CITI Good Laboratory Behavior
Which of the following facilities may the FDA inspect?
A dairy farm
An example of a common piece of laboratory equipment that provides measurement data, but cannot be calibrated by technical staff would include a graduated cylinder made of glass. What standard procedure should be advised to assure it is suitable for use?
A visual check to assure the cylinder is clean and its markings easily visible
The animal care standard operating procedure (SOP) for providing rats with water bottles attached to cages calls for them to be replaced every three days. However, a study technician has posted a direction on one rack to leave the bottles on cages for weekly measurement of water consumption. The comment part notes, "protocol instruction." As a very experienced animal care technician, you see that the bottles chosen for the rack are too small and will not even hold five days worth of water. What should be done?
Inform the study director immediately to report the problem and verify the posted instructions.
Sponsor is a term referring to a person only, unless:
It is a testing facility that both initiates and actually conducts the study
In a nonclinical testing facility, the vivarium supervisor decides to switch to a new animal room floor-cleaning product that promises to be effective and environmentally friendly. As he is reviewing the SDS, he sees that section 9 states that the product can be used in either cold or hot water. The SOP for cleaning floors at the facility directs the use of only hot water for this task. The supervisor sends management a copy of the SDS and suggests an edit to the SOP. To accomplish the company's goal for keeping their quality system current, what should management do?
Management should expediently approve a change to the SOP allowing the use of cold water so that the most current instructions are available.
In a final report for submission to the FDA or EPA, the individual reports of a contributing scientist or other professionals, such as a pathologist:
Must be appended to the sponsor's final report and the original version archived
This module outlined five goals that were representative of a quality system. Which of these statements is most correct:
The quality system represents management's overall design for keeping facility operations compliant with GLP.
FDA's and EPA's GLP Subpart G, 21 CFR 58.120 and 40 CFR 160.120, respectively, describe the minimal requirements for a protocol. Immediately following, 21 CFR 58.130 and 40 CFR 160.130 contain instructions for the conduct of a study. One of its most important points, relevant to all types of studies is:
A full description of what comprises raw data that is collected while following protocol instructions
The negative findings from the G.D. Searle and Industrial Bio-Test Laboratories (IBT) cases revealed:
A wide range of uncontrolled, unsupervised study and facility operations including major lapses in the integrity of data scientific practices
A GLP memorandum of understanding (MOU) between an OECD-member country and the U.S. would permit:
Acceptance of final reports and data that were conducted in either country under their applicable GLP regulations
Regarding commercial archives, the U.S. Food and Drug Administration (FDA) 21 CFR 58.190:
Allows contracting with such facilities to provide a repository for all material to be retained
If a laboratory refrigerator used to store chemicals and prepare solutions does not generate raw data, why would an SOP for it be necessary?
An SOP would provide instruction for cleaning, routine maintenance, and the procedures to be followed in the event of equipment failure.
The quality system goal of consistent output is most commonly met by expecting staff to follow:
Applicable standard operating procedures (SOPs) for their job description and department
What is the word used to describe the kind of personnel who shall enter the archives?
Authorized
The testing facility must have (or arrange for) archives for long-term storage of raw data. There also must be a quality assurance unit (QAU) for monitoring operations that are associated with the quality system. Which statement is most true about both of these areas of responsibility?
Both areas require written standard operating procedures (SOPs) to govern their operations.
While at a GLP-compliant field facility, the technician performing a survey of a treated plot of tomatoes is not sure if he is seeing a fungal disease on the leaves, or if the discoloration could be from the test substance application three days ago. The facility has an SOP in place to allow photographs, which are very beneficial to providing description in field studies. He takes a picture using his cell phone because he finds that the camera required to be in the field kit is not present. Then he describes the condition of the plants on the data form used for the survey. In this situation, which is the raw data, the picture or the hand-written entry on the data form?
Both of these are raw data because they were original, direct records despite the technician using completely different media.
