There are several distinct markets that are served by the Analytical Testing Division. They include Pharmaceutical, Nutraceutical, Medical Device, API (Active Pharmaceutical Ingredient), NDI (New Dietary Ingredient) and Post Sterilization Testing. Two of these categories, API and NDI require additional explanation. Their definitions are as follows:
API -An API is an active pharmaceutical ingredient, or the actual drug substance that is added to a product. The FDA has recently begun to monitor the manufacturing of API’s as closely as the manufacture of the finished drug substance. An API manufacturer must meet all the requirements of a finished drug manufacturer in that the API manufacturer must test their raw materials, in process product and finished product against established specifications. The most important tests here are purity and impurities. The tests can include titrations, HPLC, GC, AA, and others.
NDI – The newest FDA actions have centered around the nutraceutical industry and what the FDA expects from nutraceuticals. One such action by the FDA is to have the nutraceutical market identify their ingredients that carry a health benefit, prove that the substance yields the health benefit, and test to ensure that the material meets the same strenuous requirements established for drug substance manufacturers (API’s).
In each of the main categories listed above, with the exception of Post Sterilization, the same types of tests are required, each being varied to meet the requirement so the industry they are in, the type of product, and the certification desired. In general, the main types of testing that apply to all of these categories are as follows:
In Process Testing
In process testing includes production samples during the processing and prior to filling the product to ensure that the compounded product meets specifications. This testing is routinely performed when processes have not been validated and there is no assurance that the product that has been produced meets finished product specifications. The tests that are normally performed include tests to ensure purity, efficacy, and concentration. The tests can include titrations, HPLC, GC, AA, and others.
Finished Product Testing
Finished product testing must be performed routinely as a requirement by the FDA. All finished products for FDA regulated businesses must be tested prior to distribution. The tests that are performed ensure that the product meets established specifications and that these specifications account for its purity, integrity, efficacy, and concentration. The tests can include titrations, HPLC, GC, AA, and others.
Raw Material Testing
In closely regulated FDA businesses, companies are required to test the chemicals that they use to make finished products. This testing is difficult and very time consuming. Companies who have not qualified their suppliers must test each arriving lot of material. The FDA requires that each raw material at least be identified by an acceptable means to ensure that it is the right chemical. Most chemicals that are purchased have at least 7 tests per chemical and these tests are found in the USP. Most chemicals require approximately 2 full days of a chemist to complete. The most important tests here are purity and impurities. The tests can include titrations, HPLC, GC, AA, and others.
All products that carry an expiry date must have a series of tests to confirm that the expiry date is correct. These tests are performed according to world wide acceptable means and are performed under extreme conditions and at normal conditions (consumer use in the home). The testing that is required ensures for at least 5 extreme interval condition tests and at least 6 normal or room temperature interval conditions. The tests that are performed at each interval are the same tests performed on the finished product. The tests can include titrations, HPLC, GC, AA, and others.
Post Sterilization Testing
Many sterilizing methods degrade the finished product rapidly. The FDA and the manufacturers want to ensure that the products did not receive more sterilizing than necessary and that the sterilization did not degrade the product too severely. Further, some sterilization techniques may leave residuals that are harmful. The products must be tested for these residuals. Most of this testing revolves around medical devices. This testing may not be performed each time, depending on the company’s validation efforts.
Ethylene Oxide Testing
One of the most difficult, but most routinely used sterilization techniques for medical devices is ethylene oxide. This is a chemical process and the residual chemicals must be tested after each sterilization process to ensure that the residuals are not present. The residual chemicals are highly toxic and should not be released to the consumer. The testing for ETO is outlined by national and international groups such as AAMI and ISO. (American Association of Medical Instruments and EU quality group, International Standards Organization).
Product Degradation Studies
In addition to routine stability tests and due to sterilization techniques, the FDA has begun to investigate separately the determination of degradants and their impact on the patient. The degradation is forced on the final product to show that oxidation, heat, light, acid, caustic, and other similar natural degradants do not shorten the life of the product.
Product Aging Studies
With medical devices, the stability study to determine shelf life is performed differently and is classified as an aging study. Within these studies, the product is tested for a number of factors that are predetermined to ensure that the product continues to meet the consumer requirements up to the expiry date. Most of the conditions are extreme to ensure compliance and speed the product to market.