1、NSF International Standard / American National StandardNSF/IPEC/ANSI 363 - 2016Good Manufacturing Practices(GMP) for PharmaceuticalExcipientsNSF International, an independent, not-for-profit, non-governmental organization, is dedicated to being the leading global provider of public health and safety
2、-based risk management solutions while serving the interests of all stakeholders. This Standard is subject to revision. Contact NSF to confirm this revision is current. Users of this Standard may request clarifications and interpretations, or propose revisions by contacting: Chair, Joint Committee o
3、n Pharmaceutical Excipients c/o NSF International 789 North Dixboro Road, P. O. Box 130140 Ann Arbor, Michigan 48113-0140 USA Phone: (734) 769-8010 Telex: 753215 NSF INTL FAX: (734) 769-0109 E-mail: infonsf.org Web: http:/www.nsf.orgi NSF International Standard/ International Pharmaceutical Excipien
4、ts Council/ American National Standard for Pharmaceutical Excipients Good Manufacturing Practices (GMP) for Pharmaceutical Excipients Standard Developer NSF International NSF International Designated as an ANSI Standard July 7, 2016 American National Standards Institute ii Prepared by The NSF Joint
5、Committee on Pharmaceutical Excipients Adopted December 2014 Revised January 2017 Published by NSF International PO Box 130140, Ann Arbor, Michigan 48113-0140, USA For ordering copies or for making inquiries with regard to this Standard, please reference the designation “NSF/IPEC/ANSI 363 2016.” Cop
6、yright 2017 NSF International Previous editions 2014 Unless otherwise specified, no part of this publication may be reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying and microfilm, without permission in writing from NSF International. Printed in the
7、 United States of America.iii Disclaimers1 NSF, in performing its functions in accordance with its objectives, does not assume or undertake to discharge any responsibility of the manufacturer or any other party. The opinions and findings of NSF represent its professional judgment. NSF shall not be r
8、esponsible to anyone for the use of or reliance upon this Standard by anyone. NSF shall not incur any obligation or liability for damages, including consequential damages, arising out of or in connection with the use, interpretation of, or reliance upon this Standard. NSF Standards provide basic cri
9、teria to promote sanitation and protection of the public health. Provisions for mechanical and electrical safety have not been included in this Standard because governmental agencies or other national standards-setting organizations provide safety requirements. Participation in NSF Standards develop
10、ment activities by regulatory agency representatives (federal, local, state) shall not constitute their agencys endorsement of NSF or any of its Standards. Preference is given to the use of performance criteria measurable by examination or testing in NSF Standards development when such performance c
11、riteria may reasonably be used in lieu of design, materials, or construction criteria. The illustrations, if provided, are intended to assist in understanding their adjacent standard requirements. However, the illustrations may not include all requirements for a specific product or unit, nor do they
12、 show the only method of fabricating such arrangements. Such partial drawings shall not be used to justify improper or incomplete design and construction. Unless otherwise referenced, the annexes are not considered an integral part of NSF Standards. The annexes are provided as general guidelines to
13、the manufacturer, regulatory agency, user, or certifying organization. 1 The information contained in this Disclaimer is not part of this American National Standard (ANS) and has not been processed in accordance with ANSIs requirements for an ANS. Therefore, this Disclaimer may contain material that
14、 has not been subjected to public review or a consensus process. In addition, it does not contain requirements necessary for conformance to the Standard. This page is intentionally left blank.v Contents 1 General . 1 1.1 Introduction 1 1.2 Scope . 1 1.3 Purpose 2 2 Reference documents 2 2.1 Normativ
15、e references . 2 2.2 Informational references 2 3 Definitions . 3 4 Quality management system 8 4.1 General requirements 8 4.2 Documentation requirements . 9 4.3 Change control . 10 5 Management responsibility . 11 5.1 Management commitment 11 5.2 Customer focus 11 5.3 Quality policy 11 5.4 Planning
16、 . 12 5.5 Responsibility, authority, and communication 12 5.6 Management review . 13 6 Resource management 14 6.1 Provision of resources 14 6.2 Human resources . 14 6.3 Infrastructure 15 6.4 Work environment 17 7 Excipient realization 18 7.1 Planning of excipient realization 18 7.2 Customer-related
17、processes 19 7.3 Design and development (out of scope) 19 7.4 Purchasing . 19 7.5 Production and service provision . 20 7.6 Control of monitoring and measuring equipment . 23 8 Measurement, analysis and improvement 23 8.1 General. 23 8.2 Monitoring and measurement 23 8.3 Control of nonconforming pro
