Annex 6 uniformity of dosage units general chapter fda. Uniformity of mass of single dose preparations european pharmacopoeia 6. For this multiplestage test, the procedure computes a lower bound on the probability of passing the udu test, based on statistical estimates made at. 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. Uniformity of dosage unitscomparative study of methods and. Ich guideline q4b annex 6 to note for evaluation and recommendation of pharmacopoeial texts for use in the ich regions on uniformity of dosage units general chapter step 5 pdf 224. The uniformity of dosage units can be demonstrated by either of the two methods. Uniformity of dosage units test procedure all measurements of dosage units and criteria values are in percentage label claim %lc. As per usp general chapter, to ensure the consistency of dosage units uniformity of dosage unit test is. Chapter 6 will elaborate on the api release testing dissolution and disintegration from the solid oral dosage form. Uniformity of weight of tablets and capsule introduction. Uniformity of dosage units european pharmacopoeia 6. Establishing acceptance limits for uniformity of dosage.
Dosage units are defined as dosage forms containing a single dose or a part of a dose of drug substance in each unit. The degree of uniformity in the amount of the active substance among dosage units. 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. The uniformity of dosage units general chapter was incorporated into and became official with the second supplement to usp 34nf 29. Guidance for industry food and drug administration. 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.
The uniformity of dosage units can be demonstrated by either of two methods, weight variation or content uniformity. In weight variation test, measurement of contents is done by estimation of contents based on weight. Uniformity of content of single dose preparations european pharmacopoeia 5. Weight variation wv test can be done only on certain unit dose as shown in table 1. Usp gc for demonstrating uniformity of dosage units 9 table 1. All books are in clear copy here, and all files are secure so dont worry about it. Uspnf general chapter uniformity of dosage units type of posting. Uniformity of content of single dose preparations the test for uniformity of content of single dose preparations is based on the assay of the individual contents of active substances of a number of single dose units to determine. Content uniformity select not less than 30 units, and proceed as follows for the dosage form designated. As per usp general chapter, to ensure the consistency of dosage units uniformity of dosage unit test is performed.
Uniformity of dosage unit for dosage forms packaged in single unit containers uniformity of dosage units. Application of content unformity cu and mass variation mv test for dosage forms dosage forms type subtype dose and ratio of active substance. Apply these methods, where indicated, in the testing of the appropriate dosage forms. 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. It includes both the mass of the dos rb 1may2016 age form and the content of the active substance in the aluminum content. Where different procedures are used for assay of the preparation and for the content uniformity test, it may be. Sep 02, 2016 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 term uniformity of dosage unit is defined as the degree of uniformity in the amount of the drug substance among dosage units. The most common test for content uniformity cu of dosage units is described in united states pharmacopeia usp general chapter. N ote in this chapter, unit and dosage unit are synonymous. Questions and answers on current good manufacturing practicesproduction and process controls.
A unit of potency of drugs, used in the united states pharmacopeia. Passing the udu test once does not provide statistical assurance that a batch of drug. Topical semisolid dosage forms product quality and product performance testing clarence t. The key benefit of the two working limits is to guarantee that no lot of dosage unit products i. 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. This change represents usp specific national text and will not appear in the ep and jp.
The usp uniformity of dosage units udu given in general chapter uniformity of dosage units of the usp udu test is a market standard and is not intended for inspecting uniformity of finished product for lotbatch release or as a lot inspection procedure. Setting the stage content uniformity cu testing is an important assessment of unit dosage form performance. The concept of acceptance value must be redefined to remove bias and more closely reflect quality targets. Assayprocedure, performance tests uniformity of dosage units, impuritiesorganic impurities, additional requirements usp reference standards usp alprazolam related compound a rs, additional requirements usp reference standards usp chlordiazepoxide related compound a rs heather joyce revision aminobenzoate sodium pf 412 pg. Stratified sampling techniques are employed to collect inprocess dosage units throughout the compression or filling process. The second addressed revising the assay for potency. 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. Added content uniformity procedure and criteria for semi solid dosage forms, and instructions to assay 10 units. Weight and content uniformity of lorazepam halftablets.
Uniformity of dosage unit usp maintaining relevance jon clark, vp industry standards and collaboration. 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. Acceptance limits for the new ich usp 29 contentuniformity test. However, they do not have tests regarding the weight uniformity of the resultant split halves or the performance of score lines of tablets. The authors present their method for calculating acceptance limits consistent with usps revised contentuniformity test requirements. The use of stratified sampling of blend and dosage units to. 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. Contents uniformity weight or volume of packaged dosage forms. 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.
Uniformity of dosage units using large sample sizes. The first dealt with the detection of contaminants. Table 51 provides a summary of tests discussed in chapter 5. This presentation is compiled by drug regulations a non profit organization which provides free online resource to the pharmaceutical professional. Process flow diagram for assessment of blend and content. Each single unit contains within 15% of the average amount of active ingredient. Revisions to the united states pharmacopeia s usp uniformity test require manufacturers to establish new acceptance limits. Products that have higher sds for blend and dosage unit uniformity may require larger sample sizes. As sample size increases, the probability to detect one of these units becomes significant. The weight variation procedure can be used where permitted as detailed in table 1. In the case of a twocomponent tablet, uniformity of dosage units test requirement will be met by the wv.
