Medical Device Guidelines and Regulations Handbook

Contents
ISO 14155: Clinical Investigation of Medical Devices for Human Subjects
1 Introduction
2 Structure of ISO 14155:2011
3 ISO 14155-1
3.1 Scope
3.2 Terms and Definitions
3.3 Ethical Considerations
Declaration of Helsinki (DoH)
Improper Influence or Inducement
Compensation and Additional Health Care
Responsibilities
3.4 General Requirements
Formal Agreement
Qualifications
Clinical Investigation Plan
Design of the Clinical Investigation
Confidentiality
Start of Clinical Investigation
Informed Consent
Documentation
Sponsor
Monitor
Clinical Investigator
Final Report
4 ISO 14155-2
4.1 Scope
4.2 Terms and Definitions
4.3 Requirements
4.4 Clinical Investigation Plan (CIP)
4.5 General Information
Identification of the Clinical Investigation Plan
Clinical Investigators, Principal Clinical Investigator, Coordinating Clinical Investigator, Investigation Center/Site(s)
Sponsor
Monitoring Arrangements
Data and Quality Management
An Overall Synopsis of the Clinical Investigation
Approval and Agreement to the Clinical Investigation Plan
4.6 Identification and Description of the Medical Device to Be Investigated
4.7 Preliminary Investigations and Justification of the Study
Literature Review
Preclinical Testing
Previous Clinical Experience
Device Risk Analysis and Risk Assessment
Objectives of the Clinical Investigation
Design of the Clinical Investigation
Statistical Considerations
Deviations from the Clinical Investigation Plan
Amendments to the Clinical Investigation Plan
Adverse Events and Adverse Device Effects
Early Termination and Suspension of the Investigation
Publication Policy
Case Report Forms (CRF)
References
ISO 13485: Medical Devices – Quality Management Systems, Requirements for Regulatory Purposes
References
ISO 14971 and ISO 24971: Medical Device Risk Management
1 Introduction
2 Scope
3 Terms and Definitions
4 General Requirements for Risk Management
4.1 Competence of Personnel
4.2 Risk Management Plan
4.3 Risk Management File
5 Risk Analysis
5.1 Intended Use and Reasonably Foreseeable Misuse
5.2 Identification of Characteristics Related to Safety
5.3 Identification of Hazards and Hazardous Situations
5.4 Risk Estimation
6 Risk Evaluation
7 Risk Control
7.1 Risk Control Option Analysis
7.2 Implementation of Risk Control Measures
7.3 Residual Risk Evaluation
7.4 Benefit-Risk Analysis
7.5 Risks Arising from Risk Control Measures
7.6 Evaluation of Overall Residual Risk
8 Risk Management Review
9 ISO/TR 24971:2013: Guidance on Application of ISO 14971
9.1 International Product Safety Standards in Risk Management
9.2 IEC 62304: Medical Devices Software Life Cycle Processes
9.3 IEC 62366: Application of Usability Engineering to Medical Devices
9.4 ISO 10993: Biological Evaluation of Medical Devices
9.5 Developing the Policy for Determining the Criteria for Risk Acceptability
9.6 Production and Post-production Feedback Loop
References
ISO 19227: Implants for Surgery – Cleanliness of Orthopedic Implants
1 Introduction
2 General Requirements
2.1 Quality Management System
2.2 Risk Management
2.3 Design of Cleaning Process
2.4 Validation Process
2.5 Sampling Process
2.6 Manufacturing of Test Substances
2.7 Testing Methods and Efficiency
3 Cleanliness Evaluation: Test Methods and Cleanliness Acceptance Criteria After Final Cleaning
3.1 Detailed View
3.2 Visual Test
3.3 Bioburden Test
3.4 Bacterial Endotoxins
3.5 Organic Contaminants
Detailed View
Extraction Method
Detection Method
3.6 Inorganic Contaminants
3.7 Particulate Contamination
3.8 Cytotoxicity
4 Cleaning Validation
5 Continued Process Verification (CPV)
6 Documentation
Annexure A: (Informative) Potential Sources of Harm in a Cleaning Process
References
ISO 21534: Non-active Surgical Implants – Joint Replacement Implants
1 Scope
2 Normative References
3 Terms and Definitions
4 Intended Performance
5 Design Attributes
6 Materials
7 Design Evaluation
8 Manufacture and Inspection
9 Sterilization
10 Packaging and Information Supplied by the Manufacturer
Reference
