1、Designation:E247616Standard Guide forRisk Assessment and Risk Control as it Impacts the Design,Development,and Operation of PAT Processes forPharmaceutical Manufacture1This standard is issued under the fixed designation E2476;the number immediately following the designation indicates the year oforig
2、inal adoption or,in the case of revision,the year of last revision.A number in parentheses indicates the year of last reapproval.Asuperscript epsilon()indicates an editorial change since the last revision or reapproval.INTRODUCTIONThis document provides guidance on the implementation of risk assessm
3、ent and risk control forProcess Analytical Technology(PAT)processes within the pharmaceutical industry.Whereverpossible,other appropriate standards on risk assessment/management have been referenced andacknowledged.Where practical,further details of methods and additional references have beenprovide
4、d for information within the appendixes.The application of risk assessment and risk control is pivotal to the creation of PAT systems,whichare described as“science-based”and“risk-based.”Such application starts at an early stage in thedevelopment of the process and continues throughout development an
5、d production.In the productionphase,it is a crucial component of applying continuous improvement to the process.RELATIONSHIP TO ICH Q9The ICH Q9 Guideline for Quality Risk Management is intended for general application within thepharmaceutical industry.ICH Q9 describes the requirements for pharmaceu
6、tical quality riskmanagement and considers the risk as“risk to the patient.”This document provides specific guidance on the risk assessment and risk control phases identifiedin ICH Q9 in a limited set of conditions.It is applicable where the manufacturing method is compliantwith Process Analytical T
7、echnology(PAT)principles,and where the primary considerations areproduct quality and reduction of process and product variability.The only component of risk to patientconsidered here is risk to product quality.Other components fall outside the scope of the document.In addition,other areas identified
8、 in ICH Q9,such as general risk management and riskcommunication,are not considered here.This document provides guidance which applies to the design,development,and operation of PATsystems.It should be considered as a specific extension,supporting the ICH Q9 guidance for theseprocesses.1.Scope1.1 Th
9、is document provides guidance on the assessment ofrisks to product quality within and related to PAT processes inthe pharmaceutical industry.It addresses those risks to productquality arising from,associated with,identified by,or modifiedby the implementation of PAT in pharmaceutical developmentand
10、manufacturing for primary,secondary,and biotech sectorsof the industry.It does not replace those assessments of riskcurrently undertaken by pharmaceutical companies,but is,rather,an additional component focused specifically upon theevaluation and design of PAT processes.See Practice E2474,Guide E250
11、0,and ICH Q8.1This guide is under the jurisdiction of ASTM Committee E55 on Manufactureof Pharmaceutical and Biopharmaceutical Products and is the direct responsibility ofSubcommittee E55.01 on Process Understanding and PAT System Management,Implementation and Practice.Current edition approved Nov.1
12、,2016.Published November 2016.Originallyapproved in 2009.Last previous edition approved in 2009 as E2476 09.DOI:10.1520/E2476-16.Copyright ASTM International,100 Barr Harbor Drive,PO Box C700,West Conshohocken,PA 19428-2959.United States1 1.2 This standard does not purport to address all of thesafet
13、y concerns,if any,associated with its use.It is theresponsibility of the user of this standard to establish appro-priate safety and health practices and determine the applica-bility of regulatory limitations prior to use.Note that safety inthis context refers to operational and operator safety,not t
14、opatient safety.2.Referenced Documents2.1 ASTM Standards:2E2474 Practice for Pharmaceutical Process Design UtilizingProcess Analytical TechnologyE2500 Guide for Specification,Design,and Verification ofPharmaceutical and Biopharmaceutical ManufacturingSystems and EquipmentE2363 Terminology Relating t
15、o Process Analytical Technol-ogy in the Pharmaceutical Industry2.2 Other Standards:FDA Guidance for Industry PATA Framework for Inno-vative Pharmaceutical Development,Manufacturing,andQuality Assurance3ICH Q8(R2)Pharmaceutical Development4ICH Q9 Quality Risk Management4ICH Q10 Pharmaceutical Quality
16、 System4IEC 60812 Analysis Techniques for System ReliabilityProcedure for Failure Mode and Effects Analysis(FMEA)5IEC 61025 Fault Tree Analysis(FTA)5IEC 61882 Hazard and Operability Studies(HAZOPStudies)Application Guide5ISO 22000 FoodSafetyManagementSystemsRequirements for any Organization in the Food Chain6WHO Technical Report 908 WHO Expert Committee onSpecifications for Pharmaceutical Preparations3.Terminology3.1 The terminology specific to this guide will be incorpo-rated into Terminology E
