Here, we answer a question about fulfilling particulate monitoring requirements when a powder filling operation is involved in manufacturing.

 

Question:  Our manufacturing includes a powder filling operation. Do you have any recommendations for how to fulfill particulate monitoring requirements in this kind of high-particulate product environment?

 

We are occasionally asked for the most suitable method of environmental monitoring for processes that use powders. There are primarily two variables that affect how we monitor those processes that may generate high levels of powder as a result of normal production activities:

a. High levels of particles contaminate the optics of a particle counter and any associated sample tubing due to saturation. This contamination can be very difficult to remove and may take several hours, or even days, of purging with clean, particle-free air to establish normal levels. In many instances, the particle counter will need to be returned to a service center for thorough cleaning.

b. The high levels of particles make it difficult to interpret data and identify those instances when the process is running normally versus when there is a contamination event. The difference between a normal baseline result and elevated particle counts can become lost in the data set.

To that end, Particle Measuring Systems recommends the following process:

1. Perform cleanroom ISO 14644 certification on a regular basis, more frequently than annually, as the process may contaminate HVAC systems more readily.
2. START particle monitoring during the set-up phase until ready to process a powder.
3. STOP particle monitoring during the processing phase.
4. RESTART particle monitoring 15-20 minutes following the end of processing for at least 1 hour to demonstrate recovery of processing areas and that the baseline is restored.
5. Perform routine simulated processing without powder flow on a 3/6 month cycle based on the facility. Details of frequency can be specified as a part of the Risk Assessment. This simulation is performed to demonstrate that typical machine and operator activities do not create contamination events.
6. Normal microbiological monitoring is performed throughout the processing. If production is of antibiotics, use media with neutralizing agents.

These recommendations are supported by various regulatory and guidance documents such as:

FDA (2004 Guidance on Aseptic Manufacture)

Some operations can generate high levels of product (e.g. powder) particles that, by their nature, do not pose a risk of product contamination. It may not, in these cases, be feasible to measure air quality within the one-foot distance and still differentiate background levels of particles from air contaminants. In these instances, air can be sampled in a manner that, to the extent possible, characterizes the true level of extrinsic particle contamination to which the product is exposed. Initial qualification of the area under dynamic conditions without the actual filling function provides some baseline information on the non-product particle generation of the operation.

EU Annex 1 (2022 Version)

9.19: The selection of the monitoring system should take into account any risk presented by the materials used in the manufacturing operation (for example, those involving live organisms, powdery products, or radiopharmaceuticals) that may give rise to biological or chemical hazards.

9.20: In the case where contaminants are present due to the processes involved and would potentially damage the particle counter or present a hazard (e.g. live organisms, powdery products, and radiation hazards), the frequency and strategy employed should be such as to assure the environmental classification both prior to and post-exposure to the risk. An increase in viable particle monitoring should be considered to ensure comprehensive monitoring of the process. Additionally, monitoring should be performed during simulated operations. Such operations should be performed at appropriate intervals. The approach should be defined in the CCS.

PDA (TR13 Environmental Monitoring Program)

Some operations can generate high levels of product (e.g. powder) that, by their nature, do not pose a risk of product contamination. In these cases, it is acceptable to monitor prior to and post-exposure to the risk since it would be impossible to distinguish extrinsic contamination to intrinsic particle generation. Additionally, continuous monitoring of environments with intrinsic particle generation may damage the particle measuring equipment. Initial qualification of the area under dynamic conditions without the actual filling function provides some baseline information on the non-product particle generation of the operation.

Please Contact Us for any additional information.