ASTM F3127-22
(Guide)Standard Guide for Validating Cleaning Processes Used During the Manufacture of Medical Devices
Standard Guide for Validating Cleaning Processes Used During the Manufacture of Medical Devices
SIGNIFICANCE AND USE
5.1 This guide describes an approach to validate a cleaning system for a medical device. It is based on the manufacturer’s accurate and comprehensive understanding of their internal manufacturing and cleaning processes.
5.2 This guide is not intended to provide a detailed plan or road map, but will provide considerations that can be used by the device manufacturer to develop a detailed plan for performing cleaning validation.
5.3 In cleaning validation, as with other types of validations, there are multiple ways to achieve a compliant, scientifically sound, and practical cleaning validation program.
5.4 There are several reference documents identified in Appendix X3 that describe cleaning validation approaches for non-medical devices (including cleaning for oxygen-enriched environments, pharmaceuticals, and semiconductors). Any of these reference documents could provide guidance for a well-defined process for establishing a manufacturer’s minimum expectation of a specific cleaning validation program.
5.5 This guidance specifically targets cleaning validation for medical devices, in-process and at terminal cleaning so that the result is a consistently clean medical device that meets the performance expectations for that device.
SCOPE
1.1 This guide provides considerations for validating cleaning processes for medical devices during initial fabrication and assembly prior to initial use. Validated cleaning processes are important for achieving consistency in function and consistency in biocompatibility. The considerations include but are not limited to: validation approach, equipment design, procedures and documentation, analytical methods, sampling, development of limits, and other issues.
1.2 Inclusions:
1.2.1 This guide describes the validation of critical cleaning processes for medical devices to reduce contaminants to acceptable levels prior to packaging.
1.3 Exclusions—The following items / medical devices / processes are excluded from the scope of this document:
1.3.1 Reusable medical devices.
1.3.1.1 Validation of cleaning operations for reusable medical devices is not within the scope of this standard guide. Although cleaning of reusable medical devices is beyond the scope of this guide, many of the principles outlined in this guide may be applicable to the validation of cleaning operations for reusable devices.
1.3.2 Cleaning of medical devices in health care facilities.
1.3.2.1 Validation of cleaning processes in patient/health care facilities is not within the scope of this standard guide.
1.4 This standard does not purport to be a replacement for biological safety testing.
1.5 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety, health, and environmental practices and determine the applicability of regulatory limitations prior to use.
1.6 This international standard was developed in accordance with internationally recognized principles on standardization established in the Decision on Principles for the Development of International Standards, Guides and Recommendations issued by the World Trade Organization Technical Barriers to Trade (TBT) Committee.
General Information
Relations
Standards Content (Sample)
This international standard was developed in accordance with internationally recognized principles on standardization established in the Decision on Principles for the
Development of International Standards, Guides and Recommendations issued by the World Trade Organization Technical Barriers to Trade (TBT) Committee.
Designation: F3127 − 22
Standard Guide for
Validating Cleaning Processes Used During the Manufacture
of Medical Devices
This standard is issued under the fixed designation F3127; the number immediately following the designation indicates the year of
original adoption or, in the case of revision, the year of last revision. A number in parentheses indicates the year of last reapproval. A
superscript epsilon (´) indicates an editorial change since the last revision or reapproval.
1. Scope Development of International Standards, Guides and Recom-
mendations issued by the World Trade Organization Technical
1.1 This guide provides considerations for validating clean-
Barriers to Trade (TBT) Committee.
ing processes for medical devices during initial fabrication and
assembly prior to initial use. Validated cleaning processes are
2. Referenced Documents
important for achieving consistency in function and consis-
tency in biocompatibility. The considerations include but are
2.1 ASTM Standards:
not limited to: validation approach, equipment design, proce- D543 Practices for Evaluating the Resistance of Plastics to
duresanddocumentation,analyticalmethods,sampling,devel-
Chemical Reagents
opment of limits, and other issues. E1766 Test Method for Determination of Effectiveness of
Sterilization Processes for Reusable Medical Devices
1.2 Inclusions:
E2857 Guide for Validating Analytical Methods
1.2.1 This guide describes the validation of critical cleaning
E3106 Guide for Science-Based and Risk-Based Cleaning
processes for medical devices to reduce contaminants to
Process Development and Validation
acceptable levels prior to packaging.
