The document provides guidance for regulatory audits of medical device manufacturers' quality management systems. It discusses the Global Harmonization Task Force (GHTF), which aimed to harmonize medical device regulations internationally. GHTF established 5 study groups, including Study Group 4 which focused on auditing strategies and developed guidance documents. The guidance covers establishing auditing procedures, auditor competencies, and conducting and documenting audits in a harmonized manner. It provides a framework for consistent regulatory audits of medical device quality systems across countries.

1. GHTF (GLOBAL HARMONIZATION TASK
FORCE)
STUDY GROUP 4 GUIDANCE DOCUMENT
SangeethaPriya.S
M Pharmacy(regulatoryaffairs)
1

2. GLOBAL HARMONISATION TASK FORCE
 GLOBAL - considering or including all parts.
 HARMONISATION - the act of making different people, plans, situations, etc. Suitable for each other
 TASK -"a piece of work to be done," task implies work imposed by a person in authority or an employer or by
circumstance.
 FORCE-a group of people organized and trained, especially for a particular purpose.
2

3. INTRODUCTION
 The Global Harmonization Task Force (GHTF) was conceived in 1992 in an effort to respond to the growing need for
International Harmonization In The Regulation Of Medical Devices
 The Global Harmonization Task Force (GHTF) is a voluntary group of representatives from national medical device
regulatory authorities and the regulated industry.
 Since its inception, the GHTF has been comprised of representatives From Five Founding Members Grouped Into
Three Geographical Areas:
 Europe, Asia-Pacific and North America, each of which actively regulates medical devices using their own unique
regulatory framework..
 The GHTF disbanded late in 2012.Its mission has been taken over by the International Medical Device Regulators
Forum (IMDRF), a successor organization composed of officials from regulatory agencies— not industry — around the
world.The GHTF website is no longer operational.
3

4. INTERNATIONAL MEDICAL DEVICE
REGULAOTRS FORUM (IMDRF)
4
IMDRF
The International Medical Device Regulators Forum (IMDRF) is a forum of voluntary medical device
regulators from around the world who have come together
• To build on the strong foundational work of the Global Harmonization Task Force on Medical
Devices (GHTF), and
• To accelerate international medical device regulatory harmonization and convergence
PURPOSE
The purpose of the GHTF/IMDRF is to encourage convergence in regulatory practices related to
ensuring the safety, effectiveness / performance and quality of medical devices, promoting technological
innovation and facilitating international trade

5. FOUNDING MEMBERS
 A partnership between regulatory authorities and regulated industry, the GHTF was
comprised of five Founding Members: United States, European Union, Japan,Canada,
and Australia. Members also participate in the steering committee, which can recommend
the inclusion of other participants in Study Groups to be a part of all GHTF activities.
5

6. PARTICIPATING MEMBERS AND LIAISON BODIES
6 PARTICIPATING MEMBERS
 Participating members consist of representatives from regulatory agencies or medical device trade associations not a
part of the founding members. Participating members are to facilitate the adoption of as much of the GHTF's policies
in their region/agency as possible within legal parameters. Participating members can also take part in Study Groups
as well as other expert working groups.
LIAISON BODIES
 Liaison bodies are public health organizations, international standard-setting bodies or other groups who can
contribute to or benefit from participation in GHTF. Liaison Bodies are encouraged to promote GHTF guidelines to
their members and incorporate them into their work. Liaison bodies are permitted to nominate observers for GHTF
Study Groups and other expert working groups.

7. REGULATORY SYSTEM
To achieve uniformity among the national medical device regulatory systems and increase the access to safe, effective, and
clinically beneficial medical technologies, the Global Harmonization Task Force (GHTF) was conceived. All regulated
countries have clearly defined MEDICAL DEVICES, as has the GHTF.
 Although GHTF has tried to achieve harmonization with respect to medical devices, some differences still exist in the
national laws of the countries of GHTF.
 Further, regulated countries have classified medical devices on the basis of their associated risk.
 In the INDIAN REGULATORY SYSTEM, MEDICAL DEVICES ARE STILL CONSIDERED AS DRUGS.
 In 2006, the Medical Device Regulation Bill was recommended to consolidate laws for medical devices and to establish
the Medical Device Regulatory Authority of India.
 In addition, medical devices are not classified by any Indian regulatory authority. Although India has moved towards
harmonizing its medical device regulations with those of regulated countries, this study aims to identify whether India
should have a vigilance system in harmony with those of GHTF or develop its own system for medical devices.
7

