MDV-Solve Medical Device Consulting Firm GLOBAL REGULATORY AND QUALITY CONSULTING SERVICES FOR MEDICAL DEVICE INDUSTRY

2020

MDV

MDV-Solve Medical Device Consulting Firm --

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Mission is to support the medical device industry up to the applicable local and

global regulatory and quality standards in order to efficiently introduce safe and effective products to both local and global markets.

Global compliance, Fair price

Services

We offer Regulatory and Quality Management System (QMS) consulting services. Our approach is to design, implement and maintain custom-made integrated QMS models in compliance with the local and essential global regulations.

Our service includes creation, update, implementation, and maintenance, verification of effectiveness of the requested sub-systems to build up an integrated QMS, alongside training and auditing.

The services assure compliance with: The local regulation to affix registration number, CE Marking under the Medical Devices Directive (MDD 93/42/EEC) and In Vitro

Diagnostic Device Directive (IVDD 98/79/EC), CE Marking under the new EU MEDICAL DEVICE REGULATION (MDR) Canada Medical Device Regulations (SOR/98-282) cGMP requirements under 21 CFR Part 210 & 211: Pharmaceutical, EudraLex -

Volume 4 - Good Manufacturing Practice (GMP) guidelines Canadian SOR/98-282 Australian Therapeutic Goods Act 1989 Brazilian RDC ANVISA 67/2009 Japanese MHLW Ministerial Ordinance N° 136 “Ministerial Ordinance on

Standards for Quality Assurance for Drugs, Quasi-drugs, Cosmetics and Medical Devices.

MDV-Solve Medical Device Consulting Firm --

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I. THE NEW EU MEDICAL DEVICE REGULATION (MDR)

REGULATION (EU) 2017/745 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC. The new regulation has been published on Official Journal of the European Union (L 117/1) on May 5, 2017. The new rules apply three years after publication date for medical devices and five years after publication for IVDs. The new regulations – which cover not only the design and manufacture of devices, but also clinical testing, authorization and post-market surveillance – have an impact on just about every device manufacturer that sells products in the EU.

The purpose of this training course is to enable you to understand the main points under the new Medical Device Regulation (MDR): 1. Scrutiny procedure for highest risk Medical devices 2. Public transparency on vigilance and clinical investigations 3. CMR substances 4. Medical Device Classification rules 5. UDI 6. Technical documentation 7. QMS 8. Clinical evaluation 9. Risk management 10. Registration of devices and economic operators 11. Economic operators 12. Conformity assessment procedures 13. Liability insurance 14. Post Market Surveillance 15. The various Committees 16. Delegated and Implementing acts

Our services include: Upon completion of this course trainees will: A. be able to understand the basics points of the new EU MDR; B. be able to understand the actual changes of the new EU MDR; C. get familiar with the principles of new EU MDR requirements. D. EU MDR Implementation Consulting and maintenance Gap analysis, design solution (custom made system), standard operating procedures, implementation, training, verification of effectiveness, and follow up, support certification

References Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC

MDV-Solve Medical Device Consulting Firm --

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II. MDSAP PROGRAM

A. The Medical Device Single Audit Program allows an MDSAP recognized Auditing Organization to conduct a single regulatory audit of a medical device manufacturer that satisfies the relevant requirements of the regulatory authorities participating in the program. International partners that are participating in the MDSAP include: FDA medical device quality system regulation Therapeutic Goods Administration of Australia Brazil’s Agência Nacional de Vigilância Sanitária Health Canada Japan’s Ministry of Health, Labour and Welfare, and the Japanese Pharmaceuticals

and Medical Devices Agency The World Health Organization (WHO) Prequalification of In Vitro Diagnostics

(IVDs)Programme and the European Union (EU) are Official Observers References

EN ISO 13485, U.S. FDA Quality System Regulations (21 CFR PART 820), Canadian SOR/98-282, Australian Therapeutic Goods Act 1989, Brazilian RDC ANVISA 67/2009, Japanese MHLW Ministerial Ordinance N° 136 “Ministerial Ordinance on Standards for Quality Assurance for Drugs, Quasi-drugs, Cosmetics and Medical Devices

Medical Device Single Audit Program (MDSAP) Fundamentals and Readiness Training Course

MDSAP - Basic Terms and Concepts Back Ground Applicable Regulation & Guidance Standards Content of MDSAP program and audit

Main differences in your current audits and audits conducted under MDSAP Prepare you to host a MDSAP audit

Our services: A. MDSAP Training for Medical Device Companies This training is conducted on-sites. The training session tailored to the needs of your organization regarding this sub-system.

