QUALITY MANUAL · • Guide to the expression of uncertainty in measurement (GUM). BIPM, IEC, IFCC,...

Quality Manual

Rev. 4 26.01.2010

Interdepartmental Centre for Metrological Traceability in Laboratory Medicine

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QUALITY MANUAL This document, together with specific operative procedures, contains the description of the Quality

Management System of the Interdepartmental Centre for Metrological Traceability in Laboratory

Medicine (CIRME), University of Milan (UNIMI).

It has been compiled in conformity to the requirements of the ISO/IEC 17025 and ISO 15195

standards.

Address: Dipartimento di Scienze Cliniche ‘Luigi Sacco’, Polo di Vialba

via G.B. Grassi, 74

20157 Milano

Website: //users.unimi.it/cirme

Edition N° 4

Date of issue 26/01/2010

Review internal Bi-annually

Authorised by Prof. Panteghini Mauro

Author Dr.ssa Infusino Ilenia

Signed copy 1 of 1 Master File

http://users.unimi.it/cirme

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Rev. 4 26.01.2010


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Quality Manual: Table of contents

Number Section Page 0.0 Background 4 0.1 History 5 0.2 Activities 5 1.0. Scope 7 1.1 Index and revision status 8 1.2 Purpose 8 2.0 Normative references 9 3.0 Terms and definitions 11 3.1 Definitions and terminology 12 3.2 Abbreviations 13 4.0 Management system requirements 14 4.1 Organization and management 15 4.2 Quality management system 19 4.3 Personnel 21 4.4 Document control 21 4.5 Contracting 21 4.6 Subcontracting 22 4.7 Purchasing 22 4.8 Service to the client 23 4.9 Complaints 23 4.10 Control of non conforming work 23 4.11 Corrective action 24 4.12 Preventive action 24 4.13 Control of records 24 4.14 Internal audits 25 4.15 Improvement 25 4.16 Management reviews 26 5.0 Technical requirements 27 5.1 Accommodation and environmental conditions 28 5.2 Handling of samples 28 5.3 Equipment 29 5.4 Standard and Reference materials 30 5.5 Reference measurement procedure 30 5.6 Metrological traceability – Uncertainty of measurement 31 5.7 Quality assurance 33 5.8 Reporting results 34 Annex A Correspondence with ISO/IEC 17025 and ISO 15195 36 Annex B List of documents 37

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REVISION HISTORY

Rev Description of Change Author Effective Date

0 Initial release Dr.ssa Ilenia Infusino 01/06/2009

1 Introduced sec. 4.2 – 4.16 Dr.ssa Ilenia Infusino 20/11/2009

2 Update sec. 4 and 5 Dr.ssa Ilenia Infusino 10/12/2009

3 Introduced annex A and B Dr.ssa Ilenia Infusino 15/12/2009

4 Update sec. 0 – 1 –4.2 - 4.10 – 4.11 – 4.12 – 4.15 – 4.16 – 5.2 – 5.3

Dr.ssa Ilenia Infusino 26/01/2010


Quality Manual Section 0

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BACKGROUND / 37

Edition N°: 2 Rev: 2 Date of issue: 26/01/2010

Revision reason: Update par. 0.2





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BACKGROUND / 37

0.1 HISTORY The Interdepartmental Centre of Metrological Traceability in Laboratory Medicine (CIRME) of the UNIMI was created

in 2006 with the scope to join in a unique entity teachers and investigators of various UNIMI Departments interested

in the development of higher order metrological calibration materials and reference methods in the field of the

Laboratory Medicine.

The lack of comparability of analytical results, especially when they originate from different laboratories using

different methods, may cloud interpretations of reported data, creating a substantive problem for both clinicians and

laboratory communities. Suitable reference materials and reference measurement procedures are used to assign

traceable values to calibrator and control materials, allowing the implementation of standardization of laboratory

measurements, assuring interchangeability of results over time and space, significantly contributing to improvements

in healthcare since results of clinical studies undertaken in different locations or times could be universally applied.

0.2 ACTIVITIES In compliance with the UNIMI regulations, the CIRME can:

1. participate in annual comparison interlaboratory exercises organized by IFCC for the reference laboratories

(IFCC Ring Trials for Reference Laboratories), coordinated by the IFCC Committee on Traceability in Laboratory

Medicine in collaboration with the Working Group 2 of the Joint Committee for Traceability in Laboratory

Medicine (JCTLM);

2. develop new reference methods and characterize new reference materials for clinically significant blood

analytes, with particular reference to human haemoglobins (HbA1c, haemoglobin A2), enzymes (alkaline

phosphatase) and the most important cardiac biomarkers (eg cardiac troponin I, natriuretic peptides);

3. establish collaborations with companies of the diagnostic and pharmaceutical industry or with public and private

agencies and scientific groups interested in the research activities of the Centre. In addition:

4. organize courses, seminars and contribute to promote teaching of the third level on issues concerning

Traceability and Standardization in Laboratory Medicine, Clinical Biochemistry and Clinical Molecular Biology,

Clinical Pathology, Technical Sciences in Laboratory Medicine and their applications;

5. organize conferences about metrological traceability issues, development of reference materials and reference

methods, certification standards;

6. collaborate in research with public or private organisations on the basis of specific contracts or agreements;

7. institute awards or scholarships for the achievement of its objectives;

8. accommodate foreign researchers, as part of joint research projects, with the possibility of trade;

9. make publication of articles, texts and manuals concerning the metrological traceability in biomedical

diagnostics;



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BACKGROUND / 37

10. work to achieve accreditation certification, according to the standards cited above, for the following method

methods of interest:

− glicated haemoglobin (HbA1c),

− serum enzymes, in particular alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine

kinase (CK), gamma - glutamyltransferase (GGT) and lactate dehydrogenase (LDH), alkaline phosphatase

(ALP);

− serum creatinine;

11. work to maintain the accreditation, according to the standard of ISO/IEC 17025 and ISO 15195, for:

− glicated haemoglobin (HbA1c),

− serum enzymes, in particular alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase (CK), gamma - glutamyltransferase (GGT) and lactate dehydrogenase (LDH), alkaline phosphatase (ALP).



