Conducting a GLP Study

Study Director

The study director is the single point of study control and is granted authority by Texas A&M testing facility management to oversee their respective GLP studies in accordance with the regulations and Texas A&M requirements (refer to Texas A&M SOP for Study Directors for details). The Study Director must be a scientist or other professional of appropriate education, training, and experience, or a combination thereof as determined by testing facility management based on documented evidence of qualifications. Study directors must have documented training on the GLP regulations.

A study director may either be an employee of Texas A&M or may be provided by the sponsor or under contract. Study directors employed by Texas A&M are appointed by testing facility management. If the study director is not an employee of Texas A&M he/she must be approved by Texas A&M testing facility management and the sponsor. Study director appointment will be documented in writing by testing facility management. In the event a study director must be replaced, testing facility management will appoint a qualified replacement.

When only a part of GLP study services (e.g., pathology, histology, histomorphometry) are provided by Texas A&M, study director appointment is the responsibility of the sponsor and primary testing facility.

Study directors will:

  1. Oversee all study activities in accordance with GLP regulations and abide by animal welfare regulations and Texas A&M procedures and policies.
  2. Ensure that mechanisms exist to manage study activities at other test sites (as applicable).
  3. Authorize deviations to the protocol and prepare protocol amendments as necessary.
  4. Serve as the single point of control for the study. Communicate critical information to key study personnel at Texas A&M, other test sites, the sponsor, and to contributing scientists as applicable.
  5. Respond to QA noncompliance findings and ensure corrective actions are implemented in a timely manner to minimize impact on GLP study data.
  6. Work cooperatively with the attending veterinarian to ensure compliance with the Animal Welfare Act and Texas A&M Institutional Animal Care and Use policies and procedures.

Quality Assurance Unit (QAU)

Quality assurance personnel will be designated to monitor the facilities, equipment, personnel, methods, practices, records, and controls to assure they conform to the GLP regulations, study protocols, and standard operating procedures. The QAU will perform periodic inspections of the quality system program. The QAU will conduct critical phase inspections and data audits at intervals sufficient to assure that GLP studies and related activities are conducted in accordance with the GLP regulations, the protocol, and SOPs (refer to Texas A&M SOPs Quality Assurance).

Quality assurance personnel must be qualified to perform QA duties through experience, education, or a combination thereof as determined by testing facility management. GLP training and training on Texas A&M QAU SOP is required for all QAUs prior to providing services for GLP studies. QAU services provided by external sources for any GLP study must be approved by the Associate Vice President for Research. Quality assurance personnel will remain entirely separate from and independent of the personnel engaged in the direction and conduct of a GLP study for which they provide QA services.

Veterinarians

Veterinary care for GLP study animals will be supervised by the Texas A&M Attending Veterinarian. Veterinarians providing care for GLP study animals must have GLP training and must review the GLP study protocol and applicable SOP for studies to which they are assigned. Veterinarians will follow GLP regulations, standard operating procedures, and the study protocol.

Veterinarians will communicate regularly with study directors to assure humane care and treatment of animals, adherence to the IACUC approved AUP, and the GLP study protocol. The veterinarian assigned to the study is considered a contributing scientist and will collaborate with the study director to address animal health issues and will prepare a contributing scientist report for each assigned GLP study.

Sponsor

Sponsors must notify the ORCB in writing when studies must be conducted in compliance with the GLP regulations, international consensus or guidance documents, or country specific regulations. Texas A&M researchers will advise sponsors of the policies and procedures to be followed for GLP studies. Sponsors will follow all Texas A&M policies and procedures governing the care and use of research animals and GLP studies. Sponsors will provide Texas A&M with test and control articles, handling and storage instructions, perform or ensure that test and control article characterizations are performed (as agreed in writing), and provide the study director with documentation of characterization.

Contractors

Testing facility management must approve contractors that provide services that impact GLP study data. Contractors will conduct services according to a management approved contract defining the scope of work which includes their role and responsibilities in GLP studies. Contractors performing services that generate, measure, or assess data must have GLP training and SOP training applicable to the services they provide. Contractors will comply with the GLP regulations and Texas A&M policies and procedures governing GLP studies.

