Guidance for Industry

Providing Regulatory Submissions to

the Center for Biologics Evaluation
and Research (CBER) in Electronic
Format - Lot Release Protocols

This guidance is for immediate implementation.

FDA is issuing this guidance for immediate implementation in accordance with

21 CFR 10.115(g)(4)(i). Submit written comments on this guidance at anytime to the Division
of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm.
1061, Rockville, MD 20852. Submit electronic comments to either
http://www.fda.gov/dockets/ecomments or http://www.regulations.gov. You should identify all
comments with Docket No. 1998D-0315.

Additional copies of this guidance are available from the Office of Communication, Training and
Manufacturers Assistance (HFM-40), 1401 Rockville Pike, Suite 200N, Rockville, MD 20852-
1448, or by calling 1-800-835-4709 or 301-827-1800, or from the Internet at
http://www.fda.gov/cber/guidelines.htm.

For questions on the content of this guidance, contact the CBER Product Release Branch at 301-
594-6517.

U.S. Department of Health and Human Services

Food and Drug Administration
Center for Biologics Evaluation and Research
November 2007
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TABLE OF CONTENTS

I. INTRODUCTION............................................................................................................. 1

II. DISCUSSION .................................................................................................................... 1

III. GENERAL FILE AND FOLDER FORMAT ................................................................ 2

A. File and Folder Organization .................................................................................. 2
B. Hypertext Links and Bookmarks ............................................................................ 3
IV. SUBMITTING LOT RELEASE PROTOCOLS AND TEST RESULTS IN
ELECTRONIC FORMAT............................................................................................... 3
A. Media Labeling ....................................................................................................... 3
B. Packaging and Shipping.......................................................................................... 3
C. Delivery Address .................................................................................................... 3
V. APPENDIX........................................................................................................................ 5
A. Example of PDF Bookmarks From an Electronic Lot Release Protocol................ 5
B. Sample CD-ROM Label ......................................................................................... 6

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Guidance for Industry

Providing Regulatory Submissions to the Center for Biologics

Evaluation and Research (CBER) in Electronic Format - Lot
Release Protocols

This guidance represents the Food and Drug Administration’s (FDA’s) current thinking on this
topic. 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 alternate approach if the approach satisfies the requirements
of the applicable statute and regulations. If you want to discuss an alternative approach, contact
the appropriate FDA staff. If you cannot identify the appropriate FDA staff, call the appropriate
number listed on the title page of this guidance.

I. INTRODUCTION

We, the Center for Biologics Evaluation and Research (CBER), are issuing this guidance under
21 CFR 601.14(a) to assist you, manufacturers of biological products regulated by CBER, in
submitting lot release protocols in electronic format to CBER’s Product Release Branch. This
guidance supersedes the guidance of the same title dated July 2006. We are updating this
guidance to delete references to 3.5 inch diskettes due to changes in technology that are phasing
out the use of this type of electronic format.

FDA's guidance documents, including this guidance, do not establish legally enforceable
responsibilities. Instead, guidances describe the FDA'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 FDA guidances means that something is suggested or
recommended, but not required.

II. DISCUSSION

In accordance with section 610.2 (a) in Title 21 of the Code of Federal Regulations (CFR),
CBER may require you to submit, for CBER review and confirmatory testing, samples of any lot
of any licensed product, together with the protocols showing results of applicable tests.
Regulatory submissions in electronic formats, consistent with lot release requirements applicable
to your product, will facilitate our review of your submission, provided that you submit your data
to us in an electronic format that we can readily access. Pursuant to 21 CFR 11.2(b)(2), FDA has
identified such submissions in public Docket No. 92S-0251 as being the type of submission the
agency accepts in electronic form (e.g., compact disk-read only memory (CD-ROM) or other
formats that may become available in the future). This guidance is intended to provide you with
recommendations for submitting lot release protocols showing results of applicable tests in an
electronic format, as provided in 21 CFR Part 11. 1 By following these recommendations for

1
Note that FDA has issued guidance describing an interim policy of enforcement discretion relating to certain Part
11 requirements. http://www.fda.gov/cber/gdlns/prt11elect.pdf

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preparation and submission of electronic lot release documents, you might prevent a delay in the
product release processing.

In the Federal Register of December 8, 1995 (60 FR 63048), we announced that we no longer
require routine lot-by-lot release for specified categories of biological products subject to
licensure (21 CFR 601.2 (c)) previously referred to as well-characterized therapeutic
recombinant DNA-derived and monoclonal antibody biotechnology products. This guidance is
not intended to modify that document.

III. GENERAL FILE AND FOLDER FORMAT

We are not providing specific instructions for the construction of portable document format
(PDF) files in this guidance. We expect that the draft guidance titled, “Providing Regulatory
Submissions in Electronic Format – General Considerations, October 2003,” when finalized, will
do so.

A. File and Folder Organization

We recommend that you submit lot release submissions to CBER’s Product Release
Branch in an electronic format. Currently, our preferred format is CD-ROM, as formats
such as 3.5 diskettes are becoming obsolete. Each CD-ROM should include a Cover
Letter (cover.pdf) file with the following information:

• Description of the submission

• Identification of each lot release protocol as a separate PDF file with its
corresponding filename
• Statement that the submission is virus free with a description of the software
(name, version, and company) used to check the files for viruses
• Regulatory and technical point of contact for the submission

We recommend that you submit lot release information for each lot under a separate and
unique filename constructed as follows. We recommend that you use the old Disk
Operating System (DOS) standard of 8.3 characters because of the simplicity of the
naming system, and that you avoid the use of special characters. We do not recommend
that you use standard file extensions such as .pdf. We describe our recommendations
below. In order to use different extensions, we recommend that you use any conversion
program commercially available to change the word-processing document to PDF, and
select the File “Save As” command. This should allow you to change the .pdf extension
to one of the extensions described below. We recommend that you do not use the
Security option and passwords on the submission, as these will make it difficult for us to
access your data.

