Technical Requirements and CLSI Guidelines for Laboratory Test Method Life Phases

Updated June 2021 from presentation at the 2019 American Association for Clinical Chemistry Annual Meeting
“Using CLSI Guidelines to Meet quality requirements established by FDA, CLIA, and ISO
throughout the Laboratory Test Method Life”

REQUIREMENTS CLSI
Phases Activity FDA QSR1 CLIA2 NYS3* ISO4-8 GUIDELINES**
1. 21 CFR QMS FS; S1-S7 ISO 9001:2015 General: EP12, QSRLDT
Feasibility 820.30 Director: DR FS; S1-S5 Clauses: 8.2.1, 8.2.2, 8.2.3, Process Management: EP19, QMS13
and Design Human Resources: HR FS; 8.3.1 through 8.3.6 Documents: QSRLDT, QMS02
S1-S10
2. General 820.30, Facility: FD FS; S1-S3 ISO 9001:2015 Facilities: QSRLDT
Development 820.50, Safety: LS FS; S1-S17 Clauses 8.3.1 through 8.3.6 Suppliers: QSRLDT, QMS21
820.181, Resources: RM FS; GRM S1- ISO 13485:2016 Equipment: QSRLDT, QMS01, QMS13,
820.40, S7 Clauses 7.1 through 7.3 AUTO08
820.60, Equipment LEI S1-S9 Process Management: EP19, QMS18,
820.65 Reagents: RGM S1-S5 QSRLDT, EP23, EP12
QC S1 Documents: QMS13, QMS26, QSRLDT
Risk Analysis, 493.1253(b)(3) & c, QC S2 ISO 14971:2019 EP18, EP21
Evaluation, and 493.1256 ISO 17025:2017 Clause 8.5
Control ISO 22367:2020
3. General 820.30 493.1253(a), Test Performance ISO 13485:2016 General: EP19, QMS18
Establishment

Validation 820.75 493.1253(b)(2), Specifications: TPS S2-S4 Clauses 7.5, 7.6 Process Management: EP19, QMS18
820.86 493.1253(b)(2)(vii), ISO 17025:2017 Documents: QMS02, QMS26, QSRLDT
493.1253(c), 493.1254(b) Clause 7.2.2 Process Management: EP12
ISO 15189:2012 NCE Management: QSRLDT
Clauses 5.5.1.1, 5.5.1.3, Assessment: QSRLDT
5.5.1.4, 5.5.2
Precision Calibration: CAL S1-S2 EP05
Accuracy 493.1253(b)(2)(i) & c EP09
Measuring Interval 493.1253(b)(2)(v) & c EP06, EP34
Reference Interval 493.1253(b)(2)(vi) & c EP28
Detection Capability 493.1253(b)(2)(iii) & c EP17
Analytical Specificity 493.1253(b)(2)(iv) & c C56, EP07, EP37
Clinical Validation EP24, EP27
Reagent/Sample 493.1253(b)(3) & c, EP25
493.1256
Stability

TRANSFER TO IMPLEMENTATION
 Technical Requirements and CLSI Guidelines for Laboratory Test Method Life Phases
Updated June 2021 from presentation at the 2019 American Association for Clinical Chemistry Annual Meeting
“Using CLSI Guidelines to Meet quality requirements established by FDA, CLIA, and ISO
throughout the Laboratory Test Method Life”

REQUIREMENTS CLSI
Phases Activity FDA QSR CLIA NYS ISO GUIDELINES
4. 820.30 QMS FS ISO 17025:2017 Facilities: QMS01, QMS23
Preliminary 820.70 Director: DR FS; S1-S5 Clauses 6.1 - 6.4; 6.6; 7.1 Personnel: QMS03
Evaluation 820.140 Human Resources: HR FS; ISO 15189:2012 Suppliers: QMS01
820.150 S1-S6 Clauses 4.3 - 4.7; 5.1, 5.2, Equipment: QMS01, QMS13
820.160 Facility: FD FS; S1-S3 5.3, 5.10 Process Management: EP12, QMS01,
820.170 Safety: LS FS; S1-S17 ISO 15190:2020 QMS02, EP10
Documents: QMS02, QMS26
5. General 820.30 Resources: RM FS ISO 17025:2017 Personnel: QMS03, EP12
Verification 820.86 Equipment LEI S1-S9 Clause 7.2.1 Equipment: QMS23
Reagents: RGM S1-S5 Clause 7.11.2 Process Management: QMS18, EP23,
Test Performance Specs: ISO 15189:2012 C24
TPS S1: S3-S5 Clauses 4.3, 5.3.1.7, 5.5.1.2 Documents: QMS02, QMS26
Calibration: CAL S1
Implementation