B. MDSAP Auditing for Medical Device Companies Full or partial internal PMS audit. We provide internal auditing services which allow for an independent review of this part of your quality system. C. MDSAP - System Implementation Consulting and maintenance Gap analysis, design solution (custom made system), standard operating procedures, implementation, training, verification of effectiveness, and follow up.

MDV-Solve Medical Device Consulting Firm --

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III. - GMP QUALITY SYSTEM UNDER EN ISO 13485, US FDA QSR

Medical device manufacturers must establish their quality systems in compliance with the appropriate regulations and standards. Failure to do so can result in poor product quality, loss of certification or lack of process improvement. Our services assist Medical device companies to establish, update, and maintain Quality Management System including GMP (Good Manufacturing Practice) in compliance with the local regulation, FDA Quality System Regulation (FDA QSR), European Device Directives, ISO 13485, and Canadian Medical Device Regulations (CMDR).

The purpose is to enable you to establish and implement an effective tailored QMS system including GMP requirements:

Overview of the standard and the implications to your company. Benefits of adopting the standard and regulatory requirements. Why the process approach makes sense. Setting objectives and defining responsibilities. Who needs to be involved within the company. The responsibility of senior management. Role of design and development, purchasing, production, record keeping, customer

communications. Maintaining effectiveness of the quality system, how and why. Process validation, monitoring and traceability, control of measurement devices and

data analysis.

Our services include: A. EN ISO 13485 Training for Medical Device Companies This ISO 13485 training is conducted on-sites. The training session tailored to the needs of your organization.

B. EN ISO 13485 Auditing for Medical Device Companies Full or partial internal audit - ISO and FDA QSR (GMP). We provide internal auditing services which allow for an independent review of your full quality system. C. EN ISO 13485 Quality System Implementation Consulting and maintenance Gap analysis, design solution (custom made system), standard operating procedures, implementation, training, verification of effectiveness, and follow up.

References EN ISO 13485, U.S. FDA Quality System Regulations (21 CFR PART 820), EU Medical Device Directive (MDD 93/42/EEC) and new EU MDR , Canada Medical Device Regulations (SOR/98-282), local regulation.

MDV-Solve Medical Device Consulting Firm --

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IV. DESIGN CONTROL UNDER EN EN ISO 13485 & 21 CFR PART 820

Design controls are a component of a quality system that covers the life cycle of a device to ensure that specified design requirements are met and the device will reach an acceptable level of efficacy and safety. Design control begins with development and approval of device design inputs, includes the design activities and the associated manufacturing processes. Design control applies to all changes to the device design or manufacturing process, including those occurring long after a device has been introduced to the market.

References EN ISO 13485, U.S. FDA Quality System Regulations (21 CFR PART 820), EU Medical Device Directive (MDD 93/42/EEC) and new EU MDR , Canada Medical Device Regulations (SOR/98-282), local regulation.

The purpose is to enable you to establish and implement a system for design controls for various classes of medical devices for local market, the U.S. and Europe. Practical exercises will be used to ensure good understanding. Procedures and forms will be provided to implement a full design control system including :

Basic Terms and Concepts — The need for design controls Design Planning & Development Design Input Design Output Design Verification Design Review Design Validation Design Changes Design Transfer Design History File

Our services include: A. Design Control Training for Medical Device Companies This training is conducted on-sites. The training session tailored to the needs of your organization regarding this sub-system.

B. Design Control Auditing for Medical Device Companies Full or partial internal Design control audit - ISO and FDA QSR. We provide internal auditing services which allow for an independent review of this part of your quality system. C. Design Control - System Implementation Consulting and maintenance Gap analysis, design solution (custom made system), standard operating procedures, implementation, training, verification of effectiveness, and follow up.

