Full Tolerance Coverage Method for Assessing Uniformity of Dosage Units with Large Sample Sizes
The ‘full tolerance coverage method’ is introduced as a coverage estimation approach for assessing the uniformity of dosage units from large sample sizes, ensuring that no dosage unit exceeds the specification range.
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Abstract
The requirements for uniformity of dosage units using large sample size data collected and analyzed from process analytical technology (PAT) processes can be met by applying either United States Pharmacopeia (USP) <1099> Limit on Number of Large Deviations When Assessing Content Uniformity in Large Samples or European Pharmacopoeia (Ph. Eur.) 2.9.47 Uniformity of Dosage Units Using Large Sample Sizes. However, both methods are designed to detect the number of dosage units falling outside the specification range of 75–125% of the label claim (% LC) to determine whether these numbers do not exceed the predetermined values based on the sample size.The ‘full tolerance coverage method’ is introduced as a coverage estimation approach for assessing the uniformity of dosage units from large sample sizes, ensuring that no dosage unit exceeds the specification range.
Peer-Reviewed
Submitted: Nov. 25, 2024
Accepted: Jan. 17, 2025
In United States Pharmacopeia (USP) <905> Uniformity of Dosage Units (UDU; using small sample sizes) (1), the acceptance value (AV) limits are statistically adjusted (95% coverage) (2) and reintroduced in (3; Figure 1). However, a key weakness is that the AV result does not adequately describe the specific characteristics of UDU. To address this limitation, the application and use of tolerance intervals are extensively discussed in the article,“Using Tolerance Intervals to Assess Conformance to Requirements” (4).
To address the small gaps between the calculated tolerance intervals and specification ranges, the upper and lower tolerance limits (UTL and LTL) are set at 115% and 85% label claim (LC), respectively. The tolerance coverages above and below the mean are estimated and summed to obtain what is called “full tolerance coverage” (FTC), yielding a value close to 100%. Because the sample mean is directly used, larger sample sizes provide a more accurate batch mean estimate. Therefore, the FTC method is more practical and suitable for assessing UDU data in production batches, particularly those monitored through process analytical technology (PAT) instrumentation.
Click here to read the articleAbout the author
Pramote Cholayudth, cpramote2000@yahoo.com, is the founder and manager of PM Consult. He is an industrial pharmacist with more than 40 years of experience. He is a guest speaker on process validation to industrial pharmaceutical scientists organized by Thailand’s FDA.
Article details
Pharmaceutical Technology®
Vol. 49, No. 2
March 2025
Pages: 18-23
Citation
When referring to this article, please cite it as Cholayudth, P. Full Tolerance Coverage Method for Assessing Uniformity of Dosage Units with Large Sample Sizes. Pharmaceutical Technology 2025 49 (2).
