TITLE 21--FOOD AND DRUGS
标题21--食品和药品
CHAPTER I--FOOD AND DRUG ADMINISTRATION
第一章 食品药品监督管理局
DEPARTMENT OF HEALTH AND HUMAN SERVICES
卫生与公众服务部
PART 58 GOOD LABORATORY PRACTICE FOR NONCLINICAL LABORATORY STUDIES
第 58 部分:非临床实验室研究的良好实验室规范
Subpart A--General Provisions
A分部分--一般规定
Sec. 58.1 Scope.
(a) This part prescribes good laboratory practices for conducting nonclinical laboratory studies that support or are intended to support applications for research or marketing permits for products regulated by the Food and Drug Administration, including food and color additives, animal food additives, human and animal drugs, medical devices for human use, biological products, and electronic products. Compliance with this part is intended to assure the quality and integrity of the safety data filed pursuant to sections 406, 408, 409, 502, 503, 505, 506, 510, 512-516, 518-520, 721, and 801 of the Federal Food, Drug, and Cosmetic Act and sections 351 and 354-360F of the Public Health Service Act.
(a) 本部分规定了开展非临床实验室研究的良好实验室规范,这些研究支持或旨在支持食品和药物管理局监管的产品的研究或营销许可申请,包括食品和色素添加剂、动物食品添加剂、人类和动物药品、人用医疗器械、生物制品和电子产品。遵守本部分旨在确保根据《联邦食品、药品和化妆品法》第 406、409、502、503、505、506、510、512-516、518-520、721 和 801 条以及《公共卫生服务法》第 351 条和第 354-360F 条提交的安全数据的质量和完整性。
(b) References in this part to regulatory sections of the Code of Federal Regulations are to chapter I of title 21, unless otherwise noted.
(b) 除非另有说明,否则本部分对《联邦条例》监管部分的引用均指第 21 篇第一章。
[43 FR 60013, Dec. 22, 1978, as amended at 52 FR 33779, Sept. 4, 1987; 64 FR 399, Jan. 5, 1999]
Sec. 58.3 Definitions.
As used in this part, the following terms shall have the meanings specified:
在本部分中,下列术语应具有指定的含义:
(a) Act means the Federal Food, Drug, and Cosmetic Act, as amended (secs. 201-902, 52 Stat. 1040 et seq., as amended (21 U.S.C. 321-392)).
(a) 法案是指经修订的《联邦食品、药品和化妆品法》(经修订的《联邦食品、药品和化妆品法》第 201-902 节、第 52 条第 1040 条及以下各条(《美国法典》第 21 编第 321-392 条))。
(b) Test article means any food additive, color additive, drug, biological product, electronic product, medical device for human use, or any other article subject to regulation under the act or under sections 351 and 354-360F of the Public Health Service Act.
(b) 测试物品是指任何食品添加剂、色素添加剂、药品、生物制品、电子产品、人用医疗器械,或受该法或《公共卫生服务法》第 351 条和第 354-360F 条管制的任何其他物品。
(c) Control article means any food additive, color additive, drug, biological product, electronic product, medical device for human use, or any article other than a test article, feed, or water that is administered to the test system in the course of a nonclinical laboratory study for the purpose of establishing a basis for comparison with the test article.
(c) 控制物品是指任何食品添加剂、色素添加剂、药品、生物制品、电子产品、人用医疗器械,或在非临床实验室研究过程中为建立与试验物品进行比较的依据而向试验系统施用的供试物品、饲料或水以外的任何物品。
(d) Nonclinical laboratory study means in vivo or in vitro experiments in which test articles are studied prospectively in test systems under laboratory conditions to determine their safety. The term does not include studies utilizing human subjects or clinical studies or field trials in animals. The term does not include basic exploratory studies
(d) 非临床实验室研究系指在体内或体外实验中,在实验室条件下,在试验系统中对试验物品进行前瞻性研究,以确定其安全性。该术语不包括利用人体受试者的研究或动物的临床研究或田间试验。该术语不包括基本的探索性研究
carried out to determine whether a test article has any potential utility or to determine physical or chemical characteristics of a test article.
为确定测试物品是否具有任何潜在效用或确定测试物品的物理或化学特性而进行。
(e) Application for research or marketing permit includes:
(e) 研究或上市许可证的申请包括:
(1) A color additive petition, described in part 71.
(1)颜色添加剂申请书,见第71部分。
(2) A food additive petition, described in parts 171 and 571.
(2)食品添加剂申请书,见第171和571部分。
(3) Data and information regarding a substance submitted as part of the procedures for establishing that a substance is generally recognized as safe for use, which use results or may reasonably be expected to result, directly or indirectly, in its becoming a component or otherwise affecting the characteristics of any food, described in 170.35 and 570.35.
(3) 作为确定某种物质被普遍认为可以安全使用的程序的一部分而提交的有关某种物质的数据和信息,其使用结果或可能合理地预期直接或间接导致其成为170.35和570.35所述的任何食品的成分或以其他方式影响任何食品的特性。
(4) Data and information regarding a food additive submitted as part of the procedures regarding food additives permitted to be used on an interim basis pending additional study, described in 180.1.
(4) 作为程序的一部分提交的有关食品添加剂的数据和信息,这些食品添加剂在进一步研究之前被允许临时使用,如180.1所述。
(5) An investigational new drug application, described in part 312 of this chapter.
(五)本章第三百一十二编所述的研究性新药申请。
(6) A new drug application, described in part 314.
(6)新药申请,见第314部分。
(7) Data and information regarding an over-the-counter drug for human use, submitted as part of the procedures for classifying such drugs as generally recognized as safe and effective and not misbranded, described in part 330.
(7) 关于人用非处方药的数据和信息,作为对此类药物进行分类的程序的一部分提交,这些药物通常被认为是安全有效的,并且没有贴错标签,如第330部分所述。
(8) Data and information about a substance submitted as part of the procedures for establishing a tolerance for unavoidable contaminants in food and food-packaging materials, described in parts 109 and 509.
(8) 在第 109 部分和第 509 部分所述的确定对食品和食品包装材料中不可避免的污染物的耐受性的程序中提交的有关物质的数据和信息。
(9) [Reserved]
(9) [保留]
(10) A Notice of Claimed Investigational Exemption for a New Animal Drug, described in part 511.
(10) 第 511 部分所述的新型动物药物要求研究豁免通知。
(11) A new animal drug application, described in part 514.
(11)新的动物药物申请,见第514部分。
(12) [Reserved]
(12) [保留]
(13) An application for a biologics license, described in part 601 of this chapter.
(13)本章第601部分所述的生物制品许可申请。
(14) An application for an investigational device exemption, described in part 812.
(14) 第 812 部分所述的研究设备豁免申请。
(15) An Application for Premarket Approval of a Medical Device, described in section 515 of the act.
(15) 该法第515条所述的医疗器械上市前批准申请。
(16) A Product Development Protocol for a Medical Device, described in section 515 of the act.
(16) 该法案第 515 条所述的医疗器械产品开发协议。
(17) Data and information regarding a medical device submitted as part of the procedures for classifying such devices, described in part 860.
(17) 作为第 860 部分所述的医疗器械分类程序的一部分提交的有关医疗器械的数据和信息。
(18) Data and information regarding a medical device submitted as part of the procedures for establishing, amending, or repealing a performance standard for such devices, described in part 861.
(18) 在第 861 部分所述的建立、修改或废除此类器械性能标准的程序中提交的有关医疗器械的数据和信息。
(19) Data and information regarding an electronic product submitted as part of the procedures for obtaining an exemption from notification of a radiation safety defect or failure of compliance with a radiation safety performance standard, described in subpart D of part 1003.
(19) 作为获得辐射安全缺陷或未能遵守辐射安全性能标准的豁免通知程序的一部分提交的有关电子产品的数据和信息,如第 1003 部分 D 子部分所述。
(20) Data and information regarding an electronic product submitted as part of the procedures for establishing, amending, or repealing a standard for such product, described in section 358 of the Public Health Service Act.
(20) 根据《公共卫生服务法》第 358 条所述的制定、修改或废除此类产品标准的程序的一部分提交的有关电子产品的数据和信息。
(21) Data and information regarding an electronic product submitted as part of the procedures for obtaining a variance from any electronic product performance standard as described in 1010.4.
(21) 作为获得与1010.4中所述的任何电子产品性能标准差异的程序的一部分而提交的有关电子产品的数据和信息。
(22) Data and information regarding an electronic product submitted as part of the procedures for granting, amending, or extending an exemption from any electronic product performance standard, as described in 1010.5.
(22) 如 1010.5 所述,作为授予、修改或延长任何电子产品性能标准豁免程序的一部分提交的有关电子产品的数据和信息。
(23) A premarket notification for a food contact substance, described in part 170, subpart D, of this chapter.
