No. These can be filed in a retrievable fashion such as chronological in the archive.

2. Where should the QAU records be retained?

At the completion of a study, QAU records and inspection reports should be retained in the archives.

3. At the termination of a nonclinical laboratory study, can a contractor send all of the raw data, study records, and specimens to the sponsor of the study?

The regulations do not specifically address this issue. Section 58.195(g) requires contract laboratories that go out of business to transfer all raw data and records to the sponsor. Likewise, Section 58.190(b) permits raw data and study records to be stored elsewhere (other than the contract laboratory location) provided that the

contract laboratory's archives have reference to the other locations and provided that the final study report identifies the other locations as directed by Section 58.195(a)(13).

Consequently, it is permissible for the sponsor to retain all raw data and records from the date of termination of the nonclinical laboratory study. Common sense dictates, however, that the contract laboratory keep copies of the material that has been forwarded to the sponsor.

4. Can a study director or a pathologist be responsible for storing and retaining specimens and raw data?

Yes, the GLPs permit multiple archival locations provided that these locations are identified in the central archives and that they provide adequate storage conditions and authorized access features.

Section 58.195 Retention of records.

1. With regard to blood and urine specimens which are analyzed for both labile and stable constituents, is it necessary to retain the specimen until the most stable constituent deteriorates?

All specimens should be retained for the term required by the regulations or for as long as their quality permits meaningful reevaluation, whichever is shorter.

2. For a GLP regulated metabolism study, whole tissuses are homogenized and aliquots thereof are used for analysis. Is it necessary to retain all of the remaining homogenate as a reserve sample?

No, it is only necessary to retain a representative sample large enough to repeat the original measurements.

3. If animals used in acute studies are subjected to necropsy, is it necessary to retain the organs as study specimens? Yes.

CONFORMING AMENDMENTS

1. Do acute studies not done in conformity with the GLPs have to be identified in the conforming amendment statement? Yes.

2. How extensive should the conforming amendment statement be for preliminary exploratory studies that are exempt from GLP coverage?

The statement should be brief and indicate the GLP-exempt status of the study.

3. For contracted nonclinical laboratory studies, who is responsible for preparing the GLP compliance statement required by the conforming amendments?

The preparation of the conforming amendment statement is the responsibility of the product sponsor and the statement should be submitted as part of the application for a research or marketing permit. The contractor, however, should identify for the sponsor those non GLP practices which were used in each nonclinical laboratory study so that a proper conforming amendment statement can be prepared.

4. Who signs the conforming amendment statement?

This can be the same individual in the firm who signs the official application for a research or marketing permit.

5. Is a specific conforming amendment statement as required by Part 314(f)(7) to be prepared for each nonclinical laboratory study?

Yes. GLP deviations have to be identified for all nonclinical laboratory studies. This can be done by preparing a single comprehensive statement which includes all safety studies in the respective official filing. The conforming amendment statement in the official filing should be located in proximity to the animal stafty studies section.

GENERAL

1. Have any nonclinical laboratories been disqualified since June 20, 1979? No.

2. Does FDA reject nonclinical laboratory studies that have not been conducted in full compliance with the GLPs?

Not necessarily. The GLP Compliance Program provides guidance on the issue. For FDA to reject a study, it is necessary to find that there were deviations from the GLPs and that these deviations were of such a nature as to compromise the quality and integrity of the study covered by the agency inspection.

3. Must copies of the SOPs be submitted along with an application for a research or marketing permit? No.

4. What should be done about nonclinical laboratory studies that are stopped prior to completion?

The agency recognizes that a variety of circumstances (disease outbreak, power

failures, etc.) can lead to the premature termination of a nonclinical laboratory study. In thses cases, a short final report should be prepared that describes the reasons for study termination.

5. Has the agency established permissible limits for environmental controls (temperature, humidity and lighting) for the animal facilities?

No, these are scientific matters that should be described in the protocol and/or the SOPs. Of course, accurate records should be maintained.