Dust Due Diligence: Using a Safe API Substitute to Test if a Collection System Can Handle the Job

Is your dust collection system effectively controlling hazardous solid dose production dust? If you’re not sure, there’s a way to test the system to learn if it is potentially exposing employees to dangerous air-borne particles—without putting your employees at risk. Conducting surrogate testing using a safe API substitute can help you determine if your prospective or current dust collector can meet the challenges of capturing particulates generated during production. Verifying process equipment performance via surrogate testing can help you select a well-designed system during a project’s engineering phases—reducing costs, potential exposures, and contamination risks. Surrogate testing allows you to assess the risks by simulating the hazardous material with a substitute compound. 

The surrogate-testing process can help verify the effectiveness of dust isolation and containment equipment to support a purchase decision or shed light on necessary changes to an existing system.

Surrogate Testing 

The test compound simulates the active pharmaceutical ingredient (API) in the formulation that the solid dose equipment will handle or process. You manipulate the test compound to simulate operations for either a typical processing workday or a worst-case scenario. Most often, surrogate testing occurs under the guidance of a manufacturer’s health and safety team in conjunction with experts from an independent testing and analysis company.

Testing includes performing air- and surface-wipe sampling during compound manipulations. Prior to testing, the health and safety team must develop a protocol to identify which production activities the test will evaluate. Following the tests, the team will analyze the results to determine if the dust collection system has met predetermined performance criteria. 

Reasons for Surrogate Testing 

Actual test data is beneficial because it ensures that you have the right system in place for your application. An API may have unknown toxicological properties, may not have been previously evaluated, or may have no existing analytical procedure or exposure limits, such as a permissible exposure limit (PEL) from the Occupational Safety and Health Administration (OSHA) or a threshold limit value (TLV) from the American Conference of Governmental Industrial Hygienists (ACGIH). 

Data from surrogate testing is also useful when conducting factory and site acceptance tests and performance verifica- tions of process equipment to make sure that the dust containment and isolation equipment is the right fit or if any modifications to the equipment need to be made prior to being put into production.

Impact on Business Decisions 

Surrogate testing enables you to conduct an apples-to-apples comparison to determine the appropriate dust containment equipment for your application. With this information, you can select the equipment during engineering phases of projects, saving time and money on consultants and contractors. 

Surrogate testing also helps you to generate a list of acceptable vendors and equipment that meet your company’s safety and industrial-hygiene guidelines. Generating a vendor list allows you to limit the bidding process. 

Tested Device or Process 

Your testing team will determine the equipment or process to be tested. For example, you may want to test an entire process and all equipment or only specific activities or access points where potential exposures can occur. The team will evaluate operator actions to understand how the users interact with the system. The duration of the testing activities depends on whether you are testing for daily activities, a worst-case scenario, or an upset condition. Surrogate testing will help you determine if the containment equipment is functioning well or actually hindering the proper operation of the process. For example, the testing team can grade each dust-containment manipulation, such as a bag-in/bag-out process (photo), between one and five as follows: 

1. Operation is simple and easy with no issues. 
2. Operation makes a technique or manipulation difficult but possible. 
3. Operation is so difficult that improvement may be requested. 
4. Operation is so difficult that improvements must be made. 
5. Operation is impossible and must be corrected. 

Surrogate Material 

To choose a surrogate material that is sufficiently similar to your API, consider characteristics such as particle size, flowability, electrostatic properties, and sensitivity to moisture, heat, and light. Detection-limit sensitivity will vary by surrogate material. If you are handling an API that is very hazardous, the surrogate’s detection-limit sensitivity should be extremely low— down to micrograms or picograms—to ensure that the system is performing properly. 

Certain surrogate materials are inert, with no handling or decontamination issues, while other materials have an active component. Conducting the test at your facility might not be appropriate in the second case, so you will have to test at a contracted facility. 

