1. BioUtah Pre-Submission Issues Workshop April 6, 2016 Ryan O’Callaghan Phil Triolo and Associates LC

2. What is an eCopy eCopy Holds Submissions Requiring an eCopy eCopy Technical Standards Cover Letter Requirements PDF File Requirements eCopy Structure Requirements Non-PDF File Requirements What to Submit to FDA April 6, 2016US FDA eCopies © 2016 Phil Triolo & Associates2

3. An exact electronic duplicate of a paper submission Limited cases where differences may be justified Submitted to FDA on CD, DVD, or Flash Drive FDA Guidance Document: eCopy Program for Medical Device Submissions Issued: Dec. 3, 2015 http://www.fda.gov/downloads/medicaldevices/deviceregulationan dguidance/guidancedocuments/ucm313794.pdf April 6, 2016US FDA eCopies © 2016 Phil Triolo & Associates3

4. If eCopy is Missing or Fails Loading Process FDA Notifies in Writing that Submission is on eCopy Hold FDA WILL NOT Begin Review of Submission until Valid Replacement eCopy is Submitted Response to eCopy Hold Follow Directions in FDA Notification Provide Cover Letter & Complete (Valid) Replacement eCopy April 6, 2016US FDA eCopies © 2016 Phil Triolo & Associates4

5. Section 745(b) of the FD&C Act requires submission of eCopies for: Premarket Submissions (510(k), de novo, PMA) Q-Submissions (Pre-Submissions) Investigational Device Exemptions (IDEs) Exempt: Compassionate Use IDE, Emergency Use IDE, Adverse Event Reports Product Development Protocols (PDPs) Humanitarian Device Exemptions (HDEs) Certain Drug and Biologics Applications April 6, 2016US FDA eCopies © 2016 Phil Triolo & Associates5

6. Responses to Deficiency Letters do require an eCopy eCopy Requirements do not apply to information obtained during Interactive Review process (via phone, email, fax) once submission is under review If response to Interactive Review Request is sent by mail, an eCopy is required April 6, 2016US FDA eCopies © 2016 Phil Triolo & Associates6

7. Emergency Use Authorizations (EUAs) Exempt IDE Submissions Compassionate Use IDE, Emergency Use IDE, Adverse Event Reports 513(g) Requests for Information (513(g)s) Master Access Files (MAFs) Clinical Laboratory Improvement Act (CLIA) Categorization – Exempt Device submissions (CLIA “X” files) April 6, 2016US FDA eCopies © 2016 Phil Triolo & Associates7

8. To pass FDA’s eCopy Loading Process the eCopy must meet the following requirements: Cover Letter Requirements PDF File Requirements eCopy Structure Requirements Volume-Based structure Non-Volume-Based structure Non-PDF File Requirements April 6, 2016US FDA eCopies © 2016 Phil Triolo & Associates8

9. Include: Purpose of Submission Contact Info (phone, email) Signature (wet signature or valid digital signature) eCopy Statement Should Not Include: Table of Contents Submission Content Should be on Applicant’s Letterhead April 6, 2016US FDA eCopies © 2016 Phil Triolo & Associates9

10. eCopy Statement (one of the following): Standard: “The eCopy is an exact duplicate of the paper copy” Modified: “The eCopy is an exact duplicate of the paper copy except [specify all differences]” If Modified Text is included: Specify all differences & include placeholder in paper submission referring to the eCopy for that specific information e.g., “The eCopy is an exact duplicate of the paper copy except that data line listings were only provided in the eCopy. A placeholder was provided in Volume 4 of the paper copy referring back to the eCopy for that information.” April 6, 2016US FDA eCopies © 2016 Phil Triolo & Associates10

11. File Naming Convention “XXX_Descriptive Name” (XXX = 001, 002, 003) Up to 125 characters No characters other than: letters, numbers, spaces, ‘.’, ‘-’, ‘_’ Max File Size = 50 MB If > 50 MB, split into multiple files No Embedded Attachments or Attributes within PDF No PDFs that Require a Password to Open Adobe Acrobat Version 11 or below April 6, 2016US FDA eCopies © 2016 Phil Triolo & Associates11

12. Creating PDF from source document (e.g., Word document) is preferred Fonts: Times New Roman, Veranda, Arial, Tahoma, Helvetica Avoid creating PDFs by scanning Paper Documents if possible OK in some cases (e.g., signed Truthful and Accuracy Statement for a 510(k)) April 6, 2016US FDA eCopies © 2016 Phil Triolo & Associates12

13. Non-Volume-based PDF files added to Root Level Generally for small submissions Volume-based PDF files added under volume(s) (i.e., folders) For large or complex submissions Decision is up to Applicant Not dependent on the format chosen for any previous document April 6, 2016US FDA eCopies © 2016 Phil Triolo & Associates13

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16. PDF files added under volume(s) (i.e., folders) No other file types may be placed in volumes No subfolders under volumes Volumes (folders) must have the following naming convention: VOL_xxx (e.g., VOL_001) or VOL_xxx_Descriptive Name (e.g., VOL_001_Mechanical Testing); Up to 125 characters April 6, 2016US FDA eCopies © 2016 Phil Triolo & Associates16

17. Example eCopy Structure of Typical Q-Submission for Clinical Study: 001_PreSubmission for “Device” 002_Attachment 1 – Regulatory Comparison of Predicate with “Device” 003_Attachment 2 – Investigators Brochure 004_Attachment 3 – Pilot Study Report 005_Attachment 4 – Biological Safety Evaluation and Plan 006_Attachment 5 – Clinical Investigation Plan 007_Attachment 6 – NSR Determination April 6, 2016US FDA eCopies © 2016 Phil Triolo & Associates17

18. Compress (Zip) Non-PDF Files No naming convention restrictions or size limit Place Zip file(s) in a folder named “STATISTICAL DATA” or “MISC FILES” STATISTICAL DATA Statistical information (including metadata, data line listings, and program codes) in native format MISC FILES Miscellaneous files (e.g., videos, x-rays, software source code) In some cases: Word versions of PDF documents April 6, 2016US FDA eCopies © 2016 Phil Triolo & Associates18

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20. CD, DVD, or Flash Drive Be careful with flash drives that may have pre-loaded files Make sure all pre-loaded files are deleted April 6, 2016US FDA eCopies © 2016 Phil Triolo & Associates20

21. If 2 Total Copies Required (e.g., 510(k)) 1 Paper Copy, 1 eCopy (with paper Cover Letter) If >2 Total Copies Required (e.g., Original PMA) 1 Paper Copy, 5 eCopies (with 1 paper Cover Letter) Third Party 510(k) Both Accredited Person and Applicant must provide their own eCopy to FDA April 6, 2016US FDA eCopies © 2016 Phil Triolo & Associates21

22. Ship with a tracking number Save final source files so you can make modifications for responses & use as template for future April 6, 2016US FDA eCopies © 2016 Phil Triolo & Associates22

23. FDA Guidance Document http://www.fda.gov/downloads/medicaldevices/deviceregulation andguidance/guidancedocuments/ucm313794.pdf http://www.fda.gov/downloads/medicaldevices/deviceregulation andguidance/guidancedocuments/ucm313794.pdf eSubmitter-eCopies Tool (available on FDA website) eCopy Validation Module (available on FDA website) FDA contact info: CDRH-eCopyinfo@fda.hhs.gov 240-402-3717 April 6, 2016US FDA eCopies © 2016 Phil Triolo & Associates23

24. Ryan O’Callaghan Phil Triolo and Associates LC ryano@philt.com