ss0119 0808

Good Laboratory Practice (GLP) for Non-clinical Laboratory Studies

OMB No. 0910-0119

Supporting Statement

A. JUSTIFICATION

1. Circumstances Necessitating Information Collection

The Federal Food, Drug, and Cosmetic Act and related statutes require manufacturers of human drugs and biological products, animal drugs, medical devices, and food additives to demonstrate the safety and utility of their product by submitting applications to the FDA for research or marketing permits. Such applications contain, among other important items, full reports of all studies done to demonstrate product safety in man and/or other animals. In order to ensure adequate quality control for these studies and to provide an adequate degree of consumer protection, the agency promulgated the Good Laboratory Practice (GLP) regulations (21 CFR Part 58) (Attachment A). The regulations specify minimum standards for the proper conduct of safety testing and contain sections on facilities, personnel, equipment, standard operating procedures, test and control articles, quality assurance, protocol and conduct of a safety study, records and reports, and laboratory disqualification.

The various acts enforced by FDA require an adequate showing of product safety prior to introduction into the marketplace. The GLPs ensure that the data by which safety is shown have been collected in a valid and accurate manner. Therefore, FDA is requesting the extension of the approval by the Office of Management and Budget (OMB) under the Paperwork Reduction Act for the following information collection requirements. This OMB clearance is essential if FDA is to enforce the GLPs and to assure the availability of safe and useful regulated products to American Consumers. Accordingly, we are requesting the approval of the following specific requirements:

21 CFR 58.29 (b) - Recordkeeping

Personnel job descriptions and experience, and training records

21 CFR 58.35 (b) (7) - Reporting

Quality assurance unit inspection statement

21 CFR 58.35 (b) (1), (2) (3), and (c) - Recordkeeping

Master schedules, protocols, inspection reports, and standard operating procedures

21 CFR 58.63 (b) and (c) - Recordkeeping

Equipment inspection, maintenance, calibration, and testing records

21 CFR 58.81 (a), (b), and (c) - Recordkeeping

Standard operating procedures

21 CFR 58.90 (c) and (g)- Recordkeeping

Documentation of feed and water analysis and animal treatments

21 CFR 58.105 (a) and (b) - Reporting

Test and control article characterization

21 CFR 58.107 (d) - Recordkeeping

Test article accountability records

21 CFR 58.113 (a) - Reporting

Testing of mixtures

21 CFR 58.120 - Recordkeeping

Protocols and their amendments

21 CFR 58.185 - Reporting

Final report of nonclinical laboratory studies

21 CFR 58.195 - Recordkeeping

Documentation, records, and raw data

2. How, By Whom, Purpose of Collection

The information is collected as part of an application for a research or marketing permit that is voluntarily submitted to FDA by persons desiring to market new products. Failure to include the information in a filing to FDA would mean that agency scientific experts could not make a valid determination of product safety. FDA receives, reviews and approves hundreds of new product applications each year based on information received.

The recordkeeping requirements are necessary to document the proper conduct of a safety study, to assure the quality and integrity of the resulting final report, and to provide adequate proof of the safety of regulated products. FDA conducts on-site audits of records and reports, during its inspections of testing laboratories, to verify reliability of results submitted in applications. Each year FDA conducts audits and inspections of over 100 studies, at as many laboratories.

3. Consideration Given to Information Technology

FDA, as an agency, is aware of the dramatic cost improvements possible through computerization and is actively encouraging electronic recordkeeping and electronic submission of new product applications. On March 20, 1997, FDA published [62 FR 13430] a final rule that provides criteria for acceptance by FDA, under certain circumstances, of electronic records, electronic signatures, and handwritten signatures executed to electronic records as equivalent to paper records and handwritten signatures executed on paper. These regulations, which apply to all FDA program areas, are intended to permit the widest possible use of electronic technology. It is too early in the implementation of the new regulation to determine the affect on the information collection burden of the GLP regulations. Although the GLP regulations have always accommodated the use of electronic record technology, the new regulation will permit a broader use of the technology and ensure that future improvements to occur unimpeded by regulation and based solely upon wider availability and acceptance of improved information technology by the regulated industry.

4. Identification of Information

The information collection requirements in the GLPs are unique to the testing facility and to each product. There is no duplication. There are no similar data anywhere that could satisfy the purposes set forth in items 1 and 2.

5. Small Business Impact

The current regulations do not have an impact on small business that would require a regulatory flexibility analysis.

6. Less Frequent Information Collection

FDA has no control over the frequency of the information collection. The information is voluntarily submitted by persons wishing to gain approval of research or marketing applications. Each application must contain the required information. Failure to include the information in a filing to FDA would mean that agency scientific experts could not arrive at a valid decision on product safety.