ISO 16061: Instrumentation for Use in Association with Non-active Surgical Implants—General Requirements
1 Introduction
2 Terms and Definitions
2.1 Associated Implant
2.2 Instrument
2.3 Resupplied Instrument
3 Intended Performance
4 Design Attributes
5 Selection of Materials
6 Design Evaluation
6.1 General
6.2 Preclinical Evaluation
6.3 Clinical Evaluation
7 Manufacture
8 Sterilization
8.1 Products Supplied Sterile
8.2 Products Provided Non-sterile
9 Packaging
9.1 Protection from Damage in Storage and Transport
9.2 Maintenance of Sterility in Transit
10 Information Supplied by the Manufacturer
10.1 General
11 Labeling
12 Instructions for Use
13 Instruments with Measuring Function
14 Restrictions in Combinations
15 Marking on Instruments
16 Instruments Intended for Single Use
Reference
ISO 22442: Medical Devices Utilizing Animal Tissues and Their Derivatives
1 Part 1: Application of Risk Management
1.1 Scope
1.2 Terms and Definitions
1.3 Risk Management Process
Device Contact with the Patient
Material Incorporated in the Medical Device
Device Material Sterility and Other Microbiological Controls
Unwanted Outputs of Substances
Identification of Hazards and Hazardous Situations
1.4 Risk Evaluation and Risk Control
Risk Control for Viruses and TSE Agents
Risk Control of Other Hazards
Residual Risk Evaluation
Evaluation of Overall Residual Risk Acceptability
Documentation
Production and Post-production Information System
2 Part 2: Controls on Sourcing, Collection and Handling
2.1 Scope
2.2 Terms and Definitions
2.3 Quality System Elements
Procedures
Personnel
Current Regulatory Requirements and Guidance
2.4 Sourcing
Species and Strain
Geography
2.5 Inspection
Certification
2.6 Traceability
2.7 Collection
2.8 Handling
2.9 Storage and Transport
3 Part 3: Validation of the Elimination and/or Inactivation of Viruses and Transmissible Spongiform Encephalopathy (TSE) Agents
3.1 Scope
3.2 Terms and Definitions
3.3 Risk Management
Sourcing and Manufacturing Process
Documented Procedures
Calibration
Equipment
Experimental Systems
3.4 Literature Review
Conduct of the Literature Review
Viruses
TSE Agents
3.5 Elimination and/or Inactivation Study of Viruses and TSE Agents
Protocol
Conduct of the Study
3.6 Final Report
3.7 Review of Final Report
4 Part 4: Principles for Elimination and/or Inactivation of Transmissible Spongiform Encephalopathy (TSE) Agents and Validation Assays for Those Processes
4.1 Scope
4.2 Terms and Definitions
4.3 Elimination of TSE Agents: Basic Considerations
TSEs of Concern
Animal Tissues of Concern
Tissues Infected with TSE Agents
4.4 Potential Methods to Eliminate TSE Agents
Physical Methods for Inactivating TSE Infectivity
Chemical Methods for Inactivating TSE Infectivity
Treatments with Phenolic Disinfectants
Protease Treatments
Guanidine and Other Chaotropic Chemical Treatments
Combined Treatments
Ineffective Treatments
4.5 Methods for Removing TSE Infectivity Without Inactivating Infectivity
4.6 Experimental Validation of Methods for Eliminating TSE Agents from Medical Devices Utilizing Non-viable Animal Tissues
Defining of Product Families for Purposes of Designing TSE Process Validation Studies
Selection and Testing of Product for Establishing and Verifying the Infecting Dose of TSE Agent
TSE Agent Spiking Materials
4.7 Availability of Bioassay Animals
Potential Development of Cell Culture Assays for Infectivity
Correlations Between PrPTSE and Infectivity Assays
Reductions in Infectivity Compared with Failure to Detect at Limits of Detection
4.8 Requirements for Stepwise Reductions in PrPTSE and Infectivity Versus Whole-Process Validation
Annexures
Annexure A: Guidance on the Application of This Part of ISO 22442
Annexure B: Graphical Representation of Part of the Risk Management Process for Medical Devices Utilizing Animal Material
Annexure C: Special Requirements for Some Animal Materials Considering the Risk Management for TSE Agents
Annexure D: Information Relevant to the Management of TSE Risk
References
ISO 11137: An Overview on Radiation for Sterilization of Medical Devices and Healthcare Products
