Development and Regulation of Medical Products (MEDR-101)

1. Development and Regulation of Medical Products(MEDR-101) Prof. Moustafa M. Mohamed Vice dean Faculty of Allied Medical Science Pharos University in Alexandria

2. Medical Device Design Controls • Introduction to the Food and Drug Administration (FDA) • Definitions • Classes of devices • Design control overview • Risk assessment • Verification and Validation testing • Software Quality Assurance • Labeling • Post design transfer issues

3. FDA Oversight in a Medical Device Life Cycle FDA review Research Design and Development • Good Clinical Practice • Clinical Trial Controls • Good Laboratory Practice • Investigational Devices Exemptions (IDE’s) • 510(k) Clearance • Produce Marketing Association (PMA) • Document Controls • Design Controls • Good Lab Practices • Document Controls • Electronic Records Manufacture and Service Obsolescence • Recalls • Complaints • Medical Device Reporting • Quality Systems Requirements • Establishment Registration • Labeling Controls • Design controls Record Retention

4. Intended use Product Class • Class I-Simple, Low risk. • General controls needed (registration, labeling, GMP) • Class II- More complex, Medium risk. • Need approval (some exemptions ) • Class III- Complex, High risk. • Generally life support, life sustaining, preventing impairment to human health or unreasonable risk to human life. Premarket Approval (PMA) needed prior to market.

5. Requirements • All Class II and Class III devices, and some Class I devices require design controls. • Written procedures required. Procedures are controlled via document control. • Information about the design must be readily available to Food and Drug Administration FDA – Design History Files. • Design controls can continue through the manufacturing and service phase.

6. Examples

7. Quality System A Medical Device Quality System is designed to assure that products areSafe and Effectivefor their Intended Use and Consistently meet the specifications as defined by results of clinical and/or detailed technical design and validation

8. Design Process of Medical Equipment

9. Design Control Elements • Design Planning • Design Input (Requirements) • Design Output (Specifications) • Design Reviews (Technical) • Design Verification (Meets Specifications) • Design Validation (Meets clinical needs) • Design Transfer (Moves from Design to Manufacturing) • Design Changes (Formal Process) • Design History File (DHF)

10. Design Planning • Feasibility Studies • Risk Assessments • Project Plan Defines Interfaces with Others • Stage-Gate Methodology • Constantly Changing

11. Design Input-Feasibility • Where • Customers • Technical Papers • Medical experts • Service people • What • Intended Use • Technical Requirements • Safety Issues • How • Documented • Approved • Filed • Formal Change Control System

12. Risk Assessment

13. Definitions • Harm: Physical injury or damage to the health of people, or damage to property or the environment • Hazard: Potential sources of harm • Risk: Combination of the probability of Occurrence of Harm and the Severity of the harm • Risk Analysis: Systematic use of available information to identify hazards and estimate the risk • Residual Risk: Risk remaining after protective measures and mitigations are taken • Severity: A measure of the possible consequences of the risk • As Low As Reasonably Practicable (ALARP): The residual risk is reduced to a level which is as low as can be reasonable implemented without sacrificing patient safety or clinical utility. The risk/benefit ratio is determined to be acceptable in light of technical feasibility and economic feasibility of implementing additional controls.

14. Design Output • Final design specifications • Quantitative • Documented • Approved • Final specifications are contained in the design history file. • Final risk assessments completed. • Clinical testing may be needed.

15. Design Reviews • Formal Process • Required for Phase Approval • Checklists • Minutes • Attendees- one not associated with items reviewed • Areas covered • Action items/open issues • Open items closed for final release • Formal design review prior to release for manufacture and distribution

16. Design Verification and Validation • Demonstrates that all the risks have been mitigated. • Demonstrates that specifications have been met. • Uses a trace matrix between risk assessment, specs and V&V plans. • Clinical trials may be needed to demonstrate safety and/or effectiveness.

17. Design Verification And Validation • Verification - meets specification • Validation - meets intended use • Written procedure required. • Testing must be documented, reviewed and approved. • Software must be verified and validated. • Manufacturing processes must be verified and validated.

18. Design Transfer • Design moves from R&D to manufacturing • Manufacturing and production specifications are documented • Manufacturing risk assessment may be needed • Manufacturing IQ, OQ, PQ • IQ - Installation Qualification (Equipment) • OQ - Operational Qualification( 1st ones meet specs) • PQ - Performance Qualification (Consistently repeatable)

19. Design Changes • All changes to the design after release must be formally controlled (Change Control). • Re-validation may be needed • Continues for the life of product. • Documentation control system is necessary.

20. Labeling 21 CFR 801 • Section 201(k) defines "label" as a: "display of written, printed, or graphic matter upon the immediate container of any article..." The term "immediate container" does not include package liners. Any word, statement, or other information appearing on the immediate container must also appear "on the outside container or wrapper, if any there be, of the retain package of such article, or is easily legible through the outside container of wrapper." • Section 201(m) defines "labeling" as: "all labels and other written, printed, or graphic matter (1) upon any article or any of its containers or wrappers, or (2) accompanying such article" at any time while a device is held for sale after shipment or delivery for shipment in interstate commerce.

21. Rx Medical Device Labeling • Intended Use • Indications for Use • Contraindications for Use • Warnings, Cautions • Description of the Device • User Instructions • Specifications • Corrective Actions (Troubleshooting)

22. Labeling Verification • Labeling must be verified prior to FDA review and product release. • Users should also review labeling. • Risk assessment “labeling” mitigations must appear as warnings or cautions.

23. Design History File • Record of the Development Process • Plans • Specifications • V&V Test Results • Design Reviews • Changes to the Design

24. Class Exercise-Design Controls Dr. Bright and Dr. Idea have found a novel way to produce a machine to determine if a heart attack patient has additional blockage in the coronary arteries that may be caused by the surgical bypass procedure (CABG). The machine non-invasively measures arterial flow by using Doppler sonar to determine if the arteries are blocked. It can be used in a patient’s home, by itself, on post heart attack patients who may be at risk for additional heart attacks. It transfers the data to a monitoring station at a EMS facility for 24/7 monitoring. They have formed a company (The Bright-Idea Company), built a prototype and tested it in the lab on sheep and pigs. It worked great. Now they want to begin marketing it for use on humans. • Is the machine a medical device? • What steps should Dr. Bright and Dr. Idea take before they can begin marketing the machine? • What documents do they need to have on file?

25. Questions