E281019 standard practice for demonstrating capability to comply with the test for uniformity of dosage units. Uniformity of mass of single dose preparations weigh individually 20 units taken at random or, for single dose preparations presented in individual containers, the contents of 20 units, and determine the average mass. Usp biopharmaceutics expert committee and to usp staff. Establishing acceptance limits for uniformity of dosage units. Content uniformity acceptance testing for large sample sizes. Ich q6a recommended the harmonization of certain tests for dosage forms, including general chapter. Harmonized uniformity of dosage unit udu test all measurements of dosage units and criteria values are in percentage label claim %lc.
Blend uniformity and content uniformity bucu in august 20, the fda announced the withdrawal of its draft guidance document for industry, powder blends and finished dosage units stratified inprocess dosage unit sampling and assessment. This general chapter contains test methods for propellants, pressurized topical aerosols, nasal sprays, metereddose inhalers, and propellantfree dry powder inhalers used to aerosolize, or to aerosolize and meter, doses of powders for inhalation. Blend uniformity and content uniformity bucu faqs ispe. 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. In addition, a proposal of a new general chapter for the european pharmacopoeia has been introduced. This general information chapter on official preparations is proposed for revision in its entirety. 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.
Further, the article suggests that producers be allowed to control producer risk through selection of numbers of units and testing tiers. Specified time content uniformity usp the degree of uniformity in the amount of the drug substance among dosage units. A free powerpoint ppt presentation displayed as a flash slide show on id. However, if up to three individual units deviate by more than 15% but are within 25% of the average amount of the active ingredient, examine a further 20 units drawn from the same original sample as the first 10 units. See united states pharmacopeia usp 1 for more detail. Process flow diagram for assessment of blend and content uniformity for continued process verification stage 3b batches published in. The requirements of this chapter apply both to dosage units containing a single. In the test, the acceptance value avis the key statistics. The uniformity of dosage units specification is not intended to apply to suspensions, emulsions, or gels in unitdose containers intended for topical administration.
Pdf demonstration of uniformity of dosage units using. Pdf demonstration of uniformity of dosage units using large. Has the new usp assay for heparin affected dosage for. This general chapter contains test methods for propellants, pressurized topical aerosols, nasal sprays, metered dose inhalers, and propellantfree dry powder inhalers used to aerosolize, or to aerosolize and meter, doses of powders for inhalation. 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. Historically, usp units have been approximately 10% more potent than the world health organization international units for heparin 5,6. The content uniformity method may be applied in all cases. Ppt uniformity of dosage units powerpoint presentation. Uniformity of dosage units bp 2011, usp 34 frequently asked questions. Questions and answers on current good manufacturing. Even in normal distributed batches of good quality, a small number of largely deviating units is expected. Standard practice for demonstrating capability to comply. Determination and acceptance limits of uniformity of content.
Application of content uniformity cu and weight variation wv tests. The uniformity of dosage units can be demonstrated by either of two methods, content uniformity or weight variation see table 1. 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 addition, the article proposes an approach that allows regulatory agencies and compendia to clearly state allowable consumer risk. The uniformity of dosage units specification is not intended to apply to suspensions, emulsions, or gels in unit dose containers intended for topical administration. If uncoated tablet contains 2 drug substances but only one of them meets the requirement for wv, how can the requirement be met. 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. Dosage unit analysis satisfies this inprocess control requirement by indirectly measuring the uniformity of the blend by sampling and testing inprocess dosage units. Uniformity of dosage units, usp 27 page 2396 and page 1587 of.
Content uniformity cu testing for the 21st century. In the case of a twocomponent tablet, uniformity of dosage units. 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 second report is used for suppositories, transdermal systems, and inhalations packaged in premetered dosage units tested according to the usp. Uniformity of dosage units 1 is one of the most commonly employed compendial tests to evaluate the dosage units. Do the cgmps require a firm to retain the equipment status identification labels with the batch. As a result of the change in the usp monograph, the assay standard for heparin was decreased. For preparations with a content of less than 40 mg the test for 5. Development and validation of rphplc method for determination of content uniformity of rabeprazole lets dosage form s. Uniformity of weight of tablets and capsule tf lab 1. General considerations include dose uniformity, stability, bioavailability, manufacture, and route of administration.
Other considerations that can impact stage 3a sampling plans include the overall control strategy, use of spc charts, the amount of confidence in the predictive powers of models used to predict content uniformity. Dosage units are defined as dosage forms containing a single dose or a part of a dose of an active substanceineachdosageunit. Ich q4b annex 6 uniformity of dosage unites general. 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. Usp nf general chapter uniformity of dosage units type of posting. The united states pharmacopeia usp and the british pharmacopoeia bp contain a quality control test regarding the weight uniformity of dosage units. This test is given in general chapter uniformity of dosage units of the usp, in 2. Elumalai, kiran aher, girija bhavar and sachin gupta abstract the aim of the present work was to develop simple, shorter and effective hplc method and subsequent validation for the content uniformity determination of.
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