Institutional review boards (21 CFR 56.101-56.124)

356 21 CFR Ch. I (4–1–16 Edition) Pt. 56 (2) Complete records showing signifi cant payments of other sorts, as de scribed in § 54.4(a)(3)(ii), made by the sponsor of the covered clinical study to the clinical investigator. (3) Complete records showing any fi nancial interests held by clinical inves tigators as set forth in § 54.4(a)(3)(iii) and (a)(3)(iv). (b) Requirements for maintenance of clinical investigators’ financial records. (1) For any application submitted for a covered product, an applicant shall re tain records as described in paragraph (a) of this section for 2 years after the date of approval of the application. (2) The person maintaining these records shall, upon request from any properly authorized officer or employee of FDA, at reasonable times, permit such officer or employee to have access to and copy and verify these records. PART 56—INSTITUTIONAL REVIEW BOARDS Subpart A—General Provisions Sec. 56.101 Scope. 56.102 Definitions. 56.103 Circumstances in which IRB review is required. 56.104 Exemptions from IRB requirement. 56.105 Waiver of IRB requirement. 56.106 Registration. Subpart B—Organization and Personnel 56.107 IRB membership. Subpart C—IRB Functions and Operations 56.108 IRB functions and operations. 56.109 IRB review of research. 56.110 Expedited review procedures for cer tain kinds of research involving no more than minimal risk, and for minor changes in approved research. 56.111 Criteria for IRB approval of research. 56.112 Review by institution. 56.113 Suspension or termination of IRB ap proval of research. 56.114 Cooperative research. Subpart D—Records and Reports 56.115 IRB records. Subpart E—Administrative Actions for Noncompliance 56.120 Lesser administrative actions. 56.121 Disqualification of an IRB or an insti tution. 56.122 Public disclosure of information re garding revocation. 56.123 Reinstatement of an IRB or an insti tution. 56.124 Actions alternative or additional to disqualification. AUTHORITY: 21 U.S.C. 321, 343, 346, 346a, 348, 350a, 350b, 351, 352, 353, 355, 360, 360c–360f, 360h–360j, 371, 379e, 381; 42 U.S.C. 216, 241, 262, 263b–263n. SOURCE: 46 FR 8975, Jan. 27, 1981, unless otherwise noted. Subpart A—General Provisions § 56.101 Scope. (a) This part contains the general standards for the composition, oper ation, and responsibility of an Institu tional Review Board (IRB) that reviews clinical investigations regulated by the Food and Drug Administration under sections 505(i) and 520(g) of the act, as well as clinical investigations that sup port applications for research or mar keting permits for products regulated by the Food and Drug Administration, including foods, including dietary sup plements, that bear a nutrient content claim or a health claim, infant for mulas, food and color additives, drugs for human use, medical devices for human use, biological products for human use, and electronic products. Compliance with this part is intended to protect the rights and welfare of human subjects involved in such inves tigations. (b) References in this part to regu latory sections of the Code of Federal Regulations are to chapter I of title 21, unless otherwise noted. [46 FR 8975, Jan. 27, 1981, as amended at 64 FR 399, Jan. 5, 1999; 66 FR 20599, Apr. 24, 2001] § 56.102 Definitions. As used in this part: (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)). (b) Application for research or mar keting permit includes: (1) A color additive petition, de scribed in part 71. VerDate Sep<11>2014 14:18 Apr 18, 2016 Jkt 238070 PO 00000 Frm 00366 Fmt 8010 Sfmt 8010 Q:\21\21V1.TXT 31lp o w e ll o n D S K 5 4 D X V N 1 O F R w ith $ $ JO B 357 Food and Drug Administration, HHS § 56.102 (2) Data and information regarding a substance submitted as part of the pro cedures for establishing that a sub stance is generally recognized as safe for a use which results or may reason ably be expected to result, directly or indirectly, in its becoming a compo nent or otherwise affecting the charac teristics of any food, described in § 170.35. (3) A food additive petition, described in part 171. (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, de scribed in § 180.1. (5) Data and information regarding a substance submitted as part of the pro cedures for establishing a tolerance for unavoidable contaminants in food and food-packaging materials, described in section 406 of the act. (6) An investigational new drug appli cation, described in part 312 of this chapter. (7) A new drug application, described in part 314. (8) Data and information regarding the bioavailability or bioequivalence of drugs for human use submitted as part of the procedures for issuing, amend ing, or repealing a bioequivalence re quirement, described in part 320. (9) 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. (10) An application for a biologics li cense, described in part 601 of this chapter. (11) Data and information regarding a biological product submitted as part of the procedures for determining that li censed biological products are safe and effective and not misbranded, as de scribed in part 601 of this chapter. (12) An Application for an Investiga tional Device Exemption, described