Pdf practical approach to sterility testing researchgate. In this study, we demonstrated that all sda control plates grew mold within the acceptable 144h time frame, compared with only 43. Jan 30, 2019 usp chapter 71 usp 71 remains the most common method used for product sterility testing in the biopharmaceutical industry in the united states. The purpose of this article is to describe united states pharmacopeia chapter. Usp chapter are referee tests in other words they are in place solely to demonstrate conformance to qualities specified in the product monograph as. Pharmacopeial procedures are not by themselves designed to ensure that a batch of product is sterile or has been sterilized. Standards and best practices for cell, gene and tissue. Quality control analytical methodslaboratory considerations of. Incubate at the specified temperaized, then it is to be assumed that the inhibited microorganism will ture for a period of time within the range specified in the test. However, a satisfactory result only indicates that no contaminating microorganism has been found in the sample examined in the conditions of the test. Usp general chapter 62 microbiological examination of nonsterile products. Seed the indicator cell culture at a suitable density ile.
Usp 38 the united states pharmacopeia 1nf 33 the national formulary volume 4a by authority of the united states pharmacopeial convention prepared by the council of experts and its expert committees official from may 1, 2015 the designation on the cover of this publication, usp nf 2015, is for ease of identification only. Table 3 specifies the number of articles to be tested based on the batch size and table 2 specifies the quantity to be tested. Institute of validation technology ivt, scott sutton, 20 6. Usp sterility testing definition culture media and. Nova provides usp 71 sterility testing of pharmaceutical products, radiopharmaceuticals, medical devices and water.
Strains of the test microorganisms suitable for use in for products containing a mercurial preservative that cannot the growth promotion test and the method suitability. Mar 22, 2016 sterility testing is defined as a testing which confirms that products are free from the presence of viable microorganisms. One of the most important aspects of usp chapter is method suitability. Intermediate steps can and should be tested for sterility but usp chapter 71 was not written and is not intended for this purpose. A discussion of united states pharmacopeia chapter 71 sterility tests. Sterility tests microbiological tests usp 35 fluid thioglycollate medium is to be incubated at 3035. Usp 71 sterility tests applies to substances, preparations, or articles which, according to the pharmacopeia, are required to be sterile. Understanding teh role of sterility testing in compounding. Usp 71 sterility tests represents the gold standard for sterility testing. Focus laboratories can test product sterility through usp.
Situations when is unsuitable for product release testing sample size consideration. However, a satisfactory result only indicates that no con. Test design usp chapter 71 sterility tests is internationally harmonized and describes two. Usp allows for alternate tests for any compendial method so long as that alternate method is demonstrated to be at least equivalent to the standard.
Usp chapter 71 and iso 117372 im not familiar with usp 71 so i cant offer a specific judgement. This test is performed according to the recommendations in usp general chapter 71, ansiaamiiso 117372, ep 2. Understanding the role of sterility testing in compounding f. This test is specific for the detection of aerobic organisms which have been exposed. The only content in usp relative to sterility tests will be the harmonized. Sterility testing is defined as a testing which confirms that products are free from the presence of viable microorganisms. The iso radiation sterilization microbial methods 117372 19984 describes a sterility test which is a modification for the usp method. United states pharmacopeia chapter 71 sterility tests thomas c. Biological reactivity tests, in vivo and sterility 17 safety concerns with gene therapy products. Understanding usp 71 sterility tests and extending bud. Meeting uspepcfr sterility testing requirements with a.
Those portions that are not harmonized are marked with symbols to specify this fact. Sterility testing is required during the sterilization validation process as well as for routine release testing. Any modifications of or variations in sterility test procedures from those described under sterility tests 71 should be validated in the context of the entire sterility assurance program and are not intended to be methods alternative to those described in that chapter. We can test sterile product in one day via a rapid scan rdi method and are proud to produce. Negative mycoplasma direct and indirect culture method. Japanese pharmacopoeia jp and united states pharmacopeia usp. The first is 21 cfr 211 and the second is the biologics 21 cfr 610. This internationally harmonized test replaces the current method 3. Meeting uspepcfr sterility testing requirements with a two.