(23) 本章第170部分D子部分所述的食品接触物质上市前通知。
(f) Sponsor means:
(1) A person who initiates and supports, by provision of financial or other resources, a nonclinical laboratory study;
(1) 通过提供资金或其他资源发起和支持非临床实验室研究的人;
(2) A person who submits a nonclinical study to the Food and Drug Administration in support of an application for a research or marketing permit; or
(二)向食品药品监督管理局提交非临床研究以支持研究或者上市许可申请的人员;或
(3) A testing facility, if it both initiates and actually conducts the study.
(3) 检测机构,如果它既启动了研究又实际进行了研究。
(g) Testing facility means a person who actually conducts a nonclinical laboratory study, i.e., actually uses the test article in a test system. Testing facility includes any establishment required to register under section 510 of the act that conducts nonclinical laboratory studies and any consulting laboratory described in section 704 of the act that conducts such studies. Testing facility encompasses only those operational units that are being or have been used to conduct nonclinical laboratory studies.
(g) 检测设施系指实际进行非临床实验室研究的人,即在检测系统中实际使用检测物品的人。检测设施包括根据该法第510条要求注册的进行非临床实验室研究的任何机构,以及该法第704条所述进行此类研究的任何咨询实验室。检测设施仅包括那些正在或已经用于进行非临床实验室研究的运营单位。
(h) Person includes an individual, partnership, corporation, association, scientific or academic establishment, government agency, or organizational unit thereof, and any other legal entity.
(h) 人包括个人、合伙企业、公司、协会、科学或学术机构、政府机构或其组织单位,以及任何其他法律实体。
(i) Test system means any animal, plant, microorganism, or subparts thereof to which the test or control article is administered or added for study. Test system also includes appropriate groups or components of the system not treated with the test or control articles.
(i) 试验系统系指为研究而施用或添加试验品或对照品的任何动物、植物、微生物或其亚部分。测试系统还包括未用测试或对照物品处理的系统的适当组或组件。
(j) Specimen means any material derived from a test system for examination or analysis.
(j) 试样系指从试验系统衍生出来的用于检查或分析的任何材料。
(k) Raw data means any laboratory worksheets, records, memoranda, notes, or exact copies thereof, that are the result of original observations and activities of a nonclinical laboratory study and are necessary for the reconstruction and evaluation of the report of that study. In the event that exact transcripts of raw data have been prepared (e.g., tapes which have been transcribed verbatim, dated, and verified accurate by signature), the exact copy or exact transcript may be substituted for the original source as raw data. Raw data may include photographs, microfilm or microfiche copies, computer printouts, magnetic media, including dictated observations, and recorded data from automated instruments.
(k) 原始数据是指任何实验室工作表、记录、备忘录、笔记或其确切副本,这些工作表、记录、备忘录、笔记或其确切副本,是非临床实验室研究的原始观察和活动的结果,是重建和评估该研究报告所必需的。如果已经准备好了原始数据的确切誊本(例如,已经逐字转录、注明日期并通过签名验证准确无误的磁带),则可以用确切的副本或确切的誊本代替原始来源作为原始数据。原始数据可能包括照片、缩微胶卷或缩微胶片副本、计算机打印输出、磁性介质(包括口述观察结果)和来自自动仪器的记录数据。
(l) Quality assurance unit means any person or organizational element, except the study director, designated by testing facility management to perform the duties relating to quality assurance of nonclinical laboratory studies.
(l) 质量保证单位是指除研究主任外,由检测设施管理层指定以履行与非临床实验室研究的质量保证有关的职责的任何个人或组织要素。
(m) Study director means the individual responsible for the overall conduct of a nonclinical laboratory study.
(m) 研究主任是指负责全面开展非临床实验室研究的个人。
(n) Batch means a specific quantity or lot of a test or control article that has been characterized according to 58.105(a).
(n) 批次是指已根据58.105(a)进行表征的试验品或对照品的特定数量或批次。
(o) Study initiation date means the date the protocol is signed by the study director.
(o) 研究开始日期是指研究主任签署方案的日期。
(p) Study completion date means the date the final report is signed by the study director.
(p) 研究完成日期是指研究主任签署最终报告的日期。
[43 FR 60013, Dec. 22, 1978, as amended at 52 FR 33779, Sept. 4, 1987; 54 FR 9039, Mar. 3, 1989; 64 FR 56448, Oct. 20, 1999; 67 FR 35729, May 21, 2002]
[43 FR 60013,1978年12月22日,于1987年9月4日52 FR 33779修改;54 FR 9039,1989年3月3日;64 FR 56448,1999年10月20日;67 FR 35729,2002年5月21日]
Sec. 58.10 Applicability to studies performed under grants and contracts.
第 58.10 节 适用于根据赠款和合同进行的研究。
When a sponsor conducting a nonclinical laboratory study intended to be submitted to or reviewed by the Food and Drug Administration utilizes the services of a consulting laboratory, contractor, or grantee to perform an analysis or other service, it shall notify the consulting laboratory, contractor, or grantee that the service is part of a nonclinical laboratory study that must be conducted in compliance with the provisions of this part.
当申办者进行打算提交给美国食品和药物管理局或由美国食品和药物管理局审查的非临床实验室研究时,利用咨询实验室、承包商或受赠人的服务进行分析或其他服务时,应通知咨询实验室、承包商或受赠人该服务是非临床实验室研究的一部分,必须按照本部分的规定进行。
Sec. 58.15 Inspection of a testing facility.
第58.15节 检查检测设施。
(a) A testing facility shall permit an authorized employee of the Food and Drug Administration, at reasonable times and in a reasonable manner, to inspect the facility and to inspect (and in the case of records also to copy) all records and specimens required to be maintained regarding studies within the scope of this part. The records inspection and copying requirements shall not apply to quality assurance unit records of findings and problems, or to actions recommended and taken.
(a) 检测设施应允许食品和药物管理局的授权雇员在合理的时间和以合理的方式检查该设施,并检查(如果有记录,还应复制)需要保存的有关本部分范围内研究的所有记录和样本。记录检查和复制要求不适用于质量保证单位的发现和问题记录,也不适用于建议和采取的行动。
(b) The Food and Drug Administration will not consider a nonclinical laboratory study in support of an application for a research or marketing permit if the testing facility refuses to permit inspection. The determination that a nonclinical laboratory study will not be considered in support of an application for a research or marketing permit does not, however, relieve the applicant for such a permit of any obligation under any applicable statute or regulation to submit the results of the study to the Food and Drug Administration.
(b) 如果检测机构拒绝允许检查,食品和药物管理局将不会考虑非临床实验室研究以支持研究或销售许可证的申请。然而,确定非临床实验室研究将不被视为支持研究或营销许可证的申请,并不能免除此类许可证的申请人根据任何适用的法规或法规向食品和药物管理局提交研究结果的任何义务。
Subpart B--Organization and Personnel
B分部--组织与人员
Sec. 58.29 Personnel.
(a) Each individual engaged in the conduct of or responsible for the supervision of a nonclinical laboratory study shall have education, training, and experience, or combination thereof, to enable that individual to perform the assigned functions.
(a) 参与进行非临床实验室研究或负责监督非临床实验室研究的每个人都应接受过教育、培训和经验,或其结合,使该个人能够履行指定的职能。
(b) Each testing facility shall maintain a current summary of training and experience and job description for each individual engaged in or supervising the conduct of a nonclinical laboratory study.
(b) 每个检测机构都应为参与或监督非临床实验室研究的每个人保留一份最新的培训和经验摘要以及工作说明。
(c) There shall be a sufficient number of personnel for the timely and proper conduct of the study according to the protocol.
(c) 应有足够数量的人员,以便根据议定书及时和适当地进行研究。
(d) Personnel shall take necessary personal sanitation and health precautions designed to avoid contamination of test and control articles and test systems.
(d) 人员应采取必要的个人卫生和卫生预防措施,以避免污染试验和控制物品及试验系统。
(e) Personnel engaged in a nonclinical laboratory study shall wear clothing appropriate for the duties they perform. Such clothing shall be changed as often as necessary to prevent microbiological, radiological, or chemical contamination of test systems and test and control articles.
(e) 从事非临床实验室研究的人员应穿着与其履行的职责相适应的服装。此类防护服应根据需要经常更换,以防止测试系统以及测试和控制物品受到微生物、放射性或化学污染。
(f) Any individual found at any time to have an illness that may adversely affect the quality and integrity of the nonclinical laboratory study shall be excluded from direct contact with test systems, test and control articles and any other operation or function that may adversely affect the study until the condition is corrected. All personnel shall be instructed to report to their immediate supervisors any health or medical conditions that may reasonably be considered to have an adverse effect on a nonclinical laboratory study.
(f) 在任何时候发现患有可能对非临床实验室研究的质量和完整性产生不利影响的疾病的任何个人,都应被排除在直接接触测试系统、测试和控制物品以及可能对研究产生不利影响的任何其他操作或功能之外,直到病情得到纠正。应指示所有人员向其直属上司报告任何可能被合理认为对非临床实验室研究产生不利影响的健康或医疗状况。
Sec. 58.31 Testing facility management.