in part 812. (13) Data and information regarding a medical device for human use sub mitted as part of the procedures for classifying such devices, described in part 860. (14) Data and information regarding a medical device for human use sub mitted as part of the procedures for es tablishing, amending, or repealing a standard for such device, described in part 861. (15) An application for premarket ap proval of a medical device for human use, described in section 515 of the act. (16) A product development protocol for a medical device for human use, de scribed in section 515 of the act. (17) Data and information regarding an electronic product submitted as part of the procedures for establishing, amending, or repealing a standard for such products, described in section 358 of the Public Health Service Act. (18) 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. (19) Data and information regarding an electronic product submitted as part of the procedures for granting, amending, or extending an exemption from a radiation safety performance standard, as described in § 1010.5. (20) Data and information regarding an electronic product submitted as part of the procedures for obtaining an exemption from notification of a radi ation safety defect or failure of compli ance with a radiation safety perform ance standard, described in subpart D of part 1003. (21) Data and information about a clinical study of an infant formula when submitted as part of an infant formula notification under section 412(c) of the Federal Food, Drug, and Cosmetic Act. (22) Data and information submitted in a petition for a nutrient content claim, described in § 101.69 of this chap ter, and for a health claim, described in § 101.70 of this chapter. (23) Data and information from inves tigations involving children submitted in a new dietary ingredient notifica tion, described in § 190.6 of this chapter. (c) Clinical investigation means any experiment that involves a test article and one or more human subjects, and that either must meet the require ments for prior submission to the Food and Drug Administration under section VerDate Sep<11>2014 14:18 Apr 18, 2016 Jkt 238070 PO 00000 Frm 00367 Fmt 8010 Sfmt 8010 Q:\21\21V1.TXT 31lp o w e ll o n D S K 5 4 D X V N 1 O F R w ith $ $ JO B 358 21 CFR Ch. I (4–1–16 Edition) § 56.103 505(i) or 520(g) of the act, or need not meet the requirements for prior sub mission to the Food and Drug Adminis tration under these sections of the act, but the results of which are intended to be later submitted to, or held for in spection by, the Food and Drug Admin istration as part of an application for a research or marketing permit. The term does not include experiments that must meet the provisions of part 58, re garding nonclinical laboratory studies. The terms research, clinical research, clinical study, study, and clinical inves tigation are deemed to be synonymous for purposes of this part. (d) Emergency use means the use of a test article on a human subject in a life-threatening situation in which no standard acceptable treatment is avail able, and in which there is not suffi cient time to obtain IRB approval. (e) Human subject means an indi vidual who is or becomes a participant in research, either as a recipient of the test article or as a control. A subject may be either a healthy individual or a patient. (f) Institution means any public or private entity or agency (including Federal, State, and other agencies). The term facility as used in section 520(g) of the act is deemed to be syn onymous with the term institution for purposes of this part. (g) Institutional Review Board (IRB) means any board, committee, or other group formally designated by an insti tution to review, to approve the initi ation of, and to conduct periodic re view of, biomedical research involving human subjects. The primary purpose of such review is to assure the protec tion of the rights and welfare of the human subjects. The term has the same meaning as the phrase institu tional review committee as used in sec tion 520(g) of the act. (h) Investigator means an individual who actually conducts a clinical inves tigation (i.e., under whose immediate direction the test article is adminis tered or dispensed to, or used involv ing, a subject) or, in the event of an in vestigation conducted by a team of in dividuals, is the responsible leader of that team. (i) Minimal risk means that the prob ability and magnitude of harm or dis comfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of rou tine physical or psychological exami nations or tests. (j) Sponsor means a person or other entity that initiates a clinical inves tigation, but that does not actually conduct the investigation, i.e., the test article is administered or dispensed to, or used involving, a subject under the immediate direction of another indi vidual. A person other than an indi vidual (e.g., a corporation or agency) that uses one or more of its own em ployees to conduct an investigation that it has initiated is considered to be a sponsor (not a sponsor-investigator), and the employees are considered to be investigators. (k) Sponsor-investigator means an in dividual who both initiates and actu