e Copy Program for FDA Medical Device Submissions

e. Copy Program for FDA Medical Device Submissions Bio. Utah Pre-Submission Issues Workshop April 6, 2016 Ryan O’Callaghan Phil Triolo and Associates LC

Overview • What is an e. Copy • e. Copy Holds • Submissions Requiring an e. Copy • e. Copy Technical Standards • • Cover Letter Requirements PDF File Requirements e. Copy Structure Requirements Non-PDF File Requirements • What to Submit to FDA US FDA e. Copies © 2016 Phil Triolo & Associates April 6, 2016 2

e. Copy (Electronic Copy) • 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: e. Copy Program for Medical Device Submissions Issued: Dec. 3, 2015 http: //www. fda. gov/downloads/medicaldevices/deviceregulatio nandguidance/guidancedocuments/ucm 313794. pdf US FDA e. Copies © 2016 Phil Triolo & Associates April 6, 2016 3

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

Submissions Requiring an e. Copy Section 745(b) of the FD&C Act requires submission of e. Copies 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 US FDA e. Copies © 2016 Phil Triolo & Associates April 6, 2016 5

Submissions Requiring an e. Copy • Responses to Deficiency Letters do require an e. Copy • e. Copy 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 e. Copy is required US FDA e. Copies © 2016 Phil Triolo & Associates April 6, 2016 6

e. Copy is Recommended • 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) US FDA e. Copies © 2016 Phil Triolo & Associates April 6, 2016 7

e. Copy Technical Standards To pass FDA’s e. Copy Loading Process the e. Copy must meet the following requirements: • Cover Letter Requirements • PDF File Requirements • e. Copy Structure Requirements • Volume-Based structure • Non-Volume-Based structure • Non-PDF File Requirements US FDA e. Copies © 2016 Phil Triolo & Associates April 6, 2016 8

Cover Letter Requirements • Include: • Purpose of Submission • Contact Info (phone, email) • Signature (wet signature or valid digital signature) • e. Copy Statement • Should Not Include: • Table of Contents • Submission Content • Should be on Applicant’s Letterhead US FDA e. Copies © 2016 Phil Triolo & Associates April 6, 2016 9

Cover Letter - e. Copy Statement • e. Copy Statement (one of the following): • Standard: “The e. Copy is an exact duplicate of the paper copy” • Modified: “The e. Copy 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 e. Copy for that specific information • e. g. , “The e. Copy is an exact duplicate of the paper copy except that data line listings were only provided in the e. Copy. A placeholder was provided in Volume 4 of the paper copy US FDA e. Copies © 2016 Phil Triolo & Associates April 6, 2016 10 referring back to the e. Copy for that information. ”

PDF File Requirements • 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 US FDA e. Copies © 2016 Phil Triolo & Associates April 6, 2016 11

Create PDFs from Source Documents • 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)) US FDA e. Copies © 2016 Phil Triolo & Associates April 6, 2016 12

Volume-based vs. Non-Volume-based Structure • 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 US FDA e. Copies © 2016 Phil Triolo & Associates April 6, 2016 13

Non-Volume Based (e. g. , 510(k) Submission) US FDA e. Copies © 2016 Phil

Volume Based (e. g. , IDE Submission) US FDA e. Copies © 2016 Phil

Volume-based Structure • 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 US FDA e. Copies © 2016 Phil Triolo & Associates April 6, 2016 16

e. Copy for Q-Submission Example e. Copy Structure of Typical Q-Submission for Clinical Study: • 001_Pre. Submission 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 US FDA e. Copies © 2016 Phil Triolo & Associates April 6, 2016 17

Non-PDF Files • 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 US FDA e. Copies © 2016 Phil Triolo & Associates April 6, 2016 18

Non-PDF Files US FDA e. Copies © 2016 Phil Triolo & Associates April 6,

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

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

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

FDA Resources • FDA Guidance Document • http: //www. fda. gov/downloads/medicaldevices/deviceregulati onandguidance/guidancedocuments/ucm 313794. pdf • e. Submitter-e. Copies Tool (available on FDA website) • e. Copy Validation Module (available on FDA website) • FDA contact info: • CDRH-e. Copyinfo@fda. hhs. gov • 240 -402 -3717 US FDA e. Copies © 2016 Phil Triolo & Associates April 6, 2016 23

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