美国FDA对GLP常见问题的答复(中文版)

3. Do the GLPs require that access to animal rooms be limited only to authorized individuals?

No. However, undue stresses and potentially adverse influences on the test system should be mimimized.

Section 58.45 Animal Supply Facilities.

No questions were asked on the subject.

Section 58.47 Facilities for Handling Test and Control Articles.

1. Do test and control articles have to be maintained in locked storage units?

No, but accurate records of test and control article accountability must be maintained.

Section 58.49 Laboratory operation areas.

No questions were asked on the subject.

Section 58.51 Specimen and data storage facilities.

1. What do the GLPs require with regard to facilities for the archives?

Space should be provided for archives limited to access by authorized personnel. Storage conditions should minimize deterioration of documents and specimens.

Section 58.53 Administrative and personnel facilities.

No questions were asked on the subject.

SUBPART D

EQUIPMENT

Section 58.61 Equipment design.

No questions were asked on the subject.

Section 58.63 Maintenance and calibration of equipment.

1. Has FDA established guidelines for the frequency of calibration of equipment (balances) used in nonclinical laboratory studies?

The agency has not established guidelines for the frequency of calibration of balances used in nonclinical laboratory studies. This would be a large undertaking in part due to the wide variety of equipment that is available and to the differing workloads that would be imposed on the equipment. It is suggested that you work with the

equipment manufacturers and your study directors to arrive at a suitable calibration schedule. The key point is that the calibration should be frequent enough to assure data validity. The maintenance and calibration schedules should be part of the SOPs for each instrument.

2. When an equipment manufacturer performs the routine equipment maintenance, do the equipment manufacturer's maintenance procedures have to be described in the facilities' SOPs?

No. The facilities' SOPs would have to state that maintenance was being performed by the equipment manufacturer according to their own procedures.

SUBPART E

TESTING FACILITIES OPERATION

Section 58.81 Standard Operating Procedures.

1. What amount of detail should be included in the standard operation procedures (SOPs)?

The GLPs do not specify the amount of detail to be inculded in the SOPs . The SOPs are intended to minimize the introduction of systematic error into a study by ensuring that all personnel will be familiar with and use the same procedures. The adequacy of the SOPs is a key responsibility of management. A guideline of

adequacy that could be used is to determine whether the SOPs are understood and can be followed by trained laboratory personnel.

2. Can the study director authorize changes in the SOPs?

No. Approval of the SOPs and changes thereto is a function of laboratory management.

3. How many copies of the complete laboratory SOPs are needed?

Each work station should have access to the SOPs applicable to the work performed at the station. A complete set of the SOPs, including authorized amendments, should be maintained in the archives.

4. Who approves the SOPs of the Quality Assurance Unit?

Laboratory Management.

5. To what extent are computer programs to be documented as SOPs?

The GLPs do not specify the contents of individual SOPs, but the SOP that deals with computerized data acquisition should include the purpose of the program, the

specifications, the procedures, the end products, the language, the interactions with other programs, procedures for assuring authorized data entry and access, procedures for making and authorizing changes to the program, the source listing of the program and perhaps even a flow chart. The laboratory's computer specialists should determine what other characteristics need to be described in the SOP.

Section 58.83 Reagents and solutions.

1. What are the GLP requirements for labeling of reagents purchased directly from manufacturers?

All reagents used in a nonclinical laboratory have to be labeled to indicate identity, titer or concentration, storage requirements, and expiration date. Purchased reagents usually carry all these items except for the expiration date, so the laboratory should label the reagent containers with an expiration date. The expiration date selected should be in line with laboratory experience and need not require specific stability testing.

2. How extensive should the procedures be for confirming the quality of incoming reagents used in nonclinical laboratory studies?

Laboratory management should make this decision but the SOPs should document the actual procedures used.

3. Do the procedures used for preparing the S9 activator fraction (liver microsomal fraction from rats challenged with a toxin) have to be performed in accord with the GLPs?

No. The GLPs consider the S9 activator fraction to be a reagent. Therefore, it must be labeled properly, stored properly, tested prior to use in accord with adequate SOPs, and it can not be used if its potency is below established specifications.

4. Do the GLPs require the use of product accountability procedures for reagents and chemicals used in a nonclinical laboratory study? No.

Section 58.90 Animal care.

1. Can diseased animals received from a supplier be diagnosed, treated, certified \

The GLPs provide for this procedure by including provisions directed towards animal quarantine and isolation. The question of whether such animals can be entered into a study, however, is a scientific one that should be answered by the

veterinarian-in-charge and the study director and other scientists involved in the study.

2. Do the GLPs prohibit the use of primates for multiple nonclinical laboratory studies?

No. Again, the question is a scientific one and the potential impact of multiple use on study interpretation should be carefully assessed.

3. Is a photocopy of an animal purchase order which has been signed and dated by the individual receiving the shipment sufficient proof of animal receipt?

Yes, but actual shipping tickets are also acceptable.

4. Does FDA have guidelines for animal bedding?

No, but the GLPs prohibit the use of bedding which can interfere with the objectives of the study.

5. Does FDA permit the sterilization of animal feed with ethylene oxide. No.

6. For certain test system (timed-pregnant rodents), it is not possible to use long quarantime periods. Do the GLPs specify quarantine periods for each test system?

No. The quarantine period can be extablished by the veterinarian in charge of animal care and should be of sufficient length to permit evaluation of health status.

7. How are feed and water contaminants to be dealt with?

The protocol should include a positive statement as to the need for conducting feed analysis for contaminants. If analysis is necessary, the identities and specifications for the contaminants should be determined by the study scientists. Water contaminants can be handled similarly.