10. How long does FDA allow a laboratory to effect corrective actions after an inspection has been made?

If the results of an inspection reveal that significant deviations from the GLPs exist, the laboratory will be sent a regulatory letter that lists the major deviations and that requests a response within 10 days. The response should describe those actions that the laboratory has taken or plans to take to effect correction. The response should also encompass items that were listed on the FD-483 and those that were discussed during the exit discussion with laboratory management. A specific time table should be given for accomplishing the planned actions. The reasonableness of the time table will be determined by FDA compliance staff, based on the needs of the particular situation.

For less significant deviations, the laboratory will be sent a Notice of Adverse

Findings letter that also lists the deviations but that requests a response within 30 days. Again, the reasonableness of the response will be determined by FDA staff.

11. Does a laboratory's responsibility for corrective action listed on a FD-483 begins at the conclusion of an inspection or upon receipt of correspondence from the originating bureau in which corrective action is requested?

The FD-483 lists observations of violative conditions that have the capability to adversely affect nonclinical laboratory studies. Corrective actions should be instituted as soon as possible.

12. Does FDA preannounce all GLP inspections?

Laboratory management is informed of all routine GLP inspections prior to the inspection, but special compliance or investigative inspections need not be preannounced.

SUBPART B

ORGANIZATION AND PRESONNEL

Section 58.29 Personnel.

1. For what sequence in the supervisory chain should position descriptions be available?

Position descriptions should be available for each individual engaged in or supervising the conduct of the study.

2. Should current summaries of training and experience list attendance at scientific and technical meetings?

Yes. The agency considers such attendance as a valuable adjunct to the other kinds of training received by laboratory personnel.

3. If certain specialists (pathologists, statisticians, ophthalmologists, etc.) are

contracted to conduct certain aspects of a study, need they be identified in the final report? Yes.

4. Does the QAU have to be composed of technical personnel?

No. Management is, however, responsible for assuring that %understand the functions they are to perform\ and that each

individual engaged in the study has the appropriate combiantion of education, training and experience (Section 58.29(a)).

Section 58.31 Testing Facility Management.

1. Can the study director be the chief executive of a nonclinical laboratory?

No. The GLPs require that there be a separation of function between the study

director and tha QAU director. In the example, the QAU director would be reporting to the study director.

Section 58.33 Study director.

1. The GLPs permit the designation of an \responsible for a study when the study director is on leave. Should study records identify the designated \ Yes.

2. Is the study director respopnsible for adherence to the GLPs? Yes.

Section 58.35 Quality Assurance Unit.

1. As a QAU person, I have no expertise in the field of pathology. How do I audit pathology findings?

The QAU is not expected to perform a scientific evaluation of a study nor to

\ QAU inspections are made to ensure that the GLPs, SOPs and protocols are being followed and that the data

summarized in the final report accurately reflect the results of the study. A variety of procedures can be used to do this but certainly the procedures should include an examination and correlation of the raw data records.

2. Must the QAU keep copies of all protocols and amendments and SOPs and amendments?

The QAU must keep copies of all protocols as currently amended. The only SOPs that the QAU are required to keep are those concerned with the operations and procedures of the QAU.

3. Does the QAU have to monitor compliance with regulations promulgated by other government agencies?

The GLPs do not require this.

4. Can an individual who is involved in a nonclinical laboratory study perform QAU functions for portions of the study that the individual is not involved with?

No. However, the individual can perform QAU functions for a study that he/she is not involved with.

5. Does the QAU review amendments to the final report? Yes.

6. What studies are required to be listed on the master schedule sheet?

The master schedule sheet should list all nonclinical laboratory studies conducted on FDA regulated products and intended to support an application for a research or marketing permit.

7. May the QAU in its periodic reports to management and the study director recommend actions to solve existing problems?

Yes.

8. If raw data are transcribed and sent to the sponsor for (a) preparing the data in computer format or (b) performing a statistical analysis, what are the responsibilities of the QAU?

For (a) the QAU should assure that the computer formatted data accurately reflect the raw data. For (b) the statistical analyses would comprise a report from a

participating scientist, therefore it should be checked by QAU and appended to the final report.

9. Can the QAU also be responsible for maintaining the laboratory archives? Yes.

10. Can a QAU be constituted as a single person?

Yes, provided that the workload is not excessive and other duties do not prevent the person from doing an adequate job. It would be prudent to designate an alternate in case of disability/vacations/etc.

11. Who is responsible for defining study phases and designating critical study phases and can these be covered in the SOP?

The GLPs do not isolate this responsibility. Logically, the task should be done by the study director and the participation scientists working in concert with the QAU and laboratory management. It can be covered by an SOP.

SUBPART C

FACILITIES

Section 58.41 General.

No question were asked on the subject.

Section 58.43 Animal Care Facilities.

1. Do the GLPs require clean/dirty separation for the animal care areas?

No. They do require adequate separation of species and studies.

2. Do the GLPs require that separate animal rooms be used to house test systems and conduct different studies?

No. The GLPs require separate areas adequate to assure proper separation of test systems, isolation of individual projects, animal quarantine and routine or specialized housing of animals, as necessary to achieve the study objectives.