E3219 GuideforDerivationofHealth-BasedExposureLim-
1.3 Exclusions—The following items / medical devices /
its (HBELs)
processes are excluded from the scope of this document:
E3263 Practice for Qualification of Visual Inspection of
1.3.1 Reusable medical devices.
Pharmaceutical Manufacturing Equipment and Medical
1.3.1.1 Validation of cleaning operations for reusable medi-
Devices for Residues
cal devices is not within the scope of this standard guide.
F619 Practice for Extraction of Materials Used in Medical
Although cleaning of reusable medical devices is beyond the
Devices
scope of this guide, many of the principles outlined in this
F2459 Test Method for Extracting Residue from Metallic
guide may be applicable to the validation of cleaning opera-
Medical Components and Quantifying via Gravimetric
tions for reusable devices.
Analysis
1.3.2 Cleaning of medical devices in health care facilities.
F2847 Practice for Reporting and Assessment of Residues
1.3.2.1 Validation of cleaning processes in patient/health
on Single-Use Implants and Single-Use Sterile Instru-
care facilities is not within the scope of this standard guide.
ments
1.4 This standard does not purport to be a replacement for G121 Practice for Preparation of Contaminated Test Cou-
biological safety testing. pons for the Evaluation of Cleaning Agents
G122 Test Method for Evaluating the Effectiveness of
1.5 This standard does not purport to address all of the
Cleaning Agents and Processes
safety concerns, if any, associated with its use. It is the
G131 PracticeforCleaningofMaterialsandComponentsby
responsibility of the user of this standard to establish appro-
Ultrasonic Techniques
priate safety, health, and environmental practices and deter-
mine the applicability of regulatory limitations prior to use. 2.2 ANSI/AAMI/ISO Standards:
1.6 This international standard was developed in accor-
ISO 10993-5 Biological Evaluation of Medical Devices—
dance with internationally recognized principles on standard- Part 5: Tests for Cytotoxicity, In Vitro Methods
ization established in the Decision on Principles for the
1 2
This guide is under the jurisdiction of ASTM Committee F04 on Medical and For referenced ASTM standards, visit the ASTM website, www.astm.org, or
Surgical Materials and Devices and is the direct responsibility of Subcommittee contact ASTM Customer Service at service@astm.org. For Annual Book of ASTM
F04.15 on Material Test Methods. Standards volume information, refer to the standard’s Document Summary page on
Current edition approved Oct. 1, 2022. Published October 2022. Originally the ASTM website.
approved in 2016. Last previous edition approved in 2016 as F3127 – 16. DOI: Available fromAmerican National Standards Institute (ANSI), 25 W. 43rd St.,
10.1520/F3127-22. 4th Floor, New York, NY 10036, http://www.ansi.org.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States
F3127 − 22
ISO 11737-1:2018 Sterilization of Health Care Products— 3.1.5 cleaning process, n—a process that is used to remove
Microbiological Methods—Part 1: Determination of a any product, process-related material, and environmental con-
Population of Microorganisms on Products taminant introduced as part of the manufacturing process.
ISO 14971 Medical Devices—Application of Risk Manage-
3.1.6 cleaning validation, n—the documented evidence pro-
ment to Medical Devices
viding a high degree of assurance that a cleaning process will
ISO 17025 General Requirements for the Competence of
result in medical devices consistently meeting their predeter-
Testing and Calibration Laboratories
mined cleanliness requirements.
ISO19227 ImplantsforSurgery—CleanlinessofOrthopedic
3.1.7 cleaning verification, n—a one-time sampling and
Implants—General Requirements
testing to ensure that a medical device has been properly
AAMI ST72 Bacterial Endotoxins—Test Methodologies,
cleaned following a specific cleaning event.