ally conducts, alone or with others, a clinical investigation, i.e., under whose immediate direction the test article is administered or dispensed to, or used involving, a subject. The term does not include any person other than an indi vidual, e.g., it does not include a cor poration or agency. The obligations of a sponsor-investigator under this part include both those of a sponsor and those of an investigator. (l) Test article means any drug for human use, biological product for human use, medical device for human use, human food additive, color addi tive, electronic product, or any other article subject to regulation under the act or under sections 351 or 354–360F of the Public Health Service Act. (m) IRB approval means the deter mination of the IRB that the clinical investigation has been reviewed and may be conducted at an institution within the constraints set forth by the IRB and by other institutional and Federal requirements. [46 FR 8975, Jan. 27, 1981, as amended at 54 FR 9038, Mar. 3, 1989; 56 FR 28028, June 18, 1991; 64 FR 399, Jan. 5, 1999; 64 FR 56448, Oct. 20, 1999; 65 FR 52302, Aug. 29, 2000; 66 FR 20599, Apr. 24, 2001; 74 FR 2368, Jan. 15, 2009] § 56.103 Circumstances in which IRB review is required. (a) Except as provided in §§ 56.104 and 56.105, any clinical investigation which VerDate Sep<11>2014 14:18 Apr 18, 2016 Jkt 238070 PO 00000 Frm 00368 Fmt 8010 Sfmt 8010 Q:\21\21V1.TXT 31lp o w e ll o n D S K 5 4 D X V N 1 O F R w ith $ $ JO B 359 Food and Drug Administration, HHS § 56.106 must meet the requirements for prior submission (as required in parts 312, 812, and 813) to the Food and Drug Ad ministration shall not be initiated un less that investigation has been re viewed and approved by, and remains subject to continuing review by, an IRB meeting the requirements of this part. (b) Except as provided in §§ 56.104 and 56.105, the Food and Drug Administra tion may decide not to consider in sup port of an application for a research or marketing permit any data or informa tion that has been derived from a clin ical investigation that has not been ap proved by, and that was not subject to initial and continuing review by, an IRB meeting the requirements of this part. The determination that a clinical investigation may not be considered in support of an application for a research or marketing permit does not, how ever, relieve the applicant for such a permit of any obligation under any other applicable regulations to submit the results of the investigation to the Food and Drug Administration. (c) Compliance with these regula tions will in no way render inapplicable pertinent Federal, State, or local laws or regulations. [46 FR 8975, Jan. 27, 1981; 46 FR 14340, Feb. 27, 1981] § 56.104 Exemptions from IRB require ment. The following categories of clinical investigations are exempt from the re quirements of this part for IRB review: (a) Any investigation which com menced before July 27, 1981 and was subject to requirements for IRB review under FDA regulations before that date, provided that the investigation remains subject to review of an IRB which meets the FDA requirements in effect before July 27, 1981. (b) Any investigation commenced be fore July 27, 1981 and was not otherwise subject to requirements for IRB review under Food and Drug Administration regulations before that date. (c) Emergency use of a test article, provided that such emergency use is re ported to the IRB within 5 working days. Any subsequent use of the test article at the institution is subject to IRB review. (d) Taste and food quality evalua tions and consumer acceptance studies, if wholesome foods without additives are consumed or if a food is consumed that contains a food ingredient at or below the level and for a use found to be safe, or agricultural, chemical, or environmental contaminant at or below the level found to be safe, by the Food and Drug Administration or ap proved by the Environmental Protec tion Agency or the Food Safety and In spection Service of the U.S. Depart ment of Agriculture. [46 FR 8975, Jan. 27, 1981, as amended at 56 FR 28028, June 18, 1991] § 56.105 Waiver of IRB requirement. On the application of a sponsor or sponsor-investigator, the Food and Drug Administration may waive any of the requirements contained in these regulations, including the require ments for IRB review, for specific re search activities or for classes of re search activities, otherwise covered by these regulations. Subpart B—Organization and Personnel § 56.106 Registration. (a) Who must register? Each IRB in the United States that reviews clinical in vestigations regulated by FDA under sections 505(i) or 520(g) of the act and each IRB in the United States that re views clinical investigations that are intended to support applications for re search or marketing permits for FDA regulated products must register at a site maintained by the Department of Health and Human Services (HHS). (A research permit under section 505(i) of the act is usually known as an inves tigational new drug application (IND), while a research permit under section 520(g) of the act is usually known as an investigational device exemption (IDE).) An individual authorized to act on the