1、Institute of Environmental Sciences and Technology IEST-RP-CC049.1 Contamination Control Division Recommended Practice 049.1 Controlled Environments for Regulated Industries 1827 Walden Office Square, Suite 400 Schaumburg, IL 60173 Phone: (847) 981-0100 Fax: (847) 981-4130 E-mail: informationiest.or
2、g Web: www.iest.org 2 IEST 2017 All rights reserved Institute of Environmental Sciences and Technology IEST-RP-CC049.1 IEST-RP-CC049.1 Institute of Environmental Sciences and Technology IEST 2017 All rights reserved 3 This Recommended Practice was prepared by and is under the jurisdiction of Working
3、 Group 049 of the IEST Contamination Control Division. The following WG voting members contributed to the development of this edition of this Recommended Practice. Anne Marie Dixon, Cleanroom Management Associates, Inc. WG-CC049 Chair Gordon Ely, MiMedx Group, Inc. Leticia Fabiano, Genzyme Biosurger
4、y Jennifer Galvin, DuPont Protection Solutions Leo Gubenko, Vileda Professional, FHP Brad Lyon, ITW Texwipe Rick Meyer, Superior Laboratory Services, Inc. Jay Postlewaite, ITW Texwipe Matt Smyers, TSS, Inc. The Working Group also wishes to acknowledge the contributions of members who prefer to remai
5、n anonymous. Copyright 2017 by the Institute of Environmental Sciences and Technology First printing, September 2017 ISBN: 978-1-937280-34-5 (Electronic format) ISBN: 978-1-937280-35-2 (Print format) PROPOSAL FOR IMPROVEMENT: The Working Groups of the Institute of Environmental Sciences and Technolo
6、gy are continually working on improvements to their Recommended Practices and Reference Documents. Suggestions from users of these documents are welcome. If you have a suggestion regarding this document, please use the online Proposal for Improvement form found on the IEST website at www.iest.org. I
7、nstitute of Environmental Sciences and Technology 1827 Walden Office Square, Suite 400 Schaumburg, IL 60173 Phone: (847) 981-0100 Fax: (847) 981-4130 E-mail: informationiest.org Web: www.iest.org 4 IEST 2017 All rights reserved Institute of Environmental Sciences and Technology IEST-RP-CC049.1 IEST-
8、RP-CC049.1 Institute of Environmental Sciences and Technology IEST 2017 All rights reserved 5 NOTICE AND DISCLAIMER: This Recommended Practice is published by the Institute of Environmental Sciences and Technology (IEST) to advance the technical and engineering sciences. Use of this document is enti
9、rely voluntary, and determination of its applicability and suitability for any particular use is solely the responsibility of the user. Use of this Recommended Practice does not imply any warranty or endorsement by IEST. The information in this publication was considered technically sound by the con
10、sensus of persons engaged in the development and approval of the document at the time it was developed. Consensus does not necessarily mean that there is unanimous agreement among all persons participating in the development of this document. IEST standards, recommended practices, and guideline publ
11、ications, of which the document contained herein is one, are developed through a voluntary consensus standards development process. This process brings together volunteers and seeks out the views of persons who have an interest in the topic covered by this publication. While IEST administers the pro
12、cess to promote fairness in the development of consensus, the organization does not write the document and does not independently test, evaluate, or verify the accuracy or completeness of any information or the soundness of any judgments contained in IEST standards, recommended practices, and guidel
13、ine publications. IEST disclaims liability for any personal injury, property, or other damages of any nature whatsoever, whether special, indirect, consequential, or compensatory, directly or indirectly resulting from the publication, use of, application, or reliance on this document. IEST disclaims
14、 and makes no guaranty or warranty, express or implied, as to the accuracy or completeness of any information published herein, and disclaims and makes no warranty that the information in this document will fulfill any of the particular purposes or needs of users of the document. IEST does not guara
15、ntee the performance of any individual manufacturer or sellers products or services by virtue of this standard or guide. In publishing and making this document available, IEST is not undertaking to render professional or other services for or on behalf of any person or entity, nor is IEST undertakin
16、g to perform any duty owed by any person or entity to someone else. Anyone using this document should rely on his or her own independent judgment or, as appropriate, seek the advice of a competent professional in determining the exercise of reasonable care in any given circumstances. Information and
17、 other standards on the topic covered by this publication may be available from other sources, which the user may wish to consult for additional views or information not covered by this publication. IEST has no power, nor does it undertake to police or enforce compliance with the contents of this do
