Confronting MedTech Start-Ups Three Biggest Challenges: Initiating Regulatory & Quality

Transcription

1 Confronting MedTech Start-Ups Three Biggest Challenges: Initiating Regulatory & Quality April 27 th, 2018 Carol C. Ryerson, Ph.D. Sr. Principal Advisor

2 Three Biggest Challenges for MedTech Start-ups Reimbursement Reg & Quality IP 2

3 Agenda Initiating Regulatory & Quality Your Device FDA Overview Regulatory & Quality Considerations FDA Submissions 3

4 4 What is your Device?

5 Device Description The Device Description is KEY: Is it a medical device? What is the intended use and indications for use (i.e. intended users, patient populations) What components does it have? How does it work to achieve it s function? How does it work to generate a result? What are the limitations of the technology? Does it include software? 5

6 Intended Use/ Indications for Use Intended use what does the device do? Therapeutic Surgical Diagnostic Indications for use what are the clinical indications claimed for your device? Patient population Intended users/ environment 6

7 Intended use examples 23andMe Genetic Health Risk for Consumers: The 23andMe Personal Genome Service (PGS) Test uses qualitative genotyping to detect the following clinically relevant variants in genomic DNA isolated from human saliva collected from individuals >18 years with the Oragene Dx model OGD for the purpose of reporting and interpreting Genetic Health Risks (GHR): for Late-onset Alzheimer s Disease is indicated for reporting of the e4 variant in the APOE gene. The report describes if a person s genetic result is associated with an increased risk of developing Late-onset Alzheimer s Disease, but it does not describe a person's overall risk of developing Alzheimer s Disease. 7

8 Intended use examples Companion Diagnostic: Foundation One CDx [Foundation Medicine Inc.] designed to detect genetic mutations in 324 genes in any solid tumor. used to identify patients who may benefit from treatment with targeted therapies including Herceptin (trastuzumab) 8

9 US FDA Overview EU/ Canada: ISO 13485/ MDSAP Process approach Requirements, Feedback, Resource Management, Business Objective Continuous Feedback Loop FDA Device Classification Regulations Submissions: 510(k)/PMA/ De novo Special Controls Guidance Consensus Standards FDA: 21CFR820 Series of 7 subsystems Design, Manufacture, Packaging, Labeling, Storage, Installation, Servicing Top-down linkage of key subsystems used in FDA inspections 9

10 US FDA Overview: User Fees MDUFA Medical Device User Fee Amendments Registration and listing provides FDA with the location of medical device establishments and the devices manufactured at those establishments. Owners or operators of places of business that are involved in the production and distribution of medical devices in the U.S. are required to register annually with the FDA. Establishment Registration fee: $ (k): $10,566 ($2,642 small business) PMA: $310,764 ($77,691 small business) De Novo: $93,229 ($23,307 small business) 10

11 US FDA Overview: User Fees Registration and listing by activity performed. Activity Register List Pay Fee Contract manufacturer (including contract packagers) YES YES YES Contract sterilizer YES YES YES Device being investigated under IDE NO NO NO Domestic Distributor that does not import devices NO NO NO Initial Importer YES NO YES Manufacturer of accessories or components YES YES YES Manufacturer YES YES YES Refurbishers or remarketers of used devices NO NO NO Relabeler or Repackager YES YES YES Remanufacturer YES YES YES Reprocessor of single use devices YES YES YES Specification Developer YES YES YES U.S. Manufacturer of export only devices YES YES YES Wholesale distributor that is not a manufacturer or importer NO NO NO 11

12 US FDA: Quality Trends FY2017 Top Ten inspection observations Short Description Frequency 21 CFR (a) Lack of or inadequate procedures CFR (a) Lack of or inadequate complaint procedures CFR Purchasing controls, Lack of or inadequate procedures CFR (a) Lack of or inadequate process validation CFR Lack of Written MDR Procedures CFR (a) Nonconforming product, Lack of or inadequate procedures CFR (b) Documentation CFR (i) Design changes - Lack of or Inadequate Procedures CFR Quality audits - Lack of or inadequate procedures CFR (d) Lack of or inadequate final acceptance procedures 67 12

13 21 CFR 820 QSR Where to start? Document Control (820.40) Design Control (820.30) Supplier/ Purchasing Control (820.50) Risk Management (ISO 14971:2012) 13

14 Why is a Quality System important? Documentation most of your communication with FDA will be written. It is essential to establish control of versions of documents. It also saves time. Design control the FDA submission will need to include data on the final version of the device. Keep track of the versions tested during development to avoid costly re-testing. Supplier control establish early to insure consistent supply throughout development and shelf life Risk management do your homework to identify risks before contacting FDA 14

15 US FDA: Regulatory Trends Pre-submission Process De Novo pathway Breakthrough Device Program FDA - CMS Parallel Review IVD guidance documents Software/ Cybersecurity Increased emphasis on complete product life-cycle 15

16 US FDA: Clinical Trends Acknowledgement of the potential to use OUS Data Need for greater Sub- Population considerations in data analysis Risk-Benefit Considerations Human Factors/Usability 16

17 FDA Submissions Tips for Success Good science, data supports conclusions Supportable intended use/ indications for use Excellent organization: Complete device description Comprehensive analytical validation (or other nonclinical studies as applicable) Appropriate clinical validation Complete software validation (as applicable) Clear and truthful labeling ecopy, forms and fees (as applicable) 17

18 Content of Software Device Submissions Software Description Device Hazard Analysis Cybersecurity Software Requirements Specifications Architecture Design Chart Software Design Specification Traceability Analysis Software Development Environment Description Verification and Validation Documentation Revision Level History Unresolved Anomalies FDA Guidance: 1. Content of Premarket Submissions for Software Contained in Medical Devices 2. Content of Premarket Submissions for Management of Cybersecurity in Medical Devices 3. Cybersecurity for Networked Medical Devices Containing OTS Software 18

19 Pre-clinical and Clinical Studies IVDs Analytical Performance Clinical Performance Medical Devices Biocompatibility Bench testing Extractable/leachable evaluation Animal studies Human clinical studies 19

20 US FDA Submissions Basic Components Intended use/ indications for use Device description Analytical/ non-clinical performance Clinical performance Biocompatibility (as applicable) Animal studies (as applicable) Sterility; Shelf Life; Stability (as applicable) Instrumentation, software validation (as applicable) Labeling (package insert; user manual) For PMA manufacturing, design controls, QSR, BIMO pre-approval inspection 20

21 FDA.gov - 510(k) Database 21

22 Key Take-Aways Create a clear and complete Device Description Construct intended use Use FDA Pre-submission process and do your homework Plan FDA submission carefully with focus on good science 22

23 23 Questions?