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Contains Nonbinding Recommendations

eCopy Program for Medical Device

Submissions

Guidance for Industry and Food

and Drug Administration Staff

Document issued on December 3, 2015.

This document supersedes the guidance of the same title dated

October 10, 2013.

For questions regarding this document, contact CDRH’s eCopy Program Coordinators at 240-

402-3717 or cdrh-eCopyinfo@fda.hhs.gov or CBER’s Office of Communication, Outreach and

Development, at 1-800-835-4709 or 240-402-8010.

U.S. Department of Health and Human Services

Food and Drug Administration

Center for Devices and Radiological Health

Center for Biologics Evaluation and Research

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Contains Nonbinding Recommendations

Preface

Public Comment

You may submit electronic comments and suggestions at any time for Agency consideration to

http://www.regulations.gov. Submit written comments to the Division of Dockets Management,

Food and Drug Administration, 5630 Fishers Lane, Room 1061, (HFA-305), Rockville, MD, 20852.

When submitting comments, please refer to the exact title of this guidance document. Comments

may not be acted upon by the Agency until the document is next revised or updated.

Additional Copies

Additional copies are available from the Internet. You may also send an e-mail request to CDRH-

Guidance@fda.hhs.gov to receive an electronic copy of the guidance. Please use the document

number (1797) to identify the guidance you are requesting.

Additional copies of this guidance document are also available from the Center for Biologics

Evaluation and Research (CBER), Office of Communication, Outreach, and Development (OCOD),

10903 New Hampshire Ave., Bldg. 71, Room 3128, Silver Spring, MD 20993-0002, or by calling

1-800-835-4709 or 240-402-8010, by emailing ocod@fda.hhs.gov, or from the Internet at

http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/default.h

tm.

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Table of Contents

Introduction ................................................................................................................................................. 1

What is an eCopy? ....................................................................................................................................... 3

Are differences between the contents of an eCopy and paper submission acceptable? .............................. 3

For what submission types is an eCopy required? ....................................................................................... 4

Are there other submission types not subject to the eCopy legislation for which eCopies may be

submitted? .................................................................................................................................................... 5

How many copies of a submission are needed? .......................................................................................... 6

What are the processing steps for an eCopy? .............................................................................................. 7

What are the technical standards for an eCopy? ............................................................................... 7

What are the recommended methods for creating an eCopy? ........................................................... 7

Bookmarks and Hyperlinks within PDFs ...................................................................................... 7

Creating a PDF File from the Source Document (Preferred)....................................................... 8

Creating a PDF File from a Scanned Document .......................................................................... 9

Are there special considerations when developing an eCopy for an original submission versus a

response to a review hold notification? ........................................................................................... 10

Are there any issues to consider when choosing the eCopy media? ............................................... 10

What if there is another submitting party involved? ....................................................................... 10

What if this is a Third Party 510(k)? ............................................................................................... 10

What if this is a bundled submission? ............................................................................................. 11

How do you create an eCopy that meets the technical standards? .................................................. 11

How do you know if an eCopy meets the technical standards before you send it to FDA?........ ... 12

How do you submit an eCopy to FDA? .......................................................................................... 13

How does FDA process an eCopy? ................................................................................................. 14

What do you provide to FDA in response to an eCopy hold? ......................................................... 14

How does FDA process a replacement eCopy? .............................................................................. 15

What timeframes need to be considered? ........................................................................................ 15

When does review of a submission begin? ..................................................................................... 15

If you submitted an eCopy for a submission type that did not require an eCopy and you received

an eCopy hold letter, what are your options? .................................................................................. 15

What if your device is regulated by CBER? .............................................................................................. 16

Will the new eCopy requirements apply? ....................................................................................... 16

Can you submit an electronic submission instead of an eCopy? .................................................... 16

How do you prepare and submit an electronic submission to CBER? ............................................ 16

Attachment 1 – Technical Standards for eCopies ............................................................................................ 18

