The American Association for Laboratory Accreditation · PDF fileThe American Association for Laboratory Accreditation C214 – Specific Checklist: Good Laboratory Practice (GLP) Document

The American Association for Laboratory Accreditation

C214 – Specific Checklist: Good Laboratory Practice (GLP) Document Revised:

March 7, 2012

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L:\Checklists\C214 – Specific Checklist: Good Laboratory Practice (GLP)

This checklist is intended for use in association with A2LA assessments, and is not to be publicly distributed. Use of this document is restricted to A2LA employees, contractors, and applicants. Any other use of this document is prohibited. The following pages present the criteria to be used in evaluating a laboratory to U.S. Food and Drug Administration’s GLP (Good Laboratory Practices Act) requirements as specified in the Code of Federal Regulations Title 21 part 58 (21CFR58). The laboratory’s policies and procedures must meet all of these requirements. Those requirements (clauses) that include the need for a written policy, procedure or arrangement have a thick, black border. Assessor Instructions: Review the laboratory’s documented quality system to verify compliance with the applicable GLP documentation requirements. This standard pertains to pre-clinical laboratory studies. Generally these studies are toxicology studies in animals, but also apply to physical chemical property studies and chemical characterization of the test and control article. Therefore, parts of the standard may not apply in all cases. Mark NA and explain those areas that are not applicable. (i.e. animal requirements are not applicable to studies pertaining to chemical analyses only. Assess to verify that the documented quality system is indeed implemented as described. Record comments related to any requirement on the space provided. Record comments related to tests on separate sheets and/or on the method review matrix. Deficiencies should be cited using the section number. Cross-references identified in parentheses reference (58.XX) the corresponding reference in the U.S.FDA standard. All deficiencies must be identified and explained in the assessor deficiency report.



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To the best of my knowledge, all laboratory document references below as well as actual laboratory practice have been assessed for compliance with the relevant clauses of the U.S. FDA GLP and the A2LA General Requirements for Accreditation of Laboratories. Any areas of noncompliance have been fully described in the Assessor Deficiency Report.

CAB Name: Address: Contact: Phone: Email:

Master Code: Assessment ID: Certificate(s): Conformity Standard: Assessment Dates: Assessment Type: Assessor(s): Assessor Signature(s):

AcO:



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Personnel Information (Names, Titles, and Responsibilities): Technical Management: ____________________________________________________________________

________________________________________________________________________________________

________________________________________________________________________________________

Quality Manager (QM): ___________________________________________________________________

Deputy QM: ___________________________________________________________________________



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Requirement

Reference

{RESERVED FOR ASSESSORS ONLY} Compliance

Comments Y N NA

4. MANAGEMENT REQUIREMENTS

4.1 Testing Facility Management (58.31)

4.1.1: Designate a study director before the beginning of the study

4.1.2: Replace the study director promptly if it becomes necessary to do so during the conduct of the study.

4.1.3: Assure that there is a quality assurance unit.

4.1.4: Assure that the test and control articles or mixtures have been appropriately tested for identity, strength, purity, stability, and uniformity as applicable.

4.1.5: Assure that personnel, resources, facilities, equipment, materials, and methodologies are available as scheduled.

4.1.7: Assure that any deviations from these requirements reported by the QAU and communicated to the study director and corrective actions are taken and documented.

4.2: Study Director (58.33)

4.2.1: For each non-clinical laboratory study, a scientist or other professional with applicable education, training and experience shall be identified as the study director.



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Requirement

Reference


Comments Y N NA

4.2.1.1: The study director has overall responsibility for the technical conduct of the study, including interpretation, analysis, documentation and reporting of the results. The study director is the single point of control and shall ensure the following:

a) The protocol, including any changes, is approved by the sponsor and signed by the study director is followed.

b) All experimental data, including observations of unanticipated responses to the test system are accurately recorded and verified.

c) Unforeseen circumstances that may affect the quality and integrity of the study are noted when they occur, and corrective action is taken and documented.

d) Test systems are as specified in the protocol.

e) All applicable GLP requirements are followed.

f) All raw data, documentation, protocol, specimens, and the final report are transferred to the archives during or at the close of the study.