1 Introduction
2 Sterilization by Irradiation
2.1 Characterization of the Sterilizing Agent
2.2 Characterization of the Equipment
2.3 Sterilization Process
3 Validation
4 Establishing Sterilization Dose for Irradiation of Products
4.1 Factors Influencing the Bioburden on a Product
4.2 Identifying a Product Family
4.3 Sample Item Portion
5 Determination of Sterilization Dose
5.1 Based on Bioburden Information
5.2 Determination of Dose by Fraction Positive Information from Incremental Dosing
5.3 Determining Sterilization Dose by VDmax: Substantiation of 25 kGy or 15 kGy as the Sterilization Dose
6 Sterilization Dose Audits
7 Dosimetry and Dosage Measurement
7.1 Dosimetry System Selection and Calibration
7.2 Calibration of Dosimetric Systems
7.3 Uncertainty in Dose Measurement
7.4 Establishing the Maximum Acceptable Dose
7.5 Establishing the Sterilization Dose
7.6 Installation Qualification
7.7 Operational Qualification
7.8 Dose Mapping for Gamma Irradiators
7.9 Dose Mapping for Electron Beam Irradiators
7.10 Performance Qualification
Performance Qualification for Irradiators
7.11 Dosimetry Placement
7.12 Replicate Dose Mapping Exercises
7.13 Analysis of Dose Mapping Data
7.14 Routine Monitoring and Control
7.15 Frequency of Dose Measurements
8 Conclusion
References
ISO 11135: Sterilization of Health-Care Products—Ethylene Oxide, Requirements for Development, Validation and Routine Control of a Sterilization Process for Medical Devices
1 Introduction
2 Selection of Sterilization Process
3 Processing Cycle, Temperature, Time and Pressure
4 Routine Control, Efficacy, and Reproducibility
5 Sterility: Post-sterilization Processes
6 Packaging of Sterilized Product
7 Limitations
Bibliography
An Overview on Sterilization of Health Care Products using Moist Heat: ISO 17665
1 Introduction
2 Pre-sterilization
3 Steam Sterilization Process Specifications
4 Sterilizing Agent
5 Equipment Specifications
6 Sterilization Process
7 Product Specifications
8 Validation
9 Sterilization of Packed Devices
10 Indicators for Assuring the Efficacy of Sterilization
11 Assessment of Effectiveness
12 Sterilization of Used Medical Devices
13 Limitations of Steam Sterilization
14 Other Standards and Guidelines
Bibliography
ISO 10993: Biological Evaluation of Medical Devices
1 Selection and Qualification of Reference Materials for Biological Tests (ISO 10993-8)
2 Chemical Characterization of Material (ISO 10993-18)
3 Physicochemical, Morphological and Topographical (PMT) Characterization of Materials (ISO 10993-19)
4 Framework for Identification and Quantification of Potential Degradation Products (ISO 10993-9)
5 Identification and Quantification of Degradation Products from Polymeric Medical Devices (ISO 10993-13)
5.1 The Accelerated Degradation Test
5.2 Real-Time Degradation Test in a Simulated Environment
5.3 Test Report
6 Identification and Quantification of Degradation Products from Ceramics (ISO 10993-14)
7 Identification and Quantification of Degradation Products from Metals and Alloys (ISO 10993-15)
8 Compatibility Testing
8.1 Biocompatibility (ISO 10993)
8.2 Selections of Tests for Interactions with Blood (ISO 10993-4)
Preclinical Evaluation of Cardiovascular Devices and Prostheses
Advantages and Limitations of Animal Models
Advantages and Limitations of In Vitro Models
Recommended Laboratory Tests
8.3 Tests for In Vitro Cytotoxicity (ISO 10993-5)
Tests Used Under In Vitro Cytotoxicity
9 Toxicity Screening
9.1 Sample Preparation and Reference Materials
9.2 Evaluation and Testing Within a Risk Management Process (ISO 10993-1:2009)
9.3 Animal Welfare Requirements (ISO 10993-2)
9.4 Tests for Local Effects After Implantation (ISO 10993-6)
9.5 Tests for Systemic Toxicity (ISO 10993-11)
9.6 Tests for Irritation and Skin Sensitization (ISO 10993-10)
9.7 Principles and Methods for Immunotoxicology Testing of Medical Devices (ISO 10993-20)
9.8 Tests for Genotoxicity, Carcinogenicity and Reproductive Toxicity (ISO 10993-3)
9.9 Toxicokinetic Study Design for Degradation Products and Leachable (ISO 10993-16)
