ANSI ST72-2011 Bacterial endotoxins - Test methods routine monitoring and alternatives to batch testing.pdf

1、ANSI/AAMI ST72:2011/ (R)2016Bacterial endotoxins Test methods, routine monitoring, and alternatives to batch testingAmerican National StandardObjectives and uses of AAMI standards and recommended practices It is most important that the objectives and potential uses of an AAMI product standard or rec

2、ommended practice are clearly understood. The objectives of AAMIs technical development program derive from AAMIs overall mission: the advancement of medical instrumentation. Essential to such advancement are (1) a continued increase in the safe and effective application of current technologies to p

3、atient care, and (2) the encouragement of new technologies. It is AAMIs view that standards and recommended practices can contribute significantly to the advancement of medical instrumentation, provided that they are drafted with attention to these objectives and provided that arbitrary and restrict

4、ive uses are avoided. A voluntary standard for a medical device recommends to the manufacturer the information that should be provided with or on the product, basic safety and performance criteria that should be considered in qualifying the device for clinical use, and the measurement techniques tha

5、t can be used to determine whether the device conforms with the safety and performance criteria and/or to compare the performance characteristics of different products. Some standards emphasize the information that should be provided with the device, including performance characteristics, instructio

6、ns for use, warnings and precautions, and other data considered important in ensuring the safe and effective use of the device in the clinical environment. Recommending the disclosure of performance characteristics often necessitates the development of specialized test methods to facilitate uniformi

7、ty in reporting; reaching consensus on these tests can represent a considerable part of committee work. When a drafting committee determines that clinical concerns warrant the establishment of minimum safety and performance criteria, referee tests must be provided and the reasons for establishing th

8、e criteria must be documented in the rationale. A recommended practice provides guidelines for the use, care, and/or processing of a medical device or system. A recommended practice does not address device performance per se, but rather procedures and practices that will help ensure that a device is

9、 used safely and effectively and that its performance will be maintained. Although a device standard is primarily directed to the manufacturer, it may also be of value to the potential purchaser or user of the device as a frame of reference for device evaluation. Similarly, even though a recommended

10、 practice is usually oriented towards healthcare professionals, it may be useful to the manufacturer in better understanding the environment in which a medical device will be used. Also, some recommended practices, while not addressing device performance criteria, provide guidelines to industrial pe

11、rsonnel on such subjects as sterilization processing, methods of collecting data to establish safety and efficacy, human engineering, and other processing or evaluation techniques; such guidelines may be useful to health care professionals in understanding industrial practices. In determining whethe

12、r an AAMI standard or recommended practice is relevant to the specific needs of a potential user of the document, several important concepts must be recognized: All AAMI standards and recommended practices are voluntary (unless, of course, they are adopted by government regulatory or procurement aut

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15、 however, in the sense that it responds generally to perceived risks and conditions that may not always be relevant to specific situations. A standard or recommended practice is an important reference in responsible decision-making, but it should never replace responsible decision-making. Despite pe

16、riodic review and revision (at least once every five years), a standard or recommended practice is necessarily a static document applied to a dynamic technology. Therefore, a standards user must carefully review the reasons why the document was initially developed and the specific rationale for each

17、 of its provisions. This review will reveal whether the document remains relevant to the specific needs of the user. Particular care should be taken in applying a product standard to existing devices and equipment, and in applying a recommended practice to current procedures and practices. While obs

18、erved or potential risks with existing equipment typically form the basis for the safety and performance criteria defined in a standard, professional judgment must be used in applying these criteria to existing equipment. No single source of information will serve to identify a particular product as

19、 “unsafe“. A voluntary standard can be used as one resource, but the ultimate decision as to product safety and efficacy must take into account the specifics of its utilization and, of course, cost-benefit considerations. Similarly, a recommended practice should be analyzed in the context of the spe

20、cific needs and resources of the individual institution or firm. Again, the rationale accompanying each AAMI standard and recommended practice is an excellent guide to the reasoning and data underlying its provision. In summary, a standard or recommended practice is truly useful only when it is used