Routine Monitoring, and Alternatives to Batch Testing
3.1.8 contaminant, n—any material that potentially ad-
2.3 United States Pharmacopoeia (USP) – General Chap-
versely impacts the assembly, the functioning of the device,
ters:
and/or shows undesirable interaction with the host.Acontami-
USP<61> Microbiological Examination of Nonsterile Prod-
nant may be a single component or any combination of
ucts: Microbial Enumeration Test
components. Examples of possible types of contaminants
USP<62> Microbiological Examination of Nonsterile Prod-
include: (1) biological or non-biological in nature; (2) living or
ucts: Test for Specified Microorganisms
dead; (3) particles or thin films; (4) solid, liquid, or vapor; and
USP <85> Bacterial Endotoxins Test
(5) organic or inorganic.
USP <161> Transfusion and Infusion Assemblies and Simi-
lar Medical Devices
3.1.9 first use, n—the initial contact with biological materi-
USP <1225> Validation of Compendial Procedures
als or fluids.
2.4 International Conference on Harmonization of Techni-
3.1.10 installation qualification (IQ), n—establishing by
cal Requirements for Registration of Pharmaceuticals for
objective evidence that all key aspects of the process equip-
Human Use (ICH):
ment and ancillary system installation adhere to the manufac-
ICHQ2 ValidationofAnalyticalProcedures:TextandMeth-
turer’s approved specification and the recommendations of the
odology
supplier of the equipment are suitably considered.
ICH Q9 Quality Risk Management
3.1.11 monitoring, v—verification testing at predefined in-
2.5 FDA Guidance Documents:
tervals.
FDA Guidance Pyrogen and Endotoxins Testing: Questions
and Answers, issued June 2012 3.1.12 operational qualification (OQ), n—establishing by
objective evidence process control limits and action levels
2.6 European Standards and Pharmacopoeia:
which result in product that meets all predetermined require-
EN 13018 Non-Destructive Testing—Visual Testing—
ments.
General Principles
European Pharmacopoeia
3.1.13 process qualification (PQ), n—establishing by objec-
tive evidence that the process, under anticipated conditions,
3. Terminology
consistently produces a product which meets all predetermined
3.1 Definitions:
requirements.
3.1.1 analyte, n—a substance (usually a residue) for which
3.1.14 recovery study, n—a laboratory study combining the
an analysis is being performed.The residue determination may
sampling method and analytical method to determine the
bequalitative,quantitative,specific,non-specific,and/oritmay
quantitativerecoveryofaspecificresidueforadefinedsurface.
involve compositional identification. The analyte may be
3.1.15 residue, n—a substance present at the surface of an
determinedasanextractordirectlyonthesurfaceofthedevice
implant or embedded therein that is not explicitly recognized
or portion (subassembly) of the device.
and defined as part of the implant specification. It includes
3.1.2 blank, n—an analytical sample taken to establish the
processing-based residues as well as contamination by envi-
backgroundvalueforananalyticalmeasurementwhichmaybe
ronmental factors (adsorbates).
subtracted from an experimental value to determine the “true”
value.
4. Summary of Practice
3.1.3 clean, n—having a level of residues and environmen-
4.1 This guide provides an approach for validating the
tal contaminants which does not exceed a maximum permis-
removal of contaminants and residues introduced during the
sible level for the intended application.
intermediateprocessstepssothattheterminalcleaningprocess
3.1.4 cleaning, v—removal of potential contaminants from
can result in a consistently clean medical device.
an item to the extent necessary for further processing or for
intended use.
5. Significance and Use
5.1 This guide describes an approach to validate a cleaning
Available from U.S. Pharmacopeial Convention (USP), 12601 Twinbrook
system for a medical device. It is based on the manufacturer’s
Pkwy., Rockville, MD 20852-1790, http://www.usp.org.
accurate and comprehensive understanding of their internal
Available from U.S. Food and Drug Administration (FDA), 10903 New
Hampshire Ave., Silver Spring, MD 20993, http://www.fda.gov. manufacturing and cleaning processes.