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SCOPE / 37


Revision reason: New revision status





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SCOPE / 37

1.1 INDEX AND REVISION STATUS

Number

Section Revision

0

Background 2

1

Scope 2

2

Normative references 1

3

Terms and definitions 1

4

Management requirements 4

5

Technical requirements 4

Quality Manual

4

Date of issue

26/01/2010

1.2 PURPOSE This quality manual documents CIRME’s management system and demonstrates the ability of its reference

laboratories to execute the following reference procedures and to meet regulatory requirements in compliance with

ISO/IEC 17025 and ISO 15195 standards:

• glicated haemoglobin (HbA1c), with HPLC-capillary electrophoresis method;

• alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), creatine

kinase (CK), gamma - glutamyltransferase (GGT) and lactate dehydrogenase (LDH) and with kinetic

spectrophotometric methods.



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NORMATIVE REFERENCES / 37


Revision reason: introduced ISO/IEC 17000

cancelled Eurachem 1995





Rev. 1 10.12.2009

NORMATIVE REFERENCES / 37

2. NORMATIVE REFERENCES

• ISO/IEC 17000 Conformity assessment – Vocabulary and general principles

• ISO/IEC 17025 General requirements for the competence of testing and calibration laboratories

• ISO 15195 Laboratory medicine - Requirements for reference measurements laboratories

• ISO 17511, In vitro diagnostic medical devices — Measurement of quantities in biological samples —

Metrological traceability of values assigned to calibrators and control materials

• ISO 18153, In vitro diagnostic medical devices — Measurement of quantities in biological samples —

Metrological traceability of assigned values for catalytic concentration of enzymes in calibrators and control

materials

• ISO 15193, In vitro diagnostic medical devices — Measurement of quantities in samples of biological origin —

Presentation of reference measurement procedures

• ISO 15194, In vitro diagnostic medical devices — Measurement of quantities in samples of biological origin —

Description of reference materials

• International vocabulary of basic and general terms in metrology (VIM). BIPM, IEC, IFCC, ISO, IUPAC, IUPAP

and OIML, 19931)

• Guide to the expression of uncertainty in measurement (GUM). BIPM, IEC, IFCC, ISO, IUPAC, IUPAP and

OIML,19931)

• Ellison S L R, Roesslein M, Williams A (eds) (1995). Eurachem Guide: Quantifying Uncertainty in Analytical

Measurement, Eurachem, 1st edition. Uncertainty in Analytical Measurement, Eurachem

• Ellison S L R, Roesslein M, Williams A (eds) (2000). Eurachem Guide: Quantifying Uncertainty in

Analytical Measurement, Eurachem, second edition. Eurachem

• Doc 512 SIT. Prescrizioni per l’emissione del certificato di taratura SIT.

• Doc 518 SIT. Prescrizioni sulle principali regole di scrittura.

• Doc 525 SIT. Prescrizioni per l’uso del marchio SIT.



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TERMS AND DEFINITIONS / 37


Revision reason: definition of calibration and definition of requirement

according to ISO/IEC 17000





Rev. 1 10.12.2009


3. TERMS AND DEFINITIONS

3.1 DEFINITIONS AND TERMINOLOGY accreditation formal recognition that a laboratory is competent to carry out specific tests or calibrations or types of tests or

calibrations.

accuracy of measurement closeness of the agreement between the result of a measurement and a true value of the measurand

calibration operation that, under specified conditions, in a first step, establishes a relation between the quantity values with measurement uncertainties provided by measurement standards and corresponding indications with associated measurement uncertainties and, in a second step, uses this information to establisha relation for obtaining a measurement result from an indication”

certified reference material reference material, accompanied by a certificate, one or more of whose property values are certified by a procedure

which establishes its traceability to an accurate realization of the unit in which the property values are expressed,

and for which each certified value is accompanied by an uncertainty at a stated level of confidence

measurable quantity attribute of a phenomenon, body, or substance that may be distinguished qualitatively and determined quantitatively

precision of measurement closeness of agreement between independent results of measurement obtained under stipulated conditions

proficiency testing (laboratory) determination of laboratory testing performance by means of interlaboratory comparisons.

reference material material or substance, one or more of whose property values are sufficiently homogeneous and well established to

be used for the calibration of a measuring system, the assessment of a measurement procedure, or for assigning

values to materials

reference measurement laboratory laboratory that performs a reference measurement procedure and provides results with stated uncertainties (NOTE

ISO/IEC 17025 uses the term “calibration laboratory”)

reference measurement procedure thoroughly investigated measurement procedure shown to have an uncertainty of measurement commensurate with

the intended use, especially in assessing the trueness of other measurement procedures for the same quantity and

in characterizing reference materials



Rev. 1 10.12.2009


requirement Need or expectation that is stated, generally implied or obligatory.

metrological traceability property of the result of a measurement or the value of a standard whereby it can be related to stated references,

usually national or International Standards, through an unbroken chain of comparisons all having stated uncertainties

true value of a quantity value consistent with the definition of a given particular quantity

trueness of measurement closeness of agreement between the average value obtained from a large series of results of measurements and a

true value

uncertainty of measurement parameter, associated with the result of a measurement, that characterizes the dispersion of the values that could

reasonably be attributed to the measurand

validation confirmation, through the provision of objective evidence, that the requirements for a specific intended use or

application have been fulfilled

verification confirmation, through the provision of objective evidence, that specified requirements have been fulfilled

3.2 ABBREVIATIONS CIRME = Interdepartmental Centre for Metrological Traceability in Laboratory Medicine

UNIMI = University of Milan

BIPM = International Bureau of Weights and Measures

IEC = International Electrotechnical Commission

IFCC = International Federation of Clinical Chemistry and Laboratory Medicine

ISO = International Organization for Standardization

IUPAC = International Union of Pure and Applied Chemistry

IUPAP = International Union of Pure and Applied Physics

OIML = International Organization of Legal Metrology

GUM = Guide to the Expression of Uncertainty in Measurement

CLSI = Clinical and Laboratory Standards Institute

NIST = National Institute of Standards and Technology



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Revision reason: Updating of section 4.10 – 4.11 – 4.12 – 4.15 – 4.16





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4. MANAGEMENT SYSTEM REQUIREMENTS 4.1 ORGANIZATION AND MANAGEMENT 4.1.1 Legal Status The CIRME acts under its Statute and under rules and regulations of the UNIMI Interdepartmental Research

Centres, particularly in reference to: article 37 of the UNIMI Statute, article 19 of UNIMI General Regulation, article

105 and Title V of UNIMI Rules for Administration, Finance and Accounting.

