Development of a Content Uniformity Test Suitable for Large Sample Sizes
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Dennis Sandell, PhD PhRMA CM6.C Statistics Expert Team, AstraZeneca, Lund, Sweden Kim Vukovinsky PhRMA CM6.C Statistics Expert Team, Pfizer. Groton, Connecticut Myron Dierer PhRMA CM6.C Statistics Expert Team, sanofi aventis Group, Kansas City, Missouri
Jeff Hofer PhRMA CM&C Statistics Expert Team, Eli Lilly and Company, Indianapolis, Indiana James Pazdan PhRMA CMCC Statistics Expert Team, Novartis, East Hanover. New Jersey
Development of a Content Uniformity Test Suitable for Large Sample Sizes Applications of process analytical technology (PAT) are currently attracting wide interest. One of the potential applications of PAT is Iarge-scale (hundreds or thousands of tablets), real-time evaluation of tablet content uniformity An issue associated with this situation is which acceptance criteria the obtained large sample should meet. Traditionally, a sample of 10-30 tablets is assessed against criteria specified in the harmonized pharmacopeial specification for uniformity of dosage units (UDU). These criteria, howeve6 are not directly applicable to large sample sizes as application of the
acceptancecriteria in the harmonized pharmacopeial specification in these situations results in an ovdy restrictive requirement. Industry has highlighted this issue as a potential deterrent for extended applications of PAT in this area. A one-tiered counting test for UDU with associated acceptance criteria is proposed as an alternative to the harmonized pharmacopeial specification for UDU. The proposed test is applicable to large sample sizes yet provides the same assurance of uniformiv of the batch as the harmonized pharmacopeial specification.
loop limmermans, PhD PhRMA PAT Expert Team, Pfizer. Mom's Plains. New Jersey
Key Words Process analytical technology (PAT); Uniformity of dosage units (UDU); Specification; Coverage; Counting test Correspondence Address Dennis Sandell, AstraZeneca R6.D Lund, S-221 87 Lund, Sweden (e-mail: dennis.sandell@ astrazeneca.com).
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INTRODUCTION Applications of process analytical technology (PAT) are currently attracting wide interest from both regulators and the pharmaceutical industry. The vision for the future includes improved understanding of manufacturing processes through nondestructive measurement techniques. Methods such as transmission or reflectance spectroscopy (eg, near infrared), together with statistical modeling of the obtained spectrum facilitate fast and precise measures. Such techniques can significantly increase testing in real time and thereby open the possibility of improved control as well as introduction of adaptive high-tech manufacturing. In such scenarios, the added value of traditional release testing based on a random sample from the batch can be (and is) questioned. One of the potential applications of PAT is real-time evaluation of tablet content uniformity. Although testing of all units in a batch is currently not achievable, large-scale monitoring of hundreds or even thousands of tablets is technically feasible. One issue related to this situation, currently b
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