0206 SAMPLES and PROTOCOLS SUPPORTING STATEMENT 6-28-12 FINAL

Request for Samples and Protocols

0910-0206

SUPPORTING STATEMENT

A. Justification

1. Circumstances Making the Collection of Information Necessary

The Food and Drug Administration (FDA) is requesting an extension of Office of Management and Budget (OMB) Control No. 0910-0206 and OMB approval of the information collection requirements for the regulations listed below.

21 CFR 610.2	Reporting	The Center for Biologics Evaluation and Research (CBER) or the Center for Drugs Evaluation and Research (CDER) may at any time require manufacturers of licensed biological products to submit to FDA samples of any lot along with the protocols showing the results of applicable tests prior to distributing the lot of the product.
21 CFR 660.6(b)	Reporting	Along with each required sample, FDA requires the manufacturer to submit a protocol consisting of a summary of the history of manufacture of the product including all results of each test for which test results are requested by CBER.
21 CFR 660.36(a)(2) and (b)	Reporting	Section 660.36(a)(2) requires that a protocol contain information including, but not limited to, manufacturing records, certain test records, and identity test results. Section 660.36(b) requires that a copy of the antigenic constitution matrix specifying the antigens present or absent be submitted to the CBER Director at the time of initial distribution of each lot.
21 CFR 660.46(b)	Reporting	Along with each required sample, FDA requires the manufacturer to submit a protocol consisting of a summary of the history of manufacture of the product including all results of each test for which test results are requested by CBER.

Under section 351 of the Public Health Service Act (the PHS Act)(42 U.S.C. 262), FDA has the responsibility to issue regulations that prescribe standards designed to ensure the safety, purity, and potency of biological products and to ensure that biologics licenses for such products are only issued when a product meets the prescribed standards. CBER and CDER may at any time require manufacturers of licensed biological products to submit to FDA samples of any lot along with the protocols showing the results of applicable tests prior to distributing the lot of the product. In addition to § 610.2 (21 CFR 610.2), there are other regulations that require the submission of samples and protocols for specific licensed biological products: §§ 660.6 (21 CFR 660.6) (Antibody to Hepatitis B Surface Antigen); 660.36 (21 CFR 660.36) (Reagent Red Blood Cells); and 660.46 (21 CFR 660.46) (Hepatitis B Surface Antigen). In cases of certain biological products (e.g., Albumin, Plasma Protein Fraction, and therapeutic biological products) that are known to have lot-to-lot consistency, official lot release is not normally required. However, submissions of samples and protocols of these products may still be required for surveillance, licensing, and export purposes, or in the event that FDA obtains information that the manufacturing process may not result in consistent product quality.

This information collection is not related to the American Recovery and Reinvestment Act of 2009 (ARRA).

2. Purpose and Use of the Information Collection

Samples and protocols are required by FDA to help ensure the safety, purity, and potency of a product because of the potential lot-to-lot variability of a product produced from living organisms. The written protocols are reviewed by FDA scientists and other staff with expertise in the appropriate product and scientific area. FDA tests samples to verify the manufacturer’s test results. A manufacturer may not distribute a product until FDA gives the official release for the lot.

3. Use of Improved Information Technology and Burden Reduction

One of FDA’s continuing objectives is to improve the speed and quality of its review and approval programs. FDA accepts electronic lot release protocols and has issued guidance to assist manufacturers in this area. FDA believes that the increased use of computer-assisted protocol submissions will enhance the timeliness, effectiveness, and efficiency of the review process and reduce burdensome, nonessential hard-copy handling and storage.

FDA is not aware of any other improved technology to reduce the burden. FDA continues to pursue methods of applying technology to reduce the burden to the respondents of the information collection.

4. Efforts to Identify Duplication and Use of Similar Information

FDA is the only agency that requires the submission of samples and protocols for biological products for the purposes of lot release surveillance, licensing, or export. No other government agencies require similar information or data to be submitted. This information is not available from any other source.

5. Impact on Small Businesses or Other Small Entities

This collection of information applies to small as well as large facilities. Although FDA must apply the statutory and regulatory requirements equally to all enterprises, FDA does provide special help to small businesses. CBER’s Office of Communication, Outreach, and Development, Division of Manufacturer’s Assistance and Training, and CDER’s Office of Communication, Division of Drug Information and International and Consumer Assistance provide assistance to small businesses subject to FDA’s regulatory requirements.

6. Consequences of Collecting the Information Less Frequently

Less frequent collection of information will not provide the information that FDA needs to properly evaluate results of specific tests identified for lot release review in the license application.

There are no technical or legal obstacles to reducing the burden.

7. Special Circumstances Relating to the Guidelines of 5 CFR 1320.5

An applicant may be required to submit to FDA proprietary trade secret or other confidential information when submitting a protocol. FDA protects confidential information received from manufacturers to the extent permitted by law. In addition, the frequency of submissions may be more often than quarterly depending on the number of lots produced for a product over that time.

