FDA GLPs Flashcards
When was the Federal Food, Drug, and Cosmetic Act passed?
1938
When were Good Laboratory Practices adopted in the CFR?
1979
Which organization oversees GLP?
FDA
What is the CFR code of GLP standards?
7 USC 21 CFR, part 58
What do GLPs apply to?
all studies supporting application or permit for FDA, EPA
Includes food/color additives, drugs, medical devices, biological products, and electronic products but NOT basic exploratory studies, testing in support of manufacturing, or clinical human studies or clinical/field trials in animals
What is the term for a food additive, color product, drug, or article subject to regulation?
test article
What is a test article?
a food additive, color product, drug, biological product, electronic product, human medical device, or article subject to regulation?
What is a control article?
Anything other than a test article, food or water given to a test system to compare to the test article
What is the term for anything other than a test article, food or water given to a test system to compare to the test article?
control article
What is the term for the person who initiates and supports a nonclinical lab study or submits the study report to FDA or EPA in support of a permit?
Sponsor
What is the testing facility?
The person/facility that actually conducts a study
What is a test system?
Any animal, plant, microorganism, or parts thereof to which a test or control article is administered or added for a study
Who comprises the QA unit?
People designated by the testing facility management to perform QA duties, except the study director
Who is the individual responsible for the overall conduct of a study?
study director
What is the study initiation date?
date the protocol is signed by the study director
What is the study completion date?
The date the final report is signed by the study director
A testing facility refuses to allow inspection of the facility. Will FDA consider the study in support of an application?
No.
What must be made available to FDA inspectors at reasonable times?
- inspection of the facility
- inspection of records and specimens required to be maintained
Can the FDA copy findings/problems or actions recommended and taken by the QA team?
Not without permission
Can the FDA copy and study records and specimens required to be maintained by law?
Yes, with the exception of some QA documents
Does training and experience need to be documented for GLP?
Yes.
When can an individual with an illness that could affect the study return?
When the condition is corrected
When must a qualified study director be designated?
Before the study is initiated- and provisions for replacement need to be made as well
What aspects of the test article and control article must be appropriately tested?
identification, strength, purity, stability, uniformity
Any deviations from regulations reported by the QA unit must be reported to whom?
The study director
Who or what represents the single point of study control?
The study director
Who is responsible for monitoring each study to assure management that the facilities, equipment, personnel, methods, practices, records and controls are in compliance with regs?
The quality assurance unit
Can the QA unit and study personnel be part of the same unit with the same reporting structure?
No- they have to have separate reporting lines and QA must be independent of study personnel
Who has responsibility to maintain a copy of the master schedule sheet of all nonclinical lab studies conducted at the testing facility?
QA unit
How does the master schedule sheet maintained by QA need to be indexed?
by test article
Who must inspect each study at intervals to assure the integrity of the study and how often must they be inspected?
QA inspects
Every study has to be inspected at least once
Who does QA submit written status reports to?
management and the study director
Can feed storage for a GLP study be located in the same room housing an animal test system?
No- must be separate from areas that house test system
Which facilities need to be separate for test and control articles?
- receipt and storage facilities
- mixing of article with a carrier
- storage of articles and mixtures
When must equipment be tested, calibrated and/or standardized according to manufacturer’s recommendations?
If it is used in generation, measurement, or assessment of data
What is the term for comparison of a measurement or instrument of known accuracy to detect any variation in accuracy?
calibration
What is the term for comparison of equipment with a standard of known and acceptable values?
Standardization
Who must authorize all deviations in a study from SOPs?
Study director
Deviations also have to be documented in the raw data
What procedures must SOPs be established for?
All of the things: animal room prep, animal care, receipt and handling, storage, mixing, sampling of test or control articles, necropsy and histopathology, data handling, retrieval, equipment maintenance, etc.
Where must lab manuals and SOPs be kept?
They must be immediately available in or near the room where activities occur
A powder is used in a GLP study that does not have an expiration date. How is this recorded?
On the label with a ‘none’ or ‘n/a’ for expiration date
An animal contracts an illness while on a GLP study. The treatment would interfere with the study. Can the animal be treated and still remain on study?
No- treatment can’t interfere with the study and has to be properly authorized and documented
What animals must be uniquely identified for the study?
any warm-blooded animal that requires manipulation or animals to be removed from their cage
Suckling rodents don’t count
Cage cards only work if the cage is a unit and the animal is never taken from and returned to the cage during the study
Who determines the stability of each test or control article?
The sponsor or the test facility
When does the stability of the test or control article need to be determined?
Before the study initiation or concomitantly according to SOPs
How long must a study be performed before a sample from each batch of test and control articles must be retained for the period of time required in GLP?
> 4 weeks duration
What must be written on each storage container for a test or control article?
name chemical abstract number or code number batch number expiration date (if any) storage conditions necessary to maintain the identity, strength, purity, and composition of the article if needed.
Can a test article be put into a storage container that used to be used for the control article in the same study?
No- storage containers are assigned to a particular test article for the duration of the study
What must be clearly indicated in the approved written protocol for each study?
objectives and all methods for conduct of the study
What must be included in the protocol?