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Requirement

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Comments Y N NA

4.3 The Quality Assurance Unit (58.35)

4.3.1: A testing facility shall have a quality assurance unit (QAU) which shall monitor each study to assure management that the facilities, equipment, personnel, methods, practices, records and controls are in conformance with the regulation. For any given study the QAU shall be independent of the personnel engaged in the direction and conduct of the study. The QAU shall be responsible for the following:

a) Maintain a copy of the master schedule indexed by test article, and containing the test system, nature of the study, date of study initiation, current status of each study, identity of the sponsor and the name of the study director.

b) Maintain copies of all protocols.

c) Inspect each non-clinical study at intervals adequate to assure the integrity of the study and maintain written signed records of each periodic inspection, showing the date of the inspection, the study inspected, the phase or segment of the study inspected, and the person performing the inspection, findings and problems, action recommended and taken to resolve existing problems.

d) Any problems found shall be brought to the attention of the study director and management immediately.



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e) Periodically submit status report to management and the study director on each study noting problems and corrective action.

f) Determine that no deviations from approved protocols or SOPs were made without authorization and documentation.

g) Review the final report to assure that such report accurately describes the methods and SOPs and that the reported results accurately reflect the raw data of the study.

h) Prepare and sign a Quality Assurance Statement to be included in the Final Report which shall specify the dates inspection were made and findings reported to the study director and to management.

4.3.2: Responsibilities and procedures applicable to the QAU, the records maintained by the QAU, and the methods of indexing such records shall be in writing and shall be maintained.

4.3.3: Items including inspection dates, the study inspected, the phase or segment of the study inspected, and the name of the individual performing the inspection. These records shall be made available for inspection to authorized employees of the U.S. FDA.



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Comments Y N NA

4.4: Personnel (58.29)

4.4.1: Each individual engaged in the conduct of or responsibility for the supervision of a non-clinical study shall have education, training, and experience or combination thereof, to enable that individual to perform the assigned functions.

4.4.2: Each testing facility shall maintain current summary of training and experience, and job description for each individual engaged in or supervising the conduct of the study.

4.4.3: There shall be sufficient number of personnel for the timely and proper conduct of the study according to the protocol.

4.4.4: Personnel shall take necessary personal sanitation and health precautions designed to avoid contamination of test and control articles and the test system.

4.4.4.1: Personnel shall wear appropriate clothing for the duties they perform. Such clothing shall be changed as often as necessary to prevent microbiological, radiological or chemical contamination of the test systems, test and control articles.



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4.4.4.2: Any individual having an illness that may adversely affect the integrity of the study shall be excluded from direct contact with test systems, test and control articles, and any other operation that may adversely affect the study until the condition is corrected. All personnel shall be instructed to report to their immediate supervisor any health or medical condition that may reasonably be considered to have adverse effect on a non-clinical study.

4.6: The Facility: (Subpart C) (58.41)

4.6.1: Each testing facility shall be of suitable size and construction to facilitate the proper conduct of the study. It shall be designed so that there is a degree of separation that will prevent any function or activity from having adverse effects on the study.

Animal Care Facility : (58.43)

4.6.1.1: There should be sufficient number of animal rooms or areas as needed, to assure the following:

a): Separation of species or test systems

b): Isolation of individual projects

c): Quarantine of animals

d): Routine or specialized housing of animals



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Reference


Comments Y N NA

4.6.1.2: There shall be sufficient number of animal rooms or areas to ensure the isolation of studies being done with test systems, test or control articles known to be biohazardous, including volatile substances, aerosols, radioactive materials, and infectious agent.