8. MEDICAL DEVICE AND INVITRO DIAGNOSTIC MEDICAL DEVICE
‘Medical device’ means any instrument, apparatus, implement, machine, appliance, implant, reagent for in vitro use,
software, material or other similar or related article, intended by the manufacturer to be used, alone or in
combination, for human beings, for one or more of the specific medical purpose(s) of
1. Diagnosis, prevention, monitoring, treatment or alleviation of disease,
2. Diagnosis, monitoring, treatment, alleviation of or compensation for an injury,
3. Investigation, replacement, modification, or support of the anatomy or of a physiological process,
4. Supporting or sustaining life,
5. Control of conception, Disinfection of medical devices,
6. Providing information by means of in vitro examination of specimens derived from the human body; and does not
achieve its primary intended action by pharmacological, immunological or metabolic means, in or on the human
body, but which may be assisted in its intended function by such means.
8

9. IVDS
In vitro Diagnostic (IVD) Medical Device ‘In vitro Diagnostic (IVD) medical device’ means a medical device, whether used alone or in
combination, intended by the manufacturer for the in-vitro examination of specimens derived from the human body solely or principally to
provide information for diagnostic, monitoring or compatibility purposes.
 Note 1: IVD medical devices include reagents, calibrators, control materials, specimen receptacles, software, related instruments or apparatus or
other articles and are used, for example, for the following test purposes: diagnosis, aid to diagnosis, screening, monitoring, predisposition,
prognosis, prediction, determination of physiological status.
 Note2: In some jurisdictions, certain IVD medical devices may be covered by other regulations.
 Note: In some jurisdictions, some IVD medical devices may be covered by separate regulations.
 Reagent: chemical, biological or immunological components, solutions or preparations intended by the manufacturer to be used as IVD medical
devices
9

10. 10
•Design and
manufacture
•Intended
conditions and
purpose
•Clinical
condition or
safety and
health
•Risk benefit
analysis
•High level of
protection of
health and
safety
•Achieve
performance
intended
Conform to
safety principles
•Generally
acknowledged
state of the art
•Identify
hazards and
risks
•Inherently safe
design and
construction
•Adequate
protection
measures on
remaining risks
•Inform users of
residual risks
ESSENTIAL PRINCIPLES OF GHTF APPLICABLE TO ALL MEDICAL DEVICES
INCLUDING IVD MEDICAL DEVICES

11. CLASSIFICATION SYSTEM FOR MEDICAL DEVICES
 According to GHTF/IMDRF the classification of Medical Devices is the manufacturer’s responsibility.
 The Regulatory Authorities (RA) specifies procedures to be followed by manufacturers during the design,
manufacture, and marketing of each Devices.
 It describes the manner in which a manufacturer should demonstrate conformity to such specified procedures.
Classification of a Medical Devices has to be done carefully, because the risk class establishes the correct
conformity requirements.
 An incorrect classification would therefore lead to a conformity assessment procedure, which is not applicable
to the particular Devices.
 GHTF/IMDRF established a Devices classification system consisting of four classes where Class A represents
the lowest hazard and Class D the highest.
 The determination of class should be based on rules derived from the potential of a Medical Devices to cause
harm to a patient or user and thereby on its intended use and the technology/ies it utilizes
11

12. 12

13. OPERATING STRUCTURE
STEERING COMMITTEE
 The purpose of the Steering Committee is to provide policy and direction for the GHTF. It is responsible for
the assignment and oversight of new work items, adopt and monitor GHTF guidance documents and the
authorization and promotion of GHTF training events.
 The Steering Committee members consist of up to 8 members from each of the Founding Members’
regions. Of the 8 members, up to 4 may be from the regulatory sectors and up to 4 from the industry sectors.
The Chain and Vice Chair members of the controlling region are not to be included in this number.
ROLE OF SC
 Provide Strategic Planning,
 Allocate Ghtf Resources As Required
 Assign And Provide Oversight Of New Work Items,
 Actively Monitor Progress Of Assigned Work Items,
 Adopt Ghtf Guidance Documents, And Monitor Their Implementation
 Authorize And Promote Training Events As Required
13

14. STUDY GROUPS
 There are five study groups in the GHTF, each with a different focus. The size of each Study Group
is to be determined by the Study Group Chair. Recommended members include one participant
from each region with founding member status as well as appropriate numbers from regulatory
agencies and industry technical experts.
 Study Group 1 - Premarket Evaluation
 Study Group 2 - Post-Market Surveillance/Vigilance
 Study Group 3 - Quality Systems
 Study Group 4 – Auditing strategy
 Study Group 5 - Clinical Safety/Performance
14