4.1.2 Organization 4.1.2.1 Organizational chart

CIRMEDirector

Quality Manager

RepresentativeDipartimento di Scienze

Cliniche “Luigi Sacco”

RepresentativeDipartimento di Scienze e Tecnologie Biomediche

RepresentativeDipartimento di

Scienze Farmacologiche

RepresentativeDipartimento di Chimica,

Biochimica e Biotecnologieper la Medicina

RepresentativeDipartimento di Scienze Precliniche LITA Vialba

RepresentativeDipartimento di Medicina,Chirurgia e Odontoiatria

Reference Laboratory forEnzymes

Reference Laboratory forHbA1c HPLC-CE

AdministrativeStaff

CIRMEDirector

Quality Manager





















AdministrativeStaff

The Centre is based at the Dipartimento di Scienze Cliniche ‘Luigi Sacco’ (Polo di Vialba), via G.B. Grassi 74, 20157

Milano.



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4.1.2.2 Functional Chart

Dr. I. InfusinoQuality Manager

Prof. Panteghini MauroCIRMEDirector

Prof. M. PanteghiniRepresentative

Dipartimento di Scienze Cliniche “Luigi Sacco”

Prof. A. MoscaRepresentative

Dipartimento di Scienze e Tecnologie Biomediche

Prof. D. CarusoRepresentativeDipartimento di


Prof. V. ChigornoRepresentative

Dipartimento di Chimica, Biochimica e Biotecnologie

per la Medicina

Prof. G. CighettiRepresentative

Dipartimento di Scienze Precliniche LITA Vialba

Prof. GV Melzi d’ErilRepresentative

Dipartimento di Medicina,Chirurgia e Odontoiatria


Prof. M. Panteghini(Prof. A. Mosca Deputy)


Prof. A. Mosca(Prof. M. Panteghini Deputy)

Dr. O. CarbonaraAdministrative Responsible

Personnel Performing calibrationDr.ssa I. Infusino

Personnel Performing calibrationDr.ssa R. Paleari

4.1.2.3 Functions and responsibilities

a. CIRME Director The CIRME Director is a UNIMI full time Professor, elected by the CIRME Council and appointed by UNIMI Rector.

The Director remains in office for three years and can be confirmed for other three years. The Director has the same

responsibilities and the same administrative and accounting obligations of the Directors of UNIMI Departments.

The Director presents to the Centre Council:

− at the beginning of the year, a research programme together with a analytical budget plan for the use of funds;

− at the end of the year, an activity and economic report which, once approved, is transmitted to the Dean of the

Faculties and to the UNIMI Rector.

The Director:

− ensures the implementation of the Centre Council resolutions;

− coordinates and ensures the regularity of the Centre administrative management;

− coordinates the working of services and equipment available to the Centre and manages its efficiency;

− provides the orders of what is needed to the working of the Centre;

− informs the Centre Council on possible management problems and on the state of the Centre itself;

− proposes tariffs for access to the Centre;

− performs any other functions relating to the responsibilities entrusted by the Centre Council.



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The Director must send an annual report on the CIRME activities to the reference structure councils – to

communicate results with respect to the objectives of the Centre - and to the Commission for Scientific Research and

Technology Transfer and to the Area Committees that express their opinion to the Academic Senate.

The Director convokes the Centre Council at least 3 times per year or when not less than one third of the Council

members ask for a meeting. A report of the Centre meetings is drawn up; it remains available to all members and is

sent in copy to the Faculty Dean and to the Rector.

b. The Doyen of the Centre The Doyen of the Centre is the older member of the Centre Council and he has the specific duty to convoke the

Council to proceed to the Director election. c. The Centre Council The Centre Council is composed of the Directors of Departments belonging to CIRME or their delegates. The Centre

Council will also coopt up scientists and experts in the specific area, also not belonging to the UNIMI, with or without

the possibility of a consultative vote. The Centre Council elects - according to the UNIMI Regulations - the Director

(appointed by Rectorial decree).

The Centre Council is the body of policy, planning and coordination of the Centre activities. In particular, the Council:

− annually approves the outlines budget and account survey;

− approves the annual plan of activities and expenses;

− advances to the competent central bodies of the UNIMI government any requests for spaces, funds for

equipment, financial resources and technical and administrative staff;

− approves, for what pertaining to the Centre and according to the prerogatives of the central bodies of the UNIMI

government, the possibility to conduct third party studies;

− deliberates expenditure that, according to the administrative and accounting rules, requires its prior

authorization;

− uses all the skills required for the good running of the Centre.

d. The Quality Manager The Quality Manager ensures the implementation of the Quality System according to the CIRME Director’s plans and

programs. Responsible for ensuring the quality system is maintained, implemented, understood to ensure that

CIRME personnel are free from any undue pressures that might adversely affect the quality of their work at all levels

of the organization. The Quality Manager is the Management Representative responsible for reporting on the

performance and improvement of the quality system in the Record 04 “Report on Quality Status”, initiating and

implementing corrective action reports and directing and overseeing all changes regarding quality documents.

The activities carried out by the personnel performing calibration in the RLE are supervised, concerning the

coherence with the quality management system, by the Responsible of the RLE.

e. The Responsible of the reference laboratory



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The Responsible of the reference laboratory coordinates the activity of the reference laboratory, oversees and

approves the results performed by the personnel performing the calibration, signs the calibration reports and

certificates.

f. The Deputy of the Responsible of the reference laboratory The Deputy of the reference laboratory coordinates the activity of the reference laboratory, oversees and approves

the results performed by the personnel performing the calibration, signs the calibration reports and certificates only

when it is strictly necessary, i.e. in absence of the responsible.

g. Personnel performing calibration The personnel performing calibration:

- carry out the calibration measurement according to the reference procedures,

- ensures the proper storage and manipulation of standards and reference materials,

- carry out the metrological confirmation of equipment, including calibration, and the validation of methods and

estimation of measurement uncertainty,

- handle test and calibration items,

- assure the quality of test and calibration results,

- carry out all the calculation necessary to obtain the final results to be reported into the calibration report starting

from row data.

In absence of the Personnel performing calibration, the calibration activities are temporarily suspended.

4.1.3 Independence, impartiality and integrity The Director ensures that the CIRME and his personnel is independent from any pressures – commercial, financial,

or others - which may adversely affect the quality of activity and resulting reports. The Director prevents and shows

any external influences and ensures to not engage the CIRME in activities that may diminish confidence in terms of

competence, independence, impartiality and judgement or operational integrity.

4.1.4 Confidentiality All staff must maintain the confidentiality and proprietary rights of all information, including the type of work and the

results of tests performed, and the information regarding the customers. All personnel and staff are informed of this

policy.

