Where different procedures are used for assay of the preparation and. Content uniformity and dissolution acceptance limit program cudal cudal is a set of programs written in sas version 8. An fdas primary concern was a lack of confidence that the results from usp uniformity of dosage units testing ensure the content uniformity of a batch. The uniformity of dosage units general chapter was incorporated into and became official with the second supplement to usp 34nf 29. Blend uniformity in accordance with fda guidance for industry, andas. Blend uniformity bu is critical to achieving consistent content uniformity of. Content uniformity test suitable for large sample sizes, drug information journal 40 3, 337344 2006.
At first glance, the acceptance criteria for the content uniformity calculation in usp chapter 905 seem somewhat daunting. Determination and acceptance limits of uniformity of. For different sample sizes, such as n 10 and 30, their av distributions will be different in pattern, thus resulting in different critical av values i. As per usp general chapter, to ensure the consistency of dosage units uniformity of dosage unit test is performed.
Uniformity of mass of doses delivered by the measuring device. Status of general chapter usp nf general chapter uniformity of dosage units type of posting. Uniformity of dosage units test procedure all measurements of dosage units and criteria values are in percentage label claim %lc. The united states pharmacopeia the japanese pharmacopeia. Sampling plans are used to provide blend samples or dosage units that will be tested to support release of manufactured batches, process validation, or for process understanding. The term uniformity of dosage unit is defined as the degree of uniformity in the amount of the drug substance among dosage units. These criteria are different from the old criteria which were based on performing a simple arithmetic mean and standard deviation calculation. Dosage units are defined as dosage forms containing a single dose or a part of a dose of drug substance in each unit. Inprocess dosage units must be sampled over the entire batch to assure the entire blender is uniform, including beginning and end of run weight correction is not allowed when using dosage unit content uniformity data for batch release if the inprocess dosage unit is not the final dosage form e. Guidance for industry food and drug administration. Uniformity of dosage units bp 2011, usp 34 usp 28nf 23 harmonized general chapter on page 25052510 with an implementation date april 1, 2006 approved by the pharmacopeial discussion group pdg usp postponed the implementation date to january 1, 2007. The uniformity of dosage units specification is not intended to apply to suspensions, emulsions, or gels in unitdose containers intended for topical administration.
The uniformity of dosage units can be evaluated either by measuring the content uniformity or the weight of the tested units green et al. United states pharmacopeia usp is also considering the. The weight variation procedure can be used where permitted as detailed in table 1. Spreadsheet for usp content uniformity calculation. Sampling considerations for udu release testing in. The content uniformity method may be applied in all cases. Content uniformity select not less than 30 units, and proceed as follows for the dosage form designated.
The fda withdrew the draft guidance document for industry powder blends and finished dosage unitsstratified inprocess dosage unit sampling and assessment. Definition harmonized general chapter usp 34 uniformity of dosage units bp 2011 appendix xii c. Content uniformity acceptance testing for large sample sizes. Calculation of acceptance valuecalculate the acceptance value by the formula. Establishing acceptance limits for uniformity of dosage.
The manufacture of lowdose oral solid dosage form to. Pharmacopeia usp manual states that each unit within a single lot of a given medication should have drug substance content that is within a narrow range around the labeled claim. In addition, the article proposes an approach that allows regulatory agencies and compendia to clearly state allowable consumer risk. Witinee kongsuk bureau of drug and narcotic department of medical sciences june 14, 2011 1 uniformity of dosage units bp 2011, usp 34 outline. Weight variation wv test can be done only on certain unit dose as shown in table 1. The test for content uniformit y is based on the assay of the individual content of drug substances in a number of individual dosage units to determine whether the individual content is within the limits set. Status of general chapter uniformity of dosage units type of posting. Dosage units are defined as dosage forms containing a single dose or a part of a dose of an active substance in each dosage unit. Tools for blend and content uniformity assessment ispe. The test for content uniformity is based on the assay of the individual content of drug substances in a number of individual dosage units to determine whether the individual content is within the limits set.
Establishing acceptance limits for uniformity of dosage units. The uniformity of dosage units can be demonstrated by either of two methods, content uniformity or weight variation see table 1. The requirements of this chapter apply both to dosage units containing a single active ingredient and to dosage units containing two or more active ingredients. Contains nonbinding recommendations draft not for implementation g. The requirements of this chapter apply both to dosage units containing a single.
