1、Designation: E3051 16Standard Guide forSpecification, Design, Verification, and Application ofSingle-Use Systems in Pharmaceutical andBiopharmaceutical Manufacturing1This standard is issued under the fixed designation E3051; the number immediately following the designation indicates the year oforigi
2、nal 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.1. Scope1.1 This guide is intended as a complement to Guide E2500.1.2 This g
3、uide is applicable to the range of manufacturingsystems described in Guide E2500, specifically all elements ofsingle-use systems, or hybrids of single-use and traditionalcomponents, used for the manufacturing of pharmaceutical andbiopharmaceutical products, including: materials ofconstruction, compo
4、nents, assembly, manifolds, supportingutilities, associated process monitoring and control systems,automation systems, and controlled environment that have thepotential to affect product quality and patient safety.1.3 This guide is applicable for the implementation ofchanges to manufacturing system
5、design for existing systems.It may be used for continuous improvement and changes inoperation from clinical through to commercial scale.1.4 For brevity, single-use systems are referred to as SUSthroughout the rest of this guide.1.5 The approach may be applied by the end user, thesupplier of SUS, and
6、 raw materials sub-suppliers further backin the supply chain.1.6 This guide is not intended to apply to the use ofsingle-use technology for packaging, primary containers, com-bination products (products composed of any combination of adrug, device, or biological product) or devices.1.7 This guide do
7、es not address specific local requirements,which remain the responsibility of the end user.1.8 This guide does not address employee health and safety,environmental, nor other good engineering and manufacturingpractices (GXP) requirements. This standard does not purportto address all of the safety co
8、ncerns, if any, associated with itsuse. It is the responsibility of the user of this standard toestablish appropriate safety and health practices and deter-mine the applicability of regulatory limitations prior to use.2. Referenced Documents2.1 ASTM Standards:2D4169 Practice for Performance Testing
9、of Shipping Con-tainers and SystemsE2363 Terminology Relating to Process Analytical Technol-ogy in the Pharmaceutical IndustryE2500 Guide for Specification, Design, and Verification ofPharmaceutical and Biopharmaceutical ManufacturingSystems and Equipment2.2 United States Pharmacopeia:3USP Particula
10、te Matter in InjectionsUSP Visible Particulates in Injections2.3 International Conference on Harmonization of Techni-cal Requirements for Registration of Pharmaceuticals forHuman Use (ICH):4ICH Q7 Good Manufacturing Practice Guide for ActivePharmaceutical IngredientsICH Q8 (R2) Pharmaceutical Develo
11、pmentICH Q9 Quality Risk ManagementICH Q10 Pharmaceutical Quality System2.4 ISO Standards:5ISO 13485:2003 Medical DevicesQuality ManagementSystemsRequirements for Regulatory PurposesISO 14644 Cleanrooms and Associated Controlled Environ-mentsISTA 3A General Simulation Performance tests2.5 U.S. Food
12、and Drug Administration (USFDA):6Guidance for Industry Process Validation: General Prin-ciples and Practices1This guide is under the jurisdiction of ASTM Committee E55 on Manufactureof Pharmaceutical and Biopharmaceutical Products and is the direct responsibility ofSubcommittee E55.03 on General Pha
13、rmaceutical Standards.Current edition approved Feb. 1, 2016. Published March 2016. DOI: 10.1520/E3051-16.2For referenced ASTM standards, visit the ASTM website, www.astm.org, orcontact ASTM Customer Service at serviceastm.org. For Annual Book of ASTMStandards volume information, refer to the standar
14、ds Document Summary page onthe ASTM website.3Available from U.S. Pharmacopeial Convention (USP), 12601 TwinbrookPkwy., Rockville, MD 20852-1790, http:/www.usp.org.4Available from International Conference on Harmonisation of TechnicalRequirements for Registration of Pharmaceuticals for Human Use (ICH
15、), ICHSecretariat, 9, chemin des Mines, P.O. Box 195, 1211 Geneva 20, Switzerland,http:/www.ich.org.5Available from American National Standards Institute (ANSI), 25 W. 43rd St.,4th Floor, New York, NY 10036, http:/www.ansi.org.6Available from U.S. Food and Drug Administration (FDA), 10903 NewHampshi
16、re Ave., Silver Spring, MD 20993, http:/www.fda.gov.Copyright ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States1Pharmaceutical cGMPs for the 21st Century, A Risk-BasedApproach2.6 European Medicine Agency:Commission Directive 2003/94/EC of 8 Octob
17、er 20032.7 Other Publications:PDA Technical Report No. 66 Application of Single-UseSystems in Pharmaceutical ManufacturingConsensus Quality Agreement Template for Single-Use Bio-pharmaceutical Manufacturing Products BioProcess Sys-tems Alliance7TAPPI Standard Practice T 564 sp-113. Terminology3.1 De