4.1.5 Management Commitment Top management ensures that appropriate communication processes are established within the laboratories for

implementation of the management system, and that communication takes place regarding the effectiveness of the

management system



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4.2 QUALITY MANAGEMENT SYSTEM

4.2.1 Description of the instruments for the implementation of the quality management system

The Quality Management System described in this manual applies to all activities performed in the CIRME’s

reference laboratories and encompasses the controls necessary to provide qualified personnel, material, and

services in accordance with ISO/IEC 17025 and ISO 15195. This quality management system provides for activities

affecting quality to be achieved under controlled conditions in an appropriate environment and it takes into account

the need for standards, measurement and test equipment, tools, and skills to achieve the required quality. All tests

and analysis are performed according to written procedures, prepared in accordance with the applicable rules or in

accordance with the practices of the calibration laboratory. The documentation produced is at disposal of the

personnel and is located in places of free and easy access.

4.2.2 Quality Policy The CIRME has a project for Quality with the aim of obtaining and maintaining the SIT Accreditation according to

ISO/IEC 17025 and ISO15195, obtained in date 23 december 2009, for glicated haemoglobin (HbA1c), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase (CK), gamma - glutamyltransferase (GGT) and lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and obtaining SIT Accreditation according to ISO/IEC 17025 and ISO15195 for serum creatinine, commitment to obtain, maintain

and finally extend the scope of the accreditation. The CIRME is committed to continual improvement of processes

and services to achieve ongoing customer satisfaction, to providing a service of the highest quality and is aware and

takes into consideration the needs and requirements of its users.

The Quality Policy Statement is issued under the authority of the Director. The policies and objectives are

documented in this Quality Manual and in a dedicate procedure (Procedure 01 “Quality Policy”). The overall

objectives are set out in the Quality Policy Statements and reviewed during the management review first annual

meeting of the Centre Council.

Quality Policy Statement

− management commitment to good professional practice and quality of services provided to the customer:

measurements and calibrations are always carried out in accordance with stated standardized methods and

customers’ requirements;

− consistently provide quality testing services that conform to customer and regulatory requirements;

− ensure that all personnel are competent and qualified for the tasks they perform, and that all personnel

familiarize themselves with quality system documentation in order to implement the policies and procedures in

their work;

− professionally and effectively perform testing services to produce accurate results;



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− consistently comply with ISO/IEC 17025 and ISO 15195 international standards to ensure quality testing services

and to continually improve the effectiveness of the Quality Management System;

− compliance with requirements provided by SIT, EA and ILAC;

− top management ensures the integrity of the management system is maintained when changes to the

management system are planned and implemented.

It is CIRME goal to guarantee:

- active participation of all personnel in quality planning and continual improvement efforts to meet all quality,

service and cost objectives;

- the knowledge and application of the documents of Quality Management System.

The objective of this Quality Manual and its enclosures is to document the compliant policies and associated

procedures that are integrated into CIRME daily activities. Continual improvements are established, implemented,

and locked into the management system.

Additional objectives include:

to establish the level of the laboratory’s performance

to make test method changes to improve performance

to participate in proficiency testing or quality evaluation programs with peer laboratories

to ensure that all personnel are trained to a level of familiarity with the quality management system appropriate to

the individual’s degree of responsibility

to improve and validate laboratory methodologies by perform method validation studies

to establish and report on quality savings

4.2.3 Top management responsibility Top management has to demonstrate its commitment to the development and implementation of the quality

management system and maintaining its effectiveness by supporting the establishment of this Quality Manual and all

of the elements that it embodies. It further demonstrates its commitment by communicating to the organization the

importance of meeting customer, as well as statutory and regulatory requirements, establishing a quality policy and

quality objectives, conducting management reviews, and ensuring the availability of necessary resources.

4.2.4 Top management communication Top management ensures appropriate communication processes within the organization which will provide all the

personnel with information concerning the effectiveness of the quality management

4.2.5 Quality system documentation The documentation of the CIRME consists of a Quality Manual and Quality Procedures:

− Quality Manual is the governing document that defines the quality system policies and statements of intent;

− Quality Procedures are documents describing what, when, where and how quality management system

processes are performed.



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The reference laboratory documentation structure is composed by:

− Procedures and Test Instructions describing who, what, when, where and how testing processes are performed.

− Quality Records which are retained as objective evidence of compliance to the requirements of ISO 17025 and

15195.

4.3 PERSONNEL The CIRME Director and the Quality Manager strive to increase in staff:

• familiarization with quality documentation;

• implementation of the policies and procedures in the work;

• a sense of belonging and a spirit of collaboration;

• awareness of its role;

• the level of communication and cooperation by promoting multidisciplinary groups that, through a fruitful

collaboration, can achieve synergies that result in a more efficient management of strategic activities;

• skills;

• the ability to develop ideas and propose solutions.

The temporary assignment to the Centre of scientific and technical skills necessary for the conduct of research

programmes is prepared, with the consent of the parties and in agreement with the Director, by the Directors of

Department or Institute that joined the Centre, according with the limits of existing availability. All staff involved in

measurements activities must have at least a biennial experience, documented in the Curriculum vitae, in the field of

reference measurement procedures for clinically important analytes. The competence is established through

appropriate education (i.e. Post-graduate degree in scientific field), training, experience and/or demonstrated skill;

this may include relevant knowledge of the technology and legislation/standards.

4.4 DOCUMENT CONTROL The documents are approved for adequacy, uniquely identified (including revision status), periodically reviewed and

updated, legible and protected from damage. A description of the change is recorded in the revision history.

Obsolete or down revision documents are identified by the apposition on the first page of a blue cross, not available

for use and are segregated from current revisions. Rules and requirements of document control are indicated in

Procedure 03. External document are controlled as described in the procedure 03. All CIRME documents concerning

calibration procedure accredited by SIT are sent to the SIT for their approval before they are authorized for use

within the Centre.

4.5 CONTRACTING CIRME according to requirements of chapter 4.4 of ISO/IEC 17025 reviews request, tenders and contracts. These

activities are governed by specific contracts referred to the existing legislation of the UNIMI

(www.unimi.it/ateneo/normativa/2277.htm).

The requests and contracts follow this procedure:



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1. the requests and contracts are reviewed by the Director to insure that:

a. the requirements, together with the methods to be used are adequately defined documented and

understood;

b. the laboratory has the capability and resources to meet the requirements;

c. the appropriate method is capable of meeting the Customer’s requirements.

