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 
Contains Nonbinding Recommendations 

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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Contains Nonbinding Recommendations 

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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Contains Nonbinding Recommendations 

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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Contains Nonbinding Recommendations 

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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Contains Nonbinding Recommendations 

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 

DD-MMM-YYYY 

cc: 123456_0 / 0999 / XX01-B 

File Name 

20049984.PC1 

20049985.P0-20049989.P0

ABC Pharmaceuticals 

DD-MMM-YYYY 

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

20049994.PC1, 20049997.P0 

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

0999 ABC Pharmaceuticals 

DD-MMM-YYYY

STN / Product Code Lot # Filename 

123456_0 / XX01-B 8899989B 20049995.P0 

123456_0 / XX01-B 8899995A 20049996.P0 

123456_0 / XX01-FC ALT435A 20049994.PC1 

123457_0 / XY02-FC 9567418C 20049997.P0 

123457_0 / XY02-FC 9567418D 20049998.P0 

123457_0 / XY02-FC 9567419K 20049999.P0 

0999 ABC Pharmaceuticals

DD-MMM-YYYY 

123456_0 / XX01-B

Lot # Filename 

8799795A 20049984.PC1 

8799989B 20049985.P0 

9567428C 20049987.P0 

9567428D 20049988.P0 

9567429K 20049989.P0 

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