For each nonclinical laboratory study, testing facility management shall:
对于每项非临床实验室研究,检测设施管理人员应:
(a) Designate a study director as described in 58.33, before the study is initiated.
(a) 在研究开始之前,按照58.33的规定指定一名研究主任。
(b) Replace the study director promptly if it becomes necessary to do so during the conduct of a study.
(b) 在进行研究期间,如果有必要更换研究主任,应立即更换研究主任。
(c) Assure that there is a quality assurance unit as described in 58.35.
(c) 确保设立58.35所述的质量保证单位。
(d) Assure that test and control articles or mixtures have been appropriately tested for identity, strength, purity, stability, and uniformity, as applicable.
(d) 确保测试和控制物品或混合物在特性、强度、纯度、稳定性和均匀性方面已酌情进行了适当测试。
(e) Assure that personnel, resources, facilities, equipment, materials, and methodologies are available as scheduled.
(e) 确保人员、资源、设施、设备、材料和方法按计划到位。
(f) Assure that personnel clearly understand the functions they are to perform.
(f) 确保工作人员清楚地了解他们要履行的职能。
(g) Assure that any deviations from these regulations reported by the quality assurance unit are communicated to the study director and corrective actions are taken and documented.
(g) 确保将质量保证部门报告的与这些规定的任何偏差传达给研究主任,并采取并记录纠正措施。
[43 FR 60013, Dec. 22, 1978, as amended at 52 FR 33780, Sept. 4, 1987]
[43 FR 60013,1978年12月22日,于1987年9月4日52 FR 33780修订]
Sec. 58.33 Study director.
For each nonclinical laboratory study, a scientist or other professional of appropriate education, training, and experience, or combination thereof, shall be identified as the study director. The study director has overall responsibility for the technical conduct of the study, as well as for the interpretation, analysis, documentation and reporting of results, and represents the single point of study control. The study director shall assure that:
对于每项非临床实验室研究,应确定一名具有适当教育、培训和经验的科学家或其他专业人员,或其组合,作为研究主任。研究主任全面负责研究的技术实施,以及结果的解释、分析、记录和报告,并代表研究的单点控制。研究主任应确保:
(a) The protocol, including any change, is approved as provided by 58.120 and is followed.
(a) 议定书,包括任何修改,均按照58.120的规定获得批准并得到遵守。
(b) All experimental data, including observations of unanticipated responses of the test system are accurately recorded and verified.
(b) 所有实验数据,包括对测试系统意外反应的观察结果都得到准确记录和核实。
(c) Unforeseen circumstances that may affect the quality and integrity of the nonclinical laboratory study are noted when they occur, and corrective action is taken and documented.
(c) 在可能影响非临床实验室研究的质量和完整性的不可预见的情况发生时予以记录,并采取纠正措施并记录在案。
(d) Test systems are as specified in the protocol.
(d) 测试系统符合议定书的规定。
(e) All applicable good laboratory practice regulations are followed.
(e) 遵守所有适用的良好实验室规范规定。
(f) All raw data, documentation, protocols, specimens, and final reports are transferred to the archives during or at the close of the study.
(f) 所有原始数据、文件、方案、标本和最终报告均在研究期间或结束时移交给档案馆。
[43 FR 60013, Dec. 22, 1978; 44 FR 17657, Mar. 23, 1979]
[43 FR 60013,1978年12月22日;44 FR 17657,1979年3月23日]
Sec. 58.35 Quality assurance unit.
(a) A testing facility shall have a quality assurance unit which shall be responsible for monitoring each study to assure management that the facilities, equipment, personnel, methods, practices, records, and controls are in conformance with the regulations in this part. For any given study, the quality assurance unit shall be entirely separate from and independent of the personnel engaged in the direction and conduct of that study.
(a) 检测设施应有一个质量保证单位,该单位应负责监督每项研究,以确保管理层确保设施、设备、人员、方法、做法、记录和控制符合本部分的规定。对于任何特定的研究,质量保证单位应完全独立于参与指导和进行该研究的人员,并独立于这些人员。
(b) The quality assurance unit shall:
(b) 质量保证股应:
(1) Maintain a copy of a master schedule sheet of all nonclinical laboratory studies conducted at the testing facility indexed by test article and containing the test system, nature of study, date study was initiated, current status of each study, identity of the sponsor, and name of the study director.
(1) 保留一份在测试机构进行的所有非临床实验室研究的主时间表表的副本,按测试文章索引,并包含测试系统、研究性质、研究开始日期、每项研究的当前状态、申办者的身份和研究主任的姓名。
(2) Maintain copies of all protocols pertaining to all nonclinical laboratory studies for which the unit is responsible.
(2) 保留与该部门负责的所有非临床实验室研究有关的所有协议的副本。
(3) Inspect each nonclinical laboratory study at intervals adequate to assure the integrity of the study and maintain written and properly signed records of each periodic inspection showing the date of the inspection, the study inspected, the phase or segment of the study inspected, the person performing the inspection, findings and problems, action recommended and taken to resolve existing problems, and any scheduled date for reinspection. Any problems found during the course of an inspection which are likely to affect study integrity shall be brought to the attention of the study director and management immediately.
(3) 以足够的时间间隔检查每项非临床实验室研究,以确保研究的完整性,并保留每次定期检查的书面和适当签名的记录,显示检查日期、检查的研究、检查研究的阶段或部分、执行检查的人员、发现和问题、建议和采取的行动以解决现有问题, 以及任何预定的重新检查日期。在检查过程中发现的任何可能影响研究完整性的问题都应立即引起研究主任和管理层的注意。
(4) Periodically submit to management and the study director written status reports on each study, noting any problems and the corrective actions taken.
(4) 定期向管理层和研究主任提交每项研究的书面状态报告,指出任何问题和采取的纠正措施。
(5) Determine that no deviations from approved protocols or standard operating procedures were made without proper authorization and documentation.
(5) 确定在没有适当授权和文件的情况下,没有偏离批准的协议或标准操作程序。
(6) Review the final study report to assure that such report accurately describes the methods and standard operating procedures, and that the reported results accurately reflect the raw data of the nonclinical laboratory study.
(6) 审查最终研究报告,以确保此类报告准确描述方法和标准操作程序,并确保报告的结果准确反映非临床实验室研究的原始数据。
(7) Prepare and sign a statement to be included with the final study report which shall specify the dates inspections were made and findings reported to management and to the study director.
(7) 准备并签署一份声明,以包含在最终研究报告中,其中应详细说明进行检查的日期以及向管理层和研究主任报告的调查结果。
(c) The responsibilities and procedures applicable to the quality assurance unit, the records maintained by the quality assurance unit, and the method of indexing such records shall be in writing and shall be maintained. These items including inspection dates, the study inspected, the phase or segment of the study inspected, and the name of the individual performing the inspection shall be made available for inspection to authorized employees of the Food and Drug Administration.
(c) 适用于质量保证股的责任和程序、质量保证股保存的记录以及编制这些记录的索引方法应采用书面形式,并应予以维持。这些项目,包括检查日期、检查的研究、检查的研究的阶段或部分,以及执行检查的个人的姓名,应提供给食品和药物管理局的授权雇员进行检查。
(d) A designated representative of the Food and Drug Administration shall have access to the written procedures established for the inspection and may request testing facility management to certify that inspections are being implemented, performed, documented, and followed-up in accordance with this paragraph.
(d) 食品和药物管理局的指定代表应有权查阅为检查制定的书面程序,并可要求检测设施管理人员证明检查正在按照本款规定实施、执行、记录和跟踪。
[43 FR 60013, Dec. 22, 1978, as amended at 52 FR 33780, Sept. 4, 1987; 67 FR 9585, Mar. 4, 2002]
Subpart C—Facilities
Sec. 58.41 General.
Each testing facility shall be of suitable size and construction to facilitate the proper conduct of nonclinical laboratory studies. It shall be designed so that there is a degree of separation that will prevent any function or activity from having an adverse effect on the study.
每个检测设施的规模和结构应适当,以利于非临床实验室研究的适当进行。它的设计应具有一定程度的分离,以防止任何功能或活动对研究产生不利影响。
[52 FR 33780, Sept. 4, 1987]
Sec. 58.43 Animal care facilities.
(a) A testing facility shall have a sufficient number of animal rooms or areas, as needed, to assure proper: (1) Separation of species or test systems, (2) isolation of individual projects, (3) quarantine of animals, and (4) routine or specialized housing of animals.
(a) 检测设施应根据需要配备足够数量的动物房间或区域,以确保适当:(1) 物种或检测系统的分离,(2) 个别项目的隔离,(3) 动物检疫,以及 (4) 动物的常规或专门饲养。
(b) A testing facility shall have a number of animal rooms or areas separate from those described in paragraph (a) of this section to ensure isolation of studies being done with test systems or test and control articles known to be biohazardous, including volatile substances, aerosols, radioactive materials, and infectious agents.
(b) 检测设施应具有与本节(a)款所述动物室或区域分开的若干动物室或区域,以确保隔离使用已知具有生物危害性的试验系统或试验和控制物品(包括挥发性物质、气溶胶、放射性物质和传染性病原体)进行的研究。
(c) Separate areas shall be provided, as appropriate, for the 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 diseased, or of being carriers of disease, from other animals.