Compliance

All research activities conducted at Texas A&M involving animals must comply with the USDA Animal Welfare Act, 9 Code of Federal Regulations, Parts 1, 2, and 3; the Guide for the Care and Use of Animals, National Research Council, National Academic Press, Washington, D.C., 1996; and Texas A&M Institutional Animal Care and Use policies. GLP studies must comply with 21 CFR, Part 58, Good Laboratory Practices for Nonclinical Studies for FDA, or 40 CFR, Part 160, Good Laboratory Practice Standards for EPA. Studies will be evaluated on a case by case basis with the sponsor and may be required to conform to international consensus standards, guidance documents, or country-specific regulations. When conformance with international guidance documents or country-specific regulations is necessary, the ORCB will determine Texas A&M’s level of compliance prior to acceptance of the study.

IACUC

All animal use protocols must be approved by the Texas A&M IACUC. AUPs for GLP studies will be submitted to the Texas A&M IACUC to gain approval to use animals and will specify if the study is GLP.  Any proposed change in personnel, species usage, animal procedures, anesthesia, post-operative care, or biohazard procedures to the animal portion of a study must be submitted as an amendment to the IACUC for approval.  Committee approval of the proposed amendment is required prior to proceeding with the changes in procedures.

Facilities

Texas A&M facilities that are used to house, treat, test, or care for research animals must meet USDA requirements and must pass Texas A&M IACUC biannual inspections. Texas A&M facilities that are used to conduct or provide support services for GLP studies will be inspected and approved by Texas A&M QAU and must be maintained in compliance with the GLP regulations. Organizational units participating in GLP studies will ensure that all areas used in GLP studies are listed as such on a facility diagram. Facilities will be of appropriate design and adequate capacity to prevent any activity from having an adverse effect on another. Testing facility management will ensure that facilities are available as scheduled for GLP studies.

Equipment

GLP study equipment, including computerized systems, used to generate, measure, or assess data and equipment used for environmental control will be of appropriate design and adequate capacity to function according to the requirements of the GLP study protocol. Equipment used in GLP studies will be readily available for operation, inspection, cleaning, maintenance, and will be tested, calibrated, and or standardized (as applicable) according to approved SOP.

Each department engaged in GLP studies will retain records of inspection, maintenance, testing, calibration and/or standardization for equipment used in GLP studies according to the GLP regulations. Equipment approved for use in GLP studies will be clearly identified with a label affixed to the equipment. 

Equipment provided by sponsors and leased equipment must meet all GLP requirements. Study participants operating equipment, including sponsor personnel, must be trained on equipment use and will have documentation of training on the operation, inspection, cleaning, maintenance, testing, calibration and/or standardization as applicable.

Computerized systems that create, modify, maintain, archive, retrieve or distribute raw data for analysis will be of appropriate design and adequate capacity to function according to the study protocol and intended use in regulated studies.

Standard Operating Procedures

Texas A&M will maintain written SOPs for general GLP administrative functions and operations, preparation and approval of study protocols, preparation and approval of amendments and deviations, preparation and approval of final reports, data management, record retention, and quality assurance. Each organizational unit engaged in GLP studies will have written (management approved) SOP governing GLP research activities applicable to the department.

All SOPs will be reviewed at least biennially and historical records will be maintained. SOPs and forms used in GLP facility operation and study activities will be controlled. Deviations to SOPs will be documented and reported to the study director(s) for determination of study impact. Significant revisions to SOPs affecting GLP study activities will be authorized by the study director(s).

Animal Care

GLP study animals will be procured in accordance with the USDA regulations and policies and procedures of Texas A&M’s Comparative Medicine Program. Newly received animals from outside sources will be quarantined according to Texas A&M standard veterinary practice and their health status evaluated. Prior to assignment to GLP studies animals will be free of any disease or condition that might reasonably be expected to interfere with the study as determined by a veterinarian. Warm-blooded animals (except suckling rodents) used in GLP studies will be uniquely identified according to Texas A&M SOP. All information needed to identify an animal will also be posted on the outside of the animal housing unit to prevent mix-ups.

Animals used in GLP studies must be housed, handled, fed, and cared for according to SOPs approved by Texas A&M’s Comparative Medicine Program. Different species will be housed in separate rooms and same species on different studies will be housed separately when inadvertent exposure to test or control articles or animal mix-up could affect the outcome of either study.

If animals become ill during the course of a GLP study they may be treated provided the treatment does not interfere with the conduct of the study. Diagnosis, authorization to treat, dates of treatment, and descriptive details of treatment will be recorded and retained. The veterinarian(s) and the study director(s) will maintain open communication to assure compliance with animal welfare regulations, the study protocol, and the GLP regulations. 