Particle size distribution is important. For example, lactose is a common surrogate material because it’s inert, and its detection-limit sensitivity levels are low: 0.01 μg/m3 for an eight-hour total weight average (TWA) and 0.17 μg/m3 for 15 minutes. With lactose, the test operators don’t need personal protective equipment (PPE) unless they are lactose intolerant. 

The detection sensitivity of naproxen sodium is extremely low, with a sensitivity of 0.0005 μg/m3 for an eight-hour TWA and 0.017 μg/m3 for 15 minutes. This sensitivity makes it a great surrogate material, especially for testing an extremely hazardous material, but it’s an active material. If you’re testing in your facility, you need to be concerned with decontamination, cross contamination, and exposure, and the personnel involved will most likely need to use PPE. Target Performance Level 

If an API doesn’t have an official exposure limit, you will have to identify one using a contract lab and your testing team. For example, you may determine that a process-control target of 30 percent of the exposure limit for the surrogate indicates a robust containment system. It’s also important to validate the analytical methods for the test sample, preferably using an accredited laboratory. 

Key components of a validation protocol should include: 

• Selectivity. Detection without significant interferences; 
• Linearity. A linear response over the working range; 
• Recovery and precision. Sufficient detection sensitivity to enable the measurement method to meet stringent requirements; 
• Sample stability. Data for all conditions, including transportation and storage; and 
• Robustness. Detection unaffected by small changes in analytical conditions. 

Testing Activities 

You must develop the surrogate testing protocol prior to testing with the help of your health and safety department, a certified consultant, and/or the International Society for Pharmaceutical Engineering (ISPE) Good Practice Guide.1 Include test methodologies such as information recording, sample recovery, data logging, and analysis. 

You also must determine the level of operator training required. Using a dust collection expert to conduct the testing manipulations versus someone who isn’t familiar with the system will yield different results. Usually, trained dust collector operators conduct tests to demonstrate a system’s maximum performance, but if you want to stress a system or don’t use your system often, an untrained or lightly trained operator would better simulate real world operations. 

Visual recording of testing is critical because it will assist in tracing the source of an anomaly in the results. For example, video may reveal whether operator error or an equipment malfunction occurred. 

Arrange the equipment testing facility to replicate as much of the process train as possible. The test location should be a dedicated area with restricted access. You should quarantine the facility from the beginning of the pretest cleaning. The vendor should state procedures that it undertook to ensure that no surrogate contamination took place prior to the test. 

Data Recording and Reporting 

Be as detailed as possible when recording and reporting data to make your evaluation and analysis as accurate as possible and to alert you to trends or inconsistencies. If the data analysis indicates successful results, be sure to document the process so you can repeat the procedures when training personnel on the containment equipment. 

Include the following elements in your reporting: 

• Equipment. Describe all details of the equipment, including monitors, air sampling pumps, and type of surface swab; facility; and system and control conditions. 
• Surrogate-material details. The material safety data sheet (MSDS) usually can provide this information. 
• Frequency and duration of sampling. Include the area tested and personnel involved. 
• Sampler types and locations. Detail the positioning of all airborne particle samplers relative to the test unit; the dimensions of the test facility; and the directions of any conditioning airflows and locations of HVAC inlets and outlets. Note the position of swab samples for surface contamination on a sketch or with a photograph of the test unit. 
• Airborne concentration data with method used. Use continuous monitoring with instantaneous readout or time-weighted-average sampling, with off -line analysis. 
• Filter sample exposure data. Express this data as a maximum airborne concentration that will be adequate to calculate an equivalent time-weighted exposure limit based on anticipated operating cycles. 
• Surface concentration data. Include details about sampling locations and collection methods, conditions of equipment surfaces, and the location of and method for dust storage. 
• Interpretation of results and conclusions. Include the reasoning behind the summary conclusions and a statement of limitations with the data. The testing team will base this analysis on the testing protocol created prior to conducting the test. 
• Digital video recording. Capture the entire length of the testing process to catch every potential issue or event outside of protocol. Include application and removal of samples and all operations that the operator carried out. You can use digital photographs to supplement the recording process.