8. Comments in Response to the Federal Register Notice and Efforts to Consult Outside the Agency

In accordance with 5 CFR 1320.8(d), FDA published a 60-day notice in the FEDERAL REGISTER on February 17, 2012 (77 FR 9663), for public comment on the information collection provisions. No comments were received.

9. Explanation of Any Payment or Gift to Respondents

No payment or gift was provided to respondents.

10. Assurance of Confidentiality Provided to Respondents

The confidentiality of information received by FDA is consistent with the Freedom of Information Act (FOIA) and FDA’s published regulations under “Public Information” (21 CFR Part 20).

11. Justification for Sensitive Questions

Questions of a sensitive nature are not applicable to this information collection.

12. Estimates of Annualized Burden Hours and Costs

12a. Annualized Hour Burden Estimate

The total annual estimated burden for this collection of information is 20,572 hours.

Table 1 -- Estimated Annual Reporting Burden

21 CFR Section	No. of Respondents	No. of Responses per Respondent	Total Annual Responses	Average Burden per Response	Total Hours
610.2	73	92.9	6,782	3	20,346
660.6(b)	2	21.5	43	5	215
660.36(a)(2) and (b)	1	1	1	6	6
660.46(b)	1	1	1	5	5
Total	77		6,827		20,572

The burden estimate is for protocols required to be submitted with each sample. The collection of samples is not a collection of information under 5 CFR 1320.3(h)(2). Respondents to the collection of information under § 610.2 are manufacturers of licensed biological products. Respondents to the collection of information under §§ 660.6(b), 660.36(a)(2) and (b), and 660.46(b) are manufacturers of the specific products under these regulations. The estimated number of respondents for each regulation is based on the annual number of manufacturers that submitted samples and protocols for biological products, including submissions for lot release, surveillance, licensing, or export. Based on information obtained from FDA’s database system, approximately 77 manufacturers submitted samples and protocols in fiscal year (FY) 2011 under the regulations cited above. FDA estimates that approximately 73 manufacturers submitted protocols under § 610.2, and 2 manufacturers submitted protocols under the regulations for the specific products. FDA received no submissions under §§ 660.36 and 660.46; however FDA is using the estimate of one protocol submission under each regulation in the event that protocols are submitted in the future.

The estimated total annual responses are based on FDA’s final actions completed in FY 2011, which totaled 6,827, for the various submission requirements of samples and protocols for licensed biological products. The rate of final actions is not expected to change significantly in the next few years. The average burden per response is based on information provided by industry. The burden estimates provided by industry ranged from 1 to 5.5 hours. Under § 610.2, the average burden per response is based on the average of these estimates and rounded to 3 hours. Under the remaining regulations, the average burden per response is based on the higher end of the estimate (rounded to 5 or 6 hours) since more information is generally required to be submitted in the other protocols than under § 610.2.

12b. Annualized Cost Burden Estimate

The estimated annual cost to respondents is $1,316,608.00.

Activity	Total Burden Hours	Hourly Wage Rate	Total Respondent Costs
Reporting	20,572	$64.00	$1,316,608.00

The cost estimate is based on an average pay rate of $64.00/hour. This average is based on the salaries of an upper-level manager, a mid-level professional, and clerical support that may be involved in the preparation and submission of the protocol.

13. Estimates of Other Total Annual Costs to Respondents and/or Recordkeepers/ Capital Costs

There are no capital, start-up, operating or maintenance costs associated with this collection of information.

14. Annualized Cost to Federal Government

The estimated annualized cost to FDA is $1,024,050. The review of each protocol by FDA involves approximately six persons, at an average pay rate of $50.00/hour, who spend a total of approximately 3 hours per protocol. The estimate is based on FDA’s final actions completed in fiscal year 2011, which totaled 6,827. This estimate does not include the time related to the testing of samples, because the submission of samples is not a collection of information.

Activity	Number of Reviews	Review Time	Average Cost per Hour	Total Cost
Protocol Review	6,827	3 hrs.	$50.00	$1,024,050.00

15. Explanation for Program Changes or Adjustments

The previous burden estimate was 19,155 hours. The current increase to 20,572 hours (+1,417 hours) is mostly due to an increase in the total annual responses under § 610.2. The slight increase in burden is attributed to the normal variation in the submission of samples and protocols to FDA.

16. Plans for Tabulation and Publication and Project Time Schedule

There are no results to publish for this information collection.

17. Reason(s) Display of OMB Expiration Date is Inappropriate

FDA is not seeking approval to exempt the display of the expiration date of the OMB approval.

18. Exceptions to Certification for Paperwork Reduction Act Submissions

There are no exceptions to the certification.

6