4.6.1.3: Separate areas shall be provided as appropriate for diagnosis, treatment, and control of laboratory animal diseases. These areas shall provide effective isolation for the housing of animals either known or suspected of being diseases, or of being a carrier of diseases from another animal.

4.6.1.4: When animals are housed, facilities shall exist for the collection and disposal of all animal waste and refuse or for safe sanitation storage of waste before removal from the facility. Disposal shall operate to minimize vermin infestation, odor, disease, and environmental contamination.

4.6.2: Animal Supply Facility (58.45)

4.6.2.1: There shall be storage areas, as needed, for feed, bedding, supplies, and equipment. Storage areas for feed and bedding shall be separate from areas housing the test systems, and shall be protected against infestation and contamination. Perishable supplies shall be preserved by appropriate environmental means.



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Requirement

Reference


Comments Y N NA

4.6.3: Facilities for handling test and control articles (58.47)

4.6.3.1: As necessary to prevent contamination or mix-up there shall be separate areas for:

a) Receipt and storage of the test article and control articles

b) Mixing of the test and control articles with carriers or feed

c) Storage of the test and control article mixture

d) Storage area for the test and/or control article and test and control mixtures shall be separate from areas housing the test system and shall be adequate to preserve the identity, strength, purity and stability of the articles and mixtures.

4.6.4: Laboratory Operations Area (58.49)

4.6.4.1: Separate laboratory space shall be provided, as needed for the performance of the routine and specialized procedures required by the non-clinical study.

4.6.5: Specimens and Data Storage Facilities (58.51)

4.6.5.1: Space shall be provided for archiving, limited access by authorized personnel only, for the storage and retrieval of all raw data and specimens from completed studies.



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Requirement

Reference


Comments Y N NA

4.7: Equipment: (Subpart D)

4.7.1: Equipment used in the generation, measurement, or assessment of data and equipment used for facility environmental control shall be of appropriate design and adequate capacity to function according to the protocol and shall be suitably located for operation, inspection, cleaning, and maintenance.

4.7.2: Equipment shall be adequately inspected, cleaned and maintained and where needed calibrated and/or standardized.

4.7.3: Written SOPs shall set forth in sufficient detail the methods, materials, and schedules to be used in routine inspection, cleaning, maintenance, testing, calibration, and/or standardization, and shall specify remedial action to be taken in the event of failure, malfunction. The SOP shall designate the person responsible for performance of each operation.



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Reference


Comments Y N NA

4.7.5: Computer software and hardware program should be sufficiently validated and implemented to meet requirements of 21 CFR Part 11 where applicable. Procedures shall be established to document established audit trails, changes in data, updates of software and hardware, and security of data entry and transport of data. Such procedures and validation shall be documented.

5. Testing Facility Operations (Subpart E) 5.1 Standard Operating Procedures (58.81)

5.1.1: A testing facility shall have SOPs in writing setting forth non-clinical methods and procedures. SOPs shall be approved by management.

All deviations from SOPs shall be authorized by the study director and shall be documented in the raw data.

Significant changes shall be authorized in writing by management.

SOPs shall be established where applicable for the following procedures:

a) Animal Room Preparation

b) Animal Care



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Reference


Comments Y N NA

c) Receipt, identification, storage, handling, mixing, and method of sampling, of the test and control article.

d) Test system observations

e) Laboratory tests

f) Handling of animals found moribund or dead during a study

g) Necropsy of animals or postmortem examination of animals.

h) Collection and identification of specimens.

i) Histopathology

j) Data handling, storage, and retrieval.

k) Maintenance and calibration of equipment.

l) Transfer, proper placement and identification of animals.

m) Archival of test data and reports.



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Reference


Comments Y N NA

5.1.2: SOPs and manuals relevant to laboratory operations shall be immediately available to laboratory areas. Published material may supplement SOPs but not take the place of SOPs authorized by management

5.1.3: A historical file of SOPs and all revisions thereof, including dates of such revisions, shall be maintained.

