with Audrey Turley, B.S., RM (NRCM), CBA (ASQ) How to Develop a Risk Based Biological Safety Evaluation Per New US FDA Guidance Day 3: Summarize all your findings in a Biological Evaluation Report (BER) with Audrey Turley, B.S., RM (NRCM), CBA (ASQ) Research Scientist

BIOLOGICAL SAFETY EVALUATION BEP: What are your risks and how do you plan to mitigate them? Testing and risk assessments BER: Is the device safe?

WEBINAR SUMMARY DAY 1 – Biological Evaluation Plan (BEP) Assessing your biocompatibility is not a checklist approach! Send BEP to regulatory bodies BEFORE you begin.

WEBINAR SUMMARY DAY 2 – Understanding Test Options Know your material, perform useful E&L testing and follow up with a risk assessment. ISO 10993-1:2009 - Figure 1

STANDARDS FOR PRESENTATION ISO 10993-1: 2009 “Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process”. US FDA guidance document “Use of International Standard ISO 10993-1, ‘Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process’” issued June 16, 2016.

STANDARDS FOR PRESENTATION Agency advises to start using this now as most submissions will not be complete before the effective date of September 14, 2016. The link to the document is here.

What is a Biological Evaluation Report? ANSWER A BER is a summary of all the evidence gathered to support the biological safety of a device. Requested in US FDA guidance document ISO 10993-1 Clause 7 and Annex B

Why do I need a BER? 3) BER If conclusion = “device is safe”, then 1) BEP 2) Testing/risk assessments

Why can’t I just submit all my testing reports? Implant device Predicate device E&L testing Tox Risk Assessment Cytotoxicity, irritation, sensitization Particulate testing Biological Risk Assessment

What should a BER contain? ISO 10993-1 clause 7: “Interpretation of biological evaluation data and overall biological safety assessment” a) “the strategy and program content for the biological evaluation of the medical device;” BEP b) “the criteria for determining the acceptability of the material for the intended purpose, in line with the risk management plan;” Internal documentation from R&D

What should a BER contain? c) “the adequacy of the material characterization;” If used to justify out of testing Well characterized material Novel material/process

What should a BER contain? d) “the rationale for selection and/or waiving of tests;” BEP e) “the interpretation of existing data and results of testing;” Address any unusual findings

What should a BER contain? f) “the need for any additional data to complete the biological evaluation;” Extended evaluations, change in standards, etc. g) “overall biological safety conclusions for the medical device.” Have all the risks been mitigated?

Can I Write a BER myself? Yes Ensure that all the points in clause 7 are included. FDA guidance document, Attachment C

Summary of 7 points (a-g) a) Strategy to assess device. What was the BEP? b) Justification for materials used c) Was the material characterization adequate? d) Rationale for selection/waiving of tests e) Data review and interpretation f) Was everything covered? g) Is the device safety well supported?

Can I Write the BER myself? A few things to keep in mind… ISO 10993-1 states that “Expert assessors..” should review the findings and make an overall conclusion. Outside perspective Help with the submission process if it comes back

What does Nelson offer in a BER? BACKGROUND Reason for testing Device Company a) Strategy to assess device. What was the BEP?

What does Nelson offer in a BER? DEVICE DESCRIPTION What is it used for Where in the body is it used Target population b) Justification for materials used

What does Nelson offer in a BER? a) Strategy to assess device. What was the BEP? d) Rationale for selection/waiving of tests DEVICE CATEGORIZATION ISO 10993-1:2009 Device contact Biological considerations Duration

What does Nelson offer in a BER? COMPONENTS AND MATERIALS Material biocompatibility data COAs Suppliers b) Justification for materials used

What does Nelson offer in a BER? TESTING SUMMARY Tests performed Laboratory Standards followed Study numbers Results Abnormal results c) Was the material characterization adequate? e) Data review and interpretation f) Was everything covered?

What does Nelson offer in a BER? c) Was the material characterization adequate? e) Data review and interpretation f) Was everything covered? RISK ASSESSMENT DISCUSSION Biological Risk Toxicological Risk

What does Nelson offer in a BER? CONCLUSION The device is considered biocompatible. The device is safe for only the following populations… There are remaining areas of risk that need to be addressed. g) Is the device safety well supported?

What if… …I didn’t have a BEP? … the testing was done over several years? …the device has gone through several design changes since the testing? …we’re putting this all together as an afterthought?

Example Projects Catheter family Latex gloves List all components and justify the use of a representative sample Latex gloves Failing cytotoxicity results Kit with several components purchased at separate facilities Failing cyto results on one component New catheter Predicate device from same manufacturer but shorter in length

BIOLOGICAL SAFETY EVALUATION BEP: What are your risks and how do you plan to mitigate them? Testing and risk assessments BER: Is the device safe?

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