Question and Answer Section

William Brown and Margareth Marques
Will Brown and Margareth Marques share responsibilities as liaisons to the USP Expert Committee on Biopharmaceutics. United States Pharmacopeia, Rockville, MD
Email for correspondence: web@usp.org

Q ­ Why are the ranges for the USP calibrator tablets different from one lot to the next?
A ­Each lot of USP calibrator tablets should be viewed as a unique product. As the USP works to improve the calibrators through formulation changes and new manufacturing processes, lot-to-lot differences may be observed. For each lot of USP calibrator tablets the ranges are defined following analysis of the results of a multi-site collaborative study involving laboratories from the USP, FDA, pharmaceutical companies and other facilities from around the world. Additionally, as has been seen recently with Prednisone Tablets, Lot N, the test conditions can be changed by the Biopharmaceutics Expert Committee as a result of their review of data.

Q ­ Where can I obtain copies of the USP calibrator tablets information sheets?
A ­The information sheets are available through the USP Web site (ww.usp.org/standards/index) under "Official Dissolution Calibrator Ranges for Prednisone and Salicylic Acid Tablets." Just click on the product you are interested in.

Q­ Should I fill out an "Out of Specifications" report if the product does not meet the Tolerances in S1 and needs to be tested as S2?
A ­ No. The Acceptance tables in the USP General Chapter <711> Dissolution are part of the test. Going to S2 or S3 does not mean that your product is failing the test. Your product fails the dissolution or drug release test only if it does not meet the acceptance criteria for S3 or L3, respectively.

Q­ In the USP general chapter <711> Dissolution, under Apparatus Suitability Test, it says to test 1 tablet of the USP Dissolution Calibrator, Disintegrating Type and 1 tablet of the USP Dissolution Calibrator, Nondisintegrating Type. Does it mean that I need to check just one of the vessels in my equipment? Which one should be tested?
A - The USP general chapter <711> Dissolution contains the instructions to test one vessel because any number of different configurations for dissolution apparatus are available on the market with one, six, eight, or twelve vessels. You need to carry out the Apparatus Suitability Test in each one of the vessels in your apparatus simultaneously.

Remember that each vessel will be used as part of a total system in which no single unit can be separated from the whole. Thus vibration produced from one drive spindle may have an effect on the conditions in the surrounding vessels and the load on the drive from all of the stirring elements working against the contents of all vessels is a part of the apparatus design. Running individual positions separately does not represent a valid test of the suitability of the whole apparatus.

Q ­ How often should I do the calibration of my dissolution apparatus?
A ­ USP does not specify the frequency of dissolution apparatus calibration because it depends on how often you use your equipment, where the equipment is located, if your equipment has been moved from one bench to another, etc. It is up to your lab to establish, through an appropriate SOP, the calibration schedule of the dissolution apparatus. We know that there are some companies that calibrate the equipment before and after important projects. Furthermore, the FDA GMP regulations need to be taken into consideration when designing a calibration schedule.

Q ­ How can I learn more about the USP approach to dissolution testing?
A ­ USP offers a course on the Fundamentals of Dissolution that is taught by USP dissolution experts. The course also offers an opportunity to work with the USP calibrators on a variety of manufacturers' testers. For details, contact Barbara Hubert, Director, Pharmacopeial Education, at 301-816-8333 or via e-mail at PharmacopeialEducation@usp.org.