IRB’s behalf must submit the registration information. All other IRBs may register voluntarily. (b) What information must an IRB reg ister? Each IRB must provide the fol lowing information: (1) The name, mailing address, and street address (if different from the VerDate Sep<11>2014 14:18 Apr 18, 2016 Jkt 238070 PO 00000 Frm 00369 Fmt 8010 Sfmt 8010 Q:\21\21V1.TXT 31lp o w e ll o n D S K 5 4 D X V N 1 O F R w ith $ $ JO B 360 21 CFR Ch. I (4–1–16 Edition) § 56.107 mailing address) of the institution op erating the IRB and the name, mailing address, phone number, facsimile num ber, and electronic mail address of the senior officer of that institution who is responsible for overseeing activities performed by the IRB; (2) The IRB’s name, mailing address, street address (if different from the mailing address), phone number, fac simile number, and electronic mail ad dress; each IRB chairperson’s name, phone number, and electronic mail ad dress; and the name, mailing address, phone number, facsimile number, and electronic mail address of the contact person providing the registration infor mation. (3) The approximate number of active protocols involving FDA-regulated products reviewed. For purposes of this rule, an ‘‘active protocol’’ is any pro tocol for which an IRB conducted an initial review or a continuing review at a convened meeting or under an expe dited review procedure during the pre ceding 12 months; and (4) A description of the types of FDA regulated products (such as biological products, color additives, food addi tives, human drugs, or medical devices) involved in the protocols that the IRB reviews. (c) When must an IRB register? Each IRB must submit an initial registra tion. The initial registration must occur before the IRB begins to review a clinical investigation described in paragraph (a) of this section. Each IRB must renew its registration every 3 years. IRB registration becomes effec tive after review and acceptance by HHS. (d) Where can an IRB register? Each IRB may register electronically through http://ohrp.cit.nih.gov/efile. If an IRB lacks the ability to register elec tronically, it must send its registration information, in writing, to the Office of Good Clinical Practice, Office of Spe cial Medical Programs, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 32, Rm. 5129, Silver Spring, MD 20993. (e) How does an IRB revise its registra tion information? If an IRB’s contact or chair person information changes, the IRB must revise its registration infor mation by submitting any changes in that information within 90 days of the change. An IRB’s decision to review new types of FDA-regulated products (such as a decision to review studies pertaining to food additives whereas the IRB previously reviewed studies pertaining to drug products), or to dis continue reviewing clinical investiga tions regulated by FDA is a change that must be reported within 30 days of the change. An IRB’s decision to dis band is a change that must be reported within 30 days of permanent cessation of the IRB’s review of research. All other information changes may be re ported when the IRB renews its reg istration. The revised information must be sent to FDA either electroni cally or in writing in accordance with paragraph (d) of this section. [74 FR 2368, Jan. 15, 2009, as amended at 78 FR 16401, Mar. 15, 2013] § 56.107 IRB membership. (a) Each IRB shall have at least five members, with varying backgrounds to promote complete and adequate review of research activities commonly con ducted by the institution. The IRB shall be sufficiently qualified through the experience and expertise of its members, and the diversity of the members, including consideration of race, gender, cultural backgrounds, and sensitivity to such issues as commu nity attitudes, to promote respect for its advice and counsel in safeguarding the rights and welfare of human sub jects. In addition to possessing the pro fessional competence necessary to re view the specific research activities, the IRB shall be able to ascertain the acceptability of proposed research in terms of institutional commitments and regulations, applicable law, and standards of professional conduct and practice. * * * The IRB shall therefore include persons knowledgeable in these areas. If an IRB regularly reviews re search that involves a vulnerable cat egory of subjects, such as children, prisoners, pregnant women, or handi capped or mentally disabled persons, consideration shall be given to the in clusion of one or more individuals who are knowledgeable about and experi enced in working with those subjects. (b) Every nondiscriminatory effort will be made to ensure that no IRB VerDate Sep<11>2014 14:18 Apr 18, 2016 Jkt 238070 PO 00000 Frm 00370 Fmt 8010 Sfmt 8010 Q:\21\21V1.TXT 31lp o w e ll o n D S K 5 4 D X V N 1 O F R w ith $ $ JO B 361 Food and Drug Administration, HHS § 56.109 consists entirely of men or entirely of women, including the instituton’s con sideration of qualified persons of both sexes, so long as no selection is made to the IRB on the basis of gender. No IRB may consist entirely of members of one profession. (c) Each IRB shall include at least one member whose primary concerns are in the