F3127 − 22
5.2 This guide is not intended to provide a detailed plan or 7.3.2 Device Design:
road map, but will provide considerations that can be used by 7.3.2.1 The design, material composition, and intended end
thedevicemanufacturertodevelopadetailedplanforperform-
use of the device have a significant impact on the suitability of
ing cleaning validation. a cleaning process. A non-exhaustive list of examples is
provided:
5.3 Incleaningvalidation,aswithothertypesofvalidations,
(1) Acleaning process that will not reach a blind hole in a
there are multiple ways to achieve a compliant, scientifically
medical device will not get the blind hole clean.
sound, and practical cleaning validation program.
(2) Densely populated electronics assemblies may not be
5.4 There are several reference documents identified in
readily accessed by cleaning chemistries. As a result, conduc-
Appendix X3 that describe cleaning validation approaches for
tive and non-conductive residue may remain.
non-medical devices (including cleaning for oxygen-enriched
(3) The cleaning process should not have an adverse effect
environments, pharmaceuticals, and semiconductors). Any of
on the materials of construction of the medical device, the
these reference documents could provide guidance for a
cleaning equipment, or the functionality of the medical device.
well-defined process for establishing a manufacturer’s mini-
For example, for plastic devices, Practice D543 may be used
mum expectation of a specific cleaning validation program.
for guidance on how to determine the suitability of specific
5.5 Thisguidancespecificallytargetscleaningvalidationfor cleaning agents to medical devices. Chemical compatibility of
medicaldevices,in-processandatterminalcleaningsothatthe
the cleaning process should be determined prior to cleaning
result is a consistently clean medical device that meets the process validation.
performance expectations for that device. (4) In some instances, the structure of the device or the
surface of the device may cause liquid or vapor-phase residue
6. General Requirements
to be entrapped. Such occurrences are generally not considered
6.1 This guidance for the validation of cleaning processes is
toconstituteamaterialscompatibilityproblem,iftheresidueis
dividedintothreesetsofactivities:understandingtheupstream
readily removed with extensive rinsing and/or drying (bake-
manufacturing process, documenting the cleaning process, and
out). However, given the potential negative impact on perfor-
establishingthemeasurementtoolsusedtoevaluatecleanliness
mance and/or interaction with the host, the design and mate-
and to establish the cleaning performance criteria.
rials of construction may qualitatively and quantitatively
impact the rinsing and/or drying portions of the cleaning
6.2 Preliminary process characterization, whether in the
process.
laboratory or on the manufacturing floor, provides the data
7.3.2.2 While the discussion of device design (design for
necessary to establish cleaning parameter control ranges.
cleanability) is critical to a cleaning validation, a full discus-
7. Cleaning Validation Approach
sion is not within the scope of this guide.
7.1 A typical approach to a cleaning validation includes: 7.3.3 Risk Analysis:
7.1.1 Anassessmentoftherisksandbenefitsofthecleaning
7.3.3.1 The risks and benefits associated with a specific
process and the impact of the cleaning processes on the
cleaning process should be addressed. There are a number of
medical device and on downstream processes.
approaches to evaluating the risks associated with a cleaning
7.1.2 Identification of contaminants from raw materials and
process, including those described in ISO 14971, ISO 19227,
manufacturing and processing operations (for example, ma-
Guide E3106, and ICH Q9.
chine oils) that could be residuals on the medical device.
7.3.3.2 The process risks evaluated should include the risk
7.1.3 Establishment of allowable limits for contaminants
to the patient.
(determining “How clean is clean?”) based on the product and
7.3.3.3 All cleaning operations should be considered, in-
process needs.Acceptance criteria for “clean” should be stated
cluding processes conducted by contract manufacturers.
with scientific justification for the criteria.
(1) Some cleaning operations may not be termed cleaning,
7.1.4 Avalidationoftheanalyticalmethodsusedtomeasure
and the terminology may be specific to a given technical field.
the residues or contaminants.
Passivation, surface preparation, and surface modification may
7.1.5 A qualification or determination of the sampling
or may not have a cleaning function. The manufacturer should
techniques used for evaluating the cleanliness of a medical
determine the function and efficacy of ea
...
This document is not an ASTM standard and is intended only to provide the user of an ASTM standard an indication of what changes have been made to the previous version. Because
it may not be technically possible to adequately depict all changes accurately, ASTM recommends that users consult prior editions as appropriate. In all cases only the current version
of the standard as published by ASTM is to be considered the official document.