(c) 应酌情为实验动物疾病的诊断、治疗和控制提供单独的区域。这些区域应为已知或疑似患病或疾病携带者的动物提供有效的隔离,以与其他动物隔离。
(d) When animals are housed, facilities shall exist for the collection and disposal of all animal waste and refuse or for safe sanitary storage of waste before removal from the testing facility. Disposal facilities shall be so provided and operated as to minimize vermin infestation, odors, disease hazards, and environmental contamination.
(d) 当饲养动物时,应有收集和处置所有动物粪便和废物的设施,或在从检测设施中取出之前安全卫生储存废物的设施。处置设施的提供和操作应尽量减少害虫侵扰、恶臭、疾病危害和环境污染。
[43 FR 60013, Dec. 22, 1978, as amended at 52 FR 33780, Sept. 4, 1987]
[43 FR 60013,1978年12月22日,于1987年9月4日52 FR 33780修订]
Sec. 58.45 Animal supply facilities.
There shall be storage areas, as needed, for feed, bedding, supplies, and equipment. Storage areas for feed and bedding shall be separated from areas housing the test systems and shall be protected against infestation or contamination. Perishable supplies shall be preserved by appropriate means.
应根据需要为饲料、垫料、用品和设备设置储存区。饲料和垫料的储存区域应与容纳测试系统的区域分开,并应防止侵扰或污染。易腐物资应采用适当方式保存。
[43 FR 60013, Dec. 22, 1978, as amended at 52 FR 33780, Sept. 4, 1987]
[43 FR 60013,1978年12月22日,于1987年9月4日52 FR 33780修订]
Sec. 58.47 Facilities for handling test and control articles.
第 58.47 节 处理测试和控制物品的设施。
(a) As necessary to prevent contamination or mixups, there shall be separate areas for:
(a) 为防止污染或混淆,必要时,应有单独的区域供下列人员使用:
(1) Receipt and storage of the test and control articles.
(一)试验、控制物品的收存、保管。
(2) Mixing of the test and control articles with a carrier, e.g., feed.
(2) 将试验品和对照品与载体(例如饲料)混合。
(3) Storage of the test and control article mixtures.
(3)试验品和对照品混合物的贮存。
(b) Storage areas for the test and/or control article and test and control mixtures shall be separate from areas housing the test systems and shall be adequate to preserve the identity, strength, purity, and stability of the articles and mixtures.
(b) 试验和/或控制物品以及试验和控制混合物的储存区应与容纳试验系统的区域分开,并应足以保持物品和混合物的特性、强度、纯度和稳定性。
Sec. 58.49 Laboratory operation areas.
Separate laboratory space shall be provided, as needed, for the performance of the routine and specialized procedures required by nonclinical laboratory studies.
应根据需要提供单独的实验室空间,以执行非临床实验室研究所需的常规和专业程序。
[52 FR 33780, Sept. 4, 1987]
Sec. 58.51 Specimen and data storage facilities.
Space shall be provided for archives, limited to access by authorized personnel only, for the storage and retrieval of all raw data and specimens from completed studies.
应为档案提供空间,仅允许经授权的人员访问,以存储和检索已完成研究的所有原始数据和样本。
Subpart D—Equipment
Sec. 58.61 Equipment design.
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.
用于生成、测量或评估数据的设备以及用于设施环境控制的设备应具有适当的设计和足够的能力,以根据协议运行,并应位于适当的位置,以便操作、检查、清洁和维护。
[52 FR 33780, Sept. 4, 1987]
Sec. 58.63 Maintenance and calibration of equipment.
第 58.63 节 设备的维护和校准。
(a) Equipment shall be adequately inspected, cleaned, and maintained. Equipment used for the generation, measurement, or assessment of data shall be adequately tested, calibrated and/or standardized.
(a) 设备应得到充分的检查、清洁和维护。用于生成、测量或评估数据的设备应进行充分的测试、校准和/或标准化。
(b) The written standard operating procedures required under 58.81(b)(11) shall set forth in sufficient detail the methods, materials, and schedules to be used in the routine inspection, cleaning, maintenance, testing, calibration, and/or standardization of equipment, and shall specify, when appropriate, remedial action to be taken in the event of failure or malfunction of equipment. The written standard operating procedures shall designate the person responsible for the performance of each operation.
(b) 58.81(b)(11) 要求的书面标准操作程序应足够详细地规定在设备的例行检查、清洁、维护、测试、校准和/或标准化中使用的方法、材料和时间表,并应酌情规定在设备发生故障或故障时应采取的补救措施。书面的标准操作规程应指定负责执行每项操作的人员。
(c) Written records shall be maintained of all inspection, maintenance, testing, calibrating and/or standardizing operations. These records, containing the date of the operation, shall describe whether the maintenance operations were routine and followed the written standard operating procedures. Written records shall be kept of nonroutine repairs performed on equipment as a result of failure and malfunction. Such records shall document the nature of the defect, how and when the defect was discovered, and any remedial action taken in response to the defect.
(c) 应保存所有检查、维护、测试、校准和/或标准化操作的书面记录。这些记录包含操作日期,应说明维护操作是否为例行操作并遵循书面标准操作程序。对因故障和故障而对设备进行的非常规维修,应保存书面记录。此类记录应记录缺陷的性质、发现缺陷的方式和时间,以及为应对缺陷而采取的任何补救措施。
[43 FR 60013, Dec. 22, 1978, as amended at 52 FR 33780, Sept. 4, 1987; 67 FR 9585, Mar. 4, 2002]
Subpart E--Testing Facilities Operation
Sec. 58.81 Standard operating procedures.
(a) A testing facility shall have standard operating procedures in writing setting forth nonclinical laboratory study methods that management is satisfied are adequate to insure the quality and integrity of the data generated in the course of a study. All deviations in a study from standard operating procedures shall be authorized by the study director and shall be documented in the raw data. Significant changes in established standard operating procedures shall be properly authorized in writing by management.
(a) 检测设施应以书面形式制定标准操作程序,规定管理层认为足以确保研究过程中产生的数据的质量和完整性的非临床实验室研究方法。研究中与标准操作程序的所有偏差均应得到研究主任的授权,并应记录在原始数据中。对既定标准操作程序的重大更改应得到管理层的适当书面授权。
(b) Standard operating procedures shall be established for, but not limited to, the following:
(b) 应为但不限于下列各项制定标准作业程序:
(1) Animal room preparation.
(2) Animal care.
(3) Receipt, identification, storage, handling, mixing, and method of sampling of the test and control articles.
(三)供试品、控品的收货、鉴定、贮存、处理、混合、取样方法。
(4) Test system observations.
(5) Laboratory tests.
(6) Handling of animals found moribund or dead during study.
(六)研究期间发现奄奄一息、死亡的动物的处理。
(7) Necropsy of animals or postmortem examination of animals.
(七)动物尸检或者动物尸检。
(8) Collection and identification of specimens.
(八)标本的采集和鉴定。
(9) Histopathology.
(10) Data handling, storage, and retrieval.
(11) Maintenance and calibration of equipment.
(11)设备的维护和校准。
(12) Transfer, proper placement, and identification of animals.
(12)动物的转移、妥善安置和鉴定。
(c) Each laboratory area shall have immediately available laboratory manuals and standard operating procedures relative to the laboratory procedures being performed. Published literature may be used as a supplement to standard operating procedures.
(c) 每个实验室区域应立即拥有与正在执行的实验室程序相关的实验室手册和标准操作程序。已发表的文献可用作标准操作程序的补充。
(d) A historical file of standard operating procedures, and all revisions thereof, including the dates of such revisions, shall be maintained.
(d) 应保存一份关于标准作业程序及其所有修订案的历史档案,包括这些修订案的日期。
[43 FR 60013, Dec. 22, 1978, as amended at 52 FR 33780, Sept. 4, 1987]
[43 FR 60013,1978年12月22日,于1987年9月4日52 FR 33780修订]
Sec. 58.83 Reagents and solutions.
第 58.83 节试剂和溶液。
All reagents and solutions in the laboratory areas shall be labeled to indicate identity, titer or concentration, storage requirements, and expiration date. Deteriorated or outdated reagents and solutions shall not be used.
实验室区域内的所有试剂和溶液均应贴上标签,以标明身份、滴度或浓度、储存要求和有效期。不得使用变质或过期的试剂和溶液。
Sec. 58.90 Animal care.
(a) There shall be standard operating procedures for the housing, feeding, handling, and care of animals.
(a) 应有关于动物的饲养、喂养、处理和护理的标准操作程序。
(b) All newly received animals from outside sources shall be isolated and their health status shall be evaluated in accordance with acceptable veterinary medical practice.