18、finitions:3.1.1 For definitions of terms used in this guide, refer toTerminology E2363, Guide E2500, and PDA Technical ReportNo. 66. Terms requiring special consideration as they relate toSUS are detailed below.3.1.2 design reviews, npurpose of design reviews is still toevaluate design against stand
19、ards and requirements, identifyproblems, and propose corrective actions.3.1.2.1 DiscussionHowever, the scope of the review maydiffer depending on whether the end user is considering astandard design, configured variants of standard designs whichmaintain adherence to the suppliers design space, or cu
20、stom-ized designs, which incorporate one or more features that areoutside of the suppliers design space. Such features mayinclude components, design layout, design dimensions, ormaterials of construction. The end-user should first considerthe requirements for any given SUS based on the application(f
21、or example, product or process contact, temperature,volumes, flow rates, mixing, requirements for sensors andcontrols etc. as applicable) and define them clearly in adocument such as a user requirement specification (URS). Inthe case of standard or configured designs, the review willaddress the supp
22、liers criteria for selection of materials,components, and functional design and align these against theURS. In the case of end-user-specified custom designs, thedesign review should affirm that the combination of supplier-and user-derived design attributes aligns with the URS.Additionally, the revie
23、w should evaluate the risk taken indeviating from the supplier design space, and the possible needfor risk mitigation, which generally will be the end usersresponsibility. The risk assessment should be retained as part ofthe development history. Conditions and expectations shouldbe covered in a qual
24、ity agreement. The quality agreementshould outline the responsibilities of the supplier and the enduser with respect to the quality assurance of the systemmanufactured or supplied or both by the supplier to the enduser. Quality agreement templates are available from variousindustry groups (for examp
25、le, Consensus Quality AgreementTemplate for Single-Use Biopharmaceutical ManufacturingProducts BioProcess Systems Alliance).3.1.3 modular, adjSUS can consist of assemblies of com-ponents or subassemblies that can be built or reconfigured orboth in a modular manner provided that connectors arecompati
26、ble with each other.3.1.4 subject matter experts, nindividuals with expertisein a particular area or field, which will include, but are notlimited to, material sciences, plastics and moldingtechnologies, sterilization, particulate assessment, and leach-ables and extractables.3.1.5 verification, nver
27、ification is a systematic approachto verify that SUS, acting singly or in combination, are fit forintended use, have been properly installed, and are operatingcorrectly.3.1.5.1 DiscussionThe manufacturing process for an SUSconsists of multiple steps and verification activities should beappropriate f
28、or the stage of the SUS design and manufacturingprocess (for example, material selection versus componentdimensions versus configuration) and the intended purpose ofthe component or finished assembly or both. Verification is anumbrella term that encompasses all types of approaches toassuring systems
29、 are fit for use including qualification, com-missioning and qualification, verification, system validation, orother and extends across the supply chain as materials andcomponents are integrated into the completed SUS. Given thateach system is partially or completely replaced after use, it isimporta
30、nt to confirm that components have been assembledcorrectly, none of the critical attributes of the assembly aredamaged during installation, and no leaks that may compro-mise the SUS are evident before use. Suppliers of SUS andtheir materials and components should apply similar rigor andchange contro
31、l procedures to their sub-suppliers to ensureconsistent quality over the lifetime of the SUS (see also 8.2,Change Management).4. Summary of Guide4.1 This guide is based on a similar risk-based and science-based approach taken in Guide E2500 and is similar inpurpose, content, and organization.4.2 The
32、 objective of this guide is to provide additionalinformation to support defined and controlled processes rel-evant to SUS, or hybrid traditional SUS to enable the produc-tion of products that consistently meet defined quality require-ments. A further objective is to support supplier manufacturingcap
33、ability that meets quality requirements of SUS or UserRequirement Specifications (URS) or both as applicable.4.3 The approach described within this guide supportscontinuous process capability improvements and facilitatesincorporation of new capabilities as technology evolves.4.4 The main elements of