Company Cover Letter Requirements ............................................................................................. 19

Volume or Non-Volume Structure Requirements ........................................................................... 20

PDF File Requirements ................................................................................................................... 25

Requirements for How to Add Non-PDF Files via “STATISTICAL DATA” and “MISC FILES”

Folders ............................................................................................................................................. 28

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eCopy Program for Medical Device

Submissions

Guidance for Industry and Food and

Drug Administration Staff

This guidance represents the current thinking of the Food and Drug Administration (FDA or

Agency) on this topic. It does not establish any rights for any person and is not binding on

FDA or the public. You can use an alternative approach if it satisfies the requirements of the

applicable statutes and regulations. To discuss an alternative approach, contact the FDA staff

or Office responsible for this guidance as listed on the title page.

1. Introduction

This is an updated version of the guidance that was issued on October 10, 2013. It provides

clarification to the processing and technical standards for eCopies based on FDA’s experience to

date with the program.

The purpose of this guidance is to explain the new electronic copy (eCopy) Program for medical

device submissions. Section 745A(b) of the Federal Food, Drug, and Cosmetic Act (FD&C

Act), added by section 1136 of the Food and Drug Administration Safety and Innovation Act

(FDASIA) (Pub. L. 112-144), requires the submission of eCopies with the issuance of this final

guidance. This guidance describes how the Food and Drug Administration (FDA) is

implementing the eCopy Program under section 745A(b) of the FD&C Act. The inclusion of an

eCopy is expected to improve the efficiency of the review process by allowing for the immediate

availability of an electronic version for review rather than relying solely on the paper version.

This guidance provides, among other things, the standards for a valid eCopy under section

745A(b)(2)(A) of the FD&C Act. In accordance with section 745A(b), submission types

identified in this final guidance must include an eCopy in accordance with the standards

provided by this guidance for the submission to be processed and accepted for review by FDA,

unless they have been identified as being exempted or waived. Submissions submitted without

an eCopy and eCopy submissions that do not meet the standards provided in this guidance will

be placed on hold until a valid eCopy is submitted to FDA and verified to meet the standards,

unless a waiver or exemption has been granted. While the submission is on hold, the review

clock will not begin and the submission will not be reviewed.

In section 745A(b), Congress granted explicit statutory authorization to FDA to implement the

statutory eCopy requirement by providing standards, criteria for waivers, and exemptions in

guidance. Accordingly, to the extent that this document provides such requirements under

section 745A(b) of the FD&C Act (i.e., standards, criteria for waivers, and exemptions),

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indicated by the use of the words must or required, this document is not subject to the usual

restrictions in FDA’s good guidance practice (GGP) regulations, such as the requirement that

guidances not establish legally enforceable responsibilities. See 21 CFR 10.115(d).

However, this document also provides guidance on FDA’s interpretation of the statutory eCopy

requirement and the Agency’s current thinking on the best means for implementing other aspects

of the eCopy program. Therefore, to the extent that this document includes provisions that are

not “standards,” “criteria for waivers,” or “exemptions” under section 745A(b)(2), this document

does not create or confer any rights for or on any person and does not operate to bind FDA or the

public, but does represent the Agency’s current thinking on this topic. The use of the word

should in such parts of this guidance means that something is suggested or recommended, but

not required. You can use an alternative approach if the approach satisfies the requirements of

the applicable statutes and regulations. If you want to discuss an alternative approach, contact

the FDA staff listed on the title page of this guidance.

To comply with the GGP regulations and make sure that regulated entities and the public

understand that guidance documents are nonbinding, FDA guidances ordinarily contain standard

language explaining that guidances should be viewed only as recommendations unless specific

regulatory or statutory requirements are cited. FDA is not including this standard language in

this guidance because it is not an accurate description of all of the effects of this guidance. This

guidance contains both binding and nonbinding provisions. Insofar as this guidance provides

“standards,” “criteria for waivers,” and “exemptions” pursuant to section 745A(b) of the FD&C

Act, it will have binding effect.