Risk Assessment IQCP in Interpretive QC S2 ISO 17025:2017 EP18, EP21, EP23

Guidelines; refers to Clause 8.5
493.1256(d) ISO 15189:2012
https://www.cms.gov/r Clause 4.14.6
egulations-and-
guidance/legislation/CLI
A/Individualized_Qualit
y_Control_Plan_IQCP.h
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493.1253(b)(3) and c
Precision 493.1253(b)(1)(i)(B) & c ISO 15189:2012 EP15, EP09, EP21, EP12
Clauses 5.5.1.4, 5.5.2
Accuracy 493.1253(b)(1)(i)(A) & c EP07
ISO 17025:2017
Measuring Interval 493.1253(b)(1)(i)(C) & c Clauses 7.6 EP06, EP34
Reference Interval 493.1253(b)(1)(ii) & c EP28
Detection Capability EP17
 Technical Requirements and CLSI Guidelines for Laboratory Test Method Life Phases
Updated June 2021 from presentation at the 2019 American Association for Clinical Chemistry Annual Meeting
“Using CLSI Guidelines to Meet quality requirements established by FDA, CLIA, and ISO
throughout the Laboratory Test Method Life”

REQUIREMENTS CLSI
Phases Activity FDA QSR CLIA NYS ISO GUIDELINES
6. 820.30 493.1236, 493.1252, QMS: S1-S3 ISO 13485:2016 Customer Focus: QMS18, QMS19
Preparation 820.50 493.901-905, Resources: GRM S1-S7 Clauses 4.2.3, 7.4 Facilities: QMS01, GP17, M29, GP05
and Launch 820.120, 493.1100-1105, LIS: LIS-FS; S1-S6 ISO 17025:2017 Personnel: QMS16, QMS03
820.130 493.1200-1299 Documents: DC-FS; Clauses 6.5; Suppliers: QMS21, QMS05
DC S1-S5 7.3 through 7.8; 7.11 Equipment: QMS04, QMS13, QMS23
Referral Labs: RCL S1-S3 ISO 15189:2012 Process Management: QMS01,
Preanalytic: PRS FS; TR Clauses 4.3 through 4.7 QMS02, QMS18, QMS26, AUTO15,
S1-S4; SP S1-S8 Clauses 5.4 through 5.10 QMS06, EP23
Analytic: AS FS; TPC S1- Documents and Records: QMS18,
S2; TPS S1, S3-S4 QMS02, QMS26
Calibration: CAL S1 Information Management: AUTO08,
QC S1-S8 QMS22
Postanalytic: PAS-FS; RR Nonconforming Events: QMS11
S1-S2 Assessments: QMS17, QMS24,
Confidentiality: CON QMS12, QMS15
S1-S3
 Technical Requirements and CLSI Guidelines for Laboratory Test Method Life Phases
Updated June 2021 from presentation at the 2019 American Association for Clinical Chemistry Annual Meeting
“Using CLSI Guidelines to Meet quality requirements established by FDA, CLIA, and ISO
throughout the Laboratory Test Method Life”
Appendix A. (Continued)
REQUIREMENTS CLSI
Phases Activity FDA QSR CLIA NYS ISO GUIDELINES
7. General 820.30, 493.1200, 493.1201- Director: DR S5 ISO 13485:2016 Organization: QMS14
Maintenance 820.40, 493.1227, 493.1230, QMS: S4–S7 Clauses 4.2.3; 8.1 through Customers: QMS19
820.72, 493.1233, 493.1234, Human Resources: HR 8.5 Facilities: GP17
820.90, 493.1235, 493.1236, S7-S10 ISO 17025:2017 Personnel: QMS03
820.100, 493.1239, 493.1240, Equipment: LE S5-S9 Change control and Suppliers: QMS21, QMS05, EP26
820.181, 493.1241, 493.1242, Calibration: CAL S2 Clauses 7.9, 7.10, 7.11; 8.3, Equipment: QMS13, QMS23
820.184, 493.1249, 493.1251, Nonconformance: RR 8.4, 8.6 through 8.9 Process Management: QMS18, C24,
820.186, 493.1252, 493.1289 S3 ISO 15189:2012 EP23
820.198, Reporting: REP S1-S6 Change control and Documents: QMS02, QMS26
820.200 Public Health: S1-S2 Clauses 4.3; 4.8 through Information Management: AUTO08,
Confidentiality: CON 4.15 AUTO15
S1-S3 Nonconforming Events: QMS11
Implementation, continued