Designation: F3127 − 16 F3127 − 22
Standard Guide for
Validating Cleaning Processes Used During the Manufacture
of Medical Devices
This standard is issued under the fixed designation F3127; the number immediately following the designation indicates the year of
original adoption or, in the case of revision, the year of last revision. A number in parentheses indicates the year of last reapproval. A
superscript epsilon (´) indicates an editorial change since the last revision or reapproval.
1. Scope
1.1 This guide provides considerations for validating cleaning processes for medical devices during initial fabrication and
assembly prior to initial use. Validated cleaning processes are important for achieving consistency in function and consistency in
biocompatibility. The considerations include but are not limited to,to: validation approach, equipment design, procedures and
documentation, analytical methods, sampling, development of limits, and other issues.
1.2 Inclusions:
1.2.1 This guide describes the validation of critical cleaning processes for medical devices to reduce contaminants to acceptable
levels prior to packaging.
1.3 Exclusions: Exclusions—The following items / medical devices / processes are excluded from the scope of this document:
1.3.1 Reusable medical devices.
1.3.1.1 Validation of cleaning operations for reusable medical devices is not within the scope of this standard guide. Although
cleaning of reusable medical devices is beyond the scope of this guide, many of the principles outlined in this guide may be
applicable to the validation of cleaning operations for reusable devices.
1.3.2 Cleaning of medical devices in health care facilities.
1.3.2.1 Validation of cleaning processes in patient/health care facilities is not within the scope of this standard guide.
1.4 This standard does not purport to be a replacement for biological safety testing.
1.5 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility
of the user of this standard to establish appropriate safety safety, health, and healthenvironmental practices and determine the
applicability of regulatory limitations prior to use.
1.6 This international standard was developed in accordance with internationally recognized principles on standardization
established in the Decision on Principles for the Development of International Standards, Guides and Recommendations issued
by the World Trade Organization Technical Barriers to Trade (TBT) Committee.
This guide is under the jurisdiction of ASTM Committee F04 on Medical and Surgical Materials and Devices and is the direct responsibility of Subcommittee F04.15
on Material Test Methods.
Current edition approved April 1, 2016Oct. 1, 2022. Published May 2016October 2022. Originally approved in 2016. Last previous edition approved in 2016 as
F3127 – 16. DOI: 10.1520/F3127-1610.1520/F3127-22.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States
F3127 − 22
2. Referenced Documents
2.1 ASTM Standards:
D543 Practices for Evaluating the Resistance of Plastics to Chemical Reagents
E1766 Test Method for Determination of Effectiveness of Sterilization Processes for Reusable Medical Devices
E2857 Guide for Validating Analytical Methods
E3106 Guide for Science-Based and Risk-Based Cleaning Process Development and Validation
E3219 Guide for Derivation of Health-Based Exposure Limits (HBELs)
E3263 Practice for Qualification of Visual Inspection of Pharmaceutical Manufacturing Equipment and Medical Devices for
Residues
F619 Practice for Extraction of Materials Used in Medical Devices
F2459 Test Method for Extracting Residue from Metallic Medical Components and Quantifying via Gravimetric Analysis
F2847 Practice for Reporting and Assessment of Residues on Single-Use Implants and Single-Use Sterile Instruments
G121 Practice for Preparation of Contaminated Test Coupons for the Evaluation of Cleaning Agents
G122 Test Method for Evaluating the Effectiveness of Cleaning Agents and Processes
G131 Practice for Cleaning of Materials and Components by Ultrasonic Techniques
2.2 ANSI/AAMI/ISO Standards:
ISO 10993-5 Biological Evaluation of Medical Devices—Part 5: Tests for Cytotoxicity, In Vitro Methods
ISO 10993-11 Biological Evaluation of Medical Devices—Art 11: Tests for Systemic Toxicity
ISO 10993-17 Biological Evaluation of Medical Devices—Part 17: Establishment of Allowable Limits for Leachable Substances