2. the requests and contracts reviewed are sent to the “Ufficio Contratti di Ricerca Commissionata e Centri di

Ricerca” of UNIMI, that control the conformity with UNIMI requirements and eventually informs the Customer of

any deviation from the contract;

3. the requests and contracts are submitted to the approval of the Centre Council during the CIRME meeting;

4. the minutes of the meeting, in which is written that the requests and tenders are approved, is sent to the “Ufficio

Contratti di Ricerca Commissionata e Centri di Ricerca”;

5. the “Ufficio Contratti di Ricerca Commissionata e Centri di Ricerca” communicates to the Customer to send the

Contract signed by the Legal Representative of the Company;

6. the requests and contract signed is submitted to the UNIMI Rector signature;

7. the requests and contracts signed are recorded by the “Ufficio Contratti di Ricerca Commissionata e Centri di

Ricerca” and a copy are sent to the CIRME Director and to the Customer.

4.6 SUBCONTRACTING CIRME does not subcontracts any calibrations.

4.7 PURCHASING The CIRME has to purchase goods and services for the delivery of its performances and the pursuit of its

institutional purposes. The normative sources governing the procedures for purchasing goods and services are

established:

− by the Treasurer Office of Hospital ”L. Sacco” (Hospital “L. Sacco” Quality Manual sec. 7 “Implementing the

product”);

− by the Pharmacy Office of Hospital ”L. Sacco” (IFA P18 “Purchasing of drugs, medical and diagnostic

devices”);

− by the legislation of the UNIMI (circolar prot. n. 7225/26.02.07, circolar prot. 21946/13.06.07, circolar prot.

77367/25.02.08).

The Reference Laboratory evaluates suppliers of critical consumable, supplies and services which affect the quality

of testing and calibration and maintain records of these evaluations and list those approved. Suppliers are evaluated on the basis of:

− adherence to purchase order prices,

− good prices and good quality of the product/service,

− promised delivery dates,

− documentation provided with product/service complete and satisfactory,

− absence of complaints,



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− absence of recorded non conformity of the products/service,

− rapid technical assistance. Subsequent buying decisions and continuous buying by a supplier are strongly influenced by this evaluation. The integrity and the conformity, to specification or requirements defined in the methods for the calibrations activities

(i.e. temperature), are checked by the Reference Laboratories upon arrival. The personnel performing calibration:

- signed the packing list, if the requirements of integrity and conformity are satisfied;

- open a non conformity, if the requirements of integrity and conformity are not satisfied.

4.8 SERVICE TO THE CLIENT Customer standard, reference materials or reference measurement procedure received at the Reference

Laboratories for calibration shall be received and verified against the customers supplied documents as applicable.

The assigned individual shall verify that the customer’s standard or reference material is adequately identified, that

there is no apparent damage to the standard or reference material (unless pre-identified by the customer), and that

the equipment identification matches the customer paperwork. Any problems to the customer’s equipment caused by

the Reference Laboratories after receipt shall be reviewed by the Responsible of the laboratory and communicate to

the Quality Manager for reportability to the customer and determination if a corrective action report is required. A

corrective action report shall be written if the customer’s equipment is lost, damaged, or becomes unsuitable for use.

The Quality Manager shall ensure that further processing of the equipment is halted and shall consult with the

customer to determine what action is to be taken (i.e. replacement or repair).

The Laboratory support the client concerning interpretation and utilization of laboratory results.

To verify the customer satisfaction, the Quality Manager:

- sends at the end of every calibration activities the “Record of customer satisfaction” (record 01 “Customer

Satisfaction”),

- elaborates the feedback information, both positive and negative,

- shows the results in the “Report on the Quality Status” (record 04 “Report on Quality Status). The feedback are used and analysed to improve the management system, calibration activities and customer

service.

4.9 COMPLAINTS CIRME personnel receiving a potential complaint from a customer, regarding a customer -documented

requirement, shall notify the Quality Manager. The Quality Manager evaluates the potential complaint and:

a. if it’s a complaint, open a non conformity;

b. if it isn’t a complaint, reject the complaint and communicate it to the customer.

When a non conformity rends impossible to carry out activities accredited by SIT, SIT itself is immediately

informed and the Centre suspends the activities.



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4.10 CONTROL OF NON CONFORMING WORK When a nonconforming work or problems with the management system or with testing and/or calibration activities is found by the CIRME personnel, the causes of the non conformity (NC) must be analysed and the Corrective Action (AC) must be implemented. If the NC highlighted has negative effects on the activities of all the Centre, the person who shows the NC should inform the Quality Manager that will take the appropriate actions. The management of the NC are described in the Procedure 02 “Management system requirements”. CIRME nonconforming items are classified as follows:

− to a product;

− to a service;

− to a process;

− to the quality management system (eg absence of documented procedure or document management

registration etc…).

A Non-conforming Report shall be recorded and transmitted to the Quality Manager that verify implementation

and effectiveness of the corrective action.

4.11 CORRECTIVE ACTION When it is determined that an adverse quality condition exists; a Corrective Action Report shall be recorded

documenting the root cause of the issue; action taken to correct the issue; and, the action taken to prevent

recurrence. The management of AC is described in the Procedure 02 “Management system requirements”. When a serious problem is identified, the Quality Manager can activate an additional audit. The Corrective

Action Report has to be transmitted to the Quality Manager that verify implementation and effectiveness of the

corrective action. If required the Centre considers the possibility to carry out supplementary audit within the

framework of corrective action.

4.12 PREVENTIVE ACTION The Quality Manager is responsible for evaluating preventive actions reported through the corrective action

system. Records of preventive actions shall be maintained as quality records and shall be reviewed by executive

management during the periodic management review of the quality system. The management of AP is described in the Procedure 02 “Management system requirements”.

4.13 CONTROL OF RECORDS Quality and technical records are protected against damage and back-up to prevent unauthorized access. Quality

records are on paper and are held secure and in confidence by the Quality Manager. Reference Laboratories

records are held secure and in confidence by the relative Direcor and/or the personnel that performs calibration. It

also has the clear requirement that records must not be erased or deleted in case of corrections, this holds for



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/ 37

paper records as well as for electronic records. All records shall be legible and stored in a manner that permits

adequate retrievability and prevents damage, deterioration and loss.

The rules for the storage of calibration are as follows:

- the Responsible of the RLE stores the calibration record of the RLE for at least 10 years;

- the Responsible of the RHbA1c stores the calibration record of the RHbA1c for at least 10 years.

4.14 INTERNAL AUDITS An internal audit of the Quality System shall be carried at least annually. The Quality Manager, or designee, shall

prepare a report that identifies the quality elements audited, corrective action documents, and audit checklists and

present it to responsible management, as described in the Procedure 02 (Procedure 02). The Quality Manager, or

designee, shall investigate audit findings and determine timely corrective action and measures to be taken to prevent

recurrence of the adverse conditions. Follow-up audit activities shall verify and record the implementation and

effectiveness of the corrective action taken. Personnel performing audits shall be independent of the area audited, as

indicated in a procedure (Procedure 02).