18、duct 27 8.4 Analysis of data 29 8.5 Improvement 29 This page is intentionally left blank.vii Foreword2 The purpose of NSF/IPEC/ANSI 363 is to serve as an evaluation tool for analyzing pharmaceutical excipients. Certification to this Standard serves as a communication tool between manufacturers of ex
19、cipients and finished product, pharmaceutical regulators, pharmacy organizations, and consumers. This Standard provides guidance to allow for the determination that a pharmaceutical excipient is within the specifications stated by the manufacturer, either qualitatively or quantitatively, and that it
20、 does not contain specific undeclared contaminants. In some instances, validated laboratory methods are not yet available for analyzing certain ingredients. In such cases, new methods will be added to this Standard as they become available. NSF/IPEC/ANSI 363 was developed with participation from the
21、 pharmaceutical excipients manufacturers, public health regulators, and distributors of pharmaceutical excipients. This edition of the Standard contains the following revisions: Issue 2 This revision updated section 4.1.1 regarding regional regulations. Issue 3 Updates were made to language regardin
22、g the use of the terms “product” and “excipient. Issue 4 Definitions for the terms deviation and sanitary were added to section 3. Issue 5 This revision provides clarity on language in section 6.3.2.1 and 6.3.3. Issue 6 Updates to section 7.4.1 were made regarding the purchasing process. Issue 7 Sec
23、tion 7.2.1 was updated to provide clarity. Issue 8 This revision made several editorial changes throughout the Standard. Issue 9 A definition for the term data integrity was added to section 3. 2 The information contained in this Foreword is not part of this American National Standard (ANS) and has
24、not been processed in accordance with ANSIs requirements for an ANS. Therefore, this Foreword may contain material that has not been subjected to public review or a consensus process. In addition, it does not contain requirements necessary for conformance to the Standard. viii Issue 10 A definition
25、for the term backup was added to section 3. Suggestions for improvement of this Standard are welcome. This Standard is maintained on a Continuous Maintenance schedule and can be opened for comment at any time. Comments should be sent to Chair, Joint Committee on Pharmaceutical Excipients at standard
26、snsf.org, or c/o NSF International, Standards Department, P.O. Box 130140, Ann Arbor, Michigan 48113-0140, USA.1 2017 NSF NSF/IPEC/ANSI 363 2016 NSF/IPEC/ANSI Standard for Pharmaceutical Excipients Good Manufacturing Practices (GMP) for Pharmaceutical Excipients 1 General 1.1 Introduction The princi
27、ples outlined in this Standard provide a comprehensive basis for the quality management system used in the manufacture of pharmaceutical excipients. Implementation of these principles shall result in the achievement of three main objectives: a) achieve excipient realization the organization shall im
28、plement and maintain a system that delivers excipients with the quality attributes necessary to meet the requirements and expectations of customers, pharmaceutical users, and regulatory authorities; b) establish and maintain a state of control the organization shall ensure the manufacture and supply
29、 of excipients is in accordance with this Standard, thus providing customers with some assurance of continued suitability and reliability of supply; and c) facilitate continual improvement the organization shall collect objective evidence to continually develop and enhance the application of these q
30、uality management system principles to further assure excipient consistency. 1.2 Scope This Standard is intended to define Good Manufacturing Practices (GMP) for excipient manufacture and distribution3 for use in drug products. It sets minimum requirements for GMP applicable to all commercially avai
31、lable excipients. This Standard includes the minimum requirements of a quality management system for excipient manufacture drawing on principles of GMP and quality systems from other relevant standards such as those referenced in section 2.2. NOTE 1 The requirements of this Standard may not be suffi
32、cient for all applications of excipients. It is the users responsibility to determine whether or not this Standard meets the requirements for their intended use. NOTE 2 Auditing excipient manufacturers ensures conformance to this Standard. This Standard is also intended to be used by duly accredited
33、 or otherwise suitably qualified 3rd parties. NOTE 3 Each user of a 3rd party auditing service should make its own determination as to the qualifications of the 3rd party and the applicability of the report and/or certificate issued in satisfying its requirements, including those pertaining to its i
