Where different procedures are used for assay of the preparation and. Weight variation content uniformity is applied when tablet or capsules having. 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. These dosage forms include coated tablets, other than film coated tablets transdermal systems suspensions in singleunit containers or in soft capsules. The concept of acceptance value must be redefined to remove bias and more closely reflect quality targets. A unit of potency of drugs, used in the united states pharmacopeia. Guidance for industry food and drug administration. In weight variation test, measurement of contents is done by estimation of contents based on weight. Blend uniformity bu is critical to achieving consistent content uniformity of. At each stage calculate the sample average, x, and the sample.
The degree of uniformity in the amount of the active. The uniformity of dosage units can be demonstrated by either of the two methods. Ppt uniformity of dosage units powerpoint presentation. Establishing acceptance limits for uniformity of dosage units. Annex 6 uniformity of dosage units general chapter fda. Comments concerning revised texts published in supplement 9. November 29, 2006 demystifying the standardssetting.
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. It includes current chapter revision status, background information, testing. In the test, the acceptance value av is the key statisticsbased acceptance parameter with the limit of not more than 15 to measure the uniformity degree of the dosage units in terms of content uniformity or weight variation as. Weight variation wv test can be done only on certain unit dose as shown in table 1. The united states pharmacopeia the japanese pharmacopeia. Oct 07, 2011 blend uniformity in accordance with fda guidance for industry, andas. Added content uniformity procedure and criteria for semi solid dosage forms, and instructions to assay 10 units. Dosage units are defined as dosage forms containing a single dose or a part of a dose of drug substance in each unit.
The acceptance value of the first 10 dosage units is less than or equal to l1%. Uniformity of dosage units to ensure the consistency of dosage units, each unit in a batch should have an active substance content within a narrow range around the label claim. The uniformity of dosage units specification is not intended to apply to suspensions, emulsions, or gels in unit dose containers intended for topical administration. Learning the language of the usp chapter 2 brief history of the united states pharmacopeia national formulary chapter 3 usp publications. The weight variation procedure may be used for products for which it is permitted. The content uniformity method may be applied in all cases. Uniformity of weight of tablets and capsule tf lab 1. Table 51 provides a summary of tests discussed in chapter 5. The user inputs the content uniformity data and the spreadsheet provides summary statistics and a data plot. 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. Should you have any questions, please contact desmond hunt, ph. If the firm experiences problems in collecting small samples equivalent to 1 to 3 dosage units and demonstrates that small samples give lower values for bua due to sampling bias, larger samples usually no more than 10 dosage units can be collected. Therefore, the requirements of this multiple nal chapter apply to each drug substance being comprised in compo container wv wv dosage units containing one or more drug substances, unnents.
Pharmacopeia, rockville, md, usa u sp has been an important proponent of dissolution testing since the late 1960s when a usp and nf joint panel on physiological availability decided on dissolution as a test and described the apparatus that would be used. Determination and acceptance limits of uniformity of. Definition bua is an inprocess test that is useful for ensuring the adequacy of the mixing of active pharmaceutical ingredients apis with other components of the drug product. Buablend uniformity analysis 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. 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. Previous authors have estimated this impact but use of different particle size descriptors led to confusion and difficulty in applying the theoretical models developed. Blend uniformityin accordance with fda guidance for industry, andas. Further, the article suggests that producers be allowed to control producer risk through selection of numbers of units and testing tiers. Blend uniformity analysis, 1999 inprocess control 2. Chapter 6 will elaborate on the api release testing dissolution and disintegration from the solid oral dosage form. For the determination of dosage unit uniformity by assay of individual units, select not fewer than 30 units, and proceed as follows for the dosage form designated. The number of dosage units that should be assayed depends on the magnitude of the risks associated with the process and product.
The usp weight variation method was used for gabapentin split tablets based on the recommendation of the guidance. Usp unit definition of usp unit by medical dictionary. N ote in this chapter, unit and dosage unit are synonymous. With different sample sizes such as n 10 and 30, their av distributions will be different, resulting in different critical av values i. Contents uniformity weight or volume of packaged dosage forms.
Abacavir sulfate impurities organic impurities diluent, solution a, solution b, mobile phase, system suitability solution, standard solution, sample solu. Usp gc for demonstrating uniformity of dosage units 9 table 1. 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. Blend uniformity analysis, 1999 inprocess control scope. Content uniformity acceptance testing for large sample sizes. Content uniformity cu of pharmaceutical dosage units can be affected by active pharmaceutical ingredient api particle size and size distribution. The manufacture of lowdose oral solid dosage form to. Uniformity of dosage units assay doxepin hydrochloride usp 29nf 24 p. Definition blend uniformity in accordance with fda guidance for industry, andas.
This can be demonstrated by two methods, namely, content uniformity and weight variation tests. Pdf demonstration of uniformity of dosage units using. Evaluation of pharmaceutical quality of conventional. Content uniformity process validation learnaboutgmp. Defining the 5 year revision cycle chapter 5 the standard setting process. Uniformity of dosage units are determined from two ways. In the content uniformity test, the individual content of a drug substance in a number of. Weight and content uniformity of lorazepam halftablets. The weight variation procedure can be used where permitted as detailed in table 1. The uniformity of dosage units can be demonstrated by either of two methods, weight variation or content uniformity. See united states pharmacopeia usp 1 for more detail. Uniformity of dosage unit usp maintaining relevance jon clark, vp industry standards and collaboration. Dec 25, 2014 the fda withdrew the draft guidance document for industry powder blends and finished dosage unitsstratified inprocess dosage unit sampling and assessment. Not more than two of the individual weights deviate from the average weight by more than the percentage shown in the table and none deviates by more than twice that percentage.