(b) 所有从外部来源获得的动物均应被隔离,并应根据可接受的兽医医疗实践评估其健康状况。
(c) At the initiation of a nonclinical laboratory study, animals shall be free of any disease or condition that might interfere with the purpose or conduct of the study. If, during the course of the study, the animals contract such a disease or condition, the diseased animals shall be isolated, if necessary. These animals may be treated for disease or signs of disease provided that such treatment does not interfere with the study. The diagnosis, authorizations of treatment, description of treatment, and each date of treatment shall be documented and shall be retained.
(c) 在非临床实验室研究开始时,动物应没有任何可能干扰研究目的或进行的疾病或病症。如果在研究过程中,动物感染了这种疾病或病症,如有必要,应将患病动物隔离。如果这种治疗不干扰研究,这些动物可以接受疾病或疾病迹象的治疗。诊断、治疗授权、治疗描述和每个治疗日期均应记录在案并应予以保留。
(d) Warm-blooded animals, excluding suckling rodents, used in laboratory procedures that require manipulations and observations over an extended period of time or in studies that require the animals to be removed from and returned to their home cages for any reason (e.g., cage cleaning, treatment, etc.), shall receive appropriate identification. All information needed to specifically identify each animal within an animal-housing unit shall appear on the outside of that unit.
(d) 温血动物(不包括哺乳啮齿动物)在需要长时间操作和观察的实验室程序中使用,或用于需要以任何理由(例如,笼子清洁、治疗等)将动物从家庭笼子中移出并送回其家庭笼子的研究时,应获得适当的身份证明。具体识别动物饲养单元内每只动物所需的所有信息均应显示在该单元的外部。
(e) Animals of different species shall be housed in separate rooms when necessary. Animals of the same species, but used in different studies, should not ordinarily be housed in the same room when inadvertent exposure to control or test articles or animal mixup could affect the outcome of either study. If such mixed housing is necessary, adequate differentiation by space and identification shall be made.
(e) 必要时,应将不同种类的动物安置在单独的房间内。同一物种的动物,但在不同的研究中使用,当无意中暴露于对照或测试物品或动物混淆可能影响任一研究的结果时,通常不应将同一物种的动物饲养在同一房间内。如果需要这种混合住房,应通过空间和识别进行充分的区分。
(f) Animal cages, racks and accessory equipment shall be cleaned and sanitized at appropriate intervals.
(f) 动物笼子、架子和附属设备应每隔适当时间进行清洁和消毒。
(g) Feed and water used for the animals shall be analyzed periodically to ensure that contaminants known to be capable of interfering with the study and reasonably expected to be present in such feed or water are not present at levels above those specified in the protocol. Documentation of such analyses shall be maintained as raw data.
(g) 应定期分析用于动物的饲料和水,以确保已知能够干扰研究并合理预期存在于此类饲料或水中的污染物的含量不会超过议定书规定的水平。此类分析的文件应作为原始数据保存。
(h) 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 dry and clean.
(h) 动物笼子或围栏中使用的垫料不得干扰研究的目的或进行,并应根据需要经常更换,以保持动物干燥和清洁。
(i) If any pest control materials are used, the use shall be documented. Cleaning and pest control materials that interfere with the study shall not be used.
(i) 如果使用任何虫害防治材料,应记录其使用情况。不得使用干扰研究的清洁和虫害防治材料。
[43 FR 60013, Dec. 22, 1978, as amended at 52 FR 33780, Sept. 4, 1987; 54 FR 15924, Apr. 20, 1989; 56 FR 32088, July 15, 1991; 67 FR 9585, Mar. 4, 2002]
Subpart F--Test and Control Articles
F子部分--测试和控制文章
Sec. 58.105 Test and control article characterization.
第 58.105 节 测试和控制物品表征。
(a) The identity, strength, purity, and composition or other characteristics which will appropriately define the test or control article shall be determined for each batch and shall be documented. Methods of synthesis, fabrication, or derivation of the test and control articles shall be documented by the sponsor or the testing facility. In those cases where marketed products are used as control articles, such products will be characterized by their labeling.
(a) 应为每批货物确定可适当界定试验或控制物品的特性、强度、纯度、成分或其他特性,并应记录在案。试验品和对照品的合成、制造或衍生方法应由申办者或试验机构记录在案。在那些销售产品被用作控制物品的情况下,此类产品将以其标签为特征。
(b) The stability of each test or control article shall be determined by the testing facility or by the sponsor either: (1) Before study initiation, or (2) concomitantly according to written standard operating procedures, which provide for periodic analysis of each batch.
(b) 每种测试或控制物品的稳定性应由测试设施或申办者确定:(1) 在研究开始之前,或 (2) 同时根据书面标准操作程序确定,该程序规定对每批进行定期分析。
(c) Each storage container for a test or control article shall be labeled by name, chemical abstract number or code number, batch number, expiration date, if any, and, where appropriate, storage conditions necessary to maintain the identity, strength, purity, and composition of the test or control article. Storage containers shall be assigned to a particular test article for the duration of the study.
(c) 试验或控制物品的每个储存容器均应标明名称、化学摘要号或代号、批号、有效期(如有)以及在适当情况下标明维持试验或控制物品的特性、强度、纯度和成分所必需的储存条件。在研究期间,应将储存容器分配给特定的测试物品。
(d) For studies of more than 4 weeks' duration, reserve samples from each batch of test and control articles shall be retained for the period of time provided by 58.195.
(d) 对于持续时间超过4周的研究,每批试验和对照物品的储备样品应在58.195规定的期限内保留。
Sec. 58.107 Test and control article handling.
第 58.107 节 测试和控制物品处理。
Procedures shall be established for a system for the handling of the test and control articles to ensure that:
应建立试验和控制物品处理制度的程序,以确保:
(a) There is proper storage.
(a) 有适当的储存。
(b) Distribution is made in a manner designed to preclude the possibility of contamination, deterioration, or damage.
(b) 分发的方式旨在排除污染、变质或损坏的可能性。
(c) Proper identification is maintained throughout the distribution process.
(c) 在整个分发过程中保持适当的身份识别。
(d) The receipt and distribution of each batch is documented. Such documentation shall include the date and quantity of each batch distributed or returned.
(d) 每批货物的收货和分发均有记录。此类文件应包括分发或退回的每批货物的日期和数量。
Sec. 58.113 Mixtures of articles with carriers.
第 58.113 节 物品与载体的混合物。
(a) For each test or control article that is mixed with a carrier, tests by appropriate analytical methods shall be conducted:
(a) 对于与载体混合的每一种试验或控制物品,应采用适当的分析方法进行试验:
(1) To determine the uniformity of the mixture and to determine, periodically, the concentration of the test or control article in the mixture.
(1) 确定混合物的均匀性,并定期测定混合物中试验品或对照品的浓度。
(2) To determine the stability of the test and control articles in the mixture as required by the conditions of the study either:
(2) 根据研究条件的要求,确定混合物中试验品和对照品的稳定性:
(i) Before study initiation, or
(i) 在研究开始之前,或
(ii) Concomitantly according to written standard operating procedures which provide for periodic analysis of the test and control articles in the mixture.
(ii) 同时根据书面标准操作程序,规定对混合物中的测试和控制物品进行定期分析。
(b) [Reserved]
(b) [保留]
(c) Where any of the components 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.
(c) 如果试验品或控制物品载体混合物的任何成分有有效期,则应在容器上清楚地标明该日期。如果多个组件具有到期日期,则应显示最早的日期。
Subpart G--Protocol for and Conduct of a Nonclinical Laboratory Study
G子部分--非临床实验室研究的方案和实施
Sec. 58.120 Protocol.
(a) 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 contain, as applicable, the following information:
(a) 每项研究均应有一份经批准的书面方案,明确说明进行研究的目标和所有方法。在适用的情况下,该协议应包含以下信息:
(1) A descriptive title and statement of the purpose of the study.
(一)研究目的的描述性标题和说明。
(2) Identification of the test and control articles by name, chemical abstract number, or code number.
(二)对试验、管制物品按名称、化学摘要号、代号进行标识。
(3) The name of the sponsor and the name and address of the testing facility at which the study is being conducted.
(3)申办者的名称以及进行研究的检测机构的名称和地址。
(4) The number, body weight range, sex, source of supply, species, strain, substrain, and age of the test system.
(4)试验系统的数量、体重范围、性别、供应来源、种类、菌株、亚品系、年龄。
(5) The procedure for identification of the test system.
(5)试验系统的识别程序。
(6) A description of the experimental design, including the methods for the control of bias.
(6)实验设计的描述,包括控制偏置的方法。
(7) A description and/or identification of the diet used in the study as well as solvents, emulsifiers, and/or other materials used to solubilize or suspend the test or control articles 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 if present at levels greater than established by the specifications.
(7) 研究中使用的饮食的描述和/或标识,以及在与载体混合之前用于溶解或悬浮测试或对照物品的溶剂、乳化剂和/或其他材料。描述应包括可接受的污染物水平的规格,这些污染物是合理预期的,存在于膳食材料中,并且已知如果其含量高于规格规定的水平,则这些污染物能够干扰研究的目的或进行。
(8) Each dosage level, expressed in milligrams per kilogram of body weight or other appropriate units, of the test or control article to be administered and the method and frequency of administration.