5.2 Reagents and Solutions (58.83)

5.2.1: All reagents and solutions in the laboratory area shall be labeled to indicate identity, titer or concentration, storage requirements, and expiration date. Deteriorated or outdated reagents and solutions shall not be used.

5.3: Animal Care (58.90)

5.3.1: There shall be SOPs for the housing, feeding, handling and care of animals.

5.3.2: All newly received animals from outside sources shall be isolated and their health status shall be evaluated in accordance with acceptable veterinary medical practices.

5.3.3: At the initiation of a non-clinical study animals shall be free of any disease or condition that might interfere with the purpose or conduct of the study.



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Reference


Comments Y N NA

5.3.3.1: If during the course of the study, an animal contract such a disease or condition, the diseased animal shall be isolated. These animals may be treated for disease or signs of disease provided such treatment does not interfere with the study.

5.3.3.2: The diagnosis, authorization of treatment, description of treatment, and each date of treatment shall be documented and shall be retained.

5.3.4: Warm-blooded animal, excluding suckling rodents, used in laboratory procedures that require manipulation and observation over time shall be uniquely identified.

5.3.4.1: All information needed to specifically identify each animal within an animal housing unit shall appear on the outside of that unit.

5.3.5: Animals of different species shall be housed in separate rooms when necessary to avoid cross-contamination, mix-up, or species compatibility.



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Requirement

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Comments Y N NA

5.3.6: Animals of the same species, but used on different studies should not ordinarily be housed in the same room when inadvertent exposure to control or test articles or animal mix-up could affect the outcome of either study. If such mixed housing is necessary, adequate differentiation by space and identification shall be made.

5.3.7: Animal cages, racks, and accessory equipment shall be cleaned and sanitized at appropriate intervals.

5.3.8: Feed and water used for the animal shall be analyzed periodically for contaminates know to be capable of interfering with the study. (Such analyses should include heavy metals, pesticides/herbicides, PCBs, and microbial contamination.) Documentation of analyses shall be maintained.

5.3.9: Bedding used in animal cages or pens shall not interfere with the purpose or conduct of the study, and shall be changed as often as necessary to keep the animals clean and dry.

5.3.10: The use of pest control material shall be documented. Cleaning and pest control material that interfere with the study shall not be used.



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Requirement

Reference


Comments Y N NA

5.4: Test and Control Articles (Subpart F) 5.4.1: Test and Control Article Characterization (58.105)

5.4.1.1: The identity, strength, purity, and composition or other characteristics, that appropriately define the test or control article shall be determined for each batch and shall be documented.

5.4.1.2: Stability of each test or control article shall be determined by the testing facility or by the sponsor either before study initiation or concomitantly according to SOPs which provide for periodic analysis of each batch.

5.4.2: Each storage container for a test or control article shall be labeled by name, chemical abstract number, batch number, expiration date if any; (physical properties studies may be conducted to establish expiration dates, and so therefore expiration dates may not be available during the course of the study because that is the purpose of the study), storage conditions for the duration of the study.



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Requirement

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Comments Y N NA

5.5: Test and Control Article Handling: (58.107)

Procedures shall be established for a system for handling the test and control articles to ensure the following:

a) There is proper storage.

b) Distribution is such to preclude contamination, deterioration, or damage.

c) Receipt and distribution of each batch is documented. Such documentation shall include the date and quantity of each batch distributed or returned.

5.6: Mixture of Test Articles with Carriers: (58.113)

For each test or control article that is mixed with a carrier, test by appropriate (validated) analytical methods shall be conducted.

a) To determine uniformity of the mixture and to determine periodically the concentration of the test or control article in the mixture.

b) To determine stability of the test and control articles in the mixture as required either before the beginning of the study or concomitantly according to written SOPs which provide for periodic analysis of the test and control article in the mixture.



