An integrated solution for calculating results from tests for. A free powerpoint ppt presentation displayed as a flash slide show on id. Uniformity of content of single dose preparations european pharmacopoeia 5. Even in normal distributed batches of good quality, a small number of largely deviating units is expected. The content uniformity method may be applied in all cases.
Usp nf general chapter uniformity of dosage units type of posting. Guidance for industry food and drug administration. The first dealt with the detection of contaminants. The requirements of this chapter apply both to dosage units containing a single. 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 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. Development and validation of rphplc method for determination of content uniformity of rabeprazole lets dosage form s. The key benefit of the two working limits is to guarantee that no lot of dosage unit products i. Harmonized uniformity of dosage unit udu test all measurements of dosage units and criteria values are in percentage label claim %lc. 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.
The second addressed revising the assay for potency. This change represents usp specific national text and will not appear in the ep and jp. In the case of a twocomponent tablet, uniformity of dosage units. For this multiplestage test, the procedure computes a lower bound on the probability of passing the udu test, based on statistical estimates made at. Chapter 6 will elaborate on the api release testing dissolution and disintegration from the solid oral dosage form. Uniformity of dosage units test procedure all measurements of dosage units and criteria values are in percentage label claim %lc. 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.
This general information chapter on official preparations is proposed for revision in its entirety. Each single unit contains within 15% of the average amount of active ingredient. Content uniformity acceptance testing for large sample sizes. 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. 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 concept of acceptance value must be redefined to remove bias and more closely reflect quality targets. Uniformity of dosage units european pharmacopoeia 6. Weight variation wv test can be done only on certain unit dose as shown in table 1. General considerations include dose uniformity, stability, bioavailability, manufacture, and route of administration.
The use of stratified sampling of blend and dosage units to. Ich q6a recommended the harmonization of certain tests for dosage forms, including general chapter. In addition, a proposal of a new general chapter for the european pharmacopoeia has been introduced. 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. 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 term uniformity of dosage unit is defined as the degree of uniformity in the amount of the drug substance among dosage units. 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. In addition, the article proposes an approach that allows regulatory agencies and compendia to clearly state allowable consumer risk. Content uniformity select not less than 30 units, and proceed as follows for the dosage form designated. Do the cgmps require a firm to retain the equipment status identification labels with the batch. This test is given in general chapter uniformity of dosage units of the usp, in 2.
All books are in clear copy here, and all files are secure so dont worry about it. If uncoated tablet contains 2 drug substances but only one of them meets the requirement for wv, how can the requirement be met. The uniformity of dosage units can be demonstrated by either of two methods, weight variation or content uniformity. Table 51 provides a summary of tests discussed in chapter 5. N ote in this chapter, unit and dosage unit are synonymous. Topical and transdermal drug products the topicaltransdermal ad hoc advisory panel for the usp performance tests of topical and transdermal dosage forms. Revisions to the united states pharmacopeia s usp uniformity test require manufacturers to establish new acceptance limits.
Process flow diagram for assessment of blend and content uniformity for continued process verification stage 3b batches published in. Uniformity of weight of tablets and capsule tf lab 1. See united states pharmacopeia usp 1 for more detail. Added content uniformity procedure and criteria for semi solid dosage forms, and instructions to assay 10 units. Where different procedures are used for assay of the preparation and for the content uniformity test, it may be. Usp biopharmaceutics expert committee and to usp staff. In the case of a twocomponent tablet, uniformity of dosage units test requirement will be met by the wv. However, they do not have tests regarding the weight uniformity of the resultant split halves or the performance of score lines of tablets. Standard practice for demonstrating capability to comply.
As per usp general chapter, to ensure the consistency of dosage units uniformity of dosage unit test is performed. Determination and acceptance limits of uniformity of content. 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. Products that have higher sds for blend and dosage unit uniformity may require larger sample sizes.
The content uniformity procedure may be used in all cases. At each stage calculate the sample average, x, and the sample. 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 unitscomparative study of methods and. Historically, usp units have been approximately 10% more potent than the world health organization international units for heparin 5,6.
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. Pdf demonstration of uniformity of dosage units using large. 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. Blend uniformity and content uniformity bucu faqs ispe. The weight variation procedure can be used where permitted as detailed in table 1. Has the new usp assay for heparin affected dosage for. Other unit dose will need to undergo content uniformity cu test. Uniformity of weight of tablets and capsule introduction. Weight and content uniformity of lorazepam halftablets. 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.