When Audit findings cast doubt on the effectiveness of the operation or on the correctness of validity of the

laboratories calibration results, the laboratory takes timely corrective action, and share notify customers in writing if

investigations show the laboratory results may have been affected.

4.15 IMPROVEMENT

The CIRME continuously improves the effectiveness of its quality management system, using the quality policy,

the quality targets, the results of audits, data analysis, corrective and preventive actions and report of the

Direction.

The processes of monitoring, measurement, analysis and improvement are managed through the following

phases:

− collection of data and information related to various aspects of management (management processes,

satisfaction of customer and stakeholders, characteristics and process product/service, and all other data

that are required in order to always have a updated vision of our organisation) nad to this end appropriate

indicators are used;

− analysis and evaluation during the CIRME meeting,

− activation of corrective, preventive actions;

− communications of results to staff involved through the use of appropriate tools.

The process for continual quality improvement includes corrective action, preventive action and improvement

processes. The results of the quality improvement programme forms part of the development, training and

education of all staff.

The CIRME has established measurable indicators to provide evidence of the improvement; these indicators are:

− number of NC detected in one year;



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− percentage of NC closed out within specified time frame, as index of NC effectiveness;

− number of AC/AP detected in one year;

− number of complaints detected in one year;

− percentage of AC/AP closed out within specified time frame, as index of AC/AP effectiveness;

− percentage of AC/AP closed positively compared with the total;

− number of unacceptable results of EQAS compared with the total;

− number of failed calibration activities compared with the total. These indicators are measured by the Quality Manager and the results are showed in the Report on Quality Status (record 04 “Report on Quality Status”).

4.16 MANAGEMENT REVIEWS In accordance with a predetermined schedule and procedure, the CIRME’s top management periodically conducts a

review of the Centre management system, during the first CIRME’s meeting, and testing and/or calibration

activities to ensure their suitability and effectiveness, and to introduce necessary changes or improvements. The

review takes account of:

- suitability of policies and procedures;

- reports from managerial and supervisory personnel;

- the outcome of recent internal audits;

- corrective and preventive actions;

- assessment by external bodies;

- the results of interlaboratory comparisons or proficiency tests;

- changes in the volume and type of work;

- customer feedback;

- complaints;

- recommendations for improvement;

- other relevant factors, such as quality control activities, resources and staff training;

- Report on Quality Status (record 04 “Report on Quality Status”) elaborated by the Quality Manager at least one week before the management review.

The outputs consist of decision and action plan for improving performance and processes, improve effectiveness and efficiency of the system. The elements, important for quality improvement, originated by the management review are: - review of policy and quality objectives - verify/update of strategic and improvement plans - corrective and preventive actions.



Rev. 4 26.01.2010

TECHNICAL REQUIREMENTS / 37


Revision reason: Updating of section 5.2





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5 TECHNICAL REQUIREMENTS 5.1 ACCOMMODATION AND ENVIRONMENTAL CONDITIONS The environmental conditions for the execution of tests and analysis are kept under control when necessary and

environmental factors that may adversely affect test measurements are controlled to the degree necessary so as not

to invalidate test results or increase the stated measuring uncertainty. In particular:

• environmental conditions, paying attention to humidity, temperature and air pressure, are recorded;

• tests are stopped when the environmental conditions may jeopardize the results;

• areas in which there are incompatible activity are clearly separated;

• access to test area is limited to authorized people.

The spaces necessary for the functioning of the CIRME are distributed as shown in the following table :

DEPARTMENT SPACES

Scienze e Tecnologie Biomediche Reference Laboratory for HbA1c n 24, III floor

LITA Segrate

Scienze Cliniche “Luigi Sacco” Reference Laboratory for Enzymes (RLE) n. 5004 , V floor

LITA Vialba

Particular attention is paid from the CIRME for Safety at Work, in order to protect the health and safety of workers,

users, and visitors. The regulation is established in compliance with the legislation of the UNIMI

(www.unimi.it/ateneo/normativa/2088.htm).

5.2 HANDLING OF SAMPLES Upon receipt of the test or calibration item (e.g. human serum, human blood, calibration and control materials), the personnel performing calibration: - checks the item to ensure the absence of abnormalities or departures from normal or specified

conditions and opens a NC if this condition is not satisfied, according to the section 4.10 of the Quality Manual;

- when there is doubt as to the suitability of an item for test or calibration, or when an item does not conform to the description provided, or the test or calibration required is not specified in sufficient detail, consults the customer by mail for further instructions before proceeding and store the mail as proof of the discussion;

- identifies the items writing on the packaging “CIRME – RLE item n°__ or “CIRME – RLA1c item n° __” and the date of receipt;

- records the Record 16 “Calibration item”;



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- stores appropriately the item and, when it has to be stored or conditioned under specified environmental

conditions, maintains, monitors and records, these conditions until the start of calibration activities. The identification is retained throughout the life of the item in the reference laboratory to ensure that items cannot be confused physically or when referred to in records or other documents The reference laboratories have a written procedure for the identification registration and labelling of samples on

which measurements have to be performed and for any subsampling procedures.

In order to avoid deterioration or damage to the samples during transport for which the reference measurement

laboratory is responsible, documented procedures and appropriate storage facilities are available.

5.3 EQUIPMENT The CIRME uses for carrying out the tests appropriate equipment, as shown in the following table:

DEPARTMENT EQUIPMENT

Scienze e Tecnologie Biomediche 1. Capillary electrophoresis system Beckman Proteomelab PA 800

2. HPLC Kontron 400

3. Centrifuge Beckman C21

Scienze Cliniche "Luigi Sacco" 1. Spectrometer Perkin Elmer Lambda 25

Before being placed in service or before beginning measurements, the instruments are calibrated and checked to

establish that they meet the laboratory's specification requirements. Operative Instructions regarding the instruments

functioning, the internal calibration and control procedures are written and the calibration/control results are reported

in apposite records and/or tables (PRLE 01 “Test procedure for the determination of catalytic activity concentration of

enzymes in Calibrators, Human Sera and Controls Materials”, PRLA1C 02 “Test procedure for the determination of

glycated hemoglobin in human blood samples and controls materials”).

All equipment used for tests and/or calibrations, including equipment for subsidiary measurements (e.g. for

environmental conditions) having a significant effect on the accuracy or validity of the result of the calibration, are

calibrated before every calibration activities. A plan of equipment calibration is produced (record 08 “Calibration

plan”). Each item of equipment and its software used for testing and calibration and significant to the result are

uniquely identified in a label, which contains information about the identification number of the equipment, the dates

of the last and of the next calibration.

