Guidance for Industry: How to Submit a Protocol in Electronic Format by E-Mail

107
Guidance for Industry
How to Submit a Protocol in Electronic
Format by E-Mail
(THIS VERSION OF THE GUIDANCE REPLACES THE VERSION MADE
AVAILABLE IN MAY 2004)
This guidance document describes how to submit protocols in electronic format by
e-mail for studies in support of New Animal Drug Applications to the Center for
Veterinary Medicine (CVM). The guidance was revised to update the web links,
email addresses, and phone numbers.
Comments and suggestions regarding this document should be sent to Division of
Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers
Lane, Rm. 1061, Rockville, MD 20852.
Submit electronic comments to
http://www.fda.gov/dockets/ecomments. All comments should be identified with the
exact title of the document.
For questions regarding this document, contact Margaret Zabriski, Center for
Veterinary Medicine, (HFV-016), Food and Drug Administration, 7519 Standish
Place, Rockville, MD 20855, 240-276-9143, E-mail: [email protected].
According to the Paperwork Reduction Act of 1995, a collection of information
should display a valid OMB control number. The valid OMB control number for this
information collection is 0910-0524. The time required to complete this information
collection is estimated to vary between 5 and 20 minutes per response, including the
time to review instructions, search existing data resources, gather the data needed,
and complete and review the information collection.
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Veterinary Medicine
January 17, 2006

Table of Contents
I.
II.

INTRODUCTION .........................................................................................................3
ORGANIZATION AND FORMAT OF PROTOCOL SUBMISSIONS ......................4
A. Smart Form ....................................................................................................................4
B. Cover Letter ...................................................................................................................4
C. Protocol and Appendices ...............................................................................................4
D. Electronic format of PDF file ........................................................................................5
1. Version.......................................................................................................................5
2. Fonts...........................................................................................................................5
3. Page Setup..................................................................................................................5
4. Hypertext Linking and Bookmarks............................................................................5
5. Security ......................................................................................................................6
6. Searching PDF Files ..................................................................................................6
E. Protocol Evaluation by CVM ........................................................................................6

III.

PROTOCOL FORM ......................................................................................................6

IV.

CHECKLIST FOR SUBMITTING A PROTOCOL USING FORM FDA 3536..........6

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GUIDANCE FOR INDUSTRY 1
HOW TO SUBMIT A PROTOCOL IN ELECTRONIC
FORMAT BY E-MAIL
This guidance represents the Agency’s current thinking on how to submit a
protocol in electronic format by e-mail. It does not create or confer any rights
for or on any person and does not operate to bind FDA or the public. You can
use an alternative approach if the approach satisfies the requirements of the
applicable statue and regulations. If you want to discuss an alternative
approach, contact the FDA staff responsible for implementing this guidance.
If you cannot identify the appropriate FDA staff, call the appropriate number
listed on the title page of this guidance.

I.

INTRODUCTION
This guidance provides advice to industry regarding the procedures to submit a protocol
for non-clinical laboratory and effectiveness studies in electronic format to the Office of
New Animal Drug Evaluation by e-mail.
FDA’s guidance documents, including this guidance, do not establish legally
enforceable responsibilities. Instead, guidances describe the Agency’s current
thinking on a topic and should be viewed only as recommendations, unless specific
regulatory or statutory requirements are cited. The use of the word “should” in
Agency guidances means that something is suggested or recommended, but not
required.
Protocols for non-clinical laboratory studies (safety studies) are required under 21 CFR
58.120. Protocols for adequate and well-controlled effectiveness studies are required
under 21 CFR 514.117(b). Sponsors may request that CVM review protocols for safety
and effectiveness studies of new animal drugs. The review of protocols facilitates the
drug review and approval processes.
Currently, CVM receives protocols in paper. CVM is publishing this guidance to give
sponsors the option to submit a protocol as an e-mail attachment to CVM.
E-mail submissions that follow this guidance will be compatible with CVM’s current
information technology capabilities. This will help ensure the confidentiality, integrity,
security, and authenticity of data submitted to the Center. If a regulated sponsor or
1

This guidance has been prepared by CVM at FDA. For additional copies, access the document on the
CVM Home Page (http://www.fda.gov/cvm), or send a request to the Communications Staff, HFV-12,
7519 Standish Place, Rockville, MD 20855.