(1) descriptive title and statement of study purpose
(2) Id of test and control articles
(3) name of sponsor and name/address of testing facility
(4) number, BW range, sex, source of supply, species, strain, substrain, and age of test system
(5) procedure for ID of test system
(6) description of experimental design
(7) description and/or ID of diet, solvent, emulsifier, etc. including acceptable levels of contaminants
How should data be recorded?
directly, promptly, legibly
in ink or electronically
When should data entries be dated?
on the date of entry
Who should sign or initial data when it is entered?
the person entering the data
How should changes in data entries be made?
Without obscuring the original entry (ex. single line)
Indicating the reason for the change
Dated and signed/ID’ed at the time of change
What must be retained after the study?
all raw data, documentation, protocols, final reports, specimens generated as a result of nonclinical lab study must be retained
Do specimens obtained from mutagenicity tests need to be retained?
no
Do wet specimens of blood, urine, feces, and biological fluids need to be retained?
No
How long should records be retained if more than one guideline applies?
Shortest timeline is followed
How long should an application for a research or marketing permit be retained?
2 years
How long should summaries of training, experience, and job descriptions be retained?
2 years or 5 years
How long should records of maintenance and calibration and inspection of equipment be retained?
2 years or 5 years
How long should studies supporting investigational new drug applications be retained?
5 years
How long should applications for investigational device exemptions be retained?
5 years
What is an IND?
investigational new drug application
What is an IDE?
investigational device exemption
How long should non-excluded wet specimens be kept for?
as long as the quality of the preparation affords evaluation but no longer than 2 or 5 years
What must be included in the final report?
(1) Name and address of the facility performing the study and dates on which the study was initiated and completed
(2) Objectives and procedures stated in the approved protocol, including changes to the original protocol
(3) statistical methods for data analysis
(4) test and control articles
(5) stability of test and control articles under administration conditions
(6) description of methods used
(7) description of test system used
(8) description of dose, dosage regimen, route of administration, and duration
(9) description of circumstances that may have affected the quality or integrity of data
(10) name of the study director, names of other scientists or professionals, and name of supervisory personnel
(11) description of transformations, calculations, operations performed on data, summary and analysis of data, and statement of conclusions
(12) signed and dated reports of each individual scientist or professional involved in the study
(13) location where all specimens, raw data, and final report are stored
(14) statement by QA
(15) signature of the study director
What must be included in the final report?
(1) Name and address of the facility performing the study and dates on which the study was initiated and completed
(2) Objectives and procedures stated in the approved protocol, including changes to the original protocol
(3) statistical methods for data analysis
(4) test and control articles
(5) stability of test and control articles under administration conditions
(6) description of methods used
(7) description of test system used
(8) description of dose, dosage regimen, route of administration, and duration
(9) description of circumstances that may have affected the quality or integrity of data
(10) name of the study director, names of other scientists or professionals, and name of supervisory personnel
(11) description of transformations, calculations, operations performed on data, summary and analysis of data, and statement of conclusions
(12) signed and dated reports of each individual scientist or professional involved in the study
(13) location where all specimens, raw data, and final report are stored
(14) statement by QA
(15) signature of the study director
A GLP study was performed that did NOT result in the submission of the study in support of a permit application from the FDA. How long do recods need to be retained?
2 years after the date on which the study is completed, terminated or discontinued
What is the most severe penalty for failure to comply to GLP regulations?
disqualification
What are the results of disqualification?
The lab’s completed and future studies may not be acceptable as adequate support of an application for research or marketing permit
What would cause the Commissioner of the FDA to disqualify a testing facility?
All of the following:
(1) failure to comply with one or more GLP regs
(2) item of noncompliance adversely affected validity of the study
(3) other lesser regulatory actions haven’t been or will not be adequate to achieve compliance with the regs
How are testing facilities notified of disqualification?
A hearing is conducted
–The commissioner of the FDA may notify the testing facility via written notice
Who makes the final determination of whether a test facility is disqualified?
The commissioner of the FDA- must state the basis for the decision
If a test facility is disqualified, does an applicant have to submit the results to the FDA?
Yes
A study is started the day after a test facility is disqualified by the FDA commissioner. The QA team and study personnel are completely new. Is this study valid?
No. No studies started after the disqualification order are considered unless the facility has been reinstated
A study done at a disqualified test facility 1 year ago resulted in a successful IND. Does the study remain valid?
No. The sponsor has to show that the study is valid.
Are disqualification determinations available to the public?
Yes- determination and all records associated with the investigation are available to the public
can the FDA bring civil or criminal charges against a test facility?
Yes, prior to or in lieu of disqualification
If a sponsor terminates or suspends a testing facility from participation in a study using a test article with an application to the FDA, how soon must the FDA be notified?
within 15 business days
Does the sponsor of a study that has been terminated or suspended still have to submit the results to the FDA?
yes
How does a disqualified testing facility get reinstated?
Testing facility notifies the commissioner of the FDA in writing that it wants to be reinstated and details the corrective actions it is taking.
Commissioner must be assured the facility can conduct studies in compliance and ongoing studies aren’t compromised
How are non-compliances formally identified by the FDA?
Form 483- documents findings of FDA inspections
How soon must a test facility respond to a form 483?
Within 15 business days
What is issued by the FDA when a significant issue has been identified or compliance history includes repeat violations or a lack of effective corrective action?
A warning letter