scientific area and at least one member whose primary concerns are in nonscientific areas. (d) Each IRB shall include at least one member who is not otherwise affili ated with the institution and who is not part of the immediate family of a person who is affiliated with the insti tution. (e) No IRB may have a member par ticipate in the IRB’s initial or con tinuing review of any project in which the member has a conflicting interest, except to provide information re quested by the IRB. (f) An IRB may, in its discretion, in vite individuals with competence in special areas to assist in the review of complex issues which require expertise beyond or in addition to that available on the IRB. These individuals may not vote with the IRB. [46 FR 8975, Jan. 27, 1981, as amended at 56 FR 28028, June 18, 1991; 56 FR 29756, June 28, 1991; 78 FR 16401, Mar. 15, 2013] Subpart C—IRB Functions and Operations § 56.108 IRB functions and operations. In order to fulfill the requirements of these regulations, each IRB shall: (a) Follow written procedures: (1) For conducting its initial and continuing review of research and for reporting its findings and actions to the investigator and the institution; (2) for determining which projects require review more often than annually and which projects need verification from sources other than the investigator that no material changes have occurred since previous IRB review; (3) for ensuring prompt re porting to the IRB of changes in re search activity; and (4) for ensuring that changes in approved research, dur ing the period for which IRB approval has already been given, may not be ini tiated without IRB review and ap proval except where necessary to elimi nate apparent immediate hazards to the human subjects. (b) Follow written procedures for en suring prompt reporting to the IRB, appropriate institutional officials, and the Food and Drug Administration of: (1) Any unanticipated problems involv ing risks to human subjects or others; (2) any instance of serious or con tinuing noncompliance with these reg ulations or the requirements or deter minations of the IRB; or (3) any sus pension or termination of IRB ap proval. (c) Except when an expedited review procedure is used (see § 56.110), review proposed research at convened meet ings at which a majority of the mem bers of the IRB are present, including at least one member whose primary concerns are in nonscientific areas. In order for the research to be approved, it shall receive the approval of a ma jority of those members present at the meeting. [46 FR 8975, Jan. 27, 1981, as amended at 56 FR 28028, June 18, 1991; 67 FR 9585, Mar. 4, 2002] § 56.109 IRB review of research. (a) An IRB shall review and have au thority to approve, require modifica tions in (to secure approval), or dis approve all research activities covered by these regulations. (b) An IRB shall require that infor mation given to subjects as part of in formed consent is in accordance with § 50.25. The IRB may require that infor mation, in addition to that specifically mentioned in § 50.25, be given to the subjects when in the IRB’s judgment the information would meaningfully add to the protection of the rights and welfare of subjects. (c) An IRB shall require documenta tion of informed consent in accordance with § 50.27 of this chapter, except as follows: (1) The IRB may, for some or all sub jects, waive the requirement that the subject, or the subject’s legally author ized representative, sign a written con sent form if it finds that the research presents no more than minimal risk of harm to subjects and involves no proce dures for which written consent is nor mally required outside the research context; or VerDate Sep<11>2014 14:18 Apr 18, 2016 Jkt 238070 PO 00000 Frm 00371 Fmt 8010 Sfmt 8010 Q:\21\21V1.TXT 31lp o w e ll o n D S K 5 4 D X V N 1 O F R w ith $ $ JO B 362 21 CFR Ch. I (4–1–16 Edition) § 56.110 (2) The IRB may, for some or all sub jects, find that the requirements in § 50.24 of this chapter for an exception from informed consent for emergency research are met. (d) In cases where the documentation requirement is waived under paragraph (c)(1) of this section, the IRB may re quire the investigator to provide sub jects with a written statement regard ing the research. (e) An IRB shall notify investigators and the institution in writing of its de cision to approve or disapprove the pro posed research activity, or of modifica tions required to secure IRB approval of the research activity. If the IRB de cides to disapprove a research activity, it shall include in its written notifica tion a statement of the reasons for its decision and give the investigator an opportunity to respond in person or in writing. For investigations involving an exception to informed consent under § 50.24 of this chapter, an IRB shall promptly notify in writing the investi gator and the sponsor of the research when an IRB determines that it cannot approve the research because it does not meet the criteria in the exception provided under § 50.24(a) of this chapter or because of other relevant ethical concerns. The written notification shall include a statement of the rea sons for the IRB’s determination. (f) An IRB shall