21 CFR Chapter 1 Subchapter A Flashcards
GLP for nonclinical lab studies are intended to support what applications?
Research or marketing permits for products regulated by the FDA, including food and color additives, animal food additives, human and animal drugs, medical devices for human use, biological products, and electronic products
Define test artcile
Any food additive, color additive, drug, biological product, electronic product, medical device for human use, or other article subject to regulation
Define control article.
Any food additive, color additive, drug, biological product, electronic product, medical device for human use, or any article other than a test article, feed, or water administered to the test system for the purpose of establishing a basis for comparison with the test article
Define sponsor.
A person who initiates and supports, by provision of financial or other resources, a nonclinical lab study.
A person who submits a nonclinical study to the FDA in support of an application for a research or marketing permit.
A testing facility, if it both initiates and actually conducts the study.
Define testing facility.
Any establishment of person who actually conducts a nonclinical lab study.
Define test system.
Any animal, plant, microorganism, or subparts thereof to which the test or control article is administered or added for study, including those not treated with the test or control articles.
Define specimen.
Any material derived from a test system for examination of analysis.
Define raw data.
Any lab records or exact copies thereof that are the results of original observations and activities of a nonclinical lab study and are necessary for the reconstruction and evaluation of the report of that study.
Define quality assurance unit.
Any person or organizational element, except the study director, designated by the testing facility management to perform the duties relating to quality assurance of nonclinical lab studies.
Define study director.
The individual responsible for overall conduct of a nonclinical lab study.
Define bath.
A specific quantity or lot of a test or control article that has been characterized.
Define study initiation and completion date.
Date the protocol is signed by the study director or date the final report is signed by the study director.
The records inspection and copying requirement at testing facilities do not apply to what documents?
Quality assurance unit records of findings and problems or to actions recommended and taken.
When must a study director be designated?
Before the study is initiated.
What must test and control articles or mixtures be evaluated for?
Identity, strength, purity, stability, and uniformity
Who has overall responsibility for the technical conduct of the study, as well as interpretation, analysis, documentation, and reporting or results, and represents the single point of study control?
Study director
What must the master schedule sheet maintained by the quality assurance unit contain?
All nonclinical lab studies conducted at the testing facility, indexed by test article and containing the test system, nature of study, date study was initiated, current status of each study, identity of sponsor, and name of study director.
How often must quality assurance inspect each nonclinical lab study?
At intervals adequate to assure the integrity of the study.
When must problems found during the course of a QA study be brought to the attention of the study director?
Immediately, if such problems are likely to affect study integrity.
How often must QA submit written status reports on each study? To who?
Periodically, to management and study director
Which unit is responsible for reviewing the final study report? What must this group include with the report?
Quality assurance unit. Must prepare and sign a statement to be included with the final study report which specifies dates inspections were made and findings reported to the study director.
A testing facility shall have a sufficient number of animal rooms to assure what?
- Separation of species or test systems
- Isolation of individual projects
- Quarantine of animals
- Routine or specialized housing of animals
What studies may require isolation of studies?
Those with test systems or test/control articles known to be biohazardous, including volatile substances, aerosols, radioactive materials, and infectious agents.
What animals may require separate areas?
Housing of animals either known or suspected of being diseased, or of being carrier of disease
Storage areas for feed and bedding shall be separated from what areas?
Those housing the test systems.
As necessary to prevent contamination/mixup, there should be separate areas for what processes involving test and control agents?
Receipt and storage, mixing with a carrier, and storage of the mixtures.
Storage areas for the test and/or control article should be separate from what areas?
Areas housing test systems.
Where is raw data and specimens from completed studies stored?
In the archives, with access limited to authorized personnel.
What document designates the person responsible for routine equipment cleaning, maintenance, calibration, etc.?
The SOP
How are deviations to SOPs handled?
Must be authorized by the study director and shall be documented in the raw data. Sig. changes must be authorized in writing by management.
SOPs should be established for what? (12)
- Animal room prep
- Animal care
- Receipt, identification, storage, handling, mixing, and method of sampling of the test and control articles
- Test system observations
- Lab tests
- Handling of animals found moribund or dead during study
- Necropsy of animals or post-mortem exam of animals
- Collection and identification of specimens
- Histopathology
- Data handling, storage, and retrieval
- Maintenance and calibration of equipment
- Transfer, proper placement, and identification of animals
What must each lab area have immediately available?
Lab manuals and SOPs relative to the lab procedures being performed.
How must reagents and solutions in the lab area be labeled?