(八)拟给药的供试品、对照品的各剂量水平,以毫克/千克体重或者其他适当单位表示,给药方法和频率。
(9) The type and frequency of tests, analyses, and measurements to be made.
(9) 要进行的测试、分析和测量的类型和频率。
(10) The records to be maintained.
(十)需要保存的记录。
(11) The date of approval of the protocol by the sponsor and the dated signature of the study director.
(11) 申办者批准方案的日期和研究主任签字的日期。
(12) A statement of the proposed statistical methods to be used.
(12) 拟采用的统计方法的说明。
(b) 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.
(b) 对已批准的方案的所有更改或修订以及由此产生的原因都应记录在案,由研究主任签字,注明日期,并与方案一起保存。
[43 FR 60013, Dec. 22, 1978, as amended at 52 FR 33781, Sept. 4, 1987; 67 FR 9585, Mar. 4, 2002]
Sec. 58.130 Conduct of a nonclinical laboratory study.
第 58.130 节 进行非临床实验室研究。
(a) The nonclinical laboratory study shall be conducted in accordance with the protocol.
(a) 非临床实验室研究应按照方案进行。
(b) The test systems shall be monitored in conformity with the protocol.
(b) 应按照议定书对试验系统进行监测。
(c) 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 data.
(c) 标本应按检验制度、研究、性质和采集日期进行鉴定。这些信息应位于样本容器上,或应以排除数据记录和存储错误的方式与样本一起提供。
(d) Records of gross findings for a specimen from postmortem observations should be available to a pathologist when examining that specimen histopathologically.
(d) 病理学家在对标本进行组织病理学检查时,应获得尸检观察结果中标本的总体发现记录。
(e) All data generated during the conduct of a nonclinical laboratory study, except those that are generated by automated data collection systems, shall be recorded directly, promptly, and legibly in ink. All data entries shall be dated on the date of entry and signed or initialed by the person entering the data. Any change in entries shall be made so as not to obscure the original entry, shall indicate the reason for such change, and shall be dated and signed or identified at the time of the change. In automated data collection systems, the individual responsible for direct data input shall be identified at the time of data input. Any change in automated data entries shall be made so as not to obscure the original entry, shall indicate the reason for change, shall be dated, and the responsible individual shall be identified.
(e) 在进行非临床实验室研究期间产生的所有数据,除由自动数据收集系统生成的数据外,均应直接、及时和清晰地用墨水记录。所有数据录入的日期应为录入之日,并由录入数据的人签名或草签。对条目进行任何更改时,应避免使原始条目模糊不清,并应说明更改的原因,并应在更改时注明日期并签名或标识。在自动数据收集系统中,负责直接输入数据的个人应在输入数据时被识别出来。对自动数据条目进行的任何更改均应避免使原始条目模糊不清,并应说明更改原因,应注明日期,并应确定责任人。
[43 FR 60013, Dec. 22, 1978, as amended at 52 FR 33781, Sept. 4, 1987; 67 FR 9585, Mar. 4, 2002]
Subparts H-I [Reserved]
子部件 H-I [预留]
Subpart J--Records and Reports
J子部分--记录和报告
Sec. 58.185 Reporting of nonclinical laboratory study results.
第 58.185 节 报告非临床实验室研究结果。
(a) A final report shall be prepared for each nonclinical laboratory study and shall include, but not necessarily be limited to, the following:
(a) 应为每项非临床实验室研究准备一份最终报告,并应包括但不限于以下内容:
(1) Name and address of the facility performing the study and the dates on which the study was initiated and completed.
(1) 进行研究的设施的名称和地址以及开始和完成研究的日期。
(2) Objectives and procedures stated in the approved protocol, including any changes in the original protocol.
(2) 经批准的议定书中规定的目标和程序,包括对原始议定书的任何修改。
(3) Statistical methods employed for analyzing the data.
(三)采用统计方法对数据进行分析。
(4) The test and control articles identified by name, chemical abstracts number or code number, strength, purity, and composition or other appropriate characteristics.
(四)检验控制物品标识的名称、化学摘要编号或者代号、强度、纯度、成分或者其他适当特性。
(5) Stability of the test and control articles under the conditions of administration.
(5)试验、对照物品在给药条件下的稳定性。
(6) A description of the methods used.
(6)所用方法的说明。
(7) A description of the test system used. Where applicable, the final report shall include the number of animals used, sex, body weight range, source of supply, species, strain and substrain, age, and procedure used for identification.
(7) 所用测试系统的说明。在适用的情况下,最终报告应包括所用动物的数量、性别、体重范围、供应来源、种类、品系和亚系、年龄和用于鉴定的程序。
(8) A description of the dosage, dosage regimen, route of administration, and duration.
(9) A description of all cirmcumstances that may have affected the quality or integrity of the data.
(9) 对可能影响数据质量或完整性的所有因素的描述。
(10) The name of the study director, the names of other scientists or professionals, and the names of all supervisory personnel, involved in the study.
(10)研究主任的姓名,其他科学家或专业人员的姓名,以及参与研究的所有监督人员的姓名。
(11) A 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 analysis.
(十一)对数据进行的转换、计算、操作的描述,对数据的总结和分析,以及分析得出的结论的陈述。
(12) The signed and dated reports of each of the individual scientists or other professionals involved in the study.
(12) 参与研究的每位科学家或其他专业人员的签名和注明日期的报告。
(13) The locations where all specimens, raw data, and the final report are to be stored.
(十三)所有标本、原始资料和最终报告的存放地点。
(14) The statement prepared and signed by the quality assurance unit as described in 58.35(b)(7).
(14) 由质量保证单位编制并签署的声明,如58.35(b)(7)所述。
(b) The final report shall be signed and dated by the study director.
(b) 最后报告应由研究主任签名并注明日期。
(c) Corrections or additions to a final report shall be in the form of an amendment by the study director. The amendment shall clearly identify that part of the final report that is being added to or corrected and the reasons for the correction or addition, and shall be signed and dated by the person responsible.
(c) 对最后报告的更正或补充应由研究主任以修正的形式进行。修改内容应当明确标明归结报告中增加或者更正的部分以及更正或者增加的理由,并由责任人签名并注明日期。
[43 FR 60013, Dec. 22, 1978, as amended at 52 FR 33781, Sept. 4, 1987]
[43 FR 60013,1978年12月22日,于1987年9月4日52 FR 33781修订]
Sec. 58.190 Storage and retrieval of records and data.
第 58.190 节 记录和数据的存储和检索。
(a) 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 a nonclinical laboratory study shall be retained.
(a) 应保留因非临床实验室研究而产生的所有原始数据、文件、方案、最终报告和标本(从致突变性试验获得的标本和血液、尿液、粪便和生物体液的湿标本除外)。
(b) There shall be archives for orderly storage and expedient retrieval of all raw data, documentation, protocols, specimens, and interim and final reports. Conditions of storage shall minimize deterioration of the documents or specimens in accordance with the requirements for the time period of their retention and the nature of the documents or specimens. A testing facility may contract with commercial archives to provide a repository for all material to be retained. Raw data and specimens may be retained elsewhere provided that the archives have specific reference to those other locations.
(b) 应有档案,以便有序地储存和方便检索所有原始数据、文件、协议、标本以及临时报告和最后报告。储存条件应根据文件或标本的保存期限要求和文件或标本的性质,尽量减少文件或标本的变质。检测机构可以与商业档案馆签订合同,为所有需要保留的材料提供一个储存库。原始数据和标本可以保留在其他地方,只要档案馆具体提及这些其他地方。
(c) An individual shall be identified as responsible for the archives.
(c) 应确定一名个人负责档案。
(d) Only authorized personnel shall enter the archives.
(d) 只有经授权的人员才能进入档案馆。
(e) Material retained or referred to in the archives shall be indexed to permit expedient retrieval.
(e) 档案中保留或提及的材料应编入索引,以便于检索。
[43 FR 60013, Dec. 22, 1978, as amended at 52 FR 33781, Sept. 4, 1987; 67 FR 9585, Mar. 4, 2002]
Sec. 58.195 Retention of records.
(a) Record retention requirements set forth in this section do not supersede the record retention requirements of any other regulations in this chapter.
(a) 本节规定的记录保留要求不取代本章任何其他条例的记录保留要求。
(b) Except as provided in paragraph (c) of this section, documentation records, raw data and specimens pertaining to a nonclinical laboratory study and required to be made by this part shall be retained in the archive(s) for whichever of the following periods is shortest:
(b) 除本节 (c) 段另有规定外,与非临床实验室研究有关的文件记录、原始数据和标本以及本部分要求制作的标本,应在以下期限内以最短的期限为准保留在档案馆中:
(1) A period of at least 2 years following the date on which an application for a research or marketing permit, in support of which the results of the nonclinical laboratory study were submitted, is approved by the Food and Drug Administration. This requirement does not apply to studies supporting investigational new drug applications (IND's) or applications for investigational device exemptions (IDE's), records of which shall be governed by the provisions of paragraph (b)(2) of this section.