You are the manager of a mid-sized contract testing facility and are reviewing quality assurance (QA) reports. One finding reported that the study director decided not to send the 40 pages of gross necropsy raw data to the pathologist because the technicians found no abnormal effects in any of the four groups of mice. As management, what could you do to increase GLP compliance?
Check the SOP on the provision of necropsy records when pathology is required by the protocol, and add a new step to ensure these records always are sent with the specimens
The primary requirement for quality assurance unit (QAU) personnel includes:
Completely independent monitoring and reporting any findings to management
"Study Plan" and "Study Protocol" are:
Completely interchangeable OECD and U.S. regulatory (EPA, FDA) terms
In a "primary eye irritation" study in rabbits, the technician will examine and compare the appearance of the treated eye with the untreated eye. Which term applies to the untreated eye?
Control
For certain European nations, the Organisation for Economic Co-operation and Development (OECD) has developed a "Series on Principles of Good Laboratory Practice (GLP) and Compliance Monitoring." These principles share with the U.S. GLPs the intention to:
Control and direct the operations of research and testing facilities
As a manager of a small testing facility that only performs 10-12 regulated studies per year, you want to meet GLP requirements for archiving your paper raw data. However, your resources are limited. To provide the maximum degree of control and security, which of the following solutions would be most GLP-compliant and enhance the quality system, while being affordable and practical at the same time?
Decide to purchase a used, fireproof filing cabinet, have the locks replaced, and create a standard operating procedure (SOP) using a paper index to record the logging in/out of the contents.
In GLP, Standard Operating Procedures (SOPs) are intended to:
Describe study methods for ensuring the quality and integrity of data
For each testing facility that archives its own raw data, the procedures that describe how it will be done are:
Determined to be adequate by testing facility management and described in standard operating procedures (SOPs)
Quality assurance (QA) officers perform audits of:
Draft and final reports against the study raw data and the protocol
The definition for raw data found in Subpart G of the FDA and EPA GLPs is:
Identical except for FDA's use of "nonclinical laboratory study" and EPA's use of "study"
Under certain conditions, properly trained personnel may perform quality assurance (QA) duties as well as technical ones. Which description below best describes these specific conditions?
If one person has had any QA responsibility for a particular study, they cannot later work on raw data, the study file, or the reporting procedures.
The scope of the FDA's GLP regulations for nonclinical research and testing
Includes any study submitted to the FDA that supports applications for research or marketing permits for products regulated by the FDA
Investigators from the FDA were first alerted to problems by:
Inconsistent and/or unexplained entries in data submitted to the FDA
The companies presented in this module as "landmark cases" in the establishment of GLPs were:
Industrial Bio-Test Laboratories (IBT) and G.D. Searle
The FDA's 21 CFR 58.3 on definitions contains a listing of possible inclusions for which a research or marketing permit would require GLP-compliant data. This list does not include
Insecticides produced for use in home gardens or flowerbeds
The FDA or EPA does not dictate any standard for the number of quality assurance (QA) inspections of each nonclinical laboratory study. Instead:
Inspections must be adequate and of sufficient number to ensure study integrity
A technician is recording rodent body weights on a form and notices a fairly large weight loss for one animal since the last weighing period. Following the instructions received during training, the technician checks the animal's water source and finds that the valve is not operating properly. What might this situation represent?
It represents a situation where additional raw data will be necessary to describe the unforeseen circumstance and the remedial action taken, along with the need to notify the study director.
An in vivo nonclinical laboratory study is distinguished by:
Its focus upon a living test system versus a study using cell cultures grown in a petri dish
For any facility that is performing studies intended for submittal to the FDA, the equipment used to generate raw data:
Must have a written SOP describing its maintenance and calibration
"Experimental Starting Date" is a definition used by -------- to mean --------.
OECD; first date that any study specific data is collected
Three technicians are working as a team to generate and record raw data, but only one of them is actually writing the information on the form. The other two are calling out animal identification numbers and body weights. Which of the following statements is most accurate?
On the data collection form, all the technicians involved should be identified, with the additional notation of who served as the recording technician (scribe).
