Sample preparation composite and replicate strategy for assay of solid oral drug products.
In pharmaceutical analysis, the results of drug product assay testing are used to make decisions regarding the quality, efficacy, and stability of the drug product. In order to make sound risk-based decisions concerning drug product potency, an understanding of the uncertainty of the reportable assay value is required. Utilizing the most restrictive criteria in current regulatory documentation, a maximum variability attributed to method repeatability is defined for a drug product potency assay. A sampling strategy that reduces the repeatability component of the assay variability below this predefined maximum is demonstrated. The sampling strategy consists of determining the number of dosage units (k) to be prepared in a composite sample of which there may be a number of equivalent replicate (r) sample preparations. The variability, as measured by the standard error (SE), of a potency assay consists of several sources such as sample preparation and dosage unit variability. A sampling scheme that increases the number of sample preparations (r) and/or number of dosage units (k) per sample preparation will reduce the assay variability and thus decrease the uncertainty around decisions made concerning the potency of the drug product. A maximum allowable repeatability component of the standard error (SE) for the potency assay is derived using material in current regulatory documents. A table of solutions for the number of dosage units per sample preparation (r) and number of replicate sample preparations (k) is presented for any ratio of sample preparation and dosage unit variability.
Pfizer Worldwide Research and Development , Statistics, 558 Eastern Point Road, Groton, Connecticut 06340, United States.
Brent
B
Harrington
Beverly
B
Nickerson
Michele Xuemei
MX
Guo
Marc
M
Barber
David
D
Giamalva
Carlos
C
Lee
Garry
G
Scrivens
D000284:Administration, Oral; D001681:Biological Assay; D002214:Capsules / Q000737:chemistry; D002623:Chemistry Techniques, Analytical; D002626:Chemistry, Pharmaceutical / Q000379:methods* / Q000592:standards*; D011786:Quality Control
D002214:Capsules