MDV-Solve Medical Device Consulting Firm --

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V. APPLICATION OF RISK MANAGEMENT TO MEDICAL DEVICES

Risk management is considered to be an essential requirement for medical devices under Medical Device Directive, ISO13485 and FDA Quality System Regulation (QSR). EN ISO 14971: Application of risk management to medical devices Has been formally recognized by FDA and by Health Canada; the European Union has adopted it as a harmonized standard; Japan has designated it as a Japanese Industrial Standard; and Australia has made it their "de facto" standard for risk management. Purpose is to determine the possible risks associated with the use of a medical device in order to anticipate the design, manufacturing, inspection, controls and/or labelling indications required to reduce the risk of product failure for the end-user and patient as low and as far as possible. Risk management can promote innovation, leading to a reduction in the number of customer complaints, lowered service and support costs, fewer disruptions from field actions

References EN ISO 14971 standard and FDA’s guidance documents on Human Factors Engineering. The International Medical Device Regulators Forum (IMDRF) GHTF/SG3/N99 & GHTF/SG3/N15R8, local regulation.

This sub-system is intended to assist medical device manufacturers with the integration of a risk management system into their existing quality management system. The session details the use of risk management in the life cycle of medical device including the use of the ISO 14971 standard and FDA’s guidance documents on Human Factors Engineering to provide a clear understanding of what techniques to use and when they should be implemented. Practical workshop activities on use of risk analysis techniques. Procedures and forms will be provided.

What is risk management - Basic Terms and Concepts Risk management process flow Risk analysis techniques

Fault Tree Analysis (FTA), Failure Modes Effect Analysis (FMEA) Incorporation of Risk analysis in device life cycle

Our services: A. Risk Management Training for Medical Device Companies This training is conducted on-sites. The training session tailored to the needs of your organization regarding this sub-system.

B. Risk Management Auditing for Medical Device Companies Full or partial internal Risk Management audit - ISO and FDA QSR. We provide internal auditing services which allow for an independent review of this part of your quality system. C. Risk Management - System Implementation Consulting and maintenance Gap analysis, design solution (custom made system), standard operating procedures, implementation, training, verification of effectiveness, and follow up.

MDV-Solve Medical Device Consulting Firm --

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VI. PROCESS VALIDATION INCLUDING SOFTWARE – TEST METHOD VALIDATION –

CLEAN ROOM VALIDATION

Process Validation is required according to: 11 CFR Part 820.75, 11 CFR Part 820.70 (software validation), EN ISO 13485 (7.5.2). Where the result of a process cannot be fully verified by subsequent inspection and test, the process shall be validated with a high degree of assurance and approved according to established procedures. Establish documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality attributes.

References 11 CFR Part 820.75, 11 CFR Part 820.70 (software validation), EN ISO 13485 (7.5.2), local regulations.

This sub-system is intended to assist medical device & pharmaceutical manufacturers with implementation of process validation system including Installation Qualification (IQ), Operational Qualification (OQ), and Performance Qualification (PQ): establishing by objective evidence that the process, under anticipated conditions, consistently produces a product which meets all predetermined requirements.

Sample procedures and forms Conduct of a validation Getting started Protocol Development Installation Qualification (IQ) Operational Qualification (OQ) Performance Qualification (PQ) Maintaining a state of validation

Our services: A. Process Validation Training for Medical Device Companies This training is conducted on-sites. The training session tailored to the needs of your organization regarding this sub-system.

B. Process Validation Auditing for Medical Device Companies Full or partial internal Process Validation audit - ISO and FDA QSR. We provide internal auditing services which allow for an independent review of this part of your quality system. C. Process Validation - System Implementation Consulting and maintenance Gap analysis, design solution (custom made system), standard operating procedures, implementation, training, verification of effectiveness, and follow up.

MDV-Solve Medical Device Consulting Firm --

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VII. THE LITERATURE ROUTE FOR CLINICAL EVALUATIONS

Clinical evaluation is the assessment and analysis of clinical data pertaining to a medical device in order to verify the clinical safety and performance of the device according to the relevant annexes of the Medical Devices Directives and by the MOH charged with safeguarding public health.

References Medical Device Directive (MDD 93/42/EEC) new EU MDR, MEDDEV 2.7/1 rev.4, The IMDRF SG5/N2R8, local regulation, EUM MDR.