10 Other Frameworks
10.1 Ethylene Oxide Sterilization Residuals (ISO 10993-7)
Determination of EO and ECH Residuals
Factors Influencing Product Residual
10.2 Establishment of Allowable Limits for Leachable Substances (ISO 10993-17)
References
FDA-CFR Title 21-Food and Drugs: Parts 800 to 1299
1 Introduction
2 FDA-CFR Title 21-Food and Drugs: Parts 800 to 1299
2.1 Part 800: General Requirements for Specific Medical Devices [8]
2.2 Part 801: General Labeling Provisions [9]
2.3 Part 803: Medical Device Reporting [10]
2.4 Part 806: Medical Devices, Reports of Corrections and Removals [11]
2.5 Part 807: Establishment Registration and Device Listing for Manufacturers and Initial Importers of Devices [12]
2.6 Part 808: Exemptions from Federal Preemption of State and Local Medical Device Requirements [13]
2.7 Part 809: In Vitro Diagnostic Products for Human Use [14]
2.8 Part 810: Medical Device Recall Authority [15]
2.9 Part 812: Investigational Device Exemptions [16]
2.10 Part 814: Premarket Approval of Medical Devices [17]
2.11 Part 820: Quality System Regulation [18]
2.12 Part 821: Medical Device Tracking Requirements [19]
2.13 Part 822: Postmarket Surveillance [20]
2.14 Part 830: Unique Device Identification [21]
2.15 Part 860: Medical Device Classification Procedures [22]
2.16 Part 861: Performance Standards Development [23]
2.17 Part 862-898: Medical Device Listing and Premarket Approval [7]
Bibliography
EU 1907/2006 – Registration, Evaluation, Authorisation and Restriction of Chemicals
1 Introduction
1.1 Regulation EC 1907/2006
1.2 Establishment of Compliance with REACH Regulation
1.3 Purpose and Scope [1]
2 Registration of Substances [1]
2.1 General Obligation to Register and Information Requirements
2.2 Exemption to Register for Product and Process-Oriented Research or Development (PPORD)
2.3 Information to Be Submitted for General Registration Purposes (Article 10)
2.4 General Requirements for Generating Information on Intrinsic Property of Substances
2.5 Chemical Safety Report and Recommended Risk Reduction Measures
2.6 Data Sharing and Avoidance of Unnecessary Testing
2.7 Registration Process
3 Evaluation [1]
3.1 Dossier Evaluation
Compliance Check of Registrations
3.2 Substance Evaluation
Competent Authority
Follow-up to Substance Evaluation
Adoption of Decisions
Publication of Information on Evaluation
4 Authorization [1]
4.1 Requirement and Considerations for Substitution
4.2 Granting of Authorizations
Review of Authorizations
Applications for Authorizations
Procedure for Authorization Decisions
4.3 Obligation of Holders of Authorizations
5 Restrictions on the Manufacturing, Placing on the Market, and Use of Certain Dangerous Substances, Preparations, and Articles [1]
5.1 General Provisions for Introducing New and Amending Current Restrictions
5.2 Restriction Process
Preparation of Restriction Proposal
Agency Opinion: Committee for Risk Assessment and Socioeconomic Analysis
Submission of an Opinion to the Commission
Commission Decision
6 Reach Safety Data Sheet [1]
Bibliography
EU 1272/2008 – Classification, Labelling and Packaging of Substances and Mixtures
1 Introduction
2 Classification
3 Labelling
4 Packaging [39]
5 C&L Notification and Inventory
6 Safety Data Sheet
Sample Safety Data Sheet
SECTION 1: IDENTIFICATION
SECTION 2: HAZARD(S) IDENTIFICATION
SECTION 3. COMPOSITION/INFORMATION ON INGREDIENTS
SECTION 4: FIRST AID MEASURES
SECTION 5: FIREFIGHTING MEASURES
SECTION 6: ACCIDENTAL RELEASE MEASURES
SECTION 7: HANDLING AND STORAGE
SECTION 8: EXPOSURE CONTROLS/PERSONAL PROTECTION
SECTION 9. PHYSICAL AND CHEMICAL PROPERTIES
SECTION 10: STABILITY AND REACTIVITY
SECTION 11: TOXICOLOGICAL INFORMATION
SECTION 12: ECOLOGICAL INFORMATION
SECTION 13: DISPOSAL CONSIDERATIONS
SECTION 14: TRANSPORT INFORMATION
SECTION 15: REGULATORY INFORMATION
SECTION 16: OTHER INFORMATION
Bibliography
EU 2015/863: Restriction of Hazardous Substances (RoHS) -3
1 Introduction
2 Scope
3 Restriction Through Prevention
4 Adaptation of the Annexes to Scientific and Technical Progress