Other unit dose will need to undergo content uniformity cu test. 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. To take full advantage of the increased batch control that is gained by pat in general and large sample size in particular, there has been a demand for a test method that utilizes large sample sizes to demonstrate compliance with udu. Usp 39nf 34, which was scheduled to become official may 1, 2016. Situation compendial expectation 30 units for any product general notices 3.
Pharmacists often use and misuse this wv test by doing this test on all dosage units. This annex is one in a series of guidance documents that describe the. Status of general chapter uniformity of dosage units type of posting. The revision bulletin will be incorporated in the usp 40nf 35. Uniformity of dosage units 1 is one of the most commonly employed compendial tests to evaluate the dosage units.
The uniformity of dosage units test is used to evaluate content uniformity or weight variation or dosage forms such as tablets and capsules. At each stage calculate the sample average, x, and the sample standard deviation s. 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. Statistical considerations for establishing acceptance.
The uniformity of dosage units general chapter was incorporated into and became official with the second supplement to usp 34nf 29. Making sure you have uptodate information chapter 4 the usp convention process. If a product has standard deviations for the blend andor dosage units that are consistently high, the number of dosage units may be comparable to sample sizes used during process qualification stage 2. Previous authors have estimated this impact but use of different particle size descriptors led to confusion and difficulty in. In addition, the article proposes an approach that allows regulatory agencies and compendia to clearly state allowable consumer risk. Uspnf general chapter uniformity of dosage units type of posting.
The uniformity of dosage units can be demonstrated by solutions in either of two methods, content uniformity or weight unit dose variation see table 1. Usp 39 official monographs abacavir 2283 uniformity of dosage units. Weigh individually 20 units selected at random or, for single dose preparations in individual containers, the contents of 20 units, and calculate the average weight. Abacavir sulfate impurities organic impurities diluent, solution a, solution b, mobile phase, system. Uniformity of dosage unit usp maintaining relevance. The fda withdrew the draft guidance document for industry powder blends and finished dosage unitsstratified inprocess dosage unit sampling and assessment. Uniformity of dosage units, usp 27 page 2396 and page 1587 of.
The uniformity of dosage units specification is not intended to apply to suspensions, emulsions, or gels in unitdose containers intended for topical administration. Uniformity of weight of tablets and capsule introduction. Establishing acceptance limits for uniformity of dosage. The term uniformity of dosage unit is defined as the freezedegree of uniformity in the amount of the drug substance dried in fiamong dosage units. The test for content uniformity of prepacontainers rations presented in dosage units is based on the assay of and into the individual content of drug substances in a number of soft cap. Blend uniformity and content uniformity bucu faqs ispe. It is to do with the activity or potency of a drug. Ispe sponsored the blend uniformity and content uniformity group.
Uniformity of dosage units using large sample sizes. The content uniformity procedure may be used in all cases. Particle size limits to meet usp content uniformity criteria. 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. Uniformity of dosage units testing ensure the content uniformity of a batch. 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. Content uniformity select not less than 30 units, and proceed as follows for the dosage form designated. 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. Bua is an inprocess test that is useful for ensuring the adequacy of the mixing of active pharmaceutical ingredients apis with other components of the drug product.
Pdf demonstration of uniformity of dosage units using large. All whole tablets met the usp acceptance criteria for the uniformity of dosage units. You have to look up what that is for each drug, and convert it. Pdf establishing acceptance limits for uniformity of dosage. Section vii number of samples and the acceptance criteria were based on limits published in usp general chapter uniformity of dosage units this was intentional to avoid any changes to the existing quality standard or an increase number of dosage units to be tested. The test for weight variation is applicable for hard capsules, uncoated tablets and filmcoated tablets containing 25 mg or more of a drug substance. What are the limits for uniformity dosage content for tablets and capsules answer. Dec 21, 20 weight variation wv test can be done only on certain unit dose as shown in table 1. What are the limits for uniformity dosage content for. The uniformity of dosage units can be demonstrated by either of two methods, content uniformity or weight variation see table 1. Where different procedures are used for assay of the preparation and for the content uniformity test, it may be.
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. A variance component analysis is also included for blends with three replicates per location or final dosage units based on either a 20x3, 20x7, 40x3. The term uniformity of dosage unit is defined as the degree of uniformity in the amount of the drug substance among dosage units. The author introduces two different acceptance value limits n 10 and 30 in this article.
Uniformity of dosage units test procedure all measurements of dosage units and criteria values are in percentage label claim %lc. Dec 23, 2010 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. Particle size limits to meet usp content uniformity. Blend uniformity bu is critical to achieving consistent content uniformity of capsule dosage forms. Acceptance critiria for uniformity of dosage units are for. The uniformity of dosage units can be evaluated either by measuring the content uniformity or the weight of the tested units green et al. Dosage units are defined as dosage forms containing a single dose or a part of. Apr 22, 2018 this excel workbook performs an analysis of blend andor final dosage units. This excel workbook performs an analysis of blend andor final dosage units. What are the limits for uniformity dosage content for tablets. The manufacture of lowdose oral solid dosage form to support. Tools for blend and content uniformity assessment ispe.
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