CITI

A particularly large study requires the collection of blood samples from mice at three intervals over the course of six months. Due to the high skill level and time commitment required, management decides to contract this part of the study out to a qualified company. The technicians will come in to do the collections when scheduled, and the samples will be left at the sponsor testing facility for analysis. In order to "assure that personnel clearly understand the functions they are to perform," what is the most logical thing that management should request from this study partner?

Copies of the technical team's training records

Raw data, when collected electronically:

Has the advantages of being contemporaneous (time of entry is recorded automatically), and eliminates the potential for illegible data

In practice, the term "methods" has several meanings but all fall under the responsibility of management. GLP section 21 CFR 58.31(e) requires that testing facility management ensure that "methodologies are available." Which of the following would not be defined as a "method?"

Human resource procedures that explain how to evaluate the job performance of vivarium and technical staff

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

The recommended size of the quality assurance unit (QAU):

Should be adequate to properly handle the typical study volume of the facility.

The GLPs require that "Procedures shall be established for a system for the handling of the test and control articles to ensure..." proper storage; controlled distribution to reduce the possibility of contamination, deterioration, or damage; proper identification and documentation of the receipt; and distribution of each batch. Who is responsible for this requirement and how is it accomplished?

Testing facility management, by including instructions for all of these requirements in standard operating procedures (SOPs)

The Good Laboratory Practices (GLPs) require that a protocol be "approved." In this instance, approved means:

That the sponsor and study director have dated and signed/dated the protocol, respectively

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

Both technical and animal care staff are responsible for collecting various types of raw data, which is extremely important to the nonclinical laboratory study. If an error is made while recording any of this data:

The error can be corrected using a GLP-compliant method described more specifically in the facility's SOP.

Gross necropsy findings refer to:

The overall observation of internal organs using the naked eye and the documentation of the results

A large contract laboratory typically hires dozens of technicians each year for entry-level positions. Many of them leave after a year or so after gaining experience to obtain better salaries and benefits with major pharmaceutical corporations. Which statement is most true?

The quality system should require retaining all employee records in the archives, even when employees leave

The procedure for identification of a test system, such as the animals that are part of a study must be described in:

The study protocol

The process of applying or assigning unique study identification to laboratory animals is necessary when:

They are being evaluated and selected for placement into the study group(s)

The primary role of quality assurance (QA) is:

To assure management that the facility, records, and controls are in conformance with GLP requirements.

As stated in the preambles to the FDA GLPs, the primary purpose of raw data is:

To enable QA and federal investigators to reconstruct the results reported to the FDA (or EPA) in final reports

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 procedure of affixing a steel ID tag to a rabbit's ear causes some brief pain. Why is there no requirement for applying any anesthetic?

USDA defines a painful procedure as one reasonably expected to cause more than momentary distress in humans.

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 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

The use of animals in research and testing is necessary because:

A whole, biological system provides the best information.

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

One significant difference between the role of quality assurance (QA) with respect to study plans and U.S. protocols is the OECD's GLP requirement for:

A member of the quality assurance unit (QAU) to "verify" each study plan for GLP compliance

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

While an inspection of a critical phase is being conducted, it is typical for the quality assurance (QA) officer to:

Closely observe the procedure while creating minimal distraction

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.

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

The position of principal investigator (PI) is described only by which of the following?

Organisation for Economic Co-operation and Development (OECD)

Quality assurance (QA) officers perform inspections of:

Study critical phases and related facility/laboratory operations

Regarding the Organisation for Economic Co-operation and Development (OECD), its "Series on Principles of Good Laboratory Practice and Compliance Monitoring" concerning archives is:

Covered in a specific document (No. 15) that is to be used in conjunction with the OECD GLPs, which also provide some guidance for archival

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

In the protocol, including the address of the testing facility at which the study is being conducted:

Allows regulatory inspections to be scheduled at the point of study conduct

After a report has been made final (signed and dated by the study director), the need for a significant change to its contents requires the production of:

An amended final report

What is the word used to describe the kind of personnel who shall enter the archives?

Authorized

The GLPs require that equipment shall be "adequately inspected, cleaned and maintained," as stated in both the FDA and EPA's Subpart D. What kind of equipment must also be "adequately tested, calibrated and/or standardized"?

Equipment used for the generation, measurement or assessment of data.

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.

What is the primary hazard for long term archival of paper?

Loss of data integrity from destruction or deterioration of the paper

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.

A foundational principle of a quality system, "Verification and Control" is accomplished by:

Mechanisms to constantly maintain identity, accuracy, and the degree of adherence to procedures

Testing facility management has the primary responsibility to ensure that personnel, resources, facilities, equipment, materials, and -------- are available as scheduled.