conduct continuing review of research covered by these regulations at intervals appropriate to the degree of risk, but not less than once per year, and shall have authority to observe or have a third party ob serve the consent process and the re search. (g) An IRB shall provide in writing to the sponsor of research involving an exception to informed consent under § 50.24 of this chapter a copy of infor mation that has been publicly disclosed under § 50.24(a)(7)(ii) and (a)(7)(iii) of this chapter. The IRB shall provide this information to the sponsor promptly so that the sponsor is aware that such disclosure has occurred. Upon receipt, the sponsor shall provide copies of the information disclosed to FDA. (h) When some or all of the subjects in a study are children, an IRB must determine that the research study is in compliance with part 50, subpart D of this chapter, at the time of its initial review of the research. When some or all of the subjects in a study that was ongoing on April 30, 2001, are children, an IRB must conduct a review of the research to determine compliance with part 50, subpart D of this chapter, ei ther at the time of continuing review or, at the discretion of the IRB, at an earlier date. [46 FR 8975, Jan. 27, 1981, as amended at 61 FR 51529, Oct. 2, 1996; 66 FR 20599, Apr. 24, 2001; 78 FR 12951, Feb. 26, 2013] § 56.110 Expedited review procedures for certain kinds of research involv ing no more than minimal risk, and for minor changes in approved re search. (a) The Food and Drug Administra tion has established, and published in the FEDERAL REGISTER, a list of cat egories of research that may be re viewed by the IRB through an expe dited review procedure. The list will be amended, as appropriate, through peri odic republication in the FEDERAL REG ISTER. (b) An IRB may use the expedited re view procedure to review either or both of the following: (1) Some or all of the research appearing on the list and found by the reviewer(s) to involve no more than minimal risk, (2) minor changes in previously approved re search during the period (of 1 year or less) for which approval is authorized. Under an expedited review procedure, the review may be carried out by the IRB chairperson or by one or more ex perienced reviewers designated by the IRB chairperson from among the mem bers of the IRB. In reviewing the re search, the reviewers may exercise all of the authorities of the IRB except that the reviewers may not disapprove the research. A research activity may be disapproved only after review in ac cordance with the nonexpedited review procedure set forth in § 56.108(c). (c) Each IRB which uses an expedited review procedure shall adopt a method for keeping all members advised of re search proposals which have been ap proved under the procedure. (d) The Food and Drug Administra tion may restrict, suspend, or termi nate an institution’s or IRB’s use of VerDate Sep<11>2014 14:18 Apr 18, 2016 Jkt 238070 PO 00000 Frm 00372 Fmt 8010 Sfmt 8010 Q:\21\21V1.TXT 31lp o w e ll o n D S K 5 4 D X V N 1 O F R w ith $ $ JO B 363 Food and Drug Administration, HHS § 56.114 the expedited review procedure when necessary to protect the rights or wel fare of subjects. [46 FR 8975, Jan. 27, 1981, as amended at 56 FR 28029, June 18, 1991] § 56.111 Criteria for IRB approval of research. (a) In order to approve research cov ered by these regulations the IRB shall determine that all of the following re quirements are satisfied: (1) Risks to subjects are minimized: (i) By using procedures which are con sistent with sound research design and which do not unnecessarily expose sub jects to risk, and (ii) whenever appro priate, by using procedures already being performed on the subjects for di agnostic or treatment purposes. (2) Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may be expected to result. In evaluating risks and benefits, the IRB should consider only those risks and benefits that may result from the research (as distinguished from risks and benefits of therapies that subjects would receive even if not par ticipating in the research). The IRB should not consider possible long-range effects of applying knowledge gained in the research (for example, the possible effects of the research on public policy) as among those research risks that fall within the purview of its responsi bility. (3) Selection of subjects is equitable. In making this assessment the IRB should take into account the purposes of the research and the setting in which the research will be conducted and should be particularly cognizant of the special problems of research in volving vulnerable populations, such as children, prisoners, pregnant women, handicapped, or mentally disabled per sons, or economically or educationally disadvantaged persons. (4) Informed consent will be sought from each prospective subject or the subject’s legally authorized representa tive, in accordance with and to the ex tent required by part 50. (5) Informed consent will be appro priately documented, in accordance with and to the extent required by § 50.27. (6) Where appropriate, the research plan makes adequate provision for monitoring the data collected to en sure the safety of subjects. (7) Where