Parameters that must be monitored and controlled to ensure the quality of products and compliance with regulatory requirements for dietary supplements
Dietary supplement manufacturing and packaging operations utilize automatic machines to produce products in capsules, tablets, powders, softgels, and powder dosage forms. During manufacturing, compressed air is used for various applications. Some of those include pneumatic control of automatic capsule-filling equipment, tablet-compression equipment, tablet-coating pans, and packaging equipment. During tablet coating, for example, compressed air creates a fine mist, which is used to coat the tablet in the tablet-coating pan. Compressed air is also used on product contact surfaces to dry equipment and utensils after cleaning.
This article focuses primarily on the application of compressed air in the manufacturing and packaging of dietary supplements. It discusses parameters that need to be monitored and controlled to ensure the quality of products and compliance with regulatory requirements for compressed air quality with respect to dietary supplement Good Manufacturing Practices (GMP) regulations.
According to FDA’s Good Manufacturing Practices Regulation for Dietary Supplements (21 CFR Part 111.27(7)), “Compressed air or other gases you introduce mechanically into or onto a component, dietary supplement, or contact surface or that you use to clean any contact surface must be treated in such a way that the component, dietary supplement, or contact surface is not contaminated.”
In air compressors, common types of particle contamination are dust and rust particles. The source of the particle contamination is the intake air of the air compressor, storage tanks, piping, valves, pressure gauges, and other fittings. These particles can be controlled by installing filters at the intake of the air compressor before the receiving tank and at the point of use. The typical filter rating installed at the intake of the air compressor is between 1.0-10 µm, and the coalescing filter rating installed at the point of use is between 0.5-1.0 µm.
The primary source of moisture in compressed air is intake air. In the atmospheric air at Normal Temperature Pressure (NTP) conditions, water vapor molecules are interspersed in the ambient air. When air is compressed, a large amount of water vapor is collected in a small volume of compressed air and thereby converts water vapor into condensate water. The presence of moisture in compressed air can be detrimental to the permanence of the air compressor by causing corrosion in storage tanks, piping, valves, pressure gauges, and other fittings. Repairs and replacement parts are expensive not to mention time-consuming. The presence of moisture could also be a potential source of microbiological contamination in dietary supplements, which could lead to a very expensive process or product recall. Therefore, controlling moisture in compressed air is vital. This can be accomplished by installing desiccant dryers, which are cylindrical vessels filled with silica to absorb moisture generated in the air compressor.
Air compressors require a lubricating oil to prevent friction, wear, and tear of moving parts unless the compressor is an oil-free compressor. During manufacturing of dietary supplements, hydrocarbon contamination is most common with oil-based air compressors. Hydrocarbons are oily liquids and vapors that can be hazardous to consumers and products. If dietary supplements are ingested, for instance, hydrocarbons can cause consumer illnesses. The primary source of this contamination is the compressor itself. Overheating the air compressor can cause lubricants to convert into vapors, which can slip through the piston rings and mix with compressed air. Proper filtration at the point of use will minimize hydrocarbon contamination.
As per ISO 8573-4 (Compressed air-contaminant measurement – Part 4: Particle content), there are three different methods to determine particle size and concentration:
An optical particle sizing and counting instrument is the most widely used method to determine particle size and concentration. As per ISO 8573-4, there are two types of instruments used: optical aerosol spectrometer (OAS) and optical particle counter (OPC). These instruments are highly specialized electronic devices and can be effectively used to analyze air samples of different particle size ranges. This method is beneficial over filter collection with microscopy, as it provides documented, qualitative data and rapid results of particle concentrations of air samples.
As per ISO 8573-3 (Compressed air – Part 3: Test methods for measurement of humidity), there are four different methods for humidity measurement:
Even though ISO 8573-3 describes several methods for measuring humidity, the most used technique to determine moisture in compressed air is by measuring the dew point temperature. The dew point temperature is the temperature at which air will be cooled to become saturated with water vapor. When further cooled, the water vapor will condense to form liquid water. It is very important to measure dew point temperature in a compressed air line because it gives an indication of the dryness level of compressed air. The instrument used to measure dew point temperature is a hygrometer. There is a wide range of hygrometers available, and the selection will depend on different factors: specification range, ability to perform calibration, accuracy and precision of the instrument, and pressure and volumetric flow rate requirements of the compressed air.
As per ISO 8573-5 (Compressed air – Part 5: Test methods for oil vapor and organic solvent content), there are two methods available. The choice depends on the range of oil vapor content in the compressed air.
As per ISO 8573-7 (Compressed Air – Part 7: Test method for viable microbiological contaminant content), the test method suitable for distinguishing viable, colony-forming microbiological organisms from other solid particles which may be present in compressed air is exposing the agar nutrient to the compressed air sample. There are different instruments for collecting compressed air samples on the petri dish with agar. The selection of instrument depends on the compressed air line pressure and volumetric flow rate.
Installing an appropriately designed filtration system at the point of generation and installing point-of-use filters where compressed air gets in contact with product, are the best defenses against cross-contamination. The most common types of contamination—particles, moisture, and oil—can cause destructive damage to products and consumers, leading to product recalls, as well as adversely affecting the service life of equipment that requires compressed air.
Monitoring the quality of compressed air in the manufacturing of dietary supplements can help ensure compliance with 21 CFR Part 111 regulations. Documented quality checks are the only means to prove that the system is operating in compliance with the FDA’s Good Manufacturing Practices Regulation for Dietary Supplements (21 CFR Part 111.27 (7)). These verifications can help diagnose problems such as heavy accumulation of particulates, moisture, and oils that tend to clog and corrode the components of a compressed air system.
Karthik Maniam is an independent GMP and EHS consultant. Maniam is a licensed professional environmental engineer in New York, Vermont, and Massachusetts and holds a master’s degree in environmental technology from New York Institute of Technology and a master’s degree in chemical engineering.