ISO 11737-111737-1:2018 Sterilization of Medical Devices—Microbiological Health Care Products—Microbiological
Methods—Part 1: Determination of a Population of Microorganisms on Products
ISO 14971 Medical Devices—Application of Risk Management to Medical Devices
ISO 17025 General Requirements for the Competence of Testing and Calibration Laboratories
ISO 19227 Implants for Surgery—Cleanliness of Orthopedic Implants—General Requirements
AAMI ST72 Bacterial Endotoxins—Test Methodologies, Routine Monitoring, and Alternatives to Batch Testing
AAMI TIR30 A Compendium of Processes, Materials, Test Methods, and Acceptance Criteria for Cleaning Reusable Medical
Devices
2.3 United States Pharmacopoeia (USP) – General Chapters:
USP <61> Microbiological Examination of Nonsterile Products: Microbial Enumeration Test
USP <62> Microbiological Examination of Nonsterile Products: Test for Specified Microorganisms
USP <85> Bacterial Endotoxins Test
USP <87><161> Biological Reactivity Tests, In VitroTransfusion and Infusion Assemblies and Similar Medical Devices
USP <88> Biological Reactivity Tests, In Vivo
USP <1225> Validation of Compendial Procedures
2.4 International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use
(ICH):
ICH Q2 Validation of Analytical Procedures: Text and Methodology
ICH Q9 Quality Risk Management
2.5 FDA Guidance Documents:
FDA Guidance Pyrogen and Endotoxins Testing: Questions and Answers, issued June 2012
2.6 European Standards and Pharmacopoeia:
EN 13018 Non-Destructive Testing—Visual Testing—General Principles
European Pharmacopoeia
3. Terminology
3.1 Definitions:
3.1.1 analyte, n—a substance (usually a residue) for which an analysis is being performed. The residue determination may be
qualitative, quantitative, specific, non-specific, and/or it may involve compositional identification. The analyte may be determined
as an extract or directly on the surface of the device or portion (subassembly) of the device.
For referenced ASTM standards, visit the ASTM website, www.astm.org, or contact ASTM Customer Service at service@astm.org. For Annual Book of ASTM Standards
volume information, refer to the standard’s Document Summary page on the ASTM website.
Available from American National Standards Institute (ANSI), 25 W. 43rd St., 4th Floor, New York, NY 10036, http://www.ansi.org.
Available from U.S. Pharmacopeial Convention (USP), 12601 Twinbrook Pkwy., Rockville, MD 20852-1790, http://www.usp.org.
Available from U.S. Food and Drug Administration (FDA), 10903 New Hampshire Ave., Silver Spring, MD 20993, http://www.fda.gov.
F3127 − 22
3.1.2 blank, n—an analytical sample taken to establish the background value for an analytical measurement which may be
subtracted from an experimental value to determine the “true” value.
3.1.3 clean, n—having ana level of residues and environmental contaminants which dodoes not exceed a maximum permissible
level for the intended application.
3.1.4 cleaning, v—removal of potential contaminants from an item to the extent necessary for further processing or for intended
use.
3.1.5 cleaning process, n—a process that is used to remove any product, process-related material, and environmental contaminant
introduced as part of the manufacturing process.
3.1.6 cleaning validation, n—the documented evidence providing a high degree of assurance that a cleaning process will result
in products medical devices consistently meeting their predetermined cleanliness requirements.
3.1.7 cleaning verification, n—a one-time sampling and testing to ensure that a medical device has been properly cleaned
following a specific cleaning event.
3.1.8 contaminant, n—any material that potentially adversely impacts the assembly, the functioning of the device, and/or shows
undesirable interaction with the host. A contaminant may be a single component or any combination of components. Examples of
possible types of contaminants include: ((1)1) biological or non-biological in nature; ((2)2) living or dead; ((3)3) particles or thin
films; ((4)4) solid, liquid, or vapor; and ((5)5) organic or inorganic.
3.1.9 first use, n—the initial contact with biological materials or fluids.
3.1.10 installation qualification (IQ), n—establishing by objective evidence that all key aspects of the process equipment and
ancillary system installation adhere to the manufacuter’smanufacturer’s approved specification and the recommendations of the
supplier of the equipment are suitably considered.
