded expectations, the customer would accept the contained dust collection equipment as designed.
2. If results were close, but not quite within the required range, the supplier would make modifications to the equipment and then repeat the test to verify if those changes were successful.
3. In the unlikely event that the equipment fell short of performance goals even after modifications, the customer would perform a risk assessment to determine the need for supplemental Personal Protective Equipment (PPE) or for other, more costly containment technologies.

Testing Protocol and Methodology

To perform the testing, the dust collection equipment supplier engaged an independent laboratory accredited by the American Industrial Hygiene Association (AIHA). Together the supplier and laboratory outlined a test protocol conforming to the ISPE Good Practice Guide, "Assessing the Particulate Containment Performance of Pharmaceutical Equipment." As described by ISPE this guide provides a standard methodology for use in testing the containment efficiency of solids handling systems used in the pharmaceutical industry under closely defined conditions. It covers the main factors that affect the test results for specific contained solids handling systems, including material handled, room environment, air quality, ventilation, and operator technique.

The customer wanted to apply all best available methodology to the task; so in addition to ISPE Good Practice guidance, the equipment supplier and laboratory also incorporated AIHA Good Industrial Hygiene Practices in developing the test protocol. This was completed in order to supplement the ISPE testing methodology specifically for assessing dust collection systems. The AIHA provides education, training, and publications on how to recognize and evaluate chemical hazards in a wide variety of situations (www.aiha.org). Utilizing multiple resources allowed for a comprehensive testing methodology to be developed to ensure compliance with applicable industry standards.

The testing methodology incorporated the following elements:

Surrogate Compound Selection

The first task was to select a test compound that would simulate the customer's API without posing a hazard to the operators or the surrounding environment. Lactose is the most common surrogate used due to its ability to be micronized, its free flowing or non-free flowing particle size distributions, its inactivity, and its cleanability. The free flowing particle size can range from 45 to 250 µm and the non-free flowing averages around 50 µm. The detection limit sensitivity of lactose in air is 0.005 µg/m³ for an 8-hour Time Weighted Average (TWA) and 0.17 µg/m³ for a 14 minute Short Term Exposure Limit (STEL).

In this test, non-free flowing lactose milled to provide a 50µm average particle size was the surrogate of choice. Table A shows the specifications for the surrogate test dust. It should be noted that the surrogate specified was 100 percent lactose, undiluted with other materials. In real-world processes, the API is incorporated in a specified concentration and is mixed with other inactive substances and excipients. By the time it raches the dust collector, usually at the end of the process the API might account for just a very small percentage of the dust being captured. By using an undiluted test dust, the collector would thereby be challenged with a "worst case scenario." A total of 62.5 kilograms of lactose was used to conduct the testing.

Non-Free Flowing Lactose Test Dust Specification

Description: A spray-dried mixture of crystalline and amorphous lactose

Test Room

Figure 2. Mezzanine adjacent to test room, sealed off with poly sheeting with dust collector platform visible at the right.

The dust collection equipment was located in a dedicated and decontaminated area of the equipment manufacturer's factory. The test area was isolated and sealed off and personnel access was tightly controlled and limited to test personnel to keep the area pristine and avoid contamination - Figure 2. Prior to the FAT, test personnel pressure-washed the test room, cleaned the floor with a power scrubber, and manually wiped the exteriors of the equipment and other surfaces.

The area was maintained at a relative humidity of 50% (± 10%), a temperature of 20°C (± 5°), and a positive room pressure of > 10 Pa relative to the adjacent space. An air change rate of three to five changes per hour was maintained. Air sampling devices were installed in opposite corners on the east and west sides of the room, and numerous other sampling points were designated for surface swab tests.

Air and Surface Sampling Plan

The sampling plan called for a total of more than 47 air, surface wipe, and personal samples to be taken to evaluate dust collector performance as follows:

• Background general area air samples and surface swab samples to be collected prior to the liner change, continuous liner discharge, and filter change operations. the "before" testing was scheduled after cleaning of the area and about one hour prior to the test to make sure the background environment was clean and would not compromise results.
• One single-event breathing zone sample to be collected for each of two test operators during the liner change operation, during each of the three continuous liner discharge tasks, and during each of the four filter change tasks of the operational test.
• One multi-event breathing zone air sample to be collected for each of the two operators during the liner change operation, the three continuous liner discharge cycles, and the four filter change tasks of the operational test. Figure 3 shows the operators each wearing single and multi-event air sample pumps and filters.
• Four general area event air samples to be collected near the discharge chute of the dust collector during the liner change operation and each of the three continuous liner discharge cycles of the operational test - Figure 4.
• General area event samples to be collected near the top in Figure 5 and bottom of the bagging flange during the four filter change tasks of the operational test.
• Two general area background air samples to be collected during the liner change operation, three continuous liner discharge cycles, and the four filter change tasks of the oeprational test.
• Surface swab samples to be collected from the discharge chute after each of the liner change operations in Figure 6 from each of the three continuous liner discharge cycles, and from the top and bottom of the bagging flange after filter change tasks No. 2 and No. 4 only.