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c) Where any component of the test or control article carrier mixture has an expiration date, that date shall be clearly shown on the container. If more than one component has an expiration date, the earliest date shall be shown.

5.7 Protocol for and Conduct of Non-clinical Laboratory Study (58.120)5.7.1: The Protocol

Each study shall have an approved written protocol that clearly indicates the objectives and all methods for the conduct of the study. The protocol shall be signed and dated by the study director and include the following information:

a) Descriptive title and statement of purpose of the study

b) Identification of the test and control article by name, chemical abstract number, or code number

c) The name of the sponsor, and the name and address of (each) testing facility at which the study is being conducted.

d) The number, body weight range, sex, source, species, strain, substrain, and age of the test system, (where applicable; in physical chemical properties studies these items may not be applicable).

e) Procedures for identifying the test system.

f) Description of experimental design.



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Requirement

Reference


Comments Y N NA

g) Where applicable, a description and/or identification of the diet used, as well as solvents, emulsifiers or suspensions used to solubilize or suspend the test or control article before mixing with the carrier. The description shall include specifications for acceptable levels of contaminants that are reasonably expected to be present in the dietary materials and are known to be capable of interfering with the purpose or conduct of the study.

h) Each dosage level, expressed in milligrams per kilogram of body weight or other appropriate unit of test or control article to be administered, and the method and frequency of administration.

i) The types and frequency of tests, analyses and measurements to be made.

j) Records to be maintained.

k) The date of approval of the protocol by the sponsor and the dated signature of the study director.

l) A statement of the proposed statistical methods to be



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Requirement

Reference


Comments Y N NA

used.

5.7.1.2: All changes in or revisions of an approved protocol and the reasons therefore shall be documented, signed by the study director, dated and maintained with the protocol.

5.8: Conduct of a non-clinical laboratory study (58.130)

5.8.1: The non-clinical laboratory study shall be conducted in accordance with the protocol.

5.8.2: The test systems shall be monitored in conformity with the protocol.

5.8.3: Specimens shall be identified by test system, study nature, and date of collection. This information shall be located on the specimen container or shall accompany the specimen in a manner that precludes error in the recording and storage of date.

5.8.4: Records of gross findings for a specimen from postmortem observations should be available to a pathologist when examining that specimen histopathologically.



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Comments Y N NA

5.8.5: All data except those collected electronically, shall be recorded directly, promptly, and legibly in ink. All data entries shall be dated on the day of entry and signed or initialed by the person making the entry.

5.8.5.1: Any changes in entries (hand written or electronic) shall be made so as not to obscure the original entry, shall include the reason for the change, and shall be dated and signed or identified at the time and person making the change. In automated data collection systems, (21 CFR Part 11) the individual responsible for data collection systems, the individual responsible for direct data input shall be identified at the time of the input.

5.8.5.1.2: Any changes in automated data entries shall be made so as not to obscure the original entry, shall indicate the reason for the change, shall be dated, and the responsible persons shall be identified.

5.9: Records and Reports: (Subpart J)

5.9.1: Reporting of non-clinical Laboratory Study Results (58.185)

5.9.1.1:A final report shall be prepared for each non-clinical laboratory study, and shall include but not be limited to the following.

a) Name and address(s) of facility performing the study, (if



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Requirement

Reference


Comments Y N NA

more than one all must be identified), and the dates on which the study was initiated (date of study director signature), and date completed (date the study director signs the final report).

b) Objectives and procedures stated in the approved protocol, including any changes or amendments to the original protocol.

c) Statistical methods employed for analyzing the data.

d) The test and control article identification by name, chemical abstract number or code number, strength, purity, and composition or other appropriate characteristics.

e) Stability of the test and control articles under the conditions of the administration.

f) Description of the methods used.

g) Description of the test system used. (Where applicable this should include number of animals, sex, body weight range, source of supplier, species, strain/substrain, age, and means of identification. For physical chemical properties studies the test article can be the test system thus, requirements pertaining to animals are not applicable).

h) Description of the dosage, dosage regimen, route of exposure and duration.