The uniformity of dosage units general chapter was incorporated into and became official with the second supplement to usp 34nf 29. Setting the stage content uniformity cu testing is an important assessment of unit dosage form performance. Uniformity of dosage unit usp maintaining relevance jon clark, vp industry standards and collaboration. 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. Questions and answers on current good manufacturing. In the test, the acceptance value avis the key statistics. The second report is used for suppositories, transdermal systems, and inhalations packaged in premetered dosage units tested according to the usp. Uspnf general chapter uniformity of dosage units type of posting. 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. In weight variation test, measurement of contents is done by estimation of contents based on weight. The deviation of individual mass from the average mass should not exceed the. Dosage units are defined as dosage forms containing a single dose or a part of a dose of an active substanceineachdosageunit.
The united states pharmacopeia usp and the british pharmacopoeia bp contain a quality control test regarding the weight uniformity of dosage units. The degree of uniformity in the amount of the active substance among dosage units. The uniformity of dosage units specification is not intended to apply to suspensions, emulsions, or gels in unit dose containers intended for topical administration. Stratified sampling techniques are employed to collect inprocess dosage units throughout the compression or filling process. Establishing acceptance limits for uniformity of dosage. The authors present their method for calculating acceptance limits consistent with usps revised contentuniformity test requirements.
The uniformity of dosage units can be demonstrated by either of the two methods. Application of content unformity cu and mass variation mv test for dosage forms dosage forms type subtype dose and ratio of active substance. E281019 standard practice for demonstrating capability to comply with the test 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. 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. Ppt uniformity of dosage units powerpoint presentation. As per usp general chapter, to ensure the consistency of dosage units uniformity of dosage unit test is. 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. As sample size increases, the probability to detect one of these units becomes significant. Apply these methods, where indicated, in the testing of the appropriate dosage forms. Uniformity of dosage units, usp 27 page 2396 and page 1587 of. 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. Statistical considerations for establishing acceptance.
Uniformity of mass of single dose preparations european pharmacopoeia 6. Acceptance limits for the new ich usp 29 contentuniformity test. Uniformity of dosage units 1 is one of the most commonly employed compendial tests to evaluate the dosage units. Annex 6 uniformity of dosage units general chapter fda. Specified time content uniformity usp the degree of uniformity in the amount of the drug substance among 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. 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. This presentation is compiled by drug regulations a non profit organization which provides free online resource to the pharmaceutical professional. As a result of the change in the usp monograph, the assay standard for heparin was decreased.
Topical semisolid dosage forms product quality and product performance testing clarence t. Usp gc for demonstrating uniformity of dosage units 9 table 1. 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. Uniformity of dosage unit for dosage forms packaged in single unit containers uniformity of dosage units. Passing the udu test once does not provide statistical assurance that a batch of drug.
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. It includes both the mass of the dos rb 1may2016 age form and the content of the active substance in the aluminum content. Application of content uniformity cu and weight variation wv tests. A unit of potency of drugs, used in the united states pharmacopeia. Questions and answers on current good manufacturing practicesproduction and process controls. For preparations with a content of less than 40 mg the test for 5. The most common test for content uniformity cu of dosage units is described in united states pharmacopeia usp general chapter. Establishing acceptance limits for uniformity of dosage units. The uniformity of dosage units specification is not intended to apply to suspensions, emulsions, or gels in unitdose containers intended for topical administration. Process flow diagram for assessment of blend and content. Uniformity of dosage units bp 2011, usp 34 frequently asked questions.
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. Dosage units are defined as dosage forms containing a single dose or a part of a dose of drug substance in each unit. 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. Further, the article suggests that producers be allowed to control producer risk through selection of numbers of units and testing tiers. Contents uniformity weight or volume of packaged dosage forms. Pdf demonstration of uniformity of dosage units using. 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. 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. 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. Ich q4b annex 6 uniformity of dosage unites general. Situation compendial expectation 30 units for any product general notices 3. Content uniformity acceptance testing for large sample sizes 1 kim vukovinsky, pfizer james bergum, bristolmyers squibb may 25, 2011. 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.
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