15. STUDY GROUP 4 -AUDITING
Study Group 4 is concerned with examining CURRENT QUALITY SYSTEMS AUDITING PRACTICES
AND THE HARMONIZATION OF THE AUDITING PROCESS.
ROLE OF GHTF STUDY GROUP 4
 Has been charged with the task of examining quality management system auditing practices and developing
guidance documents providing harmonized principles for the medical device auditing process
 Provide guidance for parties responsible for establishing, planning, carrying out and documenting audits of
quality management systems to address regulatory requirements for manufacturers of medical devices
 Outline competence criteria for the auditing team
 Eliminate duplication of effort and inconsistencies in auditing practices Study Group 4 Began work on the
series of documents in 1994-1996
 At that time the ISO 10011 series of standards for auditing quality systems was available (1990-1991)
 Also available was ISO 14011:1996 for environmental auditing
15

16. Purpose of Study Group SG4
 Guidance to Regulatory Audit Organizations, Auditors and Manufacturers of Medical
Devices
 SG4 has been charged with the task of examining quality system auditing practices
(initially among the founding members of the GHTF) and developing guidance documents
laying harmonized principles for the medical device auditing process“
16

17. STUDY GROUP 4 MEMBERSHIP
 Unites States 2 regulatory Bodies 1 industrial Bodies
 Canada 1 regulatory Bodies 1 industry Bodies
 Australia 1 regulatory Bodies
 European Union 2 regulatory Bodies 3 industry Bodies 2 Notified Body
 Japan 2 regulatory Bodies 1 industry Bodies
 Taiwan 1 regulatory Bodies (AHWP liaison)
17

18. 18
GUIDELINES FOR REGULATORY AUDITING OF QUALITY
SYSTEMS OF MEDICAL DEVICE MANUFACTURERS

19. STUDY GROUP 4 DOCUMENTS
Introduction
 This document gives guidance to regulators and auditing organizations conducting audits of quality
management systems of medical device manufacturers based on the process approach to quality management
system requirements (e.g., ISO 13485:2003 -QMS FOR DESIGN AND MANUFACTURE OF MD and 21 CFR Part 820-CGMP
REQUIREMENTS FOR MEDICAL DEVICE MANUFACTURERS).
 The incorporation of quality management system requirements, based on ISO 13485, into regulations
applicable to manufacturers of medical devices, provides the opportunity for developing mechanisms that
would lead to global harmonization. Regulators can use these guidelines when introducing regulatory
systems for medical devices
 Note: For the purpose of these guidelines, “audit” means a regulatory audit.
Potential benefits for the patients/users, regulators, auditing organizations or auditees include
• A High Degree Of Assurance (Along With Technical Evaluation, Where Required In Addition) That Safe And Effective
Devices Will Be Available
• Independent, Reliable, Objective Evaluation Of Compliance With Regulatory Requirements Of The Manufacturer's
Quality Management System
• If Satisfactory, Results Are Evidence (Or Part Thereof) Of Compliance With Regulatory Requirements Necessary To
Market Devices
19

20. Scope
This document provides guidance for auditing organizations responsible for establishing, planning, carrying out, and
documenting audits of medical device manufacturers’ quality management systems. The document also covers related
requirements on the follow-up of corrections, corrective, preventive, or improvement actions, as applicable. In addition, it
describes the competence criteria that the audit team should meet
The purposes of this document are:
• To harmonize and to provide guidance on auditing quality management systems of medical device manufacturers
• To help the auditing organization develop their auditing procedures
• To assist auditors and auditees in preparing for, facilitating and responding to audits
Rationale
This guideline promotes consistency in auditing of medical device manufacturers’ quality management systems which is
important in harmonization and mutual acceptance of audit results
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21. ARCHIVED DOCUMENTS
GHTF code: GHTF/SG4/N28R4:2008 - Date posted: 27 August 2008
 GHTF SG4 - Guidelines for Regulatory Auditing of Quality Management Systems of Medical Device Manufacturers -
Part 1: General Requirements
GHTF code: GHTF/SG4/N30:2010 - Date posted: 27 August 2010
 GHTF SG4 - Guidelines for Regulatory Auditing Part2
GHTF code: GHTF-SG4-N33 R16 - Date posted: 2 October 2007
 GHTF SG4 - Guidelines for Regulatory Auditing of Quality Management Systems of Medical Device Manufacturers -
Part 3 Regulatory Audit Reports- October 20
GHTF code: GHTF-SG4-(00)3 - Date posted: 24 Feburary 2000
 GHTF SG4 - Training Requirements for Auditors
GHTF code: GHTF/SG4/N30R20:2006 - Date posted: 28 June 2006
 GHTF SG4 - Guidelines for Regulatory Auditing of Quality Management Systems of Medical Device Manufacturers -
Part 2: Regulatory Auditing Strategy
21