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i) Description of all circumstances that may have affected the quality or integrity of the data. (Generally given, but not required, as a list of protocol deviations. It can alternatively be given as description in the text of the study).

j) The name of the Study Director, the names of other scientists or professionals, and the names of all supervisory personnel involved in the study.

k) Description of the transformations, calculations, or operations performed on the data, a summary and analysis of the data, and a statement of the conclusions drawn from the analyses.

l) Signed and dated reports of each scientist or other professional involved in the study.

m) Location of all specimens, raw data, and the final report are to be stored.

n) Statement prepared and signed by the QAU to indicate the dates of the inspections, phase inspected, dates reported to the study director and to management.



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Requirement

Reference


Comments Y N NA

NOTE: Generally included (but only required in EPA Studies) is a GLP Compliance Statement that identifies any areas of non-compliance with the GLP Standard. It is signed by the Study Director.

o) The final report shall be signed by the Study Director.

p) Corrections or additions to a final report shall be in the form of an amendment to the final report, signed by the study director. Amendments shall clearly identify that part of the final report being amended, and the reasons for the change, and shall be signed and dated by the person responsible. (Generally the study director).

5.10 Storage and Retrieval of Records and Data (58.190)

5.10.1: All raw data, documentation, protocols, final reports, and specimens (except those specimens obtained from mutagenicity tests and wet specimens of blood, urine, feces, and biological fluids) generated as a result of non-clinical laboratory studies shall be retained.

5.10.2: There shall be an archive for orderly storage and expedient retrieval of all raw data, documentation, protocols, specimens, and interim and final reports.

5.10.3: Conditions of storage shall minimize deterioration



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Requirement

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of documents or specimens in accordance with the required time of retention.

5.10.4: The testing facility may contract with a commercial archive, provided that the commercial archive meets the requirements of the standard.

5.10.5: An individual shall be identified as responsible for the archives.

5.10.6: Only authorized personnel shall enter the archives.

5.10.7: Material retained or referred to in the archives shall be indexed to permit expedient retrieval.

5.11: Retention of Records (58.195)

5.11.1: Except for wet specimens identified, all documented records, raw data, specimens, the protocol, and final report shall be retained in the archives for the following length of time.

a) A period of 2 years following the date on which an application for a research or marketing permit is approved by FDA.



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b) A period of at least 5 years following the date on which the results of the study are submitted to FDA.

c) In situations where data are not submitted to FDA, data will be maintained for at least 2 years following the date of study completion or terminated.

d) Wet specimens (except those specifically excluded) samples of the test and control article, and specially prepared material, which are relatively fragile and differ in stability and quality during storage, shall be retained only as long as the quality of the preparation affords evaluation.

e) Facility Operation Records, including the Master Schedule, historical SOPs, training records, equipment maintenance and calibration records, QAU Inspection reports, shall be kept indefinitely.

f) for the purpose of records retention, records may be retained as either hard copy or as true copies such as photocopies, microfilm, or other accurate reproductions of the original records.

5.11.2: If a facility goes out of business, all raw data, documentation, and other material specified in this section shall be transferred to the archives of the sponsor of the study. The FDA shall be notified in writing of such a



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Requirement

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Comments Y N NA

transfer.

Document Revision History Date Description 03/7/2012 Added thick black borders around sections that are necessary for a reference to be provided. Also included instructions on first page as to how the

CAB should provide a reference for any requirement with a thick black border. Changes were made to add/update the common header. The reference to being evaluated against the U.S. FDA GLP(Good Laboratory Practice) Regulations per 21 CFR Part 58 was added

Documents

The American Association for Laboratory Accreditation · PDF fileThe American Association for Laboratory Accreditation C214 – Specific Checklist: Good Laboratory Practice (GLP) Document