Bua or homogeneity testing can be applied to all dosage forms, but is recommended for those dosage forms for which the usp requires content uniformity testing. The degree of uniformity in the amount of the active. Ppt uniformity of dosage units powerpoint presentation. As part of the international conference on harmonization ich effort, the us pharmacopeia usp has revised general chapter 905, uniformity of dosage units.
Process validation sampling plans there is a wide body of literature on sampling. At each stage calculate the sample average, x, and the sample. Weight and content uniformity of lorazepam halftablets. Avthe only quality attribute in uniformity of dosage units udu. In uniformity of dosage units udu test, the single limit for acceptance value av of not more than nmt 15 cannot discriminate between the conforming and nonconforming lots of products. Uniformity of dosage units 1 is one of the most commonly employed compendial tests to evaluate the dosage units.
The uniformity of dosage units can be demonstrated by either of two methods, weight variation or content uniformity. The content uniformity procedure may be used in all cases. Ich guideline q4b annex 6 to note for evaluation and. Liquid preparations for oral use are often the dosage form of choice for paediatric use. Therefore, the requirements of this chapter apply to each drug substance being comprised in dosage units containing one or more drug substances, unless otherwise specified in the individual monograph. To ensure the consistency of the dosage units each unit in a batch should have an active substances content within a narrow range around the label claim. The uniformity of dosage units can be demonstrated by either of the two methods. The weight variation procedure may be used for products for which it is permitted.
Uniformity of dosage units european pharmacopoeia 7. Uniformity of dosage units official december 1, 2011 in conditions of normal use, and express the results as dein which the terms are as defined in table 2. The usp content uniformity cu test methodology for batch release includes testing of individual doses of finished pharmaceuticals to ensure that the product meets quality specifications. It includes current chapter revision status, background information, testing. Uniformity of dosage unit usp maintaining relevance jon clark, vp industry standards and collaboration. Dosage units are defined as dosage forms containing a single dose or a part of. W is the weight, in mg, of clopidogrel in the portion of tablets used to prepare the test solution based on the labeled quantity of clopidogrel per tablet, tablet weight, and the weight of the portion of tablets used. The study of the applicability of content uniformity and. N ote in this chapter, unit and dosage unit are synonymous. Content uniformity t gc for demonstrating uniformity of dosage units 9 table 1. Application of content uniformity cu and mass variation mv test for dosage forms dosage forms type subtype dose and ratio of active substance. Situation compendial expectation 30 units for any product general notices 3. Usp udu test 5 usp test is a compendial criteria used to ensure that every dosage unit contains the amount of drug substance intended with little variation within a batch. The preparation complies with the test if not more than one of the individual contents of the total sample of 30 dosage units is outside 85 to 115 percent of the average content and none is outside the limits of 75 to 125 percent of the average content.
In weight variation test, measurement of contents is done by estimation of contents based on weight. The revision became official on january 1, 2007 through the sixth interim revision announcement to usp 29nf 24 in pharmacopeial forum 1. Contents uniformity weight or volume of packaged dosage forms. Usp general chapter 905 uniformity of dosage units. Further, the article suggests that producers be allowed to control producer risk through selection of numbers of units and testing tiers. Astm standard e2810 provides a methodology for establishing confidence in passing the usp uniformity of dosage units udu test, and provides acceptance limits for sample means and standard. The developed method was found precise, linear, rugged and robust for validated. Units, and united states pharmacopeia usp general chapter uniformity of dosage units, can be used as interchangeable in the ich regions subject to the following conditions. To ensure the consistency of dosage units, each unit in a given batch should contain the active drug within a narrow range around the label claim. It is highly recommended to read these references and predict what particle size and distribution is needed to achieve usp cu for an oral solid dosage form, especially for a lowdose oral solid dosage form. Analysis of drug content and weight uniformity for half. Ispe sponsored the blend uniformity and content uniformity group.1082 339 250 1346 421 855 935 926 706 1388 1052 771 429 1054 1012 948 1299 1184 316 1292 476 1080 1229 751 160 156 331 589 276 19 1217 1453 1092 778 724 293