22. GHTF code: SG4(PD1)/N33 R13 - Date posted: 27 June 2006
 GHTF SG4 - Guidelines for Regulatory Auditing of Quality Management Systems of Medical Device
Manufacturers – Part 3: Regulatory Audit Reports
GHTF code: SG 4 PD N30R16:2005 - Date posted: 15 September 2005
 GHTF SG4 - Guidelines for Regulatory Auditing of Quality Management Systems of Medical Device
Manufacturers - Part 2: Regulatory Auditing Strategy - September 2005
GHTF code: GHTF/SG4/N26R1:2001 - Date posted: 13 June 2002
 GHTF SG4 - Guidelines for Regulatory Auditing of Quality Systems of Medical Device Manufacturers
General Requirements Supplement No. 6 Observed Audits of Conformity Assessment Bodies
GHTF code: GHTF/SG4/N(99)24R3:2002 - Date posted: 12 May 2002
 GHTF SG4 - Guidelines for Regulatory Auditing of Quality Systems of Medical Device Manufacturers:
General Requirements - Supplement No. 4 - Compilation of Audit Documentation (Clause 5.7)
GHTF code: GHTF.SG4.(99)14 - Date posted: 29 June 1999
 GHTF SG4 - Audit Language Requirements
GHTF code: GHTF.SG4.(99)28 - Date posted: 29 June 1999
 GHTF SG4 - Guidelines for Regulatory Auditing of Quality Systems of Medical Device Manufacturers -
Part 1: General Requirement
22

23. FINAL DOCUMENTS
GHTF code: GHTF/SG4/N83:2010 - Date posted: 27 August 2010
 GHTF SG4 - Guidelines for Regulatory Auditing of Quality Management Systems of Medical Device
Manufacturers - Part 4 Multiple Site Auditing - August 2010
GHTF code: GHTF/SG4/N84:2010 - Date posted: 27 August 2010
 GHTF SG4 - Guidelines for Regulatory Auditing of Quality Management Systems of Medical Device
Manufacturers. Part 5 Audits of Manufacturer Control of Suppliers - August 2012
23

24. PART 1: GENERAL REQUIREMENTS
Endorsed by GHTF in 1999
 Revised in 2008
 Revised structure
 Elimination of duplicate information
 Provide guidance to regulators and auditing organizations conducting audits of quality management systems (QMS)
of medical device manufacturers based on the process approach to QMS requirements (e.g., ISO 13485 and 21 CFR
820)
 Provide the opportunity for developing mechanisms that would lead to global harmonization by incorporating QMS
requirements into applicable regulations SG4/N28R4: 2008 Part 1 General Requirements
 Provide guidance for auditing organizations responsible for establishing, planning, carrying out, and documenting
audits of medical device manufacturers’ QMS
 Provide guidance on related requirements on the follow-up of corrections, corrective, preventive, or improvement
actions Describe the competence criteria of the audit team
24

25. DEFINITIONS
 AUDIT A systematic and independent examination to determine whether quality activities and related
results comply with planned arrangements and whether these arrangements are implemented effectively
and are suitable to achieve objectives [ISO 8402 Quality management and quality assurance]
 AUDITEE Any organisation whose quality systems are to be audited for compliance with the relevant
medical device regulatory requirements Note. This can be the manufacturer and/or their subcontractor(s)
Auditee
 AUDITING ORGANIZATION A body designated, on the basis of specific regulations, to carry out
audits according to assigned tasks
 AUDITOR A person with relevant qualifications and competence to perform audits or specified parts of
such audits and who belongs to, or is authorised by, the auditing organisation
25

26.  MANUFACTURER The legal entity subject by regulation to quality system requirements In several
international standards the term 'supplier' is substituted for the term 'manufacturer'
 NONCONFORMITY The non-fulfilment of specified requirements within the planned arrangements. Other
terms with the same meaning as nonconformity are “non - compliance” and “deficiency”
 QUALITY SYSTEM The organisational structure, responsibilities, procedures, processes and resources for
implementing quality management [ISO 8402]. For the purpose of these guidelines 'implementing quality
management' is taken to include both the establishment and maintenance of the system
 REGULATORY REQUIREMENTS For the purpose of these Guidelines any part of a law, ordinance, decree
or other regulation which applies to quality systems of medical device manufacturers
26

