Genesis Plastics Welding Renée Clinard

1. Genesis Plastics Welding • Renée Clinard Contract Manufacturers’ Regulatory Responsibilities

2. Presentation Overview: About Genesis Choosing a Contract Manufacturer (CM) Responsibilities of a Contract Manufacturer vs. Original Equipment Manufacturer (OEM) Risk Assessment Additional Considerations References: OEM and CM: The Often Unexpected Division of Regulatory Responsibilities by Lianne Coppinger. Medical Product Outsourcing, mdiconsultants.com/publishing/MedProdOutArticle. Page 2

3. About Genesis Provide heat sealing services: • Radio Frequency Welding • Impulse Welding • Ultrasonic Welding ISO 13485 Certified FDA Registered and CGMP compliant Clean room manufacturing • Proprietary technology called ecoGenesis™ • is ideal for the replacement of Polyvinylchloride (PVC). Page 3

4. Is Your Contract Manufacturer ISO Certified?Do they comply with cGMP (Current Good Manufacturing Processes)? Quality Management System: establishes principles, establishes general requirements, defines authority, responsibility and accountability, focuses on making a high-quality device, not just meeting FDA requirements, utilizes prior planning to prevent poor device performance. Good Manufacturing Practices: activities required by the FDA for the use of a quality system in the design, manufacture, packaging, labeling, storage, installation, and servicing of finished medical devices The Contract Manufacturer is responsible for: • Maintaining compliance to FDA guidelines/requirements • Complying with Current Good Manufacturing Practices (cGMP) • Providing training to quality personnel and all other employees • Cleanroom compliance (Example: airborne & surface microbial testing, particle testing & certification from an outside party) ISO & FDA Registered Contract Manufacturers are audited by: • 3rd party ISO organization – 1x per year • FDA – depending upon risk every 2 to 4 years The FDA holds the OEM accountable for ensuring that the activities of the outsourcing partner are compliant. Page 4

5. Cascade of Contract Manufacturer Requirements Page 5

6. Quality Management System(Policy > SOP > WI > Job Aids; Training; Use; Updates) Page 6

7. Risk Assessment: *Ultimately the OEM (Original Equipment Manufacturer) is responsible for the quality, compliance, safety and efficacy of its medical device. The FDA considers the OEM to be the manufacturer even if they do not make product. Page 7

8. Risk Assessment & Controls: By law, FDA regulates medical devices based on the level of risk they pose to patients and users • Review results of both parties risk analysis • Pick appropriate control plan for implementation Examples of process controls: • In-Process Sampling • Reproducibility/Repeatability Study • Process Validation • First Piece Approval • Operator Training • Preventative Maintenance • Temperature Monitoring Page 8

9. OEM / “Specifications Developer” Responsibilities OEM / “Specifications Developer” Responsibilities: Quality System that addresses the applicable QSR (Quality System Regulation) & ISO 13485 Certification Assure that OEM is in FDA compliance when obtaining 510K clearance or pre-market application (PMA) Design Controls • * Confirm that CMis compliant with QSR design controls section 820.30 *if applicable • Bill of Materials • Work Instructions • Assembly Prints • Test Procedures & Records • Purchasing Controls • Device History Record • Define requirements for tests and inspection to be performed by the contract manufacturer. Example: Sampling Plan • Device Master Record • Assessing, selecting and documenting evaluation of a contract manufacturer. • Assure that the medical device is safe, effective and manufactured through compliant production. • Monitor and audit the CM and initiate corrective actions if required. • Complaint handling and Corrective Action Preventative Action procedure (CAPA). • Oversight of critical product realization activities such as: Process FMEA, Risk Assessment, Change • Control and Corrective Action Preventative Action (CAPA). Page 9

10. Contract Manufacturer Responsibilities Contract Manufacturer Responsibilities: Quality System that addresses the applicable QSR (Quality System Regulation) Register with the FDA as a contract manufacturer (if you make the final device and/or distribute the device). Maintain adequate insurance coverage Perform the tests and inspections defined by the OEM pertaining to Device History Record Example: Sampling Plan. Execute the procedures and specifications in accordance with the Device Master Record (DMR). • Complaint handling and Corrective Action Preventative Action procedure (CAPA). Notify the OEM of any past FDA regulatory actions, observations or warning letters. Also, any pending or ongoing FDA investigations. Notify the OEM in writing of any changes in the raw materials, specifications or process prior to making the changes. Notify the OEM immediately if a problem is found concerning all applicable manufacturing process that may affect the finished good. Validate all processes. Validate all software in the operating systems of all applicable manufacturing equipment. Allow the OEM to watch the manufacturing of its device without announcing their visit. Quality Inspection to the sampling plan Documentation Page 10

11. Things To Consider Clinical Trials: *Items must be production-equivalent devices, i.e. made from validated tools • This is the most representative of the final product • Provides traceability (lot #’s and certified materials) • Confirms that quality measures were taken to protect human safety • Quality compliance • Packaging & Labeling flow down requirements: • FDA regulates how the products are represented in product labeling and other promotional & • marketing materials. • Protection of Intellectual Property • Contract Manufacturer’s Responsiveness & Communication • Expertise – Design, Manufacturing, Technology, Supply Chain and Regulatory Compliance Page 11