18、cument. IEST does not certify, test, or inspect products, designs, or installations for safety or health purposes. Any certification or other statement of compliance with any health or safety-related information in this document shall not be attributable to IEST and is solely the responsibility of t
19、he certifier or maker of the statement. 6 IEST 2017 All rights reserved Institute of Environmental Sciences and Technology IEST-RP-CC049.1 IEST-RP-CC049.1 Institute of Environmental Sciences and Technology IEST 2017 All rights reserved 7 Controlled Environments for Regulated Industries IEST-RP-CC049
20、.1 CONTENTS SECTION 1 SCOPE AND LIMITATIONS 8 2 REFERENCES 8 3 TERMS AND DEFINITIONS 10 4 BACKGROUND AND PURPOSE 10 5 RISK ASSESSMENT . 10 6 FACILITY REQUIREMENTS . 11 7 OPERATIONS 13 8 MONITORING AND CONTROLS . 14 8 IEST 2017 All rights reserved Institute of Environmental Sciences and Technology IE
21、ST-RP-CC049.1 Institute of Environmental Sciences and Technology Contamination Control Division Recommended Practice 049.1 Controlled Environments for Regulated Industries IEST-RP-CC049.1 1 SCOPE AND LIMITATIONS 1.1 Scope This Recommended Practice (RP) provides criteria for the control of non-classi
22、fied environments in industries such as pharmaceuticals, biologics, medical devices, nutraceuticals, healthcare, research and development, laboratories, component manufacturing, and emerging industries. The criteria are intended to assist manufacturers in implementing production methods and process
23、controls, including facility environmental controls. 1.2 Limitations This RP is not associated with cleanroom requirements or related documentation and does not apply to the unregulated industries, including but not limited to semiconductor, electronics, aerospace, automotive, and nanotechnologies.
24、IMPORTANT NOTE: This RP does not address sterile compounding as defined by United States Pharmacopeia General Chapter Pharmaceutical CompoundingSterile Preparations (USP ). 2 REFERENCES 2.1 Normative references IEST-RP-CC003: Garment System Considerations for Cleanrooms and Other Controlled Environm
25、ents IEST-RP-CC012: Considerations in Cleanroom Design IEST-RP-CC018: Cleanroom Housekeeping, Operating, and Monitoring Procedures IEST-RP-CC023: Microorganisms in Cleanrooms ISO 14644-1 Cleanrooms and associated controlled environmentsPart 1: Classification of air cleanliness by particle concentrat
26、ion ISO 14644-2 Cleanrooms and associated controlled environmentsPart 2: Monitoring to provide evidence of cleanroom performance related to air cleanliness by particle concentration ISO 14644-3 Cleanrooms and associated controlled environmentsPart 3: Test methods ISO 14698 Cleanrooms and associated
27、controlled environmentsBiocontamination control ISO 14971 Medical Devices: Application of risk management to medical devices IEST-RP-CC049.1 Institute of Environmental Sciences and Technology IEST 2017 All rights reserved 9 2.2 Additional resources AAMI TIR52: Environmental Monitoring For Terminally
28、 Sterilized Healthcare Products IEST-RP-CC026: Cleanroom Operations ISO 14644-4 Cleanrooms and associated controlled environmentsPart 4: Design, construction and start-up ISO 14644-5 Cleanrooms and associated controlled environmentsPart 5: Operations ISPE Glossary of Pharmaceutical and Biotechnology
29、 Terminology United States Pharmacopeia, General Chapter Microbiological Evaluation of Clean Rooms and Other Controlled Environments (USP ) 2.3 Sources AAMI Association for the Advancement of Medical Instrumentation 4301 N. Fairfax Drive, Suite 301 Arlington, VA 22203-1633 Phone: 703-525-4890 Fax: 7
30、03-276-0793 www.aami.org IEST Institute of Environmental Sciences and Technology 1827 Walden Office Square, Suite 400 Schaumburg, IL 60173 Phone: 847-981-0100 Fax: 847-981-4130 www.iest.org ISO In US, ISO 14644 and ISO 14698 Standards: IEST 1827 Walden Office Square, Suite 400 Schaumburg, IL 60173 P
31、hone: 847-981-0100 Fax: 847-981-4130 www.iest.org Other ISO Standards: International Organization for Standardization ISO Central Secretariat 1, ch. de la Voie-Creuse Case postale 56 CH-1211 Geneva 20, Switzerland Phone: 41 22 749 01 11 Fax: 41 22 733 34 30 E-mail: centraliso.org www.iso.org ISPE In
32、ternational Society for Pharmaceutical Engineering 7200 Wisconsin Ave., Suite 305 Bethesda, MD 20814 Phone: 301-364-9201 Fax: 240-204-6024 www.ispe.org 10 IEST 2017 All rights reserved Institute of Environmental Sciences and Technology IEST-RP-CC049.1 USP United States Pharmacopeia 12601 Twinbrook P
33、arkway Rockville, MD 20852-1790, USA Phone: 800-227-8772 or 301-881-0666 www.usp.org 3 TERMS AND DEFINITIONS cleanroom A room within which the number concentration of airborne particles is controlled and classified, and which is designed, constructed, and operated in a manner to control the introduc