27. GENERAL REQUIREMENTS: IMPORTANT PRINCIPLES FOR REGULATORY AUDITING
 Independence of Auditors ,Auditing organisations and auditors shall be; impartial and free from
engagements and influences which could affect their objectivity
 Independence of Auditors, Auditing organisations and auditors shall not be: –Involved in design,
construction, marketing, installation, servicing or supply of devices being audited –Involved in design,
construction, implementation or maintenance of quality system being audited –An authorised
representative of the manufacturer
 The manufacturer is ultimately responsible for implementing and maintaining an effective quality
system and taking necessary corrective and preventive actions
27

28. GENERAL REQUIREMENTS :OTHER ELEMENTS OF
MANAGING THE AUDIT PROCESS
AUDIT OBJECTIVES AND SCOPE SHOULD BE:
 Clearly defined and documented by the auditing organisation and the audit team
 Agreed to by the manufacturer, as permitted by regulatory requirements
 May be modified,based on the quality audit observations
TYPES OF AUDIT
 Initial audit
 Surveillance audit
 Special audit
 Unannounced audit
28

29. Initial Audit
 First audit of manufacturer
 All elements of quality system should be audited
Surveillance Audit
 Manufacturer has been audited previously
 Audit may cover complete quality system or only part of it
Special audit An audit conducted when: –
Post-market surveillance data indicate a possible significant deficiency in the quality system
 Significant safety related information is obtained from another source
 Significant changes occur to a manufacturer, which could affect the decision on the manufacturer's
state of compliance with the regulatory requirements
Unannounced Audit
An unannounced audit may be conducted when the auditing organization has justifiable concerns about
the manufacturer’s implementation of corrective actions or compliance with regulatory requirements
29

30. 30

31. Guidelines for Regulatory Auditing of Quality Systems of
Medical Device Manufacturers Part 1: General
Requirements
 SG4(99)14, Supplement 1: Audit Language Requirements
 SG4(00)3, Supplement 3: Training Requirements for Auditors
 SG4-N(99) 24 R3, Supplement 4: Compilation of Audit Documentation
 SG4 N26 R1,Supplement No. 6 Observed Audits of Conformity Assessment Bodies
31

32. SUPPLEMENT 1: AUDIT LANGUAGE
REQUIREMENTS
Purpose:
 To assure that auditors and the auditee are able to communicate clearly during an audit
 Before the audit, determine if auditors and auditee have a common language
 Arrange for an interpreter if there is no common language
Audit language The language(s) routinely used for the communication or exchange of information
between auditee’s personnel and auditors.
Guidance The audit team must have available: as a minimum, one member able to read and
understand the quality system documentation and interview the auditee’s personnel; or an audit
interpreter, arranged and agreed in advance.
Language requirements for auditees are expected to prepare their quality documentation in the
company's operational language(s)
32

33. SUPPLEMENT 3: TRAINING REQUIREMENTS FOR
AUDITORS
33
Scope: The document describes training elements required to
• Prepare an individual to be an auditor
• Qualify auditors to conduct regulatory audits of medical device manufacturers’ quality system
• Maintain auditor qualifications
Training Topics to Prepare an Individual to Be an Auditor
1.Principles and applications of quality systems and auditing
2.Interviewing people
3.Collecting, documenting and reporting quality audit observations and non-conformities
Training Topics to Qualify Auditors to Conduct Regulatory Audits
1.Understanding, applying and enforcing laws and regulatory requirements
2.The role of the auditing organization
3.Principles and applications of quality systems and auditing for medical device manufactur
4.Overview of medical devices, their intended uses, safety and risks

34. Training to maintain auditor qualifications
1.Training courses
2.Scientific meetings
3 Independent study
Assuring that Auditors are Qualified
 Experienced auditor should observe and evaluate auditor-in-training conducting one or more audits
 Auditors should be judged competent to audit highly specialised technologies before they are
allowed to work without supervision
34

35. SUPPLEMENT 4: COMPILATION OF
AUDIT DOCUMENTATION
Purpose/Scope:
 Provides guidelines for compiling audit documentation within auditing organization for
internal use
 This document does not address the exchange of audit documentation between auditing
organizations
35

