laboratory study, it is recommended, but not required, that the study be conducted in accord with GLPs in order to ensure valid baseline data.

5. The definition of \ What is a field trial in animals?

A field trial in animals is similar to a human clinical trial. It is conducted for the purpose of obtaining data on animal drug efficacy and it is excluded from coverage under the GLPs.

6. Necropsies are done by prosectors trained by and working under the supervision of a pathologist. The necropsy data are recorded by the prosector on data sheets, and when making the final report, the pathologist summarizes the data collected by the prosector as well as by him/herself. What constitutes the raw data in this example?

Both the prosector's data sheets as well as the signed and dated report of the pathologist would be considered raw data.

7. Is a computer print-out derived from data transferred to computer media from laboratory data sheets considered to be raw data? No.

8. Are the assay plates used in the 10t1/2 mammalian cell transformation assay considered to be specimens? Yes.

9. If a firm uses parapathologists to screen tissue preparations, are the parapathologists' data sheets considered to be raw data? Yes.

Section 58.10 Applicability to studies performed under grants and contracts.

1. Certain contracts specify that a series of nonclinical laboratory studies be done on a single test article. Do the GLPs permit the designation of different study directors for each study under the contract? Yes.

2. Do the GLPs require that a sponsor approve the study director for a contracted study?

No. Testing facility management designates the study director.

3. A firm functions as a primary contractor for nonclinical laboratory studies. The actual studies are then subcontracted to nonclinical laboratories. Is the firm considered to be a \

The GLPs define \laboratory study. Sponsorship in the cited example would be determined by the specific provisions of the contract.

4. Who is responsible for test article characterization - the sponsor or the contractor?

The GLPs do not assign the responsibility in this area. The matter is a subject of the specific contractual arrangement between the sponsor and the contractor.

5. Do contract laboratories have to show the sponsor's name on the Master Schedule Sheet or can this information be coded?

The information can be coded but the code must be revealed to the FDA investigator on request.

6. A sponsor desires to contract for a nonclinical laboratory study to be conducted in a foreign laboratory. Must the sponsor notify the foreign laboratory that compliance with the U.S. GLPs is required? Yes.

7. Must a contractor include in the final report information on test article characterization and stability when such information has been collected by the sponsor?

No. The contractor should identify in its final report which information will be subsequently supplied by the sponsor.

8. Must a sponsor reveal toxicology data already collected on a test article to a contract laboratory?

No. If use of the test article involves a potential danger to laboratory personnel, the contract laboratory should be advised so that appropriate precautions can be taken.

Section 58.15 Inspection of a testing facility.

1. What is the usual procedure for the issuance of a form FD-483?

The FD-483 is the written notice of objectionable practices or deviations from the regulations that is prepared by the FDA investigator at the end of the inspection. The items listed on the form serve as the basis for the exit discussion with laboratory management at which time management can either agree or disagree with the items and can offer possible corrective actions to be taken. Management may also respond to the district office in writing after it has had sufficient time to properly study the FD-483.

2. Will a laboratory subsequently be notified of GLP deviations not listed on the FD-483?

This does happen. The FDA investigator prepares an establishment inspection report (EIR) which summarizes the observations made at the laboratory and which contains exhibits concerning the studies audited (Protocols, SOPs, CV's, etc.). The EIR is then reviewed by District personnel as well as headquarters personnel. This review may reveal additional GLP deviations that should be and are communicated to laboratory management.

3. What kinds of domestic toxicology laboratory inspections does FDA perform and how frequently are they done?

FDA performs four kinds of inspections related to the GLPs and nonclinical

laboratory studies. These include: A GLP inspection - an inspection undertaken as a periodic, routine determination of a laboratory's compliance with the GLPs, it

includes examination of an ongoing study as well as a completed study; A data audit - an inspection made to verify that the information contained in a final report

submitted to FDA is accurate and reflected by the raw data; A directed inspection - any of a series of inspections conducted for various compelling reasons (questionable data in a final report, tips from informers, etc.); A followup inspection - an inspection made sometime after a GLP inspection which revealed objectionable practices and conditions. The purpose of the followup inspection is to assure that proper corrective actions have been taken. GLP inspections are scheduled once every two years whereas the other kinds of inspections are scheduled as needed.

4. Should GLP investigators comment on the scientific merits of a protocol or the scientific interpretation given in the final report?

No. Their function is strictly a noting of observation and verification. Scientific judgments are made by the respective headquarters review units that deal with the test article.

5. Can a GLP EIR be reviewed by laboratory management prior to issuance?

No. The GLP EIR is an internal agency document which reflects the observations and findings of the FDA investigator. It can not be released to anyone outside the agency until agency action has been completed and the released copy is purged of all trade secret information. Laboratories that disagree with portions of the EIR should write a letter which contains the areas of disagreement to the local FDA District

Office. The laboratories can ask that their letters accompany the EIR whenever it is requested under the Freedom of Information Act.

6. Can FDA investigators take photographs of objectionable practices and conditions?

It is the agency position that photographs can be taken as a part of the inspection and this position has been sustained by a District Court decision.

7. The GLP Compliance Program requires the FDA investigator to select an ongoing study in order to inspect current laboratory operation. What criteria are used to select the study?

The studies are selected in accord with agency priorities, i.e. the longest term study on the most significant product.

8. Does FDA inspect international nonclinical laboratoies once every two years?

No. Overseas laboratories are scheduled for inspection on the basis of having submitted to FDA the results of signigicant studies on important products.

9. What background materials are used by agency investigators to prepare for a GLP inspection?

Prior to an inspection, the folloing materials are ususally reviewed:

(a) The GLP regulations;

(b) The Management Briefings Post-Conference Report;

( c) Assorted memoranda and policy issuances;

(d) The GLP Compliance Program;

(e) The protocol of an ongoing study, if available;

(f) The final report of a completed study, if available;

(g) The inspection report of the most recent inspection.