Animal facilities will be maintained so that they are clean, orderly, and free of odors, vermin, and insects. Chemicals and bedding that may interfere with the GLP study will not be used. Feed and water will be analyzed periodically to ensure that contaminants known to be capable of interfering with the GLP study and reasonably expected to be present in feed or water are not present above levels specified in the study protocol.

Reagents and Solutions

Reagents and solutions used in facilities where GLP studies are conducted or where GLP study animals are housed will be labeled to indicate their identity, titer or concentration, storage requirements, and expiration date. Deteriorated or expired solutions and reagents will not be used.

Expired Supplies and Materials

Expired materials, drugs, or supplies, and out of date surgical packs will not be used in GLP studies.

Test and Control Articles

  1. Test and Control Article Characterization (Receipt, storage, mixing, characterization, reserve samples, documentation): The identity, strength, purity, or other characterization that will define test or control articles will be determined and documented for each batch or lot. Test and control article identity, storage, handling, and use will be defined in the study protocol. The methods of synthesis, derivation, or fabrication of test articles will be documented by the sponsor and all essential information will be provided to the study director. Protocols will include reference to the location of such documentation. Control articles will be characterized by their labeling. Stability under conditions of use will be determined by the sponsor or testing facility either prior to study initiation or concomitantly according to written procedures (refer to Texas A&M Test and Control Article SOP).

    The responsibility for test and control article characterization must be defined in the study protocol. Test and control article characterization is expected to be performed in compliance with the GLP regulations. Laboratories analyzing test articles will be approved by Texas A&M’s QAU when Texas A&M is responsible for characterization. If the sponsor is responsible for characterization they are responsible for assuring the laboratory’s compliance. When characterization is not performed according to GLP the non-compliance must be stated in the study protocol.
  1. Mixtures of Test and Control Articles: All test and control articles mixed with a carrier will be appropriately tested for uniformity of the mixture and periodically tested for concentration of the test or control article in the mixture. Stability of the mixture will be tested prior to study initiation or concomitantly according to written procedures. Test article characterization must be performed in compliance with the GLP regulations. Laboratories analyzing test articles will be approved by Texas A&M’s QAU unless the sponsor selects a laboratory that has been inspected and approved by the sponsor in which case the sponsor will provide Texas A&M with an inspection report verifying GLP compliance.
  2. Test and Control Article Storage: Test and control article storage containers will be labeled with the name, chemical abstract number or code, batch and/or lot number or other distinguishing identification, expiration date (as applicable) and storage conditions. Test and control articles will be stored under conditions sufficient to maintain viability and stability. Records establishing traceability will be maintained from receipt of test and control articles to final disposition. Storage containers will be retained for the duration required by the GLP regulations.
  3. Reserve Samples of Test and Control Articles: Studies longer than four weeks in duration will have reserve samples of test and control articles retained for each batch or lot. Either Texas A&M or the sponsor will retain the reserve samples as agreed in writing and signed by both Texas A&M and the sponsor.

Study Protocol and Study Conduct

The study director will prepare a written protocol that meets GLP and Texas A&M requirements. The GLP study protocol will be audited by the Texas A&M QAU to ensure that the protocol meets the GLP requirements. Prior to study initiation the protocol must be reviewed and signed by the sponsor. Unless otherwise agreed in advance, Texas A&M will retain the original (signed) protocol, amendments, and deviations, and exact copies will be submitted to the QAU and the sponsor upon request. The study director will ensure that a copy of the study protocol and any subsequent amendments are submitted to each sub-contract site (as applicable).

Each GLP study must have an IACUC-approved AUP. The information contained in the AUP must correlate with the contents of the study protocol. During the conduct of GLP studies, any determination of differences between SOPs and the study protocol will be resolved on the basis that the approved study protocol supersedes SOPs.

A Texas A&M protocol template may be utilized for writing the GLP study protocol. The Texas A&M template may be modified to suit individual GLP studies, but in no case will required elements be omitted. The sponsor may prefer to use a different template for the protocol in which case the Texas A&M QAU will audit the template to ensure that it adheres to Texas A&M requirements. (Refer to Texas A&M Protocol SOP TAMU-01-006)

GLP protocols must contain the following information at a minimum:

