Acceptance Limits for the New ICH USP 29 Content-Uniformity Test - Pharmaceutical Technology

Latest Issue
PharmTech

Latest Issue
PharmTech Europe

 Pharmaceutical Technology All results
Acceptance Limits for the New ICH USP 29 Content-Uniformity Test
Revisions to the United States Pharmacopeia's (USP) uniformity test require manufacturers to establish new acceptance limits. The authors present their method for calculating acceptance limits consistent with USP's revised content-uniformity test requirements.
 Oct 2, 2007 Pharmaceutical Technology

n = number of observations at each location

Then the upper confidence limit for the sum of the between-location and within-location variance components (i.e., σ) is:

Given the sample within-location standard deviation (SE) and the sample between-location standard deviation (SM), one computes a confidence interval for σ using the Graybill–Wang method. Since the sample mean and mean squares for the between-location and within-location standard deviations are independent, the overall confidence level (1– α) is the product of the two individual confidence levels for μ and σ. Each individual confidence level is the square root of the overall confidence level (μ is two-sided and σ is upper one-sided). One can generate an acceptance limit table by finding the largest combinations of within- and between-location standard deviations for a fixed sample mean, such that the resulting confidence region remains below the prespecified LBOUND.

Sample content uniformity acceptance limit tables

Tables assume that the target (i.e., the average of potency specification) is 100% and that the sampling plan is to test one dosage unit from each of n separate locations throughout the batch. Passing the tabled limit ensures, with the chosen level of confidence, that there is at least a 95% chance of passing the USP uniformity of dosage units test ‹905› for samples taken from that batch.

James S. Bergum, PhD,* is an associate director in the nonclinical biostatistics department of Bristol-Myers Squibb, One Squibb Dr., New Brunswick, NJ 08903, tel. 732.227.5981,
Hua Li, PhD, is a vice-president of management science at Merrill Lynch & Co.

*To whom all correspondence should be addressed.

Submitted: Feb. 16, 2007. Accepted: Aug. 20, 2007.

| Weekly
| Monthly
|Monthly
| Weekly
 Survey
What do you think the role of continuous (rather than batch) processes in pharmaceutical manufacturing will be over the next five years?
Many companies in the industry will be using continuous processes for some products.
Companies in both pharmaceutical and biopharmaceutical production will be evaluating continuous processes but few will implement.
Only a few companies will be evaluating or implementing; most will stay with batch processing.
Many companies in the industry will be using continuous processes for some products. 34%
Companies in both pharmaceutical and biopharmaceutical production will be evaluating continuous processes but few will implement. 29%
Only a few companies will be evaluating or implementing; most will stay with batch processing. 38%
Most Viewed Articles
 Columnists Outsourcing Outlook Eric LangerNovel Expression Systems Opening CMO Opportunities sponsored by Ingredients Insider Cynthia Challener, PhDSecuring the Global API Supply Chain Regulatory Watch Jill Wechsler FDA Focuses on Drug Appearance and Attributes European Regulatory WatcchSean MilmoEMA Collaborates with HTA Assessment Networks
 UPCOMING CONFERENCES Serialization Summit San Diego, CA Feb. 27-28, 2014 Advances in Aseptic Processing San Diego, CA Mar. 10-12, 2014 ClinTech 2014 Cambridge, MA Mar. 11-13 2014 Investigator-Initiated and Sponsored Research (IISR) Philadelphia, PA Mar. 19-20 2014 See All Conferences >>
 VALIDATION RESOURCES FROM IVT NETWORK Process Validation Special Editions 19th Annual Validation Week Compendium Computer and Software Validation Volume II Special Edition Analytical Method Validation Toolkit More from IVT