Retention: DSR FS; S1- Improvement: QMS06

S12
Investigation: ICA FS;
S1-S5
Quality Assessment Subpart H, 493.1236, Director: DR S4 ISO 17025:2017 QMS17, QMS24, QMS12, QMS15
493.1254, 493.1255, QC: S9-S14 Clause 7.7
493.1256 Proficiency Testing: PT ISO 15189:2012
FS; S1-S16 Clause 5.6

Result 493.1281(a) TPS S5 EP26, EP31

Comparability 493.1281(b)
Results Review and 493.1290, 493.1291, RR S1-S2 EP31
Follow-up 493.1299
8. 820.180 493.1105 Document Control: DC
ISO 13485:2016 Organization: QMS14
Retirement S6 Clauses 4.2.3, 4.2.4, 4.2.5 Customers: QMS18, QMS19
Retention: DSR FSISO 17025:2017 Equipment: QMS13, M29
Safety: LS S13 Clauses 7.11, 8.3, 8.4 Documents: QMS02, QMS26
ISO 15189:2012
Clauses 4.3, 4.13, 5.3.1.7,
5.10
* NYS Clinical Laboratory Standards Tables 1 and 2 contain discipline-specific requirements. Readers should refer to the standards document for this information.
 Technical Requirements and CLSI Guidelines for Laboratory Test Method Life Phases
Updated June 2021 from presentation at the 2019 American Association for Clinical Chemistry Annual Meeting
“Using CLSI Guidelines to Meet quality requirements established by FDA, CLIA, and ISO
throughout the Laboratory Test Method Life”

References

1. U.S. Food and Drug Administration, Quality System Regulation, 21CFR, Part 820, accessed on October 9, 2020.
https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=820&showFR=1
2. U.S. Centers for Medicare and Medicaid Services, Clinical Laboratory Improvement Amendments, 42 CFR, Part 493, accessed on October
9, 2020. https://www.ecfr.gov/cgi-bin/text-idx?SID=1248e3189da5e5f936e55315402bc38b&node=pt42.5.493&rgn=div5
3. New York State Department of Health. Clinical Laboratory Standards of Practice, General Systems Standards, accessed on October 9,
2020. https://www.wadsworth.org/sites/default/files/WebDoc/General Systems Standards - Effective August 2020 - Corrected
090920.pdf
4. ISO. Quality management systems—Requirements. ISO 9001. Geneva, Switzerland: International Organization for Standardization, 2015.
5. ISO. Medical Devices—Quality management systems—Requirements for regulatory purposes. ISO 13485. Geneva, Switzerland:
International Organization for Standardization, 2016.
6. ISO. Quality management systems—Requirements for the competence of calibration and testing laboratories. ISO 17025. Geneva,
Switzerland: International Organization for Standardization, 2017.
7. ISO. Medical laboratories—Requirements for quality and competence. ISO 15189. Geneva, Switzerland: International Organization for
Standardization, 2012.
8. ISO. Medical devices—Application of risk management to medical devices. ISO 14971. Geneva, Switzerland: International Organization
for Standardization, 2019.