FDA Regulatory review in Minutes: What Product Development Executives Need-to-Know. Specifically, frequent causes of recalls and related areas that investigators review. LCDR Stephen Smith FDA Medical Device Investigator 1

Overview RECALLS – Definition, process, audits Design Controls Purchasing Controls – Suppliers contracts, initial evaluations, annual audits Acceptance Activities Non- Conformances 2

What is a Medical Device Recall A recall is an action taken to address a problem with a medical device that violates FDA law. Recalls occur when a medical device is defective, could be a risk to health, or both defective and a risk to health. A recall does not always mean that you must stop using the product or return it to the company. A recall sometimes means that the medical device needs to be checked, adjusted, or fixed. If an implanted device (pacemaker/artificial hip) is recalled, it does not always have to be removed.

Examples of the types of actions that may be considered recalls: Inspecting the device for problems Repairing the device Adjusting settings on the device Re-labeling the device Destroying device Notifying patients of a problem Monitoring patients for health issues 4

Recall Process 5

Distinguishing Medical Device Recalls from Enhancements tionandguidance/guidancedocuments/ucm pdf tionandguidance/guidancedocuments/ucm pdf New Guidance issued on October 15, 2014 Quick read, 10 pgs. long. 6

Distinguishing Medical Device Recalls from Enhancements The guidance contains clear definitions and practical examples to help manufacturers distinguish a recall from an enhancement. Clarifying when a change to a device represents a recall or an enhancement will help manufacturers better understand when reporting device changes to the FDA is required. 7

Who are your Resources? 8

Additional Guidance 21 CFR Part 7 - Subparts A and C - Recalls - General guidelines 21 CFR Part 7 21 CFR Part Medical Device Corrections and Removals 21 CFR Part 806 – Do you have a plan, a procedure? FD&C Act, 518(e) - Mandatory Device Recalls PHS Act - 42 U.S.C Mandatory recall of biological products 9

Recall Process 10

FDA Recall Audit Checks We randomly go to hospital, clinics and distribution sites where your product was sent. We ask to see when and if your recall Notifications were received (Recall monitor). We physically check their shelves for product and ask them remove and process it if they didn’t. We review their responses, actions and timeliness. We evaluate if the audit was effective. 11

Recall Classes defined: 12

New England Recalls… Why so many? January 1, December 31,

Medical Device Recall Report FY 2003 to FY 2012 Why the increase? – CDRH efforts to improve Medical Device safety – Cites for reporting violations – Enhanced awareness by device firms Most Frequent Causes – 1. Device Design, 2. Software – 3. Non-conforming material or component issues – (Not far behind) – Receiving and Labeling 14

Design Control The preamble, states, “Since early 1984, FDA has identified lack of design controls as one of the major causes of device recalls… unless appropriate design controls are observed during preproduction stages of development, a finished device may be neither safe nor effective for its intended use.” (Federal Register/Vol. 61, No. 195/Monday October 7, 1996) 15

Evaluating the most common cause of Recall - Software Software may be in a medical device, May be itself a medical device, May be used to manufacture a medical device Failure to implement software design controls, and where proper, testing procedures, as well as increasing complexity of the medical device use environment, can lead to software anomalies often requiring correction/removal 16

Design Control 21 CFR Design Validation: (g) – Each manufacturer shall establish/maintain procedures for validating the device design. Design validation shall include software validation/risk analysis, where appropriate. The results of the design validation, including identification of the design, method(s), the date and the individual(s) performing the validation, shall be documented in the DHF. 17

From Design to Production The Quality System Inspection Technique a.k.a.(QSIT) – One way to inspect a firm with a focus on key elements (Management, Design, Production & Process Controls and CAPA) – It provides an alternative order to 21 CFR 820 – It is a guidance document. 18

Purchasing Controls (21 CFR ) – Supplier contracts, initial & annual audits Each manufacture shall establish and maintain procedures to ensure that all purchased or otherwise received product and services conform to specified requirements. (a) Evaluation of Suppliers, Contractors, and Consultants (SC&C). Each manufacturer shall establish and maintain the requirements, including quality requirements, that must be met by (SC&C). 19

Purchasing Controls (21 CFR ) – Supplier contracts, initial & annual audits Each Manufacturer Shall: 1.Evaluate & select potential Suppliers, Contractors, and Consultants on the basis of their ability to meet specified requirements. Evaluation shall be documented. 2.Define the type and extent of control to be exercised over the product, services, SC&C, based on the evaluation results. 20

Purchasing Controls (21 CFR ) – Supplier contracts, initial & annual audits 3. Establish/maintain records of acceptable Suppliers, Contractors, and Consultants (b) Purchasing data. Manufacturer shall establish & maintain data that clearly describe or reference the specified requirement, including quality requirement, for purchased or otherwise received product and services. 21

Purchasing Controls (21 CFR ) – Supplier contracts, initial & annual audits Purchasing document shall include where possible, an agreement that Suppliers, Contractors, and Consultants agree to notify the manufacturer of changes in the product or services. 22

Acceptance Activities The Receiving Inspection is the first line defense to protecting your manufacturing process. People responsible for ensuring parts are passing required specifications are the ones who get first shot at stopping a recall before it happens... 23

Acceptance Activities Where are we finding issues… Receiving, in-process, and finished device acceptance (b) “… Incoming product shall be inspected, tested or otherwise verified as conforming to specified requirements (C) & (D) In-process acceptance activities and final acceptance activities. 24

Non-Conformances (a) Control of Non-conforming Product Each manufacturer shall establish and maintain procedures to control product that does not conform to specified requirements. The procedures shall address the identification, documentation, evaluation, segregation, and disposition of nonconforming product. 25

Non-Conformances The evaluation of non-conformances shall include a determination of the need for an investigation and notification of the persons or organizations responsible for the non- conformance. The evaluation and any investigation shall be documented. 26

Non-Conformances (b) Non-conformity review/disposition (b)(1) Each manufacturer shall establish and maintain procedures that define the responsibility for review and the authority for the disposition of non-conforming product. 27

Almost the Conclusion “The average number of days it takes for pre- market review of a new medical device has been reduced by about one-third since The % of pre-market approval (PMA) device applications that we approve annually has increased since then”. Margaret A. Hamburg, M.D. (2015) Commissioner of Food and Drugs 28

Conclusion ( part 1) Analysis of recall data can help us understand common causes of device failures. Review of the Recall process, who to call, and new guidance to differentiate recalls from enhancements will help new device firms. Understanding an inspectors approach to the common causes of device failures will provide a preview as to what to expect. 29

Conclusion ( part 2) We continue to see greater reporting by industry. We continue to see a more concerted effort by CDRH and industry working together to improve the quality and safety of medical device (efficiency of communication and time) I thank you for your time and do you have any QUESTIONS??? 30