36. SUPPLEMENT NO. 6 OBSERVED AUDITS OF
CONFORMITY ASSESSMENT BODIES
Purpose:
 Sets out guidance for observing audits conducted by Conformity Assessment
Bodies (CABs).
 Observing audits enables a regulatory authority to evaluate the adequacy of the
audits
 Remember: To audit = to listen > need to understand language!
 Only trained auditors will do a good job!
 No job is finished until paperwork is done
36

37. PART 1 DOCUMENT
37

38. PART 1 SUPPLEMENT DOCUMENTS
38

39. PART 2: REGULATORYAUDITING STRATEGY
 Endorsed by GHTF in 2005
 Revised in 2006 and 2010
 Revised structure
This guideline applies to initial and surveillance audit
 To promote consistency in conducting audits – a necessity for harmonization and mutual recognition of audit results
 The audit should be process-oriented and should preferably follow the workflow processes of the medical device
manufacturer
 The audit should be risk-based with a focus on key processes of QMS necessary to manufacture the medical devices
covered by the audit
 The auditor should concentrate on factors that are most likely to affect safety of the medical devices while at the same time
ensuring adequate coverage of all classes of medical devices within the scope of the audit
39

40. Scope
ISO 13485:2003 & 21 CFR 820
 Risk Management Software,
 Human Factors
 Additional Regulatory Requirements
 Initial & Surveillance Audits
Definitions
Audit: Systematic independent and documented process for obtaining audit evidence and evaluating it objectively to
determine the extent to which the audit criteria are fulfilled. (ISO 19011:2002)
Regulatory audit: The audit of a quality management system to demonstrate conformity with quality management
system requirements for regulatory purposes. Note: For the purpose of these guidelines, “audit” means a regulatory
audit.
Audit criteria: Set of policies, procedures or requirements. (ISO 19011:2002) Audit evidence: Records, statements
of fact or other information, which are relevant to the audit criteria and verifiable. (ISO 19011:2002)
40

41.  Auditing organization: See document SG4/N28: “Guidelines for Regulatory Auditing of Quality Systems of
Medical Device Manufacturers – Part 1: General Requirements”.
 Establish: Establish means define, document (in writing or electronically), and implement Note: This
definition differs from the usage of the word “establish” in ISO 13485:2003
 Medical device: As defined in the document GHTF SG 1 N 29 R 16:2005 “Information Document
Concerning the Definition of the Term “Medical Device”. Process: Set of interrelated or interacting activities
which transform inputs into outputs (ISO 9000:2000)
 Residual risk: Risks remaining after protective measures have been taken (ISO/IEC Guide 51:1999)
 Risk management: Systematic application of management policies, procedures, and practices to the task of
analyzing, evaluating and controlling risk (ISO 14971:2000)
 Product documentation: These documents are the final output for a particular product resulting from a
design and development process whether or not the design and development process is regulated or under the
scope of the quality management system.
41

42. GENERAL REMARKS ON REGULATORY AUDITING
STRATEGY
 Objectives
 Auditing Quality Management Systems (system and sub system)
 Auditing Approaches
 Process Based Auditing
 Sampling
 Audit Planning
 Guidance for Logistics During an Audit
 Linkage
42

43. AUDITING SUB-SYSTEMS
 Associated with clauses of ISO 13485:2003 and sections of 21 CFR Part 820
 Subsystems based in part on the Quality System Inspection Technique (QSIT): Management, Design and
Development, Production Processes Controls, Corrective and Preventive Actions
 GHTF SG4 has identified additional subsystems: Product Design Documentation, Purchasing Controls,
Documentation and Records, Customer requirements
 Auditing Subsystems
 Management Subsystem
 Design and Development Subsystem
 Product Documentation Subsystem
 Production and Process Controls Subsystem
 Corrective and Preventive Actions (CAPA) Subsystem
 Purchasing Controls Subsystem
 Documentation and Records Subsystem
 Customer Related Processes Subsystem
43

44. AUDIT APPROACHES AND PROCES BASED
AUDITING
 Top-down approach
 Bottom-up approach
 Combination of these two approaches
 Horizontal Approach
Process Based Auditing
 Check if all subsystems and processes of the quality management system are structured as a self-
regulating control process –
 for example according to Deming‘s PDCA cycle: Plan, Do, Check, Act Process Based Auditing
44

45. 45

46. APPENDICES OF PART 2
 Appendix 1: Binominal Staged Sampling Plans
 Appendix 2: Factors Used to Determine Audit Duration
 Appendix 3: Cross-reference between ISO 13485:2003 and 21 CFR Part 820
 Appendix 4: Sterilization Process
 Appendix 5: Software Auditing
46