21、 in conjunction with other sources of information and policy guidance and in the context of professional experience and judgment. INTERPRETATIONS OF AAMI STANDARDS AND RECOMMENDED PRACTICES Requests for interpretations of AAMI standards and recommended practices must be made in writing, to the AAMI

22、Vice President, Standards Policy and Programs. An official interpretation must be approved by letter ballot of the originating committee and subsequently reviewed and approved by the AAMI Standards Board. The interpretation will become official and representation of the Association only upon exhaust

23、ion of any appeals and upon publication of notice of interpretation in the “Standards Monitor“ section of the AAMI News. The Association for the Advancement of Medical Instrumentation disclaims responsibility for any characterization or explanation of a standard or recommended practice which has not

24、 been developed and communicated in accordance with this procedure and which is not published, by appropriate notice, as an official interpretation in the AAMI News. American National Standard ANSI/AAMI ST72:2011/(R)2016 (Revision of ANSI/AAMI ST72:2002/(R)2010) Bacterial endotoxinsTest methods, rou

25、tine monitoring, and alternatives to batch testing Developed by Association for the Advancement of Medical Instrumentation Approved 19 December 2011 and reaffirmed 9 June 2016 by American National Standards Institute, Inc. Abstract: This recommended practice specifies general criteria to be applied

26、in the determination of bacterialendotoxins (pyrogens) on sterilized or sterilizable healthcare products, components or raw materials. Endotoxin methodologies covered include both qualitative (limit) methods and quantitative (end-point) methods. The recommended practice excludes determination of pyr

27、ogens other than bacterial endotoxins. Keywords: Limulus amebocyte lysate, LAL, pyrogenic labeling, maximum valid dilution, MVD, RSE:CSEstandardization, analyst qualification, product qualification, gel-clot technique, chromogenic technique, turbidimetric technique, medical device, batch testing, la

28、boratory quality system, product family, set, sample frequency, kinetic assay AAMI Recommended Practice This Association for the Advancement of Medical Instrumentation (AAMI) recommended practice implies a consensus of those substantially concerned with its scope and provisions. The existence of an

29、AAMI recommended practice does not in any respect preclude anyone, whether they have approved the recommended practice or not, from manufacturing, marketing, purchasing, or using products, processes, or procedures not conforming to the standard. AAMI recommended practices are subject to periodic rev

30、iew, and users are cautioned to obtain the latest editions. CAUTION NOTICE: This AAMI recommended practice may be revised or withdrawn at any time. AAMI procedures require that action be taken to reaffirm, revise, or withdraw this recommended practice no later than five years from the date of public

31、ation. Interested parties may obtain current information on all AAMI documents by calling or writing AAMI. All AAMI standards, recommended practices, technical information reports, and other types of technical documents developed by AAMI are voluntary, and their application is solely within the disc

32、retion and professional judgment of the user of the document. Occasionally, voluntary technical documents are adopted by government regulatory agencies or procurement authorities, in which case the adopting agency is responsible for enforcement of its rules and regulations. Published by Association

33、for the Advancement of Medical Instrumentation 4301 N. Fairfax Drive, Suite 301 Arlington, VA 22203-1633 www.aami.org 2011 by the Association for the Advancement of Medical Instrumentation All Rights Reserved Publication, reproduction, photocopying, storage, or transmission, electronically or otherw

34、ise, of all or any part of this document without the prior written permission of the Association for the Advancement of Medical Instrumentation is strictly prohibited by law. It is illegal under federal law (17 U.S.C. 101, et seq.) to make copies of all or any part of this document (whether internal

35、ly or externally) without the prior written permission of the Association for the Advancement of Medical Instrumentation. Violators risk legal action, including civil and criminal penalties, and damages of $100,000 per offense. For permission regarding the use of all or any part of this document, co

36、mplete the reprint request form at www.aami.org, or contact AAMI at 4301 N. Fairfax Drive, Suite 301, Arlington, VA 22203-1633. Phone: +1-703-525-4890; Fax: +1-703-525-1067. Printed in the United States of America ISBN 1570204268 Contents Page Glossary of equivalent standards iv Committee representa