    1. A descriptive title and statement of purpose
    2. Identification of the test and control articles by name, chemical abstract number, or code number
    3. The name of the sponsor and the name and address of the testing facility
    4. The name and addresses of any sub-contract sites (including the sponsor site) where study activities will be performed
    5. The number, body weight range, sex, source of supply, species, strain, sub-strain, and age of the test system
    6. The procedure for identification of the test system
    7. A description of the experimental design, including methods for the control of bias
    8. A description and/or identification of the diet to be used as well as solvents, emulsifiers, and/or materials used to solubilize or suspend the test or control articles before mixing with the carrier. The description will include specifications for acceptable levels of contaminants that are reasonably expected to be present in the diet and/or are known to be capable of interfering with the purpose or conduct of the study if present at levels greater than established by the specifications.
    9. The type and frequency of tests, analyses, and measurements to be made
    10. A description of the necropsy procedure, tissue collection, histological processing, and histopathological analyses to be performed
    11. Instructions for handling moribund or terminal animals prior to study completion
    12. The records to be maintained and the retention location
    13. The dated signatures of the study director and the sponsor
    14. A statement of the proposed statistical methods to be used and acceptable levels of statistical significance
    15. Specify responsibility for performance of characterization of test and control articles including appropriate testing for identity, strength, purity, composition or other characteristics for each batch or lot and methods of synthesis, fabrication, or derivation of the test and control articles and stability testing as applicable
    16. If the study is conducted at multiple sites the location of the lead QAU will be included along with the names of principal investigators and/or contributing scientists. A flowchart, table, or narrative description of the roles and responsibilities and flow of communication for each site is recommended.
    17. When Texas A&M is the only testing facility, the protocol will include a description of responsibilities of the sponsor.
    18. Specify that reserve samples of each batch or lot of test and control articles will be retained for studies longer than 4 weeks in duration and the location where reserve samples will be retained
    19. The location where raw data and specimens will be retained including residual tissues not used for histological analyses
    20. A regulatory compliance section stating the GLP status of the study and any other federal or international regulations (including USDA regulations), consensus documents, and guidance documents that must be adhered to.
    21. Define reporting requirements (e.g., interim reports and contributing scientists reports)
    22. Method for documenting deviations and amendments to the study protocol

      Amendments to GLP study protocols will be promptly prepared. Amendments must be approved by the study sponsor and exact copies provided to the QAU (See also IACUC section). Personnel providing support services for GLP studies will review study protocols prior to study initiation and amendments prior to performing activities associated with the amendment. The reviews will be documented. Deviations to protocols and SOPs will be documented with justification. Prior approval for deviations to the study protocol must be obtained from the study director whenever feasible. When prior approval is not possible, the study director will be promptly notified of deviations.

      Data Collection and Data Management: Study data will be collected in adherence with the study protocol and SOPs. Data will be recorded promptly, legibly, and in ink. The use of pencils, white out, correction tape, and erasers in GLP studies is strictly prohibited. Manually recorded data will include identification of the study, test system identification, date, name of person obtaining and recording the data, and all other information necessary for the reconstruction of the study. Corrections or changes to raw data and facility operational and administrative records (i.e., equipment logs, training records, room maintenance records, reagent logs) will be done so as not to obscure the original entry, will be dated at the time of the change, will identify the person making the change, and will give the reason for the change or correction.

      Automated data systems generating, measuring, or assessing data will identify the person responsible for data entry or assessment at the time of entry. If electronic systems do not provide a means to identify the person responsible for entry, a use log will be retained documenting each time the system is used in regulated activities. Electronic records, including environmental control records, will be assessed to determine the extent to which they meet GLP requirements and 21 CFR, Part 11, Electronic Records, Electronic Signature regulations (as applicable). When software does not provide audit trails, solutions designed to meet regulatory requirements will be developed in cooperation with the Texas A&M department responsible for managing information technology at the facility. Corrections or changes to electronic records will not obscure the original entry and will be dated at the time of the change, will identify the person making the change, and will give the reason for the change or correction. Electronic records will be retained in accordance with the GLP regulations.

      Access to GLP study data will be restricted to authorized personnel. Data control procedures will be established by each organizational unit and adhered to by study personnel.

      Electronic records will be maintained on secure systems with access limited to authorized personnel. Electronic study files will be organized in a manner that allows for expedient retrieval by authorized personnel. Computer systems or networks used to store electronic records will be backed up in accordance with Texas A&M policies and procedures approved by the institution information technology department.

      Document Control

      GLP study protocols, amendments, standard operating procedures, and forms used in data collection will be maintained as controlled documents to ensure that personnel involved in the direction or conduct of GLP studies are using the correct version of the document. Each department is responsible for establishing a procedure to ensure that only current versions of documents are distributed and used by personnel.