3.1.11 lowest observed adverse effect level (LOAEL), n—lowest concentration or amount of a substance found by experiment or
observation which causes detectable adverse alteration of morphology, functional capacity, growth, development, or life span of
the target organism under defined conditions of exposure.
3.1.11 monitoring, v—verification testing at predefined intervals.
3.1.13 no observed adverse effect level (NOAEL), n—greatest concentration or amount of a substance found by experiment or
observation which causes no detectable adverse alteration of morphology, functional capacity, growth, development, or life span
of the target organism under defined conditions of exposure.
3.1.12 operational qualification (OQ), n—establishing by objective evidence process control limits and action levels which result
in product that meets all predetermined requirements.
3.1.13 process qualification (PQ), n—establishing by objective evidence that the process, under anticipated conditions,
consistently produces a product which meets all predetermined requirements.
3.1.14 recovery study, n—a laboratory study combining the sampling method and analytical method to determine the quantitative
recovery of a specific residue for a defined surface.
3.1.15 residue, n—a substance present at the surface of an implant or embedded therein that is not explicitly recognized and
defined as part of the implant specification. It includes processing-based residues as well as contamination by environmental factors
(adsorbates).
F3127 − 22
3.1.18 tolerable intake (TI), n—estimate of the average daily intake of a substance over a specified time period, on the basis of
body mass, that is considered to be without appreciable harm to health.
4. Summary of Practice
4.1 This guide provides an approach for validating the removal of contaminants and residues introduced during the intermediate
process steps so that the terminal cleaning process can result in a consistently clean medical device.
5. Significance and Use
5.1 This guide describes an approach to validate a cleaning system for a medical device. It is based on the manufacturer’s accurate
and comprehensive understanding of their internal manufacturing and cleaning processes.
5.2 This guide is not intended to provide a detailed plan or road map, but will provide considerations that can be used by the device
manufacturer to develop a detailed plan for performing cleaning validation.
5.3 In cleaning validation, as with other types of validations, there are multiple ways to achieve a compliant, scientifically sound,
and practical cleaning validation program.
5.4 There are several reference documents identified in Appendix X3 that describe cleaning validation approaches for non-medical
devices (including cleaning for oxygen-enriched environments, pharmaceuticals, and semiconductors). Any of these reference
documents could provide guidance for a well defined well-defined process for establishing a manufacturer’s minimum expectation
of a specific cleaning validation program.
5.5 This guidance specifically targets cleaning validation for medical devices, in-process and at terminal cleaning so that the result
is a consistently clean medical device that meets the performance expectations for that device.
6. General Requirements
6.1 This guidance for the validation of cleaning processes is divided into 3three sets of activities: understanding the upstream
manufacturing process, documenting the cleaning process, and establishing the measurement tools used to evaluate cleanliness and
to establish the cleaning performance criteria.
6.2 Preliminary process characterization, whether in the laboratory or on the manufacturing floor, provides the data necessary to
establish cleaning parameter control ranges.
7. Cleaning Validation Approach
7.1 A typical approach to a cleaning validation includes:
7.1.1 An assessment of the risks and benefits of the cleaning process and the impact of the cleaning processes on the medical
device and on downstream processes.
7.1.2 Identification of contaminants from raw materials and manufacturing and processing operations (e.g. (for example, machine
oils) that could be residuals on the medical device.
7.1.3 Establishment of allowable limits for contaminants (determining “How clean is clean?”) based on the product and process
needs. Acceptance criteria for “clean” should be stated with scientific justification for the criteria.
7.1.4 A validation of the analytical methods used to measure the residues or contaminants.
7.1.5 A qualification or determination of the sampling techniques used for evaluating the cleanliness of a medical device.
7.1.6 A determination that statistical requirements and documentation are adequate to conclude that the result of testing meets the
output specification of the process.
F3127 − 22
7.2 A general process flow for a cleaning validation program is represented by the presented in Fig. 1:.
7.3 Definition of the Cleaning Process:
FIG. 1 Process Flow for a Cleaning Validation
F3127 − 22
7.3.1 The definition of the process should include an evaluation of the device, the equipment to be used for the cleaning process,
the process parameters, the process chemicals, and the manufacturing materials that should
...
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