This sub-system provide a practical solution on evaluation of clinical data as a necessary part of the European technical file or design dossier for CE marking medical devices and local regulation. This part focuses on the literature route for providing clinical data. Sample procedures and forms will be provided.

Clinical Evidence - Basic Terms and Concepts Back Ground Applicable Regulation & Guidance Standards Clinical Literature Review Process Stages

General principles of clinical evaluation Data generated through literature searching Data generated through clinical experience Appraisal of clinical data Analysis of the clinical data The Clinical Evaluation Report

Our services: A. Clinical Evaluation Training for Medical Device Companies This training is conducted on-sites. The training session tailored to the needs of your organization regarding this sub-system.

B. Clinical Evaluation Auditing for Medical Device Companies Full or partial internal Clinical Evaluation Validation audit. We provide internal auditing services which allow for an independent review of this part of your quality system. C. Clinical Evaluation - System Implementation Consulting and maintenance Gap analysis, design solution (custom made system), standard operating procedures, implementation, training, verification of effectiveness, and follow up.

MDV-Solve Medical Device Consulting Firm --

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VIII. POST-MARKET SURVEILLANCE

A well functioning vigilance system is the 'backbone' of a robust regulatory framework in this sector because complications with medical devices that are designed to be implanted or to operate for many years or even decades might come to light only after a certain period of time. Therefore, PMS is an obligation in local and global regulations.

References EN ISO 13485, U.S. FDA Quality System Regulations (21 CFR PART 820), EU Medical Device Directive (MDD 93/42/EEC) & New EU MDR, Canada Medical Device Regulations (SOR/98-282), local regulation, EU MDR PMS Chapter VII.

This sub-system provide a practical solution on establishment and implementation of Post-Market Surveillance (PMS) to review experience gained from devices in the post-production phase and to implement appropriate means to apply any necessary corrective action.

Post-Market Surveillance (PMS) - Basic Terms and Concepts Back Ground Applicable Regulation & Guidance Standards Post-Market Surveillance (PMS):

o Complaint handling system o Vigilance reporting system (incidents and Field Safety corrective Actions-FSCA) o PMS methodology for data analysis, trending o Integration of PMS in the risk management process o Corrective action for safety and improvement o Use of PMS data for innovation and device improvement

Our services: A. Post-Market Surveillance (PMS) Training for Medical Device Companies This training is conducted on-sites. The training session tailored to the needs of your organization regarding this sub-system.

B. Post-Market Surveillance (PMS) Auditing for Medical Device Companies Full or partial internal PMS audit. We provide internal auditing services which allow for an independent review of this part of your quality system. C. Post-Market Surveillance (PMS) - System Implementation Consulting and

maintenance Gap analysis, design solution (custom made system), standard operating procedures, implementation, training, verification of effectiveness, and follow up.

MDV-Solve Medical Device Consulting Firm --

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IX. GOOD MANUFACTURING PRACTICE (CGMP)

A GMP is a system for ensuring that products are consistently produced and controlled according to quality standards. It is designed to minimize the risks involved in any pharmaceutical production that cannot be eliminated through testing the final product. GMP covers all aspects of production from the starting materials, premises and equipment to the training and personal hygiene of staff. Detailed, written procedures are essential for each process that could affect the quality of the finished product. There must be systems to provide documented proof that correct procedures are consistently followed at each step in the manufacturing process - every time a product is made.

The purpose is to enable you to establish and implement an effective tailored cGMP system in line with requirements:

Quality Systems Documentation Good Documentation Practices Personnel Premises and Equipment Facilities and Equipment Systems Materials Systems Production Systems Packaging and Labeling Systems Laboratory Control Systems Complaints and Recalls

Our services include: Upon completion of this course, trainees will: E. be able to understand the basics of Good Manufacturing Practice for medicinal

products for human use and the current legal regulations and guidelines; F. have the confidence to outline the main GMP requirements; G. get familiar with the principles of the GMP quality system and quality control and the

important procedures when dealing with complaints and recalls. H. Implementation Consulting and maintenance Gap analysis, design solution (custom made system), standard operating procedures, implementation, training, verification of effectiveness, and follow up, support certification

References 21 CFR Part 210 & 211: Pharmaceutical EudraLex - Volume 4 - Good Manufacturing Practice (GMP) guidelines