Indicate identity, titer or concentration, storage requirements, and expiration dates.
What must newly received animals undergo?
Isolation and verification of health status in accordance with acceptable veterinary medical practice.
Can animals be treated for disease? What must be documented?
May be treated for disease or signs of disease provided that it does not interfere with the study. Diagnosis, authorizations of treatment, description of treatment, and each date of treatment shall be documented and retained.
What animals require identification? Where should this information appear?
Warm-blood animals, excluding suckling rodents, use in lab procedures that require manipulations and observations over an extended period of time or in studies that require the animals to be removed from and returned to their home cage for any reason shall receive appropriate identification.
All information needed to specifically identify each animal within an animal housing unit shall appear on the outside of the unit.
How should animals of different species and on different studies be housed?
Animals of different species shall be housed in separate rooms when necessary.
Animals of the same species on or different studies should not ordinarily be house in the same room when inadvertent exposure to control or test articles or animal mixup could affect the outcome of either study.
If mixed housing is necessary, adequate differentiation by space and identification.
Per GLP, how often must animal cages, racks, and accessory equipment be cleaned and sanitized?
At appropriate intervals
What must feed and water be analyzed for and how often?
Periodically to ensure that contaminants known to be capable of interfering with the study and reasonably expected to be present are not present at levels above those specified in the protocol.
Per GLP, how often must bedding be changed?
As often as necessary to keep the animals dry and clean.
What information must be determined for each batch of test or control article?
The identity, strength, purity, and composition, or other characteristics which will appropriately define the test or control article. If the product is a marketed product used as a control article, it is characterized by its labeling.
How are storage containers for test articles assigned? What labeling information do they include?
Assigned to a particular test article for the duration of the study.
Labeled by name, chemical abstract number or code number, batch number, expiration date, and appropriate storage conditions PRN
Samples from each batch of test and control articles are retained for studies of which length?
More than 4 weeks duration.
What information about the test system must be included in the protocol?
Number, body weight range, sex, source of supply, species, strain, substrain, and age.
What information must specimens include?
Test system, study, nature, date of collection
How must data be collected? What happens if a change is needed?
Directly, promptly, and legibly in ink. Shall be dated on the date of entry and signed or initialed by the person entering the data.
If a change is needed, it must not obscure the original entry, shall indicate the reason for such change, and shall be dated and signed or identified at time of change.
How is automated data collection managed?
The individual responsible for direct data input is identified at the time of data input.
If a change is needed, it must not obscure the original entry, shall indicate the reason for such change, and shall be dated and signed or identified at time of change.
What specimens do not need to be retained?
Those obtained from mutagenicity tests and wet specimens of blood, urine, feces, and biological fluids.
How must material retained or referred to in the archives be identified?
Must be indexed to permit expedient retrieval.
How long must documents be retained?
- 2 years following the date on which an application for a research or marketing permit is approved by the FDA
- 5 years following the date that the results were submitted to the FDA in support of an application for a research or marketing permit. Same for maintenance and calibration results.
- 2 years since study was completed, if the study does not result in submission of the study results
- Only as long as the quality of wet specimens, article samples, and specifically prepared fragile materials can be maintained in a manner that affords evaluation.
May be as original copies or true copies.
When two storage lengths conflict, which wins?
Whichever period is shortest.
What occurs if a facility goes out of business?
All data, documentation, and other material is transferred to the archives of the sponsor of the study.
What are the grounds for disqualification of a testing facility?
- Failed to comply with one or more regulations
- Noncompliance adversely affected the validity of the nonclinical lab studies
- Other lesser regulatory actions have not or will probably not be adequate to achieve compliance with GLP regulations
What role disqualifies a facility?
The Commissioner
What occurs to studies done by a testing facility before or after a disqualification?
May be presumed to be unacceptable, and the person relying on the study may be required to establish that the study was not affected by the circumstances that led to the disqualification.
No study begun after the date of disqualification shall be considered in support of any application.
Must the FDA disqualify a facility if it refuses to consider a study that it finds was not conducted in accordance with GLP?
No
When must a Sponsor notify the Center regarding termination of a testing facility by a sponsor?
15 working days, must include reason
Can a testing facility be reinstated?
Yes, if they present in writing to the Commissioner reasons why they believe they should be reinstated and a detailed description of the corrective actions it has taken or intends to take to assure that the acts or omissions which led to its disqualification will not recur.
Can condition reinstatement upon testing facility being found in compliance with an inspection.