34、tion, generation and retention of particles inside the room. contaminant Any particulate, molecular, non-particulate, or biological entity that can adversely affect the product or process. controlled environment A defined zone in which sources of viable and non-viable particulates are controlled by
35、specific means. monitoring Measurement of physical variables and comparison of the values obtained with the values specified for the process. monitoring program Observations made by measurement in accordance with a defined method and plan to detect changes in operational states, to provide process s
36、upport, and to provide evidence of the proper performance of an installation. viable A living particle capable of performing biochemical processes and reproducing. 4 BACKGROUND AND PURPOSE Improper control of elements that are critical to an operational controlled environment can pose a risk to the
37、cleanliness and quality of the product and process. Various types of controlled environments may be used in regulated industries, depending on the application. A controlled environment is an area, room, or zone using design controls to maintain air cleanliness, surface cleanliness, gases, water, and
38、 chemical purity at a specific level based on the risk of the product and process. The operational limits include controls for cleaning, gowning, and monitoring. Controlled areas should be maintained according to guidance and regulatory documents. A classified controlled environment, or a cleanroom,
39、 is designated by the cleanliness of the air. Classified areas must undergo thorough testing and qualification to comply with cleanroom classifications under ISO 14644-1. Controlled non-classified areas use supplied filtered air but do not have defined airborne particle limits. These areas are clean
40、able, access controlled, and may have additional controls depending on the type of process. Healthcare products require appropriate controls for consumer and patient safety. Control of the environmental conditions during all aspects of the manufacturing process helps ensure a consistent and contamin
41、ation-free product. Product quality is controlled by eliminating or minimizing risk of unwanted materials, substances, microorganisms, or particles. 5 RISK ASSESSMENT “Risk” refers to the combination of the probability of the occurrence of harm and the severity of that harm. “Harm” is defined as phy
42、sical injury or damage to the health of people and damage to property or environment. The risk management process is intended to identify hazards associated with controlled environment processes and clean air device monitoring equipment. Risk management systems allow users to estimate and evaluate t
43、he associated risks, and to control and monitor the effectiveness of the control. Per the requirements of ISO 14971, four key components of the risk management process are risk analysis, risk evaluation, risk control, and post-production information. Risk assessment uses tools such as, but not limit
44、ed to, the following: IEST-RP-CC049.1 Institute of Environmental Sciences and Technology IEST 2017 All rights reserved 11 a) Hazard Analysis Critical Control Point (HACCP) b) Failure Mode Effect Analysis (FMEA) c) Fishbone Diagram d) Fault Tree Analysis Risk assessments are used primarily to determi
45、ne the risk to the quality of product. A risk assessment should be performed to determine the cleanliness requirements and controls for any controlled environment used for the manufacture of products. The risk assessment should be applied to the facility and equipment used in the manufacturing proce
46、ss. Risk assessments are used throughout the process to identify potential issues with materials, process flow, and controls, safety, and to determine methods for removal or mitigation of those risks. Refer to ISO 14644-2 for risk assessment considerations. To maintain the safety and quality of the
47、product in controlled environments throughout the manufacturing processes, environmental monitoring data and trend analysis data for critical parameters should be reviewed to assess the risk. Objectives of risk assessment are to: Provide a harmonized approach to perform hazard analysis Determine sam
48、ple locations Establish action and alarm levels and response plan (see section 8.5) Establish sample testing frequency Perform annual or biannual risk review to monitor the effectiveness of controls that allows users to reduce risk and identify mitigation methods (preventive control). Additional ris
49、k assessment should be performed to establish the monitoring requirements for particles (airborne viable and surface viable), gases, utilities, personnel, and facility requirements, and to identify critical parameters in the process. 6 FACILITY REQUIREMENTS 6.1 Design process The design process should clearly identify the needs of the project. The risk assessment discussed in section 5 should be used to establish a design specification. In addition, the following items should be considered: a) All room designs should meet minimum air changes