Records shall be maintained of each equipment and its software significant to the calibrations performed. The

records shall include at least the following:

a. the identity of the item of equipment and its software;

b. the manufacturer's name, type identification, and serial number or other unique identification;

c. the current location;

d. the manufacturer's instructions, if available, or reference to their location;



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e. dates, results and copies of reports and certificates of all calibrations, adjustments, acceptance criteria, and the

due date of next calibration;

f. the maintenance plan, where appropriate, and maintenance carried out to date;

g. any damage, malfunction, modification or repair to the equipment.

The technical assistance and maintenance of instruments and measuring devices, computers, printers and other

peripherals are managed:

• by UNIMI.

• by the Clinical Engineering Office for the instruments owned by the Hospital ”L. Sacco” (Hospital “L. Sacco”

Quality Manual sec. 6 “Management of resources”);

• if necessary, by the company providing the instruments.

Equipment that has been subjected to overloading or mishandling, gives suspect results, or has been shown to be

defective or outside specified limits, are taken out of service. It is isolated to prevent its use or clearly labelled or

marked as being out of service until it has been repaired and shown by calibration or test to perform correctly. The

laboratory examines the effect of the defect or departure from specified limits on previous tests and/or calibrations

and applies the requirements specified in the section 4.10 of the Quality Manual institutes the “Control of

nonconforming work” procedure (see 4.10).

5.4 STANDARD AND REFERENCE MATERIALS The reference laboratories use only certified reference materials internationally recognized and issued by national

metrology institutes or international organizations. In the absence, they characterize their reference materials. The

reference materials are adequately labelled and stored according to the instructions of the certificate.

The instructions for reconstitution of the lyophilised reference materials and the storage are described in apposite

Instructions.

Standards are calibrated before and after any adjustment.

5.5 REFERENCE MEASUREMENTS PROCEDURE The CIRME adopts test methods recommended by national and international organizations

(http://www.bipm.org/en/committees/jc/jctlm/jctlm-db) or, when these are not available or in response to specific

requests of the customer, draws up its own methods that are submitted to adequate validation. With regard to the

procedures adopted in various stages of testing, where possible, methods supported by relevant scientific

publications are used.

The reference methods currently used are indicated in the following table:

http://www.bipm.org/en/committees/jc/jctlm/jctlm-db



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ANALYTE ANALYTICAL PROCEDURE REFERENCE METHOD REFERENCE

Alanine aminotransferase (ALT) Kinetic spectrophotometry

IFCC Reference Measurement Procedure (37°C) for ALT

Schumann G et al. Clin Chem Lab Med 2002;40:718-24

Alkaline phosphatase (ALP) Kinetic spectrophotometry IFCC Reference Measurement Procedure for (37°C) for ALP

In press

Aspartate aminotransferase (AST) Kinetic spectrophotometry

IFCC Reference Measurement Procedure (37°C) for AST

Schumann G et al., Clin Chem Lab Med 2002;40:725-33

Creatine kinase (CK) Kinetic spectrophotometry IFCC Reference Measurement Procedure (37°C) for CK


Gamma-glutamyltransferase (GGT) Kinetic spectrophotometry

IFCC Reference Measurement Procedure (37°C) for GGT


Lactate dehydrogenase (LDH) Kinetic spectrophotometry IFCC Reference Measurement Procedure (37°C) for LDH


Glycated Haemoglobin (HbA1c) HPLC – capillary electrophoresis

IFCC Reference Measurement Procedure for HbA1c

Jeppsson JO et al. Clin Chem Lab Med 2002; 40:78-89.

The reference measurement procedures are designed, described, and applied so that traceability of results to higher

reference procedures or higher reference materials is achieved with the stated level of uncertainty of measurement.

5.6 METROLOGICAL TRACEABILITY – UNCERTAINTY OF MEASUREMENT The aim of the CIRME efforts to standardise Laboratory Medicine measurements is to achieve comparable test

results for human samples independent of the test kits and instruments used and also independently of the

laboratory where the measurement is performed.

To achieve this goal one approach is presented by the reference measurement system, based on the concepts of

metrological traceability and of hierarchy of analytical measurement procedures. Key elements of the system are the

reference measurement procedure and reference materials: the reference procedure is used to assign a certified

value to a given reference material; once the appropriate reference material is certified, this material and the

manufacturer’s testing procedure can be used in industry to assign values to commercial calibrators. Clinical

laboratories use routine procedures with validated calibrators, both from commercial sources, to measure human

samples. In this way, the obtained value on patient samples will be traceable to the reference procedure and

materials, and the standardization of measurement, that is, the process of realizing traceability, will be reached.

Essential elements of a comprehensive reference measurement system include:

- clear definition of the analyte to be measured in the human samples;

- reference measurement procedure(s) which specifically measures the analyte as being defined;

- primary and secondary (commutable) reference materials;

- reference measurement laboratories, possibly collaborating in a network.

In Laboratory Medicine, with regard to the implementation of traceability, it is important to differentiate the analytes

between:



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1. Type A analytes :

− well defined compounds;

− concentrations expressed in SI units;

− results are not method-dependent;

− full traceability chains available.

2. Type B analytes:

− not well defined (often heterogeneous mixtures);

− analytes can be bound or in free state;

− not traceable to SI units, but to arbitrary units (e.g., WHO international units);

− usually measured with immunochemical procedures, that show inherent variability (different epitopes);

− full traceability chains frequently not available (calibration on widely used methods).

Enzymes and HbA1c are type B analytes and for them the implementation of standardization is in general more

difficult than type A analytes.

With respect to HbA1c, the IFCC has established a complete reference measurement system based on the concepts

of metrological traceability, that includes:

definition of HbA1c as haemoglobin molecules having a stable adduct of glucose to the N-terminal valine of the

haemoglobin β chain (β N-1-deoxyfructosyl-haemoglobin)

development of two equivalent reference methods specifically measuring this hexapeptide, with a combination of

HPLC and electron-spray mass spectrometry (MS) or, alternatively, a two dimensional approach using HPLC

and capillary electrophoresis (CE) with UV detection

preparation of a primary reference materials (purified HbA0 and HbA1c) to calibrate the reference procedures.