CONTAINS NON-BINDING RECOMMENDATIONS
person wishes to use an electronic approach other than that set forth in this guidance
document, the Center will, on request, discuss alternative methods of submitting
information.
The electronic submission of protocols is part of the Center’s ongoing initiative to
provide a method for paperless submissions.
This document reflects the principles behind the Government Paperwork Elimination
Act, Pub. L. No. 105-277, 112 Stat. 2681 (1998), which requires that executive agencies,
by October 21, 2003, provide: (1) for the option of the electronic maintenance,
submission, or disclosure of information, if practicable, as a substitute for paper; and (2)
for the use and acceptance of electronic signatures when practicable.
This document contains specific instructions for submitting protocols electronically.
Guidance #108, “How to Submit Information in Electronic Format by E-Mail”, contains
general instructions and specifications on submitting information electronically to CVM
by e-mail. It is available on the CVM Home Page (http://www.fda.gov/cvm).

II.

ORGANIZATION AND FORMAT OF PROTOCOL SUBMISSIONS
The protocol submission will contain a SMART FORM, cover letter, protocol, and any
appendices. The cover letter, protocol and any appendices should be contained in one
Portable Document Format (PDF) file (protocol file).
A.

Smart Form
All applicable fields of the “Protocol for Non-clinical Laboratory and
Effectiveness Studies” form (FORM FDA 3536) (SMART FORM) should be filled
out. The form cannot be transmitted until all required fields are completed. The
use of this SMART FORM allows for quality control of the information about the
protocol and reduces the chance incomplete information will be submitted. The
information requested on the form also allows the submitted material to be
automatically logged into the Center’s tracking system (Submission Tracking and
Reporting System, known as STARS).

B.

Cover Letter
If the sponsor chooses to include a cover letter, it should be submitted as part of
the PDF file in the order specified in step 2 of the Section III, “Checklist for
Submitting a Protocol using form FDA 3536.” The cover letter should be the first
page of the protocol file.

C.

Protocol and Appendices
The protocol must contain the elements described in 21 CFR 58.120 for safety
studies and 21 CFR 514.117(b) for adequate and well-controlled effectiveness
studies. Additional guidance for protocols for effectiveness studies is contained

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in Guidance for Industry: Good Clinical Practices: VICH GL9, Final Guidance,
May 5, 2001.
D.

Electronic format of PDF file
The following recommendations are intended to assist sponsors in creating PDF
files that are compatible with CVM’s current information technology capabilities
and to ensure the confidentiality, integrity, security, and authenticity of data
submitted to the Center.
1. Version
CVM is currently using version 5.0 of Adobe® Acrobat® for review of electronic
submissions. All PDF files submitted to CVM should be created using software
that permits the Center to read, search, copy, and paste information from the PDF
file into a word processing document using version 5.0 of Adobe® Acrobat®.
2. Fonts
All fonts should be embedded in the PDF file to ensure that those fonts will
always be available to the reviewer. Font substitution can affect a document’s
appearance and structure, and in some cases (for example, Greek letters) it can
affect the information conveyed by a document. Therefore, all characters for the
font and the subset of the characters should be embedded.
CVM recommends that the following settings be used for general text:
•
•
•

Arial, 12-point font
Black font color for general text
Blue text for hyperlinks

3. Page Setup
The print area for pages should fit on a sheet of paper that is 8.5 inches by 11
inches.
4. Hypertext Linking and Bookmarks
Tools such as bookmarks and hypertext links enable the reviewer to move
efficiently through the document.
Bookmarks should be provided for each item listed in the table of contents
including all major section headings and subheadings. All tables, figures,
publications, references, and appendices should also be bookmarked.
Hypertext links should be used to connect text to supporting annotations, related
sections, references, appendices, tables, or figures that are not located on the same
page as the text. Hypertext links should be designated by blue text.