5 Review and Amendment of the List of Restricted Substances in Annex II
6 Obligations of Manufacturers
7 Obligations of Authorized Representatives
8 Obligations of Importers
9 Obligations of Distributors
10 EU Declaration of Conformity
11 Rules and Conditions for Affixing the CE Marking
12 Formal Objection to a Harmonized Standard
13 Exercise, Revocation, and Objection to Delegation
14 Penalties, Review, Repeal, and Entry into Force
References
EU 722/2012 – Animal Tissue Regulations in Effect for Some Medical Devices
1 Introduction
2 Risk Analysis and Risk Management
2.1 Justification for the Use of Animal Tissues or Derivatives
2.2 Process of Risk Assessment
2.3 Animals as a Source of Material
2.4 Nature of Starting Tissue
2.5 Inactivation or Removal of TSE Infectious Agents
2.6 Review of the Risk Assessment
3 Evaluation by Notified Bodies
3.1 Information of the Notified Body Regarding Changes and New Information
3.2 Renewal of Certificates
3.3 Rigorous Processes for Tallow Derivatives
3.4 Summary Evaluation Report in Accordance with Article 5(4) of Regulation (EU) No 722/2012
Reference
EU 2017/746 – In Vitro Diagnostic Medical Devices
1 Scope
2 Definitions
3 Regulatory Status of Products and Counselling
4 Marketing and Service
5 Identification, Traceability, and Registration of Devices
6 Notified Bodies (Article 31–46)
7 Classification and Conformity Assessment (Article 47–55)
8 Clinical Evidence, Performance Evaluation (Articles 56–77)
9 Post-market Surveillance, Vigilance, and Market Surveillance (Article 78–95)
10 EU Reference Laboratories and Device Registers (Articles 96–101)
11 Confidentiality, Data Protection, Funding, and Penalties (Articles 102–106)
Annexure
Reference
Device Regulations of Other Countries
1 Introduction
1.1 Steps to Import Medical Devices in India
1.2 Steps to Manufacture Medical Devices for Sale or for Distribution
2 China Medical Device Regulations
3 Canada Medical Device Regulations
3.1 General
3.2 Distribution Records
3.3 Complaint Handling
3.4 Mandatory Problem Reporting
3.5 Recall
3.6 Implant Registration
3.7 Custom-Made Devices and Medical Devices to Be Imported or Sold for Special Access
Application
General
Authorization
Additional Information
Labeling
Distribution Records
Reporting an Incident
Implant Registration
3.8 Medical Devices for Investigational Testing Involving Human Subjects
General
Records
Authorization
Additional Information
Labeling
Advertising
Other Requirements
4 New Zealand Medical Device Regulations
4.1 Legislation
4.2 Medicines Act 1981
5 Australia Medical Device Regulations
5.1 The Regulation of Medical Devices
5.2 The Medical Device Classification System
5.3 Conformity Assessment and ARTG Inclusion
5.4 Medical Device Inclusion Process
5.5 Declaration of Conformity Templates (Medical Devices)
5.6 Medical Devices with Predetermined Classifications
Group A
Group B
Group C
Group D
Group E
5.7 Comparable Overseas Regulators for Medical Device Applications
5.8 Varying Entries in the ARTG: Medical Devices and IVDs
5.9 Changing the Sponsor of Therapeutic Goods
5.10 Clinical Evidence Guidelines: Medical Devices
5.11 ARTG Search
5.12 Regulatory Affairs Consultants
5.13 Adverse Event Reporting
5.14 Process of Reporting
5.15 Annual Charge Exemption Scheme
6 Japan Medical Device Regulations
7 Singapore Medical Device Regulations
8 United Kingdom Medical Device Regulations
8.1 The Customer Protection Act from 1987
8.2 The Medical Devices Regulations 2002
8.3 The General Product Safety Regulations 2005
8.4 Failure to Comply with the Regulations
8.5 Inspections
8.6 Appeals Procedure
8.7 Exceptional Use of Noncomplying Devices
8.8 Complaints
9 European Medical Device Regulations
9.1 General Requirements
9.2 Requirements Regarding Design and Manufacture
9.3 Requirements Regarding the Information Supplied with the Device
9.4 Post-market Surveillance
9.5 Cooperation Between Member States, Medical Device Coordination Group, Expert Laboratories, Expert Panels, and Device Registers
9.6 Confidentiality, Data Protection, Funding, and Penalties
References
Index