appropriate, there are ade quate provisions to protect the privacy of subjects and to maintain the con fidentiality of data. (b) When some or all of the subjects, such as children, prisoners, pregnant women, handicapped, or mentally dis abled persons, or economically or edu cationally disadvantaged persons, are likely to be vulnerable to coercion or undue influence additional safeguards have been included in the study to pro tect the rights and welfare of these subjects. (c) In order to approve research in which some or all of the subjects are children, an IRB must determine that all research is in compliance with part 50, subpart D of this chapter. [46 FR 8975, Jan. 27, 1981, as amended at 56 FR 28029, June 18, 1991; 66 FR 20599, Apr. 24, 2001] § 56.112 Review by institution. Research covered by these regula tions that has been approved by an IRB may be subject to further appropriate review and approval or disapproval by officials of the institution. However, those officials may not approve the re search if it has not been approved by an IRB. § 56.113 Suspension or termination of IRB approval of research. An IRB shall have authority to sus pend or terminate approval of research that is not being conducted in accord ance with the IRB’s requirements or that has been associated with unex pected serious harm to subjects. Any suspension or termination of approval shall include a statement of the rea sons for the IRB’s action and shall be reported promptly to the investigator, appropriate institutional officials, and the Food and Drug Administration. § 56.114 Cooperative research. In complying with these regulations, institutions involved in multi-institu tional studies may use joint review, re liance upon the review of another qualified IRB, or similar arrangements VerDate Sep<11>2014 14:18 Apr 18, 2016 Jkt 238070 PO 00000 Frm 00373 Fmt 8010 Sfmt 8010 Q:\21\21V1.TXT 31lp o w e ll o n D S K 5 4 D X V N 1 O F R w ith $ $ JO B 364 21 CFR Ch. I (4–1–16 Edition) § 56.115 aimed at avoidance of duplication of ef fort. Subpart D—Records and Reports § 56.115 IRB records. (a) An institution, or where appro priate an IRB, shall prepare and main tain adequate documentation of IRB activities, including the following: (1) Copies of all research proposals re viewed, scientific evaluations, if any, that accompany the proposals, ap proved sample consent documents, progress reports submitted by inves tigators, and reports of injuries to sub jects. (2) Minutes of IRB meetings which shall be in sufficient detail to show at tendance at the meetings; actions taken by the IRB; the vote on these ac tions including the number of members voting for, against, and abstaining; the basis for requiring changes in or dis approving research; and a written sum mary of the discussion of controverted issues and their resolution. (3) Records of continuing review ac tivities. (4) Copies of all correspondence be tween the IRB and the investigators. (5) A list of IRB members identified by name; earned degrees; representa tive capacity; indications of experience such as board certifications, licenses, etc., sufficient to describe each mem ber’s chief anticipated contributions to IRB deliberations; and any employ ment or other relationship between each member and the institution; for example: full-time employee, part-time employee, a member of governing panel or board, stockholder, paid or unpaid consultant. (6) Written procedures for the IRB as required by § 56.108 (a) and (b). (7) Statements of significant new findings provided to subjects, as re quired by § 50.25. (b) The records required by this regu lation shall be retained for at least 3 years after completion of the research, and the records shall be accessible for inspection and copying by authorized representatives of the Food and Drug Administration at reasonable times and in a reasonable manner. (c) The Food and Drug Administra tion may refuse to consider a clinical investigation in support of an applica tion for a research or marketing per mit if the institution or the IRB that reviewed the investigation refuses to allow an inspection under this section. [46 FR 8975, Jan. 27, 1981, as amended at 56 FR 28029, June 18, 1991; 67 FR 9585, Mar. 4, 2002] Subpart E—Administrative Actions for Noncompliance § 56.120 Lesser administrative actions. (a) If apparent noncompliance with these regulations in the operation of an IRB is observed by an FDA investi gator during an inspection, the inspec tor will present an oral or written sum mary of observations to an appropriate representative of the IRB. The Food and Drug Administration may subse quently send a letter describing the noncompliance to the IRB and to the parent institution. The agency will re quire that the IRB or the parent insti tution respond to this letter within a time period specified by FDA and de scribe the corrective actions that will be taken by the IRB, the institution, or both to achieve compliance with these regulations. (b) On the basis of the IRB’s or the institution’s response, FDA may sched ule a reinspection to confirm the ade quacy of corrective actions. In addi tion, until the IRB or the parent insti tution takes appropriate corrective ac tion, the agency