You should divide the filename into three sections: (1) the first four digits represent the
year of the submission (e.g., 2004), (2) the next four digits represent the sequential
submission number of that year (e.g., 0003), (3) the two to three alphanumeric extension
(the three allowable characters, numbers or letters following the period) represents the

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type of submission (e.g., .P0 (zero) designates a submission under the original protocol).
Thus, 20040003.P0 represents the third lot release submission of 2004 under the original
protocol.

A corrected lot release protocol is a submission to correct minor clerical or transcription

errors, or to clarify lot release information in response to questions by FDA. For
submissions under a corrected lot release protocol, designate each corrected protocol
using “.PC” followed by the correction number (i.e., .PC1 for first corrected protocol,
.PC2 for second corrected protocol, etc.). Thus, the first correction of the third original
protocol submission of 2004 should be 20040003.PC1.

B. Hypertext Links and Bookmarks

Lot release protocols are typically 8-10 pages in length. We recommend that you use
functional bookmarks to facilitate navigating the protocols. We provide an example of
PDF bookmarks in Appendix 1 at the end of this guidance.

IV. SUBMITTING LOT RELEASE PROTOCOLS AND TEST RESULTS IN

ELECTRONIC FORMAT

A. Media Labeling

We recommend that you attach physical labels constructed as follows on CD-ROMs, and
CD-ROM jewel cases to provide visible identification of your submission. You should
include the following information: (1) manufacturer name, (2) date of submission in the
format of DD-MMM-YYYY, with DD and YYYY being numerical and MMM being the
first three letters of the month (e.g., AUG for August), (3) title, including cc, STN,
license number, product code(s) (if applicable), and type of lot, (4) electronic protocol
filename(s), and (5) lot number(s) of the protocol(s). We provide examples of labeled
media in Appendix 2 and 3 at the end of this guidance. We recommend that you consult
the CD-ROM manufacturer before using felt-tip pens on CD-ROMs, as some pens
contain dangerous solvents that may damage the CD-ROM.

B. Packaging and Shipping

You should package CD-ROMs carefully to ensure that they arrive in a usable condition.
Jewel cases are less vulnerable when shipped in envelopes with bubble type protective
material or stiff backing. Mailing envelopes padded with paper material only typically do
not provide adequate protection for shipping CD-ROMs.

C. Delivery Address

You should send electronic protocol(s) and test results, with or without lot release
samples, to the following address. If you are sending lot release samples, you must send
them by courier service (21 CFR 600.2(c)).

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Sample Custodian (ATTN: HFM-672)

Food and Drug Administration
Center for Biologics Evaluation and Research
Bldg: NLRC-B, Room: 113
5516 Nicholson Lane
Kensington, MD 20895

To facilitate our review of your submission, you may contact Joseph Quander at the
CBER, Product Release Branch, at (301) 594-6517, or (301) 594-6924 (fax) before
switching from submission on paper to submission on electronic format.

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V. APPENDIX

A. Example of PDF Bookmarks From an Electronic Lot Release Protocol

À ELECTRONIC PROTOCOL – 20040001.PO

License No./ Product Code /Type of Lot[-B, -FC, -C]
Lot Number
Proper Name of Product
Firm Name and Address
Reason for Submission
À Test Results
Potency
Specific Activity
pH
Moisture
Total Protein
Solubility
À Sterility
Sterility Bulk
Sterility Final Container
General Safety
À Purity
LAL (limulus amebocyte lysate)
Pyrogen
À Laser Densitometer Scan
LD Scan
LD Scan Reference
Pass Statement
Signature Block
Electronic Protocol: 20040001.P0

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B. Sample CD-ROM Label

A) Single Product Submission B) Multiple Product Submission

ABC Pharmaceuticals ABC Pharmaceuticals

DD-MMM-YYYY DD-MMM-YYYY
cc: 123456_0 / 0999 / XX01-B cc: 0999
123456_0 123457_0
XX01-B XY02-FC
File Name File Name
20049995.P0- 20049998.P0-
20049996.P0 20049999.P0

123456_0 / XX01-FC
File Name
File Name
20049984.PC1
20049994.PC1, 20049997.P0
20049985.P0-20049989.P0

C) CD Jewel Case, inside cover for Disk A D) CD Jewel Case, inside cover for Disk B

0999 ABC Pharmaceuticals

0999 ABC Pharmaceuticals
DD-MMM-YYYY
DD-MMM-YYYY STN / Product Code Lot # Filename
123456_0 / XX01-B
Lot # Filename 123456_0 / XX01-B 8899989B 20049995.P0
8799795A 20049984.PC1
123456_0 / XX01-B 8899995A 20049996.P0
8799989B 20049985.P0
123456_0 / XX01-FC ALT435A 20049994.PC1
9567428C 20049987.P0
123457_0 / XY02-FC 9567418C 20049997.P0
9567428D 20049988.P0
123457_0 / XY02-FC 9567418D 20049998.P0
9567429K 20049989.P0
123457_0 / XY02-FC 9567419K 20049999.P0