The primary purpose for the retention of nonclinical laboratory study raw data and other associated records in an archive is to:
Protect the records from loss or damage for at least the time period required by the study protocol and/or GLP requirements
This document will be the most influential in assigning the number of personnel for the timely and proper conduct of a study:
Protocol
The GLPs describe "raw data" but this module also addressed "supporting data." What is the difference?
Raw data is collected directly from study operations according to the protocol and SOP instructions.
All of the GLPs include requirements for these two things for all personnel "engaged in or supervising" any study:
Records of training and a job description
Once the experimental termination date is reached for a study being submitted to the EPA, its protocol:
Remains in force because the study is not completed until the final report is signed
During an EPA or FDA testing facility inspection, the technical staff is advised to:
Respond briefly to any direct questions asked of them, or state they do not know the answer to the question
n The study protocol will require many specific operations and methods for all aspects of study conduct. To help keep the document to a manageable length, standard operating procedures (SOPs) will describe how the study conduct operations and methods are to be done. The relationship of SOPs to the protocol is best understood as:
SOPs are subordinate with respect to the protocol, allowing necessary deviations to be authorized by the study director, and documented in the raw data.
Nonclinical research and testing refers to that performed using:
Several species of laboratory animals
If the quality assurance (QA) officer asks a technician a question during an inspection, the response should be:
Simple and honest, offering explanation or other information when necessary to explain a situation
Study procedures required in the protocol may conflict with:
Standard operating procedures (SOPs)
Quality assurance (QA) officers perform inspections of:
Study critical phases and related facility/laboratory operations
In the first FDA preambles for Good Laboratory Practice (GLP), one section appeared to place too great a responsibility on one personnel group. In response to public comment, the commissioner agreed to move some items from the -------- to --------.
Study director to management
The EPA has developed a "tolerance" for the active ingredients in the pest control products that are used on food and feed crops. A tolerance allows:
Test results to be measured against the allowable level of residue, typically in parts per million, billion or trillion (ppm, ppb, ppt)
An animal weighing balance is being moved on a wheeled cart to a work area. Earlier, the same technician had put a range of check weights in the bowl to verify the equipment's accuracy per standard operating procedure (SOP). The technician accidentally bumps the cart on the doorframe, causing the bowl to fall off. It is retrieved and replaced, and the weighing operation begins. How could the quality system for this facility be improved?
The SOP should be revised to direct a technician to perform a recheck of the equipment's accuracy.
A document used to inform and protect users of commercial products generated by chemical suppliers, including products formulated for sanitization and cleaning of animal housing and vivarium areas, is known as:
The Safety Data Sheet
In public comments, primary objection(s) to the proposed GLP regulations was:
The anticipated cost of achieving compliance and potential restriction of scientific freedom in research
All studies at Bes-Tever, Inc. are to be compliant with FDA GLPs. A particular study protocol designates the Test Substance as "All-Slide3, CAS # 7001-12-3891, Batch # EZ-509." Several different batches of All-Slide3 were received from the sponsor. Where will those who are handling these test substances look to find the batch designated in the protocol?
The container label must include the batch identification for GLP compliance.
An animal care technician is responsible for recording the temperature of each room holding animals twice each day. In one particular room, there are four studies in progress. How will the routine work of this technician be reflected in the final reports of these studies?
The data generated by the technician will demonstrate that protocol requirements for room environment were achieved or were not achieved.
As the G.D. Searle and IBT "landmark" cases demonstrate, an essential difference between fraud and error is:
The intentional nature of fraudulent actions
To show that equipment is being properly maintained and operated according to the SOP is part of the requirements in the GLPs. These written records will need to include the date of the operation, a verification that the SOP was followed, and will note if the operation performed followed the routine for the procedure. What is required as additional documentation if the operation was not routine, for example, if the equipment was found damaged by the user?
The nature of the defect, when discovered, and any remedial action taken.
The work of caring for the laboratory animals requires much attention and time, but it is governed by standard operating procedures (SOPs). To reduce time spent changing bedding in cages, which statement describes a choice that would be compliant with both the GLPs and the animal welfare regulations?