7. Information Collection Circumstances

The subject information collection requirements are consistent with 5 CFR §1320.6 with the exception of the 5-year retention of records for the toxicology studies. This extended retention period is necessary because it is approximately a 5-year process. These records must be available to FDA inspectors so they can be examined during on-site visits to verify the quality and integrity of the data.

8. Consultations with Persons Outside FDA

FDA has extensive contacts and consults with the affected industry, other government agencies, and international organizations which have an interest in the implementation of the GLP regulations. The regulations have been revised four times since their inception in 1978, to refine and improve their application. These consulting efforts continue.

In accordance with 5 CFR 1320.8(d), on July 22, 2004 in Volume 69, No. 140, page 43853 (69 FR 43853) a 60-day notice for public comment was published in the Federal Register. No comments were received from the public in response to that notice.

FDA regularly interacts with trade associations such as the Society of Quality Assurance (SQA) and the Pharmaceutical Manufacturers Association (PhRMA) which represent a broad cross-section of GLP laboratories, and has not received requests to modify the recordkeeping or reporting requirements of the GLP regulations. FDA is also actively involved, internationally, with the Organization for Economic Cooperation and Development (OECD) effort to draft international GLP principals.

At the present time no significant revisions to the GLP regulations have been presented, and no revisions have occurred in the last three years.

9. Payment or Gift

All records and reports maintained by FDA are kept in limited access areas. The materials are kept confidential in accordance with 18 U.S.C. 1905 as well as section 301 (j) of the Federal Food, Drug, and Cosmetic Act.

10. Confidentiality Provisions

The information collection does not contain questions pertaining to sex, behavior, attitude, religious beliefs, or any matters that are commonly considered private or sensitive in nature.

11. Privacy

The government’s cost to review the reports specifically covered by these regulations is negligible. Applications for research or marketing applications submitted to the FDA are usually large and contain a great deal of information on the safety, utility, manufacturing and control chemistry, labeling, and other characteristics of the product. The cost to review the overall applications is included in the cost section of Requests for OMB Approval for each specific application.

The cost to the respondents is estimated by assuming a cost of $31.36 per hour for 1,301,400 burden hours for a total cost of $40,811,904.

12. Burden of Information Collection

The annual burden for the information collection requirements in these regulations is estimated at 1,311,157 burden hours.

The agency used estimates from 300 domestic nonclinical toxicology laboratories and a total of 18,100 non-clinical safety studies per year to calculate the total workload. The estimates, per activity, were developed and then multiplied by either the number of laboratories or the number of nonclinical safety studies, as appropriate. These estimates were reviewed for the current submission by the personnel in the agency most familiar with this program. They were found to accommodate current laboratory practice.

13. Costs to Respondents

There have been no amendments to existing collections.

14. Costs to Federal Government

This does not apply.

Estimated Annual Reporting Burden*
21 CFR Section	No. of Recordkeepers	Annual Frequency per Recordkeeping	Total Annual Records	Hours per Recordkeeper	Total Hours
58.35(b)(7)	300	60.25	18,075	1	18,075
58.185	300	60.25	18,075	27.65	499,774
Total					517,849

* There are no capital costs or operating maintenance costs associated with this collection of information.

Estimated Annual Recordkeeping Burden*
21 CFR Section	No. of Recordkeepers	Annual Frequency per Recordkeeping	Total Annual Records	Hours per Recordkeeper	Total Hours
58.29(b)	300	20	6,000	.21	1,260
58.35(b)(1)-(6), (c)	300	270.76	81,228	3.36	279,926
58.63(b), (c)	300	60	18,000	.09	1,620
58.81(a)-(c)	300	301.8	90,540	.14	12,676
58.90(c), (g)	300	62.7	18,810	.13	2,445
58.105(a), (b)	300	5	1,500	11.8	17,700
58.107(d)	300	1	300	4.25	1,275
58.113(a)	300	15.33	4,599	6.8	31,273
58.120	300	15.38	4,614	32.7	150,878
58.195	300	251.5	75,450	3.9	294,255
Total					793,308

*There are no capital costs or operating maintenance costs associated with this collection of information.

15. Reason for Change

Updated census of active nonclinical laboratories.

16. Statistical Reporting

The reporting requirements contained in this proposal are not statistical in nature and the records are not published for statistical use.

16. Display of OMB Approval Date

We are not seeking approval to exempt display of the OMB approval date on any documents that are associated with this information collection.

16. Exceptions to “Certification for Paperwork Reduction Act Submissions”

There are no exceptions to “Certification for Paperwork Reduction Act Submissions” for this collection of information.