The following procedures are applicable for determining whether a pharmacopeial article purporting to be sterile complies with the requirements set forth in the individual monograph with respect to the test for sterility. Pharmaceutical sterility testing usp sterility testing of sterile pharmaceuticals is an important part of gmp microbiology, and is used to ensure that pharmaceutical and biopharmaceutical therapeutics are actually sterile and safe for human use. Usp requirements for sterile and nonsterile preparations. Related tests qc sterility assurance microbiology sterility. It is apparent that the quality assurance program of a compounding pharmacy cannot adhere to the strict requirements of some of the general chapters in the united states pharmacopeia. Growth promotion test and method validation usp sterility test contains two qualifying. This chapter examines some practical approaches to sterility test method validation.
Compare the microscopic appearance of the test cultures with that of the negative and positive controls, examining for extranuclear fluorescence. Since there was no web posting at the time of signoff of this chapter, all previous pdg signoffs and stage 6 postings are summarized as below. Comprehensive evaluation of compendial usp, bactalert. Usp chapter 71 contains two tables that describe sampling. Quality control analytical methodslaboratory considerations. The only content in usp relative to sterility tests will be the harmonized 71. Tests storage and beyonduse dating maintaining sterility. All samples are prepared and plated in iso 5 hoods in iso 7 clean rooms, to eliminate laboratory contamination. There are two different gmps describing sterility in the united states. Usp chapter are referee tests in other words they are in place solely to demonstrate conformance to qualities specified in the product monograph as described in the current national.
Sterility test, and usp sterility tests, can be used as interchangeable in the ich regions subject to the conditions detailed below. Pharmaceutical testing lab sterility testing usp 71. Only content in usp relative to sterility tests will be the harmonized 71. Test and general chapter sterility tests have been included, which harmonizes with general chapter. Usp chapter 71 sterility tests in usp 30, the second paragraph of chapter 71 states the following. The pharmaceutical microbiology manual pmm evolved from the sterility analytical manual and is a supplement to the united states. Those chapters containing such strict requirements that may impact pharmacy compounding should be studied thoroughly by the appropriate united states pharmacopeia. Method suitability control studies for microbial testing. Download the sterility test pdg signoff cover pages. United states pharmacopeia usp chapter sterility tests as the principle source used for sterility testing methods, including information on test procedures and media. Portions of this general chapter have been harmonized with the corresponding texts of the european pharmacopeia andor the japanese pharmacopeia. Milliflex rapid method for sterility testing demonstrated that it is a viable alternative to traditional sterility testing and reduces time to result from 14 to five days. Microbiological examination microbiological tests usp 31 the appropriate microorganism.
Validating and implementing a rapid sterility testing method a. Sterility test, and usp sterility tests, can be used as interchangeable in the ich regions. Federal food, drug, and cosmetics act designates the uspnf as the official compendia for. Usp sterility tests represents the gold standard for sterility testing. They may also produce pinpoints and filaments in the intercellular spaces. Pharmaceutical compoundingste rile preparations introduction the objective of this chapter is to describe conditions and practices to prevent harm, including death, to patients that could result from. New harmonization with international compendia and overview duration. The sterility test must be validated to determine if a contamination could be isolated if one were present as well as to determine the sensitivity of the assay usp chapter sterility test. Products, from usp chapter release test examples criteria sterility usp. In this method, portions of inprocess andor final release product with the inoculation volume being based on the batch size of the product, as defined in usp 71 are inoculated into portions of. Usp prescribes the sterility testing method used for pharmaceuticals and biologics. Testing conditions for medical devices, such as sutures, are outside the scope of the ich recommendation. Kupiec, phd analytical research laboratories oklahoma city, oklahoma abstract it is apparent that the quality assurance program of a compounding pharmacy cannot adhere to the strict requirements of some of the general chapters in the united states pharmacopeia.