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When creating bookmarks and hyperlinks, you should choose the magnification
setting Inherit Zoom. This allows the destination page to display at the same
magnification level that the reviewer is using for the document.
The open dialog box sets the document view when the file is opened. The initial
view of the PDF files should be Bookmarks and Page. You should set the
Magnification and Page Layout to default.
5. Security
No security settings should be selected that would prevent printing, changes to the
protocol, or selecting text and graphics. CVM’s internal security and archival
processes are designed to maintain the integrity of the submitted files.
6. Searching PDF Files
PDF files should be created in a manner that allows CVM to do full text searches.
Because scanned images cannot be indexed, they cannot be searched and their use
should be kept to a minimum.
E.

Protocol Evaluation by CVM

The Center intends to transmit the results of its evaluation of the protocol to the sponsor
by a signed paper letter. Until the Center sets specific standards for the use of electronic
signatures that meet the requirements of 21 CFR 11, all official responses will be in paper
format, including letters intended to transmit the results of protocol evaluations.

III.

PROTOCOL FORM
A copy of the Protocol for Nonclinical Laboratory and Effectiveness Studies Form (FORM
FDA 3536) is available on the CVM Electronic Submission Page at
http://www.fda.gov/cvm/esubstoc.html.

IV.

CHECKLIST FOR SUBMITTING A PROTOCOL USING FORM FDA
3536

Note these instructions are for Adobe Acrobat 5.0. Other versions may be different.
This checklist describes the process CVM recommends for creating a Portable Document
Format (PDF) file using a word processing program, printing it to the Acrobat® Distiller,
and submitting the information.
1.

You should build the protocol file from source documents. Scanned PDF
documents may be used for pages unavailable for word processing such as
diagrams and observations forms but should be kept to a minimum.

2.

The protocol file should contain in order: a cover letter (if you choose to submit
one), the protocol, and any appendices. The cover letter, protocol, and any
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appendices should be converted into PDF files by printing the word processing
documents using Acrobat® Distiller. Use the Documents → Insert Pages in
Adobe Acrobat® to combine several PDF files into one file. After the file is
constructed, the PDF file should be saved using File → Save As. All hyperlinks
and bookmarks should be verified after creating the single PDF file. Document
Information Fields of the PDF file may be filled out at the sponsor’s discretion.
3.

Open the Protocol FORM FDA 3536.

4.

Fill out the pertinent sections in Form FDA 3536. If the protocol has been
previously submitted to CVM, provide the correct information in section I.3a and
I.3b.

5.

Select the “Insert Comments” button to add a PDF file containing any comments
regarding the form.

6.

Select the “Insert Protocol” button to add the protocol file created in steps 1 and 2.
The form cannot be successfully validated unless a protocol file has been attached.

7.

Once the form is completed, select the “Validate” button to verify all of the
required fields are completed. Those fields that are required will be highlighted and
must be completed before the form can be sent to CVM.

8.

Select the “Add Password” button to change Document Security
a. Select “Adobe Standard Security” in the “Document Security” window.
b. Select the “Change Settings” button.
c. In the “Specify Password” section select the “Password Required to Open
Document” checkbox.
d. Enter your “Current” Electronic Submissions System (ESS) password in the
“User Password” field.
e. Press “Ok” and save your PDF form to your local system.

9.

Select “Save” to save all information on the form.

10.

The “Signature” button is currently disabled on the form.

11.

Once the form is validated and secured, select the “Send to CVM” button.
a. The form will be automatically addressed to [email protected]. Additional
addresses can be added to the addressee and/or the cc block.
b. The form automatically adds “PROTOCOL” as the subject line.

12.

If you have not received an acknowledgment receipt from CVM by the third
business day after you have sent the submission, call the Electronic Document
Control Unit at 301-827-8277 to report the problem and find out whether your
submission was received.

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