47. PART 2 DOCUMENT
47

48. PART 3 REGULATORY AUDIT REPORTS
48
 Endorsed by GHTF in 2006
 Revised in 2007
 Revised structure
 Will provide harmonized content for reporting results of regulatory audits of quality systems
 Purpose is to facilitate the exchange of regulatory audit reports among regulatory authorities
 FIrst Steps Reporting requirements in different
GHTF-regions are identified
Administrative data
Contents of the audit report

49. DEFINITIONS
 Adverse event: An “Adverse Event” is either a malfunction or a deterioration in the
characteristics or performance of a sold medical device [including accessory(s) and labeling] or
use error, which either has caused or could have caused or contributed to death, or serious injury
to health of patients or other persons. (GHTF SG 2/N36R7)
 Audit findings Results of the evaluation of the collected audit evidence against audit criteria
Note: Audit findings can indicate either conformity or nonconformity with audit criteria or
opportunities for improvement (ISO 19011:2002)
 Compliance / Conformity Fulfillment of regulatory requirements Note: In this document the
terms “compliance” and “conformity” are used interchangeably whereas in some jurisdictions
they may have distinct and different meanings.
 Critical supplier A critical supplier is a supplier delivering materials, components, or services,
that may influence the safety and performance of the product.
49

50. 50
Designating Authority (DA) Body established within government or empowered by government to designate
auditing organizations, suspend or withdraw their designation or remove their suspension from designation.
Objectives and User Needs of a Regulatory Audit Report
Audit report objectives
User needs for the auditing organization/regulatory authority
User needs for the designating authority that oversees the auditing organizations
 User needs for the manufacturer and/or auditee

51. MAIN POINTS OF A REGULATORY AUDIT REPORT
 The auditing organization/regulator may adopt reporting procedures that suit its needs. The report shall be
typed and may be in a format that can be stored and transferred electronically. Trade secrets and
proprietary information should be identified in the report to ensure confidentiality.
 Data concerning auditee
 Data concerning audit
 Audit trail
 Conclusion
 Signature and dating of report
 Attachments
51

