An expert reviews the important compliance checks needed to ensure the quality of dietary supplements during packaging.
The packaging of dietary supplement into final retail containers is a step equally as important as the manufacturing of the products themselves. Many factors need to be considered to prevent cross-contamination during packaging.
This article focuses primarily on the Good Manufacturing Practices (GMP) that must be monitored to minimize the possibility of cross-contamination. This includes prevention-of-disease control, environmental monitoring, and cleaning verifications of the product-contact packaging equipment.
Prevention of Microbial Contamination
As per 21 CFR Part 111.10(b), in an operation where the adulteration of the component or dietary supplement, or contact surfaces, could possibly occur, then personnel must follow hygienic practices to protect against contamination. These hygienic practices include wearing the appropriate personal protective equipment, following hand sanitation procedures, and following rules related to jewelry policy, personal effects, and consumption of food and other items.
In dealing with prevention-of-disease control, any personnel with a health condition that could threaten the safety of products must be restricted from entering packaging areas. Any personnel involved in the packaging of dietary supplements must also immediately report to their supervisor any health condition that could threaten the safety of products with microbiological organisms.
Personal hygiene is an essential factor for controlling the prevention of microbial contamination, and employees must be trained on the following hygienic practices:
Smocks: For personnel who work in GMP-controlled areas where they are exposed to in-process materials, finished products, product-contact packaging components, or equipment product–contact surfaces, clean outer garments must be worn that provide maximum coverage for both arms and legs. These personnel may not wear unprotected street clothes on the job; smocks or lab coats must be worn over street clothes.
Gloves and Sleeve Guards: Single-use sanitary gloves approved for food contact use shall be worn by all personnel who handle exposed in-process materials, finished products, product-contact packaging components, or equipment product–contact surfaces. Gloves must always be intact and kept clean, and they must be replaced whenever they become damaged or contaminated.
Hair Restraints: Personnel must wear approved hairnets in GMP-controlled areas. Hairnets must be worn over the ears in a manner that covers all hair. Mustaches and beards must be covered with a beard/mustache cover.
Face Masks: Face masks that cover the nose and mouth shall be worn by all personnel who handle exposed in-process materials, finished products, product-contact packaging components, or equipment product–contact surfaces.
Shoes: Prior to entering any GMP-controlled area, all personnel must wear appropriate shoe covers. Open-toe shoes may not be worn in any packaging or warehouse areas of the plant.
Hand Sanitation: Hands must be thoroughly washed using liquid soap and hot water and dried using single-use paper towels or air dryers before starting work, after breaks, after using restrooms, after leaving the packaging area, or whenever hands become contaminated.
Jewelry Policy: Personnel who work in packaging areas are not permitted to wear jewelry such as chains, necklaces, bracelets, and watches.
Typically, in the packaging of dietary supplements, an environmental program includes monitoring the quality of air and water.
The most commonly used techniques for monitoring the quality of the air are active and passive air monitoring.
In active air monitoring, a known volume of air is collected and passed through a particle-collection device, which analyzes the quantity of microorganisms present in the air. The unit of measure is CFU (colony forming units)/m3 of air.
In passive air monitoring, standard petri dishes containing culture media utilizing the settling plate technique are used to determine the air quality in the packaging and warehouses. This procedure includes labeling the bottom of the petri dish with the sample location and sampling date, removing and placing the lid under the petri dish, allowing the settling plate to remain open in the sampling location for 60 minutes, then replacing the lid. Incubate settling plate at 25 ± 1°C for five (5) days, read plates, and document the test results. The unit of measure is CFU (colony forming units)/m3 of air.
As per 21 CFR Part 111.15(e)(2), water that becomes a component of a finished product or that contacts components or product-contact surfaces at a minimum must comply with applicable federal, state, and local requirements and not contaminate the dietary supplement.
Water in a dietary supplement packaging facility is primarily used for personnel use, facilities cleaning, equipment cleaning, and microbiological testing. Even though the water is not used as an ingredient in the packaging of dietary supplements, it is recommended to use purified water for cleaning product-contact surfaces. Typically, the steps involved in purification of water are activated carbon filtration, deionization, micron cartridge filtration, and ultraviolet disinfection.
On a continuous basis, it is very important to monitor the quality of the incoming water supply and purified water. The typical quality parameters that are monitored are conductivity and microbiological impurities. The frequency of testing is determined based on the risk assessment and the trend analysis. Water in the packaging operation of dietary supplements is primarily used for cleaning and sanitation purposes. So, monitoring the water quality is very important for analyzing the controls.
Cleaning of the Packaging Equipment
As per 21 CFR Part 111.27(d), all the equipment, utensils, and any other contact surfaces used to manufacture, package, label, or hold components or dietary supplements must be maintained in clean and sanitary conditions. Cleaning procedures should be developed to be effective at removing product residues and residues of cleaning agents within established acceptance limits in order to minimize the risk of product cross-contamination as well as chemical and microbial contamination of dietary supplements.
The cleaning verification methods that are commonly utilized to evaluate the effectiveness of cleaning procedures are:
Visual Inspection: Visual inspection is effective in determining the cleanliness of packaging equipment and should never be unsatisfactory.
Rinse Water Sampling and Analysis: Cleaning chemicals contain ionic constituents that are inherently alkaline or acidic; therefore, following cleaning of product-contact packaging equipment, analysis of rinse water for the presence of trace amounts of product from the previous run, and traces of cleaning agents, provides excellent indirect evidence of the cleanliness of the equipment.
Adenosine Triphosphate (ATP) Swab Method: ATP is present in all biological material, including bacteria, yeast, and mold. The detection of ATP on the surface of product-contact packaging equipment is an indirect method of cleaning. Relative Light Units (RLU) as measured by the Luminometer, and ATP testing swabs correlate with the amount of ATP present on a surface.
In conclusion, training employees on hygienic practices, implementing documented procedures for monitoring the quality of air and water, and verifying cleaning of the packaging equipment will not only minimize the prevention of cross-contamination but also helps to ensure compliance with FDA’s Good Manufacturing Practices Regulations for Dietary Supplements.
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.