Methodologies

The quality assurance (QA) officer notes that the records from mouse necropsies have not been copied for sending to the pathologist for a particular study. The study director's response is that no abnormal effects were found in any of the four groups of mice, so he/she felt it was not necessary to send the 40 pages of data to the pathologist. As management reviewing the QA report, are you satisfied with the study director's response?

No, because the study conduct portion of the GLPs requires that pathologists be provided with the records of gross findings from the necropsy.

"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).

According the GLP regulations on standard operating procedures (SOPs), animal room maintenance operations using _________ shall be documented.

Pest control materials

USDA's Animal Welfare Act defines "petting, stroking, or other touching" as:

Positive physical contact

21 CFR 59.190 of the U.S. Food and Drug Administration (FDA) GLPs requires the retention of "all raw data, documentation, protocols, final reports and specimens..." What are typical specimens from a complete necropsy?

Preserved tissues, organs in fixative and/or wax blocks and microscopic slides

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

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.

Study procedures required in the protocol may conflict with:

Standard operating procedures (SOPs)

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.

With respect to balances used to weigh objects, animals, or chemicals, the term "capacity" includes:

The highest amount of weight the unit can measure with accuracy

In the U.S., quality assurance (QA) inspections of critical study phases are connected to individual studies. When following GLPs of the Organisation for Economic Co-operation and Development (OECD):

The inspection can represent the procedure and be applicable to several studies

In all of the GLPs, the single point of study control always rests with:

The study director

A technician is preparing solutions that will be administered to test and control rats. For the test group, the protocol instructs the test article to be prepared as a 50 percent weight-to-weight (w/w) solution in corn oil. Which of the choices below reflect this solution's composition?

30 grams of test article and 30 grams of corn oil

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

Subpart D of both the FDA and EPA GLPs provides the regulations for data-generating equipment. Testing facility management will need to develop a quality system to ensure the validity of equipment raw data. Which of the following pieces of equipment does not generate any raw data?

A locked freezer that is used to store samples of blood from study animals conducted under GLPs

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.

Certain materials are not appropriate for the collection or correction of raw data, such as: pencils, masking fluid or tape, and pens that use erasable ink. What are the GLP-compliant requirements for a change to the body weight of a rabbit entered in the wrong box on a form?

By keeping the original entry while showing who made the change, when, and the reason for the change

"Study Plan" and "Study Protocol" are:

Completely interchangeable OECD and U.S. regulatory (EPA, FDA) terms

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 in any of the four groups of mice found no abnormal effects. 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.

Each individual engaged in the conduct of or is responsible for the supervision of a [nonclinical laboratory] study shall have:

Education, training, and experience, or a combination thereof

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)

Raw data, if not collected electronically, are recorded using ink rather than pencil, because:

EPA and FDA GLPs specifically require Ink in their subpart governing study conduct

A study protocol requires a crystallized test article to be uniformly mixed into distilled water. What is meant by "uniformly"?

It means that no sediment of the test article can be seen after mixing

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

Raw data and specimens for each study must be stored for potentially long periods of time. What is the process of control instituted by the U.S. Food and Drug Administration (FDA)?

The requirement for establishing at least one area designated as an archive for secure storage and indexing of raw data, under control of an archivist

The term, "test system" in the FDA, EPA, and OECD GLPs refers to:

The living or chemical system that will be treated with or administered the test article (FDA), test item (OECD), or test substance (EPA)

This module addressed common commercial products used for cleaning and sanitation of vivarium areas, as well as the materials that are intended for use in nonclinical and other studies. Which of the following statements is most accurate with respect to GLP?

The most emphasis is placed on materials that are intended for use in studies

In both the FDA and EPA GLPs, one of the requirements for a protocol that most directly influences raw data generation and collection are:

The records to be maintained

Once management has approved an SOP for a laboratory balance that will be used to weigh mice or rats, and technicians are trained to perform the procedure with the equipment, what else will be necessary for GLP compliance?

To verify that the operations did occur as directed in the SOP, appropriate documentation will be necessary whenever the equipment is used.

An animal care technician is about to prepare a bucket of solution to pour into a cage-cleaning device. The plastic jug of detergent is fitted with a pump dispenser set to measure out the required 2 ounces. Just as she is about to depress the pump, the technician sees a large crack along the side of the pump, which is allowing some leakage of the detergent. There is a set of measuring cups in the equipment bin. What should be done to accurately prepare the solution so that cage-cleaning can proceed?

Use clean a quarter-cup vessel to measure the required 2 ounces

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? TITLE Receipt of Test Articles SCOPE Any employee that is reasonably expected to come into contact with laboratory chemicals, reagents and test articles arriving at the Receiving Department. OVERVIEW OF PROCEDURE To provide direction in accordance with Bes-Tever's Chemical Hygiene Plan for receiving and storing all chemicals, reagents and the test articles received from Sponsors.

