Karthik Maniam Nature’s Value
The final rule of the FDA’s Dietary Supplement GMP Regulation 21 CFR Part 111.30(c) requires dietary supplement manufacturers to “routinely calibrate, inspect, or check the equipment to ensure proper performance.” Additionally, per 21 CFR Part 111.55, dietary supplement manufacturers must implement a system of production and process controls that covers all stages of manufacturing, packaging, labeling, and holding of products to ensure the quality of the dietary supplement. This includes in-process tablet coater controls such as supply and exhaust air volumetric flowrates, supply and exhaust air temperatures, pan rotation speed, coating solution spray rate, and atomizing air pressure. Verifying each of these controls using appropriate methods will ensure GMP compliance and maintain consistent tablet quality from batch to batch.
Verifying In-Process Controls
Supply and exhaust air volumetric flowrates. Ensure that the supply and exhaust air volumetric flowrates are within the specified limits. Excessively high flowrates can prematurely evaporate the moisture from the coating solution before the solution contacts the tablet bed, causing the dried solution particles to exhaust with the airstream and resulting in undercoated tablets. On the other hand, supply and exhaust volumetric flowrates that are too low may overwet the tablet bed, which can lead to tablet sticking and picking problems
You can verify the volumetric flowrates using an anemometer and the principle of traverse flow measurements1. According to this principle, if the duct diameter is 4 inches or larger, you can obtain the average volumetric flowrate by taking a series of readings at points of equal area, also known as traverse readings. Figure 1 shows the five recommended traverse reading points for round ducts. To avoid turbulence in the airflow, identify four locations in the duct where there are no elbows, transitions, takeoffs, dampers, or other obstructions. Using a calibrated anemometer as a known test standard, measure the supply volumetric flowrate at the five traverse points for each of the four duct locations. Then average these 20 flowrate measurements to determine the supply air flowrate. You can calculate the percent error of your supply air flowrate measurement using the equation:
acceptance criteria is ±5 percent. In a similar manner, verify the volumetric flowrate of the exhaust air.
Supply and exhaust air temperatures
The supply and exhaust air temperatures are important for effectively drying the coated tablets. These temperatures must be carefully controlled so that the fine mist of coating solution discharged by the spray guns evaporates quickly once it contacts the tablet bed, leaving a thin film on the tablets2. If the temperature is too low, overwetting of the tablet bed can occur.
You can verify the supply and exhaust air temperatures using a thermocouple thermometer. Select low, middle, and high temperature set points for the supply air within the system’s operating limits. Measure the supply and exhaust air temperatures at these established set points and at the sampling points selected for the air flowrates using the calibrated thermocouple as a known test standard. The input value will be the measured temperature display on the thermocouple, and the output value will be the actual temperature probe display. Obtain the reading error by subtracting the output value from the input value. The acceptance criteria for the supply and exhaust air temperatures is ±1°C.
Pan rotation speed
The coating pan must rotate at a speed that will provide coverage of the pan without causing the tablets to break3. The pan rotation speed should be increased gradually in conjunction with the coating solution spray rate, supply air temperature, and supply and exhaust air volumetric flowrates.
The tablet coating pan rotation speed is expressed in terms of revolutions per minute (rpm) that can be verified using a calibrated tachometer as the known test standard. For the best results, four set points should be selected within the coater’s operating limits. Using the tachometer, measure and record the pan’s rotation speed and record the rpm displayed on the coater controller. The input value is the actual measurement obtained by the tachometer, and the output value is the value displayed on the coater. Calculate the reading error by subtracting the output value from the input value. The acceptance criteria for the pan rotation speed should be ±0.5 rpm of the value for each set point.
Spray rate
The coating solution spray rate is directly proportional to the supply air temperature and supply and exhaust air volumetric flowrates. Pumping the coating solution into the tablet bed at an excessively high rate with an insufficient airflow temperature and volumetric flowrate will result in overwetting. If it is too low, the coating does not build up fast enough, resulting in tablet erosion. Note: The method described here fo verifying the coating solution volumetric flowrate applies to systems using a peristaltic pump. The pumping flowrate can be expressed in terms of rpm that can be verified using a calibrated tachometer as a test standard. For the best results, select four set points within in the operating limits. Using the tachometer, measure the pump speed and record the speed displayed on the pump. The input value is the value obtained using the tachometer, and the output value is the value displayed on the pump. The percent error of the full span of the pump can be calculated using the equation:
The acceptance criteria for the pump rpm should be ±0.25 percent of the full span of the pump for each set point.
Atomizing air pressure
Once the pump delivers the coating solution to the spray nozzles, the solution combines with atomizing air to create a fine mist that is directed at the tablet bed. If the atomizing air pressure is too low, overwetting of the tablets can result2, 3.
Verify the atomizing air pressure gauge on the coater using a calibrated reference pressure gauge as a known test standard4. Select five set points within the operating range. Isolate the pressure gauge from the coating machine and connect the gauge to the calibrated reference standard gauge. Record the readings on the reference gauge as the input value, and the reading on the pressure gauge on the equipment as the output value. Calculate the percent error using the equation:
The acceptance criteria for the pressure gauge reading should be ±1 percent of each set point.
Conclusion
Verifying your tablets coater’s operating parameters using known reference standards can help to ensure compliance with the 21 CFR Part 111 regulation. Records should include equipment identification using unique non-repetitive numbers, verification dates, identification of the reference standards used, and the signatures of both the individual who performed the verifications and the individual who reviewed and approved the verification record.
Karthik Maniam is a quality assurance manager at Nature’s Value, Coram, NY (631 846 2500, www.naturesvalue.com, kmaniam7@gmail.com). He is a licensed professional environmental engineer in New York and Vermont and holds a master’s degree in environmental technology from New York Institute of Technology and a master’s degree in chemical engineering.
References
1. http://www.dwyer-inst.com/ApplicationGuides /?ID=16
2. Fred A. Rowley. “Engineering for Success: The Aqueous Film Coating Process,” The International Society of Pharmaceutical Engineers, Los Angeles Chapter, May 12, 2005.
3. Michael D. Tousey, “Tablet Coating Basics,” Tablets & Capsules, 2005, April, 20-24. http://bit.ly/TabletCoating Basics
4. http://en-us.fluke.com/industries/chemical-process ing/verifying-process-gauges.html