34、ntended use of the excipient. 3 GMP applies to distribution per the Federal Food, Drug, and Cosmetic Act (FD 3.58 retest/re-evaluation interval; 3.59 retest interval). 3.69 significant change: Any change that has the potential to alter an excipients physical, chemical, or microbiological property fr
35、om the norm, and/or that may alter the excipients performance in the dosage form. 3.70 solvent: An inorganic or organic liquid used as a vehicle for the presentation of solutions or suspensions in the manufacture of an excipient. 3.71 specification: A test or list of tests, references to analytical
36、procedures and appropriate acceptance criteria that are numerical limits, ranges or other criteria that a material is required to meet. 3.72 specificity: The ability to assess unequivocally the analyte in the presence of components that may be expected to be present. Typically these might include im
37、purities, degradants, matrix, etc. 3.73 stability: The continued conformance of the excipient to its specifications. 3.74 state of control: A condition in which the set of controls consistently provides assurance of continued process performance and product quality. 3.75 subcontractor: A third party
38、 for outsourced work or services that contribute in whole or in part to the manufacture of excipients. 3.76 top management: A person or group of people who direct and control an organization at the highest level. The highest level may either be at the site or corporate level and will depend on how t
39、he quality management system is organized. 3.77 traceability: The ability to determine the history, application, or location that is under consideration (for example, origin of materials and parts, processing history, or distribution of the product after delivery). 3.78 validation: A documented prog
40、ram that provides a high degree of assurance that a specific product, method, procedure (e.g., cleaning), or system will consistently produce a result meeting 2017 NSF NSF/IPEC/ANSI 363 2016 8 predetermined acceptance criteria. 3.79 verification: The application of methods, procedures, tests, and ot
41、her evaluations, in addition to monitoring, to determine compliance with GMP principles. 4 Quality management system 4.1 General requirements The organization shall document, manage, and implement the quality management systems and GMP required to assure excipient quality. NOTE The elements of the q
42、uality management should be applied in a manner that is appropriate and proportionate to each of the product lifecycle stages, recognizing the different goals and knowledge available at each stage. The organization shall maintain and continually improve the quality management system and GMP in accor
43、dance with the requirements of this Standard. 4.1.1 General quality management systems organization In defining the quality management processes the organization shall: a) define individual and collective roles, responsibilities, authorities and inter-relationships of all organizational units relate
44、d to the excipient quality management system; ensure these interactions are communicated and understood at all relevant levels of the organization (see 5.5.1); b) define the interactions of the processes stated herein, with the operations needed for the quality management system and the implementati
45、on of GMP; c) determine the criteria and methods to ensure that the operation and control of these processes and GMP are effective; d) ensure that there are suitable resources, including availability of information, to support the operation and measurement of these processes; e) monitor, and, where
46、applicable, measure and analyze these processes and procedures to gain knowledge and understanding of them; and NOTE Processes here include the quality management system and the manufacturing and delivery operations. f) apply actions based on the science and knowledge gained to improve these process
47、es and the quality management system while maintaining consistent excipient quality. NOTE Quality risk management may be useful for identifying and prioritizing areas for continual improvement.12 4.1.2 Outsourcing general requirements Where manufacturing, testing, or other operations that may affect
48、 excipient quality are outsourced, the organization shall: 12 ICH Harmonised Tripartite Guideline, Q9: Quality Risk Management, November 2005 2017 NSF NSF/IPEC/ANSI 363 2016 9 a) define the responsibility for quality and the control measures within the quality management system (see 7.4); and b) dem
49、onstrate that the applicable GMP principles in accordance with this Standard are applied to those operations. 4.2 Documentation requirements 4.2.1 General The design, organization, and documentation of the quality system shall be structured to facilitate common understanding and consistent application. The use of appropriate quality risk management principles shall be incorporated into changes to the quality management system. NOTE Quality risk management may be a useful aid to identifying activities, operations, and processes that pose a risk t