(1) 自食品和药物管理局批准研究或上市许可申请之日起至少 2 年,该申请支持非临床实验室研究的结果。本要求不适用于支持研究性新药申请 (IND) 或研究性设备豁免申请 (IDE) 的研究,其记录应受本节 (b)(2) 段规定的管辖。
(2) A period of at least 5 years following the date on which the results of the nonclinical laboratory study are submitted to the Food and Drug Administration in support of an application for a research or marketing permit.
(2) 自向美国食品和药物管理局提交非临床实验室研究结果以支持研究或营销许可申请之日起至少 5 年的期限。
(3) In other situations (e.g., where the nonclinical laboratory study does not result in the submission of the study in support of an application for a research or marketing permit), a period of at least 2 years following the date on which the study is completed, terminated, or discontinued.
(3) 在其他情况下(例如,如果非临床实验室研究未导致提交研究以支持研究或营销许可的申请),自研究完成、终止或中止之日起至少 2 年。
(c) Wet specimens (except those specimens obtained from mutagenicity tests and wet specimens of blood, urine, feces, and biological fluids), samples of test or control articles, and specially prepared material, which are relatively fragile and differ markedly in stability and quality during storage, shall be retained only as long as the quality of the preparation affords evaluation. In no case shall retention be required for longer periods than those set forth in paragraphs (a) and (b) of this section.
(c) 湿试样(通过致突变性试验获得的试样和血液、尿液、粪便和生物体液的湿试样除外)、试验品或对照品样品以及特殊制备的材料,这些试样相对易碎,在储存期间的稳定性和质量上有明显差异,只有在制剂的质量能够进行评价的情况下才应予以保留。在任何情况下,保留期限均不得超过本节 (a) 和 (b) 段规定的期限。
(d) The master schedule sheet, copies of protocols, and records of quality assurance inspections, as required by 58.35(c) shall be maintained by the quality assurance unit as an easily accessible system of records for the period of time specified in paragraphs (a) and (b) of this section.
(d) 根据58.35(c)的要求,总时间表、议定书副本和质量保证检查记录,应由质量保证单位在本条(a)和(b)段规定的期限内作为易于查阅的记录系统进行保存。
(e) Summaries of training and experience and job descriptions required to be maintained by 58.29(b) may be retained along with all other testing facility employment records for the length of time specified in paragraphs (a) and (b) of this section.
(e) 58.29(b)要求保存的培训和经验摘要以及职务说明,可在本节(a)和(b)段规定的时间内与所有其他检测设施就业记录一起保留。
(f) Records and reports of the maintenance and calibration and inspection of equipment, as required by 58.63(b) and (c), shall be retained for the length of time specified in paragraph (b) of this section.
(f) 根据58.63(b)和(c)的要求,设备的维护、校准和检查的记录和报告,应在本条(b)款规定的期限内保留。
(g) Records required by this part may be retained either as original records or as true copies such as photocopies, microfilm, microfiche, or other accurate reproductions of the original records.
(g) 本部分规定的记录可以作为原始记录保存,也可以作为真实副本保存,例如影印本、缩微胶卷、缩微胶片或原始记录的其他准确复制品。
(h) If a facility conducting nonclinical testing 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 Food and Drug Administration shall be notified in writing of such a transfer.
(h) 如果进行非临床测试的设施倒闭,本节中规定的所有原始数据、文件和其他材料应转移到研究申办者的档案中。应将此类转移书面通知食品药品监督管理局。
[43 FR 60013, Dec. 22, 1978, as amended at 52 FR 33781, Sept. 4, 1987; 54 FR 9039, Mar. 3, 1989]
Subpart K--Disqualification of Testing Facilities
K子部分--取消检测设施的资格
Sec. 58.200 Purpose.
(a) The purposes of disqualification are:
(a) 取消资格的目的是:
(1) To permit the exclusion from consideration of completed studies that were conducted by a testing facility which has failed to comply with the requirements of the good laboratory practice regulations until it can be adequately demonstrated that such noncompliance did not occur during, or did not affect the validity or acceptability of data generated by, a particular study; and
(1) 允许将未能遵守良好实验室规范规定的已完成研究排除在考虑范围之外,除非能够充分证明这种不遵守行为并非在以下过程中发生,或不影响由以下机构产生的数据的有效性或可接受性: 一项特定的研究;和
(2) To exclude from consideration all studies completed after the date of disqualification until the facility can satisfy the Commissioner that it will conduct studies in compliance with such regulations.
(2) 将取消资格之日后完成的所有研究排除在考虑范围之外,直到设施能够使专员确信它将按照此类规定进行研究。
(b) The determination that a nonclinical laboratory study may not be considered in support of an application for a research or marketing permit does not, however, relieve the applicant for such a permit of any obligation under any other applicable regulation to submit the results of the study to the Food and Drug Administration.
(b) 然而,确定非临床实验室研究不得被视为支持研究或销售许可证的申请,并不能免除此类许可证的申请人根据任何其他适用法规向食品和药物管理局提交研究结果的任何义务。
Sec. 58.202 Grounds for disqualification.
第 58.202 条 取消资格的理由。
The Commissioner may disqualify a testing facility upon finding all of the following:
如果发现以下所有情况,专员可以取消检测机构的资格:
(a) The testing facility failed to comply with one or more of the regulations set forth in this part (or any other regulations regarding such facilities in this chapter);
(a) 检测设施未能遵守本部分规定的一项或多项规章(或本章中有关此类设施的任何其他规章);
(b) The noncompliance adversely affected the validity of the nonclinical laboratory studies; and
(b) 不遵守规定对非临床实验室研究的有效性产生不利影响;和
(c) Other lesser regulatory actions (e.g., warnings or rejection of individual studies) have not been or will probably not be adequate to achieve compliance with the good laboratory practice regulations.
(c) 其他较轻的监管行动(例如,警告或拒绝个别研究)已经或可能不足以实现对良好实验室规范条例的遵守。
Sec. 58.204 Notice of and opportunity for hearing on proposed disqualification.
第 58.204 条:关于拟议取消资格的通知和听证机会。
(a) Whenever the Commissioner has information indicating that grounds exist under 58.202 which in his opinion justify disqualification of a testing facility, he may issue to the testing facility a written notice proposing that the facility be disqualified.
(a) 每当专员有资料表明,根据第58.202条存在理由,他认为有理由取消检测设施的资格时,他可以向检测设施发出书面通知,建议取消该设施的资格。
(b) A hearing on the disqualification shall be conducted in accordance with the requirements for a regulatory hearing set forth in part 16 of this chapter.
(二)关于取消资格的听证,应当按照本章第16编规定的监管听证要求进行。
Sec. 58.206 Final order on disqualification.
第 58.206 条关于取消资格的最终命令。
(a) If the Commissioner, after the regulatory hearing, or after the time for requesting a hearing expires without a request being made, upon an evaulation of the administrative record of the disqualification proceeding, makes the findings required in 58.202, he shall issue a final order disqualifying the facility. Such order shall include a statement of the basis for that determination. Upon issuing a final order, the Commissioner shall notify (with a copy of the order) the testing facility of the action.
(a) 如果专员在监管听证会之后,或在要求举行听证会的时间届满而没有提出请求后,在撤销资格程序的行政记录后,得出了 58.202 中要求的调查结果,他应发布最终命令,取消该设施的资格。该命令应包括关于该决定的依据的声明。在发布最后命令后,专员应将行动通知(连同命令的副本)检测设施。
(b) If the Commissioner, after a regulatory hearing or after the time for requesting a hearing expires without a request being made, upon an evaluation of the administrative record of the disqualification proceeding, does not make the findings required in 58.202, he shall issue a final order terminating the disqualification proceeding. Such order shall include a statement of the basis for that determination. Upon issuing a final order the Commissioner shall notify the testing facility and provide a copy of the order.
(b) 如果专员在监管听证会后或在请求听证会的时间届满而未提出请求后,在评估取消资格程序的行政记录后,没有做出 58.202 中要求的调查结果,他应发出终止取消资格程序的最终命令。该命令应包括关于该决定的依据的声明。在发出最后命令后,专员应通知检测机构并提供命令的副本。
Sec. 58.210 Actions upon disqualification.
第 58.210 条:取消资格后的行动。
(a) Once a testing facility has been disqualified, each application for a research or marketing permit, whether approved or not, containing or relying upon any nonclinical laboratory study conducted by the disqualified testing facility may be examined to determine whether such study was or would be essential to a decision. If it is determined that a study was or would be essential, the Food and Drug Administration shall also determine whether the study is acceptable, notwithstanding the disqualification of the facility. Any study done by a testing facility before or after disqualification may be presumed to be unacceptable, and the person relying on the study may be required to establish that the study was not affected by the circumstances that led to the disqualification, e.g., by submitting validating information. If the study is then determined to be unacceptable, such data will be eliminated from consideration in support of the application; and such elimination may serve as new information justifying the termination or withdrawal of approval of the application.