The eCopy program is not intended to impact (reduce or increase) the type or amount of data the

applicant

includes in a submission to support clearance or approval. Please refer to other FDA

device or program-specific guidance documents from CDRH

(http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/defau

lt.htm) and CBER

http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guida

nces/General/ucm214106.htm) for the appropriate contents for submissions.

For additional eCopy Program resources, please refer to FDA’s webpage entitled, eCopy

Program for Medical Device Submissions

(http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/

UCM370879.htm).

For the purposes of this guidance, applicant includes “submitter,” “sponsor,” or “holder.”

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2. What is an eCopy?

An electronic copy (eCopy) is defined as an exact duplicate of the paper submission, created and

submitted on a compact disc (CD), digital video disc (DVD), or a flash drive. An eCopy is

accompanied by a paper copy of the signed

cover letter and the complete paper submission.

3. Are differences between the contents of an eCopy and

paper submission acceptable?

While an eCopy is defined as an exact duplicate of the paper copy, there are limited cases in

which differences between the eCopy and the paper copy may be justified because a paper copy

is not practical or appropriate for analysis purposes (e.g., raw data and statistical analysis

programs,

data line listings to facilitate a bioresearch monitoring review) or is not feasible (e.g.,

videos, x-rays). The critical attribute of an eCopy is that it must include in electronic form all

data required for that submission type.

In other words, the eCopy must include all of the

required information for FDA review, whereas the paper copy can include a placeholder cross-

referencing the location of certain information in the eCopy.

The cover letter must contain the modified eCopy statement described in Attachment 1 and

describe any differences between the paper version and the eCopy. If information is included in

the eCopy that is not in the paper copy, then the paper copy must have a placeholder to redirect

the reviewer (e.g., a piece of paper with a statement directing the reviewer to a particular section

in the eCopy).

FDA will consider the eCopy, with the cover letter, loaded into the appropriate Center’s official

document repository to be the official record. Any undisclosed differences between the eCopy

and the paper version may need to be rectified and could delay the review of the submission.

The cover letter signature may be a wet (i.e., ink) signature or a valid digital signature. Please note that other

forms submitted within an IDE or premarket submission (e.g., Truthful and Accurate Statement for 510(k)s) can

also be signed with either a wet signature or digital signature.

An eCopy is not considered to be an electronic submission. For information on eSubmissions, refer to “FDA

eSubmitter” (http://www.fda.gov/ForIndustry/FDAeSubmitter/default.htm) and “Regulatory Submissions in

Electronic Format for Biologic Products”

(http://www.fda.gov/BiologicsBloodVaccines/DevelopmentApprovalProcess/ucm163685.htm).

For information on electronically submitted data, refer to “Clinical Data for Premarket Submissions”

(http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/PremarketSubmissi

ons/ucm136377.htm).

For example, the content requirements for a 510(k) submission are found in 21 CFR 870.87 and 807.92; those for

original PMA submissions are found in 21 CFR 814.20.

4. For what submission types is an eCopy required?

In accordance with Section 745A(b) of the FD&C Act, as added by section 1136 of FDASIA,

and the CDRH guidance on Q-submissions

, an eCopy is required for the following submission

types:

•

Premarket notification submissions (510(k)s), including third party 510(k)s;

•

Evaluation of automatic class III designation petitions (de novos);

•

Premarket approval applications (PMAs), including Transitional PMAs;

•

Modular PMAs;

•

Product development protocols (PDPs);

•

Investigational device exemptions (IDEs) [see partial Exemptions below];

•

Humanitarian device exemptions (HDEs)

•

Emergency Use Authorizations (EUAs)

[see Exemptions below];

•

Certain investigational new drug applications (INDs);

•

Certain biologics license applications (BLAs);

•

Q-submissions;

and

eCopies for all subsequent submissions to an original submission, including amendments

(amendments include add-to-files, CLIA categorization add-to-files, and appeals), supplements,

and reports (reports include annual/periodic and post-approval reports)

to the submission types

identified above would also be required. Whether it is a single-page submission (i.e., the

company cover letter is the only content) or a multi-volume submission, the eCopy requirements

apply. Although there is no maximum total submission size restriction, it is recommended that

the total package submission not exceed 1 GB to avoid possible load time failures that may delay

the submission process.