HbA1c TRACEABILITY CHAIN

Including CIRME reference laboratories

A special class of B analytes are enzymes, defined in terms of the amount of an agree-upon substrate they convert

in an agreed-upon measurement system, the so- called “catalytic amount”. Oppositely to other analytes, the



Rev. 4 26.01.2010


numerical results of catalytic activity measurements depend entirely on the experimental conditions under which the

measurements are made. In the standardization of enzyme assays, therefore, a reference measurement procedure,

which defines the conditions under which a given enzyme activity is measured, occupies the uppermost position

filled, with regard to non-enzyme analytes, by primary reference materials. Complete reference measurement

systems, comprising reference measurement procedures, reference materials, and reference laboratories, are

currently available for alanine aminotransferase, aspartate aminotransferase, creatine kinase, lactate

dehydrogenase, gamma-glutamyltransferase, and amylase.

ENZYMES TRACEABILITY CHAIN

Performed by CIRME reference laboratory

Estimation of measurement uncertainty is a crucial portion of ensuring traceability and is performed in accordance

with the Guide to the Expression of Uncertainty in Measurement (GUM). The reference laboratories use appropriate

methods to develop their uncertainty budget. The method used to develop the uncertainty budget is defined and

documented.

5.7 QUALITY ASSURANCE Certified reference materials are investigated to validate the CIRME laboratories results, and the measurement value

obtained must agree with the assigned value and its uncertainty.

The CIRME laboratories participate in annual exercises organized by IFCC (IFCC Ring Trials for Reference

Laboratories), coordinated by the Committee on Traceability in Laboratory Medicine in collaboration with the Working

Group 2 of JCTLM. The results provided by these yearly measurements are displayed on the EQAS website

(www.dgkl-rfb.de:81) where they are computed with those obtained by other reference laboratories.

http://www.dgkl-rfb.de:81/



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5.8 REPORTING RESULTS 5.8.1 MINIMUN REQUIREMENTS FOR REPORTING The results of the calibration activities, validated by the Responsible of the Reference Laboratory, are issued in the

form of a report or certificate (Record 06 “Calibration certificate”).

The Calibration certificate is:

- drawn up by the personnel performing the calibration activities and signed (second page, Operator);

- approved and signed by the Responsible of the Reference Laboratory or the Deputy (second page, Responsible

of Reference Laboratory);

- signed by the Director of the Centre for the official issue (first page, Head of the Centre).

The Calibration Certificates contains the following elements, according to the SIT document 512:

a. name,

b. address,

c. number of accreditation (calibration centre),

d. logo SIT,

e. date of issue,

f. addressee,

g. application and date,

h. item,

i. manufacturer,

j. model,

k. serial number,

l. date of measurements,

m. laboratory reference,

n. signature.

In the next pages the information reported are:

a. description of the object(s) to be calibrated,

b. identification of the procedure,

c. reference (first line) standard,

d. reference laboratory name,

e. calibration environmental condition,

f. results of measurement with the expanded uncertainty.

5.8.2 OPTIONAL ELEMENTS When appropriate or requested by the customer, the technical report or certificate also contains (usually as

appendix) the following:

a) any legal disclaimer;

b) interpretations of the results;

c) use of the values for calibration or for verification;



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d) professional judgement of other uses of the results;

e) copyright restrictions;

f) a statement that the report or the certificate complies with International Standard, i.e. ISO 17025 and ISO 15195, if

applicable.



Rev. 0 14.12.2009

LIST OF DOCUMENTS / 37

ANNEX A. Correspondence with ISO/IEC 17025 and ISO 15195 Correspondence Table Number Section ISO/IEC 17025 ISO 15195 1.0. Scope 1 1 2.0 Normative references 2 2 3.0 Terms and definitions 3 3 4.1 Organization and management 4.1 4.1 4.1.1 Legal status 4.1.1 4.2 4.1.2 Organization 4.1.5 a, e, f, g, h, i;

4.2.6

4.1.3 Independence, impartiality, and integrity

4.1.5 b, d 4.1

4.1.4 Confidentiality 4.1.5 c 4.1 4.1.5 Management commitment 4.1.6 4.1 4.2 Quality management system 4.2 4.2 4.2.1 Description of the instruments for the

implementation of the quality management system

4.2.1 4.2

4.2.2 Quality policy 4.2.2; 4.2.3; 4.2.4; 4.2.7

4.2

4.2.3 Top management responsibility 4.2.3 4.2 4.2.4 Top management communication 4.2.4 4.2 4.2.5 Quality system documentation 4.2.5; 4.1.5 k; 4.1.6 4.3 Personnel 4.1.5; 5.2 4.3 4.4 Document control 4.3 4.4 4.5 Contracting 4.4 4.5 4.6 Subcontracting 4.5 4.5 4.7 Purchasing 4.6 4.8 Service to the client 4.7 4.9 Complaints 4.8 4.2 4.10 Control of non conforming work 4.9 4.2 4.11 Corrective action 4.11 4.2 4.12 Preventive action 4.12 4.2 4.13 Control of records 4.13 4.2 4.14 Internal audits 4.14 4.2 4.15 Improvement 4.10 4.16 Management reviews 4.15 4.2 5.1 Accommodation and environmental

conditions 5.3 5.1

5.2 Handling of samples 5.8 5.2 5.3 Equipment 5.5; 5.6.1 5.3 5.4 Standard and Reference materials 5.6.3 5.4 5.5 Reference measurement procedure 5.4 5.5 5.6 Metrological traceability – Uncertainty

of measurement 5.4.6 5.6

5.7 Quality assurance 5.9 5.7 5.8 Reporting results 5.10 5.8



Rev. 0 14.12.2009

LIST OF DOCUMENTS / 37

ANNEX B. List of documents

QUALITY MANUAL

PROCEDURE

− Procedure 01: Quality Policy

− Procedure 02: Management System Requirements

− Procedure 03: Document Control

− PRLE 01: Test procedure for the determination of catalytic activity concentration of enzymes in Calibrators, Human Sera and Controls Materials

− PRLE 02: Test procedure for the determination of alanine aminotransferase (ALT)

− PRLE 03: Test procedure for the determination of aspartate aminotransferase (AST)

− PRLE 04: Test procedure for the determination of creatine kinase (CK)

− PRLE 05: Test procedure for the determination of γ-glutamyltransferase (GGT)

− PRLE 06: Test procedure for the determination of lactate dehydrogenase (LDH)

− PRLE 07: Test procedure for the determination of alkaline phosphatase (ALP)

− PRLE 08: Estimation of measurement uncertainty

− PRLA1C 01: Test procedure for the determination of glycated hemoglobin

− PRLA1C 02: Test procedure for the determination of glycated hemoglobin in human blood samples and controls

material

− PRLA1C 03: Estimation of measurement uncertainty

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