Sterility tests69 method the test is applied to substances, preparations, or articles which, according to the pharmacopeia, are required to be ster1. In accordance with usps rules and procedures of the council of experts rules, and except as provided in section 7. A harmonized standard for sterility test has been approved by the pharmacopeial discussion group pdg as described in its pdg signoff cover page. The product sterility cleanroom test is necessary for medical devices, pharmaceuticals, preparations, tissue materials and other materials that claim to be sterile or free from viable microorganisms. P o r ti o ns o f thi s ge ne r a l c ha pte r ha v e be e n ha r m o ni z e d w i th the c o r r e s po ndi ng te x ts o f the eur o pe a n. Mycoplasmas produce pinpoints or filaments over the indicator cell cytoplasm. Inprocess bioburden testing of pharmaceuticals the story. The views and opinions presented are entirely my own. Usp revision process chapter revisions now official. Understanding the role of sterility testing in compounding. The assay is a regulatory expectation that has been in existence for some time and is mentioned in fda warning letters. Usp chapter sterility tests in usp 30, the second paragraph of chapter states the following. Sterility testing is very important for medical devices, pharmaceuticals, preparations, tissue materials and other materials that claim to be sterile or free from viable microorganisms. Kastango, mba, rph, fashp clinical iq, llc july 10, 20 disclaimer although i am an expert consultant to the usp, i am speaking today in my individual capacity and not as a member of the committee or as a usp representative.
When the volume or the quantity in a single container is. Only content in usp relative to sterility tests will be the harmonized. Usp chapter sterility tests is internationally harmonized and describes two separate types of testsmembrane filtration and direct inoculation. Portions of this general chapter have been harmonized with the. The test is applied to substances, preparations or articles which, according to the pharmacopoeia, are required to be sterile. I wonder if their deliberations bear on the relationship between the two approaches, and in particular if the committee is on record as expressing an opinion about usp 71. Usp chapter 71 are referee tests in other words they are in place solely to demonstrate conformance to qualities specified in the product monograph as described in the current national formulary nf the other part of the book. Annex 8r1 sterility test general chapter guidance for industry. United states pharmacopeia scientific nonprofit organization that sets standards for the quality, purity, identity, and strength of medicines usps drug standards are enforceable in the united states by the food and drug administration the u. Annex 8r1 sterility test general chapter guidance for. This study shows that the bactec fx system is suboptimal for product sterility testing, and it provides strong data to support the use of bactalert testing at 32. Chapter sterility tests as the prin ciple source used for. Understanding usp 71 sterility tests and extending bud pages.
By common consensus, the 21 cfr 211 cgmp looks to the compendial sterility tests, while 21 cfr 610 describes a separate test in 21 cfr 610. Thus, the challenge for rapid or alternate sterility tests is to demonstrate equivalence to usp 71. U s pharmacopeia usp 71 sterility testing reference standards. The tests for bacterial and fungal sterility are carried out on the same sample of the product to be examined. The methodology for the bioburden test is commonly modified from usp, usp sterility tests, and watertesting guidelines, such as usp water for pharmaceutical purposes. Usp provides guidance on this in chapter validation of microbial recovery from phar. Sterility the test is applied to substances, preparations or articles which, according to the pharmacopoeia, are required to be sterile. Sepoct 2007 veterinary compounding view all articles in issue.
Glp assay number gmp assay number assay description media. The pharmaceutical microbiology manual pmm evolved from the sterility analytical manual and is a supplement to the united states pharmacopeia usp for pharmaceutical. U s pharmacopeia usp 71 sterility testing reference. Eliminated the entire discussion of sterility testing at the conclusion of the chapter. It is apparent that the quality assurance program of a compounding pharmacy cannot adhere to the strict requirements of some of the general chapters in the united states. The sterility test usp section 71 is categorized under general requirements and is therefore a legal requirement. Note in the context of this chapter, sterilized refers to an item or surface that has been subjected to a process that eliminates viable bioburden. This chapter provides guidelines for the validation of isolator systems for use in sterility testing of compendial articles. Pdf general difficulties associated with sterility test validation. Test design usp chapter sterility tests is internationally harmonized and describes two.
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