“Requests for Feedback on Medical Device Submissions: The Pre-Submission Program and Meetings with Food

and Drug Administration Staff” (http://www.fda.gov/ucm/groups/fdagov-public/@fdagov-meddev-

gen/documents/document/ucm311176.pdf).

This includes all PMA submission types, including, but not limited to, original PMAs, panel-track supplements,

180-day supplements, manufacturing site change supplements, 30-Day Notices, 135-Day Supplements, and post-

approval study supplements and reports, as well as amendments involving changes in the correspondent or

ownership and requests for extensions.

This includes all HDE submission types, including, but not limited to, original HDEs, 180-day supplements,

manufacturing site change supplements, 30-Day Notices, 135-Day Supplements, and post-approval study

supplements and reports, as well as amendments involving changes in the correspondent or ownership and requests

for extensions.

Refer to the guidance entitled, “Emergency Use Authorization of Medical Products”

(http://www.fda.gov/RegulatoryInformation/Guidances/ucm125127.htm) for more information on EUAs.

Applicable only to those devices that are regulated by CBER as biological products under Section 351 of the

Public Health Service (PHS) Act and that also require submission of an IND prior to submission of a BLA. Such

devices are generally those intended for use in screening donated blood for transfusion transmissible diseases.

Applicable only to those devices that are regulated by CBER as biological products under Section 351 of the PHS

Act, including those that do not require submission of an IND prior to the submission of the BLA. Such devices

generally include those reagents used in determining donor/recipient compatibility in transfusion medicine.

Section 745A(b) of the FD&C Act does not apply to Medical Device Reports submitted under 21 CFR Part 803.

Responses to deficiency letters are required to be formally submitted to CDRH’s or CBER’s

Document Control Center

(DCC) to be logged in as an amendment or a supplement and, thus,

are subject to the eCopy requirements.

Please note that eCopy requirements do not apply to information obtained during the

Interactive Review process (via email, phone, and/or fax) once a submission is under

review, if that information is not mailed to FDA. However, should an applicant choose to

mail a response to an Interactive Review request (which should only occur if the size of the

response makes communication by email or fax infeasible), it will be logged in as an amendment

and be subject to the eCopy requirements.

Exemptions

Above, FDA identified the submission types cited in the legislation as being subject to the eCopy

requirements. However, the legislation also allows for FDA to set forth criteria for exemptions

from eCopy requirements. Accordingly, due to the potentially urgent nature of the following

types of submissions, FDA considers these to be exempt from the requirement for an eCopy:

•

three specific types of IDEs - compassionate use IDE submissions, emergency use IDE

submissions

, and adverse event reports; and

•

all EUAs.

Although these submission types do not require eCopies as per this exemption, FDA encourages

you to submit eCopies of these submissions, when feasible, in order to facilitate the review

process.

If you choose to submit an eCopy, it must meet the technical standards outlined in

Attachment 1.

Waivers

FDA believes that, given the widespread availability of software to enable the creation of an

acceptable eCopy at little to no cost, all applicants should have the ability to provide an eCopy.

5. Are there other submission types not subject to the eCopy

legislation for which eCopies may be submitted?

Although an eCopy is not required under Section 745A(b) of the FD&C Act, FDA also accepts

and encourages you to submit eCopies for:

Refer to 21 CFR 807.90 for the DCC addresses for CDRH and CBER.