37、tion . vi Foreword . ix Introduction x 1 Scope 1 2 Normative references . 1 3 Definitions . 1 4 Quality management system elements . 3 5 Non-pyrogenic labeling . 4 6 Selection of product units . 4 7 Selection of technique 5 8 Validation of methodology 5 9 Use of technique . 8 10 Alternatives to batc

38、h testing 11 Annex A Background on the bacterial endotoxins test 14 Annex B Guidance on test methods, routine monitoring, and alternatives to batch testing 17 Annex C Guidance on out of specification (OOS) and failure investigation 31 Annex D Bibliography 33 Tables 1 Preparation of solutions for inh

39、ibition/enhancement test: Gel-clot technique 7 2 Preparation of solutions for inhibition/enhancement test: Chromogenic and turbidimetric techniques 8 3 Preparation of solutions for gel-clot limit test . 10 4 Preparation of solutions for gel-clot assay . 10 B.1 Selection of number of samples 19 B.2 S

40、election of product units for testing 20 B.3 Calculation of test endotoxin limit 22 B.4 Calculation of Maximum Valid Dilution . 22 B.5 Calculation of geometric mean Worked example . 23 Figure B.1 Key questions in evaluating the appropriateness and risk associated with alternatives to endotoxin batch

41、 testing 28 iv 2011 Association for the Advancement of Medical Instrumentation ANSI/AAMI ST72:2011 Glossary of equivalent standards International Standards adopted in the United States may include normative references to other International Standards. For each International Standard that has been ad

42、opted by AAMI (and ANSI), the table below gives the corresponding U.S. designation and level of equivalency to the International Standard. NOTE: Documents are sorted by international designation. The code in the US column, “(R)20xx” indicates the year the document was officially reaffirmed by AAMI.

43、E.g., ANSI/AAMI/ISO 10993-4:2002/(R)2009 indicates that 10993-4, originally approved and published in 2002, was reaffirmed without change in 2009. Other normatively referenced International Standards may be under consideration for U.S. adoption by AAMI; therefore, this list should not be considered

44、exhaustive. International designation U.S. designation Equivalency IEC 60601-1:2005 Technical Corrigendum 1 and 2 ANSI/AAMI ES60601-1:2005 and ANSI/AAMI ES60601-1:2005/A2:2010 ANSI/AAMI ES60601-1:2005/C1:2009 (amdt) Major technical variations C1 Identical to Corrigendum 1 “should” indicates that amo

45、ng several possibilities one is recommended as particularly suitable, without mentioning or excluding others, or that a certain course of action is preferred but not necessarily required, or that (in the negative form) a certain possibility or course of action should be avoided but is not prohibited

46、; “may” is used to indicate that a course of action is permissible within the limits of the standard; and “can” is used as a statement of possibility and capability. “Must” is used only to describe “unavoidable” situations, including those mandated by government regulation. This recommended practice

47、 should be considered flexible and dynamic. AAMI and ANSI procedures require that recommended practice be reviewed every five years and, if necessary, revised to reflect technological advances that may have occurred since publication. Suggestions for improving this recommended practice are invited.

48、Comments and suggested revisions should be sent to Technical Programs, AAMI, 4301 N. Fairfax Dr., Suite 301, Arlington, VA 22203-1633. NOTEThis foreword does not contain provisions of the American National Standard, Bacterial endotoxinsTest methods, routine monitoring and alternatives to batch testi

49、ng (ANSI/AAMI ST72:2011), but it does provide important information about the development and intended use of the document. x 2011 Association for the Advancement of Medical Instrumentation ANSI/AAMI ST72:2011 Introduction A pyrogen is any substance that can induce fever. Testing for pyrogens is required for release of many health care products. Pyrogens can be classified into two groups: microbial (e.g., bacteria, fungi, viruses) and non-microbial (e.g., drugs, device materials, steroids, plasma fractions). The most significant pyrogens have been found to be endo