(a) 一旦检测机构被取消资格,凡是包含或依赖被取消资格的检测机构进行的任何非临床实验室研究的研究或销售许可证申请,无论是否获得批准,均可进行审查,以确定这种研究是否对决定至关重要。如果确定某项研究是必要的或将是必不可少的,食品和药物管理局还应确定该研究是否可接受,尽管该机构被取消资格。检测机构在取消资格之前或之后进行的任何研究都可能被推定为不可接受的,并且可能需要依赖该研究的人证明该研究没有受到导致取消资格的情况的影响,例如,通过提交验证信息。如果该研究随后被确定为不可接受,则此类数据将从支持申请的考虑中删除;这种消除可以作为终止或撤回批准申请的新信息。
(b) No nonclinical laboratory study begun by a testing facility after the date of the facility's disqualification shall be considered in support of any application for a research or marketing permit, unless the facility has been reinstated under 58.219. The determination that a study may not be considered in support of an application for a research or marketing permit does not, however, relieve the applicant for such a permit of any obligation under any other applicable regulation to submit the results of the study to the Food and Drug Administration.
(b) 除非检测设施已根据第58.219条恢复,否则在检测设施被取消资格之日后开始的任何非临床实验室研究均不得被视为支持任何研究或销售许可证的申请。然而,确定一项研究不得被视为支持研究或营销许可证的申请,并不能免除此类许可证的申请人根据任何其他适用法规向食品和药物管理局提交研究结果的任何义务。
[43 FR 60013, Dec. 22, 1978, as amended at 59 FR 13200, Mar. 21, 1994]
Sec. 58.213 Public disclosure of information regarding disqualification.
第 58.213 节 公开披露有关取消资格的信息。
(a) Upon issuance of a final order disqualifying a testing facility under 58.206(a), the Commissioner may notify all or any interested persons. Such notice may be given at the discretion of the Commissioner whenever he believes that such disclosure would further the public interest or would promote compliance with the good laboratory practice regulations set forth in this part. Such notice, if given, shall include a copy of the final order issued under 58.206(a) and shall state that the disqualification constitutes a determination by the Food and Drug Administration that nonclinical laboratory studies performed by the facility will not be considered by the Food and Drug Administration in support of any application for a research or marketing permit. If such notice is sent to another Federal Government agency, the Food and Drug Administration will recommend that the agency also consider whether or not it should accept nonclinical laboratory studies performed by the testing facility. If such notice is sent to any other person, it shall state that it is given because of the relationship between the testing facility and the person being notified and that the Food and Drug Administration is not advising or recommending that any action be taken by the person notified.
(a) 在根据第58.206(a)条发出取消检测设施资格的最终命令后,专员可以通知所有或任何利害关系人。只要局长认为有关披露会促进公众利益,或会促进公众遵守本部分所载的良好实验室作业规范规例,便可酌情作出该通知。此类通知(如果发出)应包括根据 58.206(a) 发布的最终命令的副本,并应说明取消资格构成美国食品和药物管理局的决定,即食品和药物管理局将不会考虑该设施进行的非临床实验室研究以支持任何研究或营销许可证的申请。如果将此类通知发送给另一个联邦政府机构,食品和药物管理局将建议该机构也考虑是否应接受由检测机构进行的非临床实验室研究。如果向任何其他人发出此类通知,则应说明该通知是由于检测机构与被通知人之间的关系而发出的,并且食品和药物管理局没有建议或建议被通知者采取任何行动。
(b) A determination that a testing facility has been disqualified and the administrative record regarding such determination are disclosable to the public under part 20 of this chapter.
(b) 根据本章第20部分的规定,可以向公众披露检测设施被取消资格的裁定,以及有关这种裁定的行政记录。
Sec. 58.215 Alternative or additional actions to disqualification.
第 58.215 节 取消资格的替代或额外行动。
(a) Disqualification of a testing facility under this subpart is independent of, and neither in lieu of nor a precondition to, other proceedings or actions authorized by the act. The Food and Drug Administration may, at any time, institute against a testing facility and/or against the sponsor of a nonclinical laboratory study that has been submitted to the Food and Drug Administration any appropriate judicial proceedings (civil or criminal) and any other appropriate regulatory action, in addition to or in lieu of, and prior to, simultaneously with, or subsequent to, disqualification. The Food and Drug Administration may also refer the matter to another Federal, State, or local government law enforcement or regulatory agency for such action as that agency deems appropriate.
(a) 根据本分节取消检测设施的资格,与该法授权的其他程序或行动无关,既不代替该法授权的其他程序或行动,也不作为该法的先决条件。美国食品和药物管理局可以在任何时候对已提交给食品和药物管理局的非临床实验室研究的检测机构和/或非临床实验室研究的申办者提起任何适当的司法程序(民事或刑事)和任何其他适当的监管行动,除了或代替之前和之前, 在取消资格的同时或之后。美国食品和药物管理局也可以将此事提交给另一个联邦、州或地方政府执法或监管机构,以采取该机构认为适当的行动。
(b) The Food and Drug Administration may refuse to consider any particular nonclinical laboratory study in support of an application for a research or marketing permit, if it finds that the study was not conducted in accordance with the good laboratory practice regulations set forth in this part, without disqualifying the testing facility that conducted the study or undertaking other regulatory action.
(b) 如果美国食品和药物管理局发现该研究未按照本部分规定的良好实验室规范规定进行,则可以拒绝考虑支持研究或销售许可证申请的特定非临床实验室研究,而无需取消进行研究的检测设施的资格或采取其他监管行动。
Sec. 58.217 Suspension or termination of a testing facility by a sponsor.
第 58.217 节 担保人暂停或终止测试设施。
Termination of a testing facility by a sponsor is independent of, and neither in lieu of nor a precondition to, proceedings or actions authorized by this subpart. If a sponsor terminates or suspends a testing facility from further participation in a nonclinical laboratory study that is being conducted as part of any application for a research or marketing permit that has been submitted to any Center of the Food and Drug Administration (whether approved or not), it shall notify that Center in writing within 15 working days of the action; the notice shall include a statement of the reasons for such action. Suspension or termination of a testing facility by a sponsor does not relieve it of any obligation under any other applicable regulation to submit the results of the study to the Food and Drug Administration.
申办者终止检测设施独立于本子部分授权的程序或行动,既不代替本子部分,也不作为本子部分授权的程序或行动的先决条件。如果申办者终止或暂停检测机构进一步参与作为已提交给食品和药物管理局任何中心(无论是否获得批准)的研究或营销许可申请的一部分而进行的非临床实验室研究,则应在采取行动后 15 个工作日内以书面形式通知该中心;通知应包括说明采取此类行动的理由。申办者暂停或终止检测设施并不能免除其根据任何其他适用法规向食品和药物管理局提交研究结果的任何义务。
[43 FR FR 60013, Dec. 22, 1978, as amended at 50 FR 8995, Mar. 6, 1985]
[43 FR FR 60013,1978年12月22日,于1985年3月6日修订于50 FR 8995]
Sec. 58.219 Reinstatement of a disqualified testing facility.
第 58.219 节 恢复不合格的检测设施。
A testing facility that has been disqualified may be reinstated as an acceptable source of nonclinical laboratory studies to be submitted to the Food and Drug Administration if the Commissioner determines, upon an evaluation of the submission of the testing facility, that the facility can adequately assure that it will conduct future nonclinical laboratory studies in compliance with the good laboratory practice regulations set forth in this part and, if any studies are currently being conducted, that the quality and integrity of such studies have not been seriously compromised. A disqualified testing facility that wishes to be so reinstated shall present in writing to the Commissioner reasons why it believes it should be reinstated and a detailed description of the corrective actions it has taken or intends to take to assure that the acts or omissions which led to its disqualification will not recur. The Commissioner may condition reinstatement upon the testing facility being found in compliance with the good laboratory practice regulations upon an inspection. If a testing facility is reinstated, the Commissioner shall so notify the testing facility and all organizations and persons who were notified, under 58.213 of the disqualification of the testing facility. A determination that a testing facility has been reinstated is disclosable to the public under part 20 of this chapter.
被取消资格的检测机构可以恢复为可接受的非临床实验室研究来源,提交给食品和药物管理局,如果专员在评估该检测设施的提交情况后确定,该设施能够充分确保它将按照本部分规定的良好实验室实践规定进行未来的非临床实验室研究,并且, 如果目前正在进行任何研究,则这些研究的质量和完整性没有受到严重损害。被取消资格的检测机构如希望恢复资格,应以书面形式向专员说明其认为应恢复资格的理由,并详细说明其已采取或打算采取的纠正措施,以确保导致其丧失资格的作为或不作为不再发生。在检查后发现检测设施符合良好实验室规范规定后,处长可提出恢复检测设施的条件。如果检测设施恢复,专员应根据第58.213条将检测设施的资格被取消一事通知该检测设施以及所有被通知的组织和个人。根据本章第20部分的规定,可以向公众披露检测设施已恢复的确定。