Please refer to CDRH’s device advice page entitled “IDE Early/Expanded Access”

(http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/InvestigationalDevi

ceExemptionIDE/ucm051345.htm#compassionateuse) and FDA’s “Guidance on IDE Policies and Procedures”

(http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm080202.htm) for

additional details on compassionate and emergency use IDE submissions.

If submission of an eCopy is not feasible, but there is pertinent electronic information, such as imaging data, to

supplement the information in the paper copy, please contact the lead reviewer to submit this information via

Interactive Review.

•

Master Access Files (MAFs);

•

513(g) Requests for Information (513(g)s); and

•

Clinical Laboratory Improvement Act (CLIA) Categorization – Exempt Device

submissions (CLIA “X” files).

eCopies for these three submission types are voluntary; however, if you choose to submit an

eCopy, it must meet the technical standards outlined in Attachment 1.

6. How many copies of a submission are needed?

The eCopy Program does not change the overall number of copies to submit to FDA. Table 1

below provides the number of copies associated with each submission type for which an eCopy

is either required or voluntary.

Table 1 – Number of Copies for Submission

Submission Type

Required or

Voluntary

eCopy

Total Number of

Copies

510(k)s

Required

Third Party 510(k)s

Required

De Novos

Required

PMAs, including Transitional PMAs

•

Original PMAs

Required

•

Panel-Track Supplements

Required

•

All other PMA supplement types (e.g., 180-Day

Supplements, Real-Time Supplements, 30-Day

Notices, 135-Day Supplements)

Required

•

PMA reports (annual reports and post-approval

study reports)

Required

PDPs

Required

See PMAs for

corresponding type

HDEs

Required

See PMAs for

corresponding type

Modular PMAs

Required

IDEs

•

Compassionate use IDEs

Voluntary

•

Emergency use IDEs

Voluntary

•

Adverse Event Reports

Voluntary

See 21 CFR 807.90(a)(3)(c).

See 21 CFR 814.20(b)(2).

See 21 CFR 814.39(c).

See 21 CFR 814.104(b)(4).

See 21 CFR 812.20(a)(3).

Submission Type

Required or

Voluntary

eCopy

Total Number of

Copies

•

All other types of IDE submissions

Required

EUAs

Voluntary

Q-Submissions

Required

MAFs

Voluntary

513(g)s

Voluntary

CLIA X Files

Voluntary

INDs

Required

BLAs

Required

For submission types for which eCopy requirements apply:

•

If a total of two copies are required, you must submit one full paper copy and one eCopy

(with a cover letter with a signature and an adequate eCopy statement).

•

If more than two copies are required, then you must submit one full paper copy and all

remaining copies as eCopies (with a single cover letter with a signature and an adequate

eCopy statement). For example, for an original PMA, you must submit one paper copy

and five eCopies.

On the other hand, for compassionate use IDE submissions, emergency use IDE submissions,

EUAs, MAFs, 513(g)s, and CLIA X files, you may choose to submit only paper copies because

an eCopy is voluntary. However, if you choose to submit an eCopy for one of these submission

types, it must meet the technical standards outlined in Attachment 1.

7. What are the processing steps for an eCopy?

Below are the processing steps for the submission and acceptance of an eCopy.

a. What are the technical standards for an eCopy?

The technical standards for an eCopy are detailed in Attachment 1. An eCopy that does not

meet the technical standards in Attachment 1 will not be accepted.

b. What are the recommended methods for creating an eCopy?

Bookmarks and Hyperlinks within PDFs

Bookmarks and hyperlinks within a single PDF file should be used to assist the reviewers in

navigating through the content of the submission. However, while these are not required

elements for an eCopy, bookmarks and hyperlinks are essential for the efficient navigation

through documents. If you use either bookmarks or hyperlinks, consider the following:

See 21 CFR 312.23(d).

FDA review staff should not request an additional eCopy or paper copy of a submission from the applicant.

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