52. 52

53. PART 4: MULTIPLE SITE AUDITING
SUPPLEMENTS AUDIT STRATEGY GUIDANCE
 Endorsed by GHTF in 2010
 Revised structure
 Supplements audit strategy guidance in Part 2 document
 Provides guidance on developing, executing, and completing an audit program for the auditing
of a manufacturer with multiple sites operating with one Quality Management System
DEFINITIONS
 Audit program A set of one or more audits planned for a specific time frame and directed
towards a specific purpose Note: An audit program includes all activities necessary for planning,
organizing and conducting the audits. (ISO 9000:2005 3.9.2)
 Centralized function A quality management system function that is applicable to one or more
sites, but is controlled from a single site (which may not necessarily be the lead site)
 Common function A quality management system function defined by a single site that is
applicable to more than one site and may be controlled by multiple sites
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54.  Lead site A site having an identified central function, by which the quality management system applied to
the sites is established and subject to continuous surveillance and internal audits. The lead site can require
any site to implement corrective actions when needed. Where applicable this should be set out in the formal
agreement between the lead site and the other sites.
 Manufacturer “Manufacturer” means any natural or legal person with responsibility for design and/or
manufacture of a medical device with the intention of making the medical device available for use, under his
name; whether or not such a medical device is designed and/or manufactured by that person himself or on his
behalf by another person(s).
 Manufacturer with multiple sites A manufacturer which conducts activities under the same quality
management system at more than one site
 Site A place where a manufacturer conducts activities
 Overall lead auditor The auditor who has oversight of the audit program described in this document
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55. AUDIT PROGRAM FOR A MANUFACTURER WITH
MULTIPLE SITES
Objectives and criteria of audit program
 Audit program objectives
 Audit criteria
 Scope of audit program
Preparation of audit program
 Objectives, criteria and scope of individual site audits
 Sequence of audits
 Determination of resource needs
 Determination of communication and reporting needs
 Completion of audit program preparation
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56. EXECUTION OF AUDIT PROGRAM
 Execution of individual site audits
 Opening meeting
AUDITING OF SUBSYSTEMS
 Management subsystem
 Design and development subsystem
 Product documentation subsystem
 Production and process controls subsystem
 Corrective and preventive actions - CAPA subsystem
 Purchasing controls subsystem
 Documentation and records subsystem
 Customer related processes subsystem
 Closing meetings
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57. AUDIT REPORT
 Audit program synthesis
 Communication of overall findings
 Synthesis report
AUDIT PROGRAM COMPLETION
AUDIT FOLLOW-UP
AUDIT PROGRAM REVIEW
 Audit program effectiveness
 Modifying the audit program
 Corrective and corrective action
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58. AUDIT PROGRAM FOR A MANUFACTURER WITH
MULTIPLE SITES
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59. Part 5: Audits of Manufacturer Control of Suppliers
 Endorsed by GHTF in 2010
 Revised structure
DEFINITIONS
Supplier (ISO 9000:2005, Clause 3.3.6) Organization or person that provides a product EXAMPLE: Producer,
distributor, retailer or vendor of a product, or provider of a service or information.
 This document addresses suppliers outside of the QMS of the manufacturer. IN the context of auditing medical
device manufacturers, this definition applies regardless of the legal or financial relationship between the
manufacturer and the supplier.
Critical supplier A supplier delivering materials, components, or services, that may influence the safety and
performance of the product. Note: In the context of audit of medical device manufacturers, a critical supplier is a
supplier of a product or service, the failure of which to meet specified requirements could cause unreasonable risk to
the patient, clinician or others, or could cause a significant degradation in performance. This can include suppliers of
services which are needed for compliance with QMS or regulatory requirements.
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60. AUDIT PRINCIPLES
1.GENERAL PRINCIPLES
 Verify that procedures for conducting supplier evaluations have been established.(ISO 13485:2003:)
 Verify that the manufacturer evaluates and maintains effective controls over suppliers, so that specified
requirements are met. (ISO 13485:2003:)
 Verify that the manufacturer assures the adequacy of specifications for products and services that suppliers are to
provide, and defines risk management responsibilities and any necessary risk control measures. (ISO
13485:2003:)
 Verify that records of supplier evaluations are maintained. (ISO 13485:2003:)
 Determine that the verification of purchased products and services is adequate. (ISO 13485:2003:)
2.DECISION ON WHETHER TO AUDIT AT THE SUPPLIER PREMISES
3. AT SUPPLIER PREMISES
4.REPORTING
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61. STUDY GROUP 4 GUIDANCE DOCUMENT
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62. VALUE OF GHTF SG 4 GUIDANCE
 Used as a reference in several harmonization efforts
 FDA-Health Canada Pilot Multipurpose Audit Program
 Advanced Common Template Working Group
 Health Canada Registrar guidance documents Used in training initiatives for emerging regulatory
models
 Being incorporated into the medical device regulatory regimes of countries and areas implementing new
legislation
 Incorporated into a new proposed global certification program by the International Accreditation Forum
(IAF)
 ISO 13485 Medical Device Conformity Assessment System (MDCAS)
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63. GHTF SUCCESSES AND CONTROVERSIES
GHTF SUCCESSES
 Adverse event reporting
 Health Canada maintains the electronic National Competent Authority Report (NCAR) system
 ISO 13485 and FDA Quality System Requirements
 Auditing strategies and format finalized
 Summary Technical Documentation for Demonstrating Conformity to the Essential Principles of Safety
and Performance of Medical Devices (STED)
CONTROVERSIES
 • Classification of devices: 3 vs. 4 classes
 • When is “clinical evidence” needed and to what degree – considerable variation
 The Founding Members have work to do on implementing the GHTF documents, and also opening up the
GHTF process to other countries that are becoming significant consumers and producers of medical devices
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64. EMERGING DEVICE ISSUES
 NEW PRODUCTS
• Combination products
• Software driven
• Software as devices
•“Omics” diagnostics
 OUTSOURCING
 HOSPITAL TO HOME CARE
• Environmental issues
• Use issues
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66. REFERENCES
 GHTF/SG4/N28R4:2008 Guidelines for Regulatory Auditing of Quality Management Systems of
Medical Device Manufacturers - Part 1: General Requirements
 GHTF/SG4/N30R20:2006 Guidelines for Regulatory Auditing of Quality Management Systems of
Medical Device Manufacturers – Part 2: Regulatory Auditing Strategy
 GHTF/SG4/N33R16:2007 Guidelines for Regulatory Auditing of Quality Management Systems of
Medical Device Manufacturers – Part 3: Regulatory Audit Reports
 GHTF/SG4/N83 R6:2010 Guidelines for Regulatory Auditing of Quality Management Systems of
Medical Device Manufacturers – Part 4: Multiple Site Auditing
 Santiago de Chile, May 9 – 12, 2006 1 Latin America APEC Funded Medical Device Regulatory
 https://www.imdrf.org/
 http://www.ghtf.org/
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