Yes, the TITLE should be updated to include "laboratory chemicals and reagents" to be consistent with SCOPE and OVERVIEW

In the process of federal rulemaking (regulation), the preambles serve to:

Announce the effective date for compliance after presenting reasons for the new law and response to public comments, when applicable

Errors made during collecting any raw data or supporting data during a nonclinical laboratory study:

Are not unusual and so SOPs for handling corrections will be established by management to guide GLP compliance

The FDA term "nonclinical laboratory study" excludes:

Basic exploratory studies carried out to determine whether a test article has any potential utility

The quality assurance unit (QAU) conducts inspections during critical phases of the study protocol, such as the weighing or dosing of test subjects. Which of the following statements is most correct?

Because animal care and use operations are governed by standard operating procedures (SOPs) they are also subject to QA inspection, independently or during a critical phase.

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

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

In GLP, Standard Operating Procedures (SOPs) are intended to:

Describe study methods for ensuring the quality and integrity of data

Quality assurance (QA) officers perform audits of:

Draft and final reports against the study raw data and the protocol

"Reference item" in OECD GLP definitions, and "reference substance" in the -------- GLPs, --------.

EPA; are different, and so reference item must be understood in whatever context is applicable to the study plan

A study director is often free to ignore or downplay quality assurance (QA) findings under certain conditions. This may be allowed when the:

Finding does not relate to GLP compliance

A member of the Quality Assurance Unit has been observing the work of many technicians in the facility's analytical laboratory for several years. He sees a posting for a position in the laboratory, and decides to apply for it because he has been thinking of making a change and meets the qualifications. Which of the following statements is true when considering GLP compliance?

He will need to have the same level of training in SOPs for equipment operations and other procedures.

Which of the following best describes the reason for inclusion of health precautions and sanitation issues in the GLPs for nonclinical studies?

Human-animal disease transmission is possible in laboratory settings, posing a concern for individuals as well as the corporation.

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"

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 technician or the study director as soon as possible so the improper size bottles are replaced.

Sponsor is a term referring to a person only, unless:

It is a testing facility that both initiates and actually conducts the study

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

Although it can be provided to any kind of animal, "environmental enrichment to promote psychological well-being" is required for what category of animal in the USDA/APHIS specifications?

Nonhuman primates

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

A study protocol intended for submittal of a final report to the FDA requires that rabbit body weights be collected during a dermal toxicity study on Days 0, 7, 14, and 21 (study termination). After the collection of weights on Day 7, the technician notes that all of the females have lost weight, and that some of the males' weight gain was minimal. The technician informs the study director, who reviews the raw data. As a result, the study director decides to add a weighing interval on study Day 10, and prepares a:

Protocol amendment

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.

When a testing facility's study report is being inspected by the U.S. Food and Drug Administration (FDA), the targeted raw data and other supporting records:

Should remain in the archives until requested because the inspectors will want to see that the archivist can expediently retrieve them

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

A large chest freezer is used to store crop samples at a field-testing facility. An electronic device with a probe that constantly monitors and creates a record of the inner temperature is mounted on the wall next to the freezer. Which statement is correct with respect to the raw data in this situation?

The electronic device is generating raw data

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.

It has been firmly established that the quality assurance unit (QAU) cannot become involved with study conduct. How could a very small company utilize technical personnel to also perform QA functions and be compliant with GLP?

The personnel would be trained in QA responsibilities, but only perform them for projects in which they had no participation.

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.

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.

Regardless of which employee performs a remedial operation (one that corrects conditions caused by an unforeseen circumstance), which staff member is responsible for noting, correcting, and ensuring the actions were documented?

The study director

During an oral toxicology study, one of the animals escapes its enclosure during the night and cannot be located. Only two days of a 14-day study have elapsed. Which answer best describes what should be done after the escape is documented?

The study director must be notified.

During the conduct of a nonclinical study for submittal to the FDA, a group of rats was to be observed hourly for four hours following the time of dosing. The administration of the test article occurred at 8:30 a.m. For the first three hours, all the rats appeared active and healthy. Because of an important staff meeting scheduled by management during the lunch hour, the study technician performed the last observation at noon. What is the appropriate action to be taken to comply with GLPs?

The study director should prepare a protocol deviation.

The Animal Welfare Act is monitored by unannounced, on-site inspections by employees of this government agency:

U.S. Department of Agriculture (USDA)

The responsibilities of the quality assurance unit (QAU) are described in all three GLP regulations. One different requirement of quality assurance (QA) found only in the OECD GLPs is for the QAU to:

Verify the study plan contains the information required for compliance (with their GLPs) and document that verification

If auditing a newly proposed protocol for GLP compliance, would the QAU have regulatory guidance to detect any problems?

Yes, because the requirements for the basic elements of a compliant protocol are listed in the GLPs