The necessary supplies may be moved from the assigned storage area into the animal room, shortly in advance of the work.
A facility's animal care standard operating procedure (SOP) for providing rats with water bottles attached to cages requires them to be replaced every three days. However, a study technician has posted a notice on one rack, with different instructions for a particular study. It states to leave the bottles on cages for measurement of water consumption every five days, per protocol. As an animal care technician, which instruction do you follow in this particular instance (knowing that you do not have the protocol for reference?
The notice posted by the study technician, because these particular animals are now involved in a research study. The protocol's directions may differ from those in the general SOP.
To provide a single point of control during the conduct of each nonclinical study, FDA mandated:
The position of study director
A person speaking into a recording device while examining study specimens is creating raw data - an original documentation of their observations. What is necessary to produce GLP-compliant raw data from the recording?
The recording must be transcribed and verified by the person who made the voice tape, which is validated by their signature (or initials), date, and statement of accuracy.
A pesticide manufacturing company has its own small nonclinical laboratory and normally conducts and submits its own reports as the study sponsor. It prefers to use contract quality assurance (QA) to fulfill those GLP requirements. Because several animal rooms are undergoing renovation, the sponsor decides to place several high-priority studies with a reputable contract nonclinical laboratory that has full-time QA. This facility will only provide raw data and its study file. Which quality assurance unit (QAU) has the responsibility for study monitoring for the sponsor?
The sponsor's usual contract QA retains this responsibility and will determine the necessary arrangements between the two facilities.
When a decision is needed about any aspect of animal care or technical interaction regarding a group of study animals, the best person to make that decision is:
The study director
Which of the following is directly responsible for data integrity and determining the accuracy of final reports?
The study director and the quality assurance unit (QAU)
For a very small testing facility that conducts a limited number of GLP studies, it is permissible for this staff member to be responsible for storing and retaining (archiving) specimens and raw data under the conditions described:
The study director, when also authorized as the archivist
The environment of an animal housing room refers to:
The temperature and the relative humidity range at any point in time
Certain laboratory animals (test systems) are recommended for specific testing guidelines because:
Their use is justified based upon the existing body of documented and reliable responses to the route of administration
Animal vivarium space is often limited, or there may be a greater number of ongoing studies than is typical for a facility. What risk is involved and how can that risk be overcome?
There is a risk that study animals could be confused with those on another study. Each study's animals should be separated by adequate differentiation, such as space and identification.
If a study is disqualified by the FDA in accordance with Subpart K of their GLPs, will the agency continue to consider other studies submitted by the same nonclinical testing facility?
They may be considered if their submission was prior to the date of disqualification of the substandard study.
Which of the following is true about Good Laboratory Practice (GLP) standards?
They represent federal law, carrying penalties or other sanctions if fraud is detected.
A unique requirement in the OECD GLPs for a study director is:
To ensure that computerised systems used in the study have been validated
The Animal Welfare Act is monitored by unannounced, on-site inspections by employees of this government agency:
U.S. Department of Agriculture (USDA)
In the OECD GLPs, the term study plan is:
Understood to be equivalent to the term protocol as defined by the EPA and FDA
The GLP regulations in both the FDA's and EPA's Subpart E require the same method to indicate the identity, titer or concentration, storage requirements, and expiration date on containers of reagents and solutions. What is the required method?
Using a label to provide this information
The general personnel section of the FDA GLPs requires that "Personnel shall take necessary personal sanitation and health precautions designed to avoid contamination of test and control articles...and test systems." In an EPA study conducted outdoors in a farm setting, instead of an indoor facility typical of FDA work, which of the following precautions represents "sanitation" to avoid contamination of the test system during harvest of control and treated green bean specimens?
Using separate clean containers for each test group and harvesting the control beans before the treated ones
Bes-Tever, Inc. is a contract testing facility. Management has approved SOP #702 that begins with the following three sections. Does any section need to be updated?
Yes, the TITLE should be updated to include "laboratory chemicals and reagents" to be consistent with SCOPE and OVERVIEW
