Packaging and USP Standards

Packaging and USP Standards

by Douglas M. Williams

Although standards for pharmaceutical products are well established and commonly used, the standards for dietary and nutritional supplements are still in the infant stages of development. Because of this, many manufacturers of nutritional supplements voluntarily follow the same standards required of pharmaceutical manufacturers to ensure product integrity. These standards include those outlined in the United States Pharmacopeia (USP), a not-for-profit, volunteer-based, private organization that sets legally recognized standards of identity, quality, strength, purity, packaging and labeling of health care-related products.

"USP seeks to establish standards appropriate to the packaging, storage and distribution of drugs and other compendial articles to assure their continued quality from the time they leave the manufacturers' shipping docks through the distribution warehouses and pharmacies until they are dispensed to patients," stated Jerome A. Halperin, former executive vice president and chief executive officer of USP. "We fully understand that once the product is in the hands of the [consumer], it is beyond the control of the manufacturer, shipper, wholesaler, or pharmacist. However, we believe that through cooperation, USP and industry representatives can reach consensus on standards to protect the quality and strength of drugs in transit so that patients receive the high-quality drugs they expect, thereby serving the public health." Although Halperin was referring specifically to pharmaceuticals, the sentiment is also highly applicable to the manufacturers of dietary supplements and the closures and containers in which they are packaged.

USP monographs outline many of the requirements for pharmaceuticals, and responsible manufacturers of nutritional supplements have adapted their processes to meet those guidelines. In addition to its monographs, the USP recently launched a pilot program that will form the basis for a nationwide effort to assess the quality of dietary supplement ingredients and their packaging.

Two USP Tests for Product Quality

For those manufacturers that supply closures and containers to the pharmaceutical industry, USP 24 <661> and USP 24 <671> define the packaging properties that will maintain the highest level of product quality. The dietary supplement industry has adopted those same regulations. Containers and closures used to package dietary supplements typically include HDPE, PET, unit dose blisters, pouches and blister cards. Because the ingredients intended for these packages can be sensitive to moisture, light, oxygen and heat, it is vital that the packaging prevents disintegration of the product.

Tests performed under USP 24 <671> are used to determine the moisture permeability of containers utilized for prescription drugs. These tests are completed on packages intended for dispensing dry prescription drugs in oral dosage. The testing is used to gauge the moisture permeability for multiple unit containers that will be used for capsules and tablets. Because a wide variety of the ingredients used in dietary supplements degrade under moist conditions, it is extremely important that closures and containers resist moisture and humidity.

A product that meets <671> requirements must go through an exacting regimen. Testing is conducted on sealed containers and containers that have been opened and then resealed. The testing consists of a desiccant of set quantity 4-8 mesh, anhydrous calcium chloride being first dried at 110 degrees for one hour and cooled in a desiccator. Then 12 containers of uniform size are selected, opened and closed 30 times each. Closures are applied to the torque specified in the USP monograph. Desiccant is then added to 10 of the packages labeled test containers. These are then filled to within 13 mm of the opening on containers larger than 20 ml and to two-thirds full on containers smaller than 20 ml. The closures are then applied to the torque specified in the monograph.

Weight is recorded to the nearest 0.1 mg for containers smaller than 20 ml, to the nearest mg for 20 ml to 200 ml, or to the nearest centigram if the container is larger than 200 ml. The containers are stored at 75 percent, plus or minus 3 percent, with relative humidity at a temperature of 23 degrees, plus or minus two degrees. After 336 hours, plus or minus one hour, the weight is recorded, with the moisture permeability calculated in milligrams per day, per liter.

The containers are considered "tight" containers if 90 percent of the test containers do not exceed 100 mg per day, per liter, in moisture permeability; none can exceed 200 mg per day, per liter.

The containers are considered "well-closed" containers if not more than one of the test containers exceeds 2,000 mg per day, per liter, in moisture permeability and none exceed 3,000 mg per day, per liter.

Tests performed under USP 24 <661- Polyethylene> characterize high density and low density polyethylene containers that are suitable for packaging dry oral dosage forms not meant for solution. This includes analysis of the container's resistance to light and a determination of heavy metals and extractables. The following physical tests are performed in accordance to USP 24 <661>:

USP 24 <661> also has test procedures for Polyethylene Terephthalate (PET) and Polyethylene Terephthalate G (PETG). Since there are no USP monographs that specifically address closures, USP <671> and <661> are used to ensure package integrity in that area.

Future of USP National Program

To further assist in product integrity for nutritional supplements, in February of this year, the USP announced the launch of a voluntary pilot program to assess the quality of dietary supplement ingredients. The program is intended to fulfill the need for a standards certification program for dietary supplements and botanicals. The program will include testing of ingredient samples by the manufacturer, with a USP review of the test results, post-marketing product surveillance by the USP and compliance with the principles of good manufacturing processes.

Doug Williams is the business development manager for Rexam Closures & Containers, where he is responsible for new package design and development. He can be reached at[email protected].