34、 this guide are:4.4.1 The underlying key concepts,4.4.2 A description of the specification, design, and verifi-cation process, and4.4.3 A description of the required supporting processes.5. Significance and Use5.1 Application of the approach described within this guideis intended to satisfy internat
35、ional regulatory expectations inensuring that SUS are fit for their intended use and to satisfy7Available from BioProcess Systems Alliance, http:/www.bpsalliance.org.E3051 162requirements for sourcing, supply, design, specification,installation, operation, and performance.5.2 The approach described
36、in this guide applies conceptsand principles introduced in the FDAinitiative, PharmaceuticalcGMPs for the 21st Century A Risk-Based Approach. Itsupports and is consistent with the framework described inFDA Guidance for Industry, Process Validation: General Prin-ciples and Practices, in ICH Q7, ICH Q
37、8 (R2), ICH Q9, andICH Q10.5.3 This guide includes concepts developed in the PDATechnical Report No. 66.5.4 This guide may be used independently or in conjunctionwith other ASTM Committee E55 proposed standards to bepublished by ASTM International.5.5 Specific standard practices about extractables,l
38、eachables, particulate matter, and integrity testing/leakdetection, biocompatibility, and raw materials as availableshould be used by suppliers and end users and applied to theirown manufacturing process facilities.6. Key Concepts6.1 This guide follows similar key concepts to those cov-ered by Guide
39、 E2500 focusing on clarification and discussionof SUS, good engineering practice, good manufacturingpractice, and use of supplier and end user documentation. Theconcepts are listed in the following:6.1.1 Risk-based approach,6.1.2 Science-based approach,6.1.3 Critical aspects of SUS,6.1.4 Quality by
40、design,6.1.5 Good engineering/manufacturing/distribution/documentation practices,6.1.6 Subject matter expert,6.1.7 Use of supplier documentation,6.1.8 Continuous improvement and change management,and6.1.9 Supply chain.6.2 Risk-Based Approach:6.2.1 The underlying principle of risk management focuseso
41、n the issues which have the highest probability of occurring orhave the greatest effect on the product quality and consequentlypatient safety.6.2.2 Risk management underpins the specification, design,verification, and documentation activities as described inGuide E2500 and in ICH Q9.6.2.3 SUS are an
42、 integral part of the drug manufacturingprocess and it is critical that SUS suppliers provide SUS in atimely manner. Special consideration should be given tomitigating the risk of an interruption of the supply chain ofSUS, which may have an impact on the security of supply ofdrug to patients.6.3 Sci
43、ence-Based Approach:6.3.1 Product and process information, as it relates toproduct quality and patient safety, remain the basis for makingscience- and risk-based decision that ensure that the SUS aredesigned and verified to be fit for their intended use.6.3.2 Examples of end-user product and process
44、 informa-tion to consider include: critical quality attributes (CQAs),critical process parameters (CPPs), process control strategyinformation, and prior production experience. For SUS, thesecan include extractables information, certificates of analysis,sterilization records, change control documents
45、, and productdesign specifications.6.3.3 Additional information to consider is the processingparameters and materials for the SUS themselves. Materialsand designs should be selected and developed based on theintended use of the SUS (for example, cell culture, buffer bag,and product container) using
46、quality by design approaches,such that sources of variability are understood and are managedsuch that they do not impact the performance of the end usersprocess or product quality.6.3.4 Special consideration should be given to the suppliersevaluation and selection of materials of construction (forex
47、ample, films, tubing, and connectors) as related to theirfitness for intended use based on parameters such as physico-chemical properties, mechanical strength, optical properties,and anticipated operating temperature. Materials should berobust and compatible with product and process fluids andshould
48、 not be excessively prone to damage, which compro-mises structural integrity. The shedding of any materials, eitheras solid particles or soluble leachables, that impact productquality or process performance should be well characterized.For SUS, this is particularly important since changes may bemade
49、 in the construction materials, production and sterilizationprocesses, additives such as anti-oxidants and dyes, andmaterial origin based on their availability over the lifetime ofa given process. Such changes should be evaluated with theappropriate diligence based on the risk to the product or theprocess.6.3.5 Consideration should be given to the possible impactof materials of construction or in-process leachables frommaterials of construction, or both, on product quality or processperformance.6.4 Critical Aspects of SUS:6.4.1 Critical aspects of SUS are typical