may: (1) Withhold approval of new studies subject to the requirements of this part that are conducted at the institution or reviewed by the IRB; (2) Direct that no new subjects be added to ongoing studies subject to this part; (3) Terminate ongoing studies subject to this part when doing so would not endanger the subjects; or (4) When the apparent noncompliance creates a significant threat to the rights and welfare of human subjects, notify relevant State and Federal regu latory agencies and other parties with a direct interest in the agency’s action of the deficiencies in the operation of the IRB. (c) The parent institution is pre sumed to be responsible for the oper ation of an IRB, and the Food and Drug VerDate Sep<11>2014 14:18 Apr 18, 2016 Jkt 238070 PO 00000 Frm 00374 Fmt 8010 Sfmt 8010 Q:\21\21V1.TXT 31lp o w e ll o n D S K 5 4 D X V N 1 O F R w ith $ $ JO B 365 Food and Drug Administration, HHS § 56.124 Administration will ordinarily direct any administrative action under this subpart against the institution. How ever, depending on the evidence of re sponsibility for deficiencies, deter mined during the investigation, the Food and Drug Administration may re strict its administrative actions to the IRB or to a component of the parent institution determined to be respon sible for formal designation of the IRB. § 56.121 Disqualification of an IRB or an institution. (a) Whenever the IRB or the institu tion has failed to take adequate steps to correct the noncompliance stated in the letter sent by the agency under § 56.120(a), and the Commissioner of Food and Drugs determines that this noncompliance may justify the dis qualification of the IRB or of the par ent institution, the Commissioner will institute proceedings in accordance with the requirements for a regulatory hearing set forth in part 16. (b) The Commissioner may disqualify an IRB or the parent institution if the Commissioner determines that: (1) The IRB has refused or repeatedly failed to comply with any of the regu lations set forth in this part, and (2) The noncompliance adversely af fects the rights or welfare of the human subjects in a clinical investiga tion. (c) If the Commissioner determines that disqualification is appropriate, the Commissioner will issue an order that explains the basis for the deter mination and that prescribes any ac tions to be taken with regard to ongo ing clinical research conducted under the review of the IRB. The Food and Drug Administration will send notice of the disqualification to the IRB and the parent institution. Other parties with a direct interest, such as sponsors and clinical investigators, may also be sent a notice of the disqualification. In addition, the agency may elect to pub lish a notice of its action in the FED ERAL REGISTER. (d) The Food and Drug Administra tion will not approve an application for a research permit for a clinical inves tigation that is to be under the review of a disqualified IRB or that is to be conducted at a disqualified institution, and it may refuse to consider in sup port of a marketing permit the data from a clinical investigation that was reviewed by a disqualified IRB as con ducted at a disqualified institution, un less the IRB or the parent institution is reinstated as provided in § 56.123. § 56.122 Public disclosure of informa tion regarding revocation. A determination that the Food and Drug Administration has disqualified an institution and the administrative record regarding that determination are disclosable to the public under part 20. § 56.123 Reinstatement of an IRB or an institution. An IRB or an institution may be re instated if the Commissioner deter mines, upon an evaluation of a written submission from the IRB or institution that explains the corrective action that the institution or IRB plans to take, that the IRB or institution has provided adequate assurance that it will operate in compliance with the standards set forth in this part. Notifi cation of reinstatement shall be pro vided to all persons notified under § 56.121(c). § 56.124 Actions alternative or addi tional to disqualification. Disqualification of an IRB or of an institution is independent of, and nei ther in lieu of nor a precondition to, other proceedings or actions authorized by the act. The Food and Drug Admin istration may, at any time, through the Department of Justice institute any appropriate judicial proceedings (civil or criminal) and any other appro priate regulatory action, in addition to or in lieu of, and before, at the time of, or after, disqualification. The agency may also refer pertinent matters to an other Federal, State, or local govern ment agency for any action that that agency determines to be appropriate. VerDate Sep<11>2014 14:18 Apr 18, 2016 Jkt 238070 PO 00000 Frm 00375 Fmt 8010 Sfmt 8010 Q:\21\21V1.TXT 31lp o w e ll o n D S K 5 4 D X V N 1 O F R w ith $ $ JO B 366 21 CFR Ch. I (4–1–16 Edition) Pt. 58 PART 58—GOOD LABORATORY PRACTICE FOR NONCLINICAL LABORATORY STUDIES Subpart A—General Provisions Sec. 58.1 Scope. 58.3 Definitions. 58.10 Applicability to studies performed under grants and contracts. 58.15 Inspection of a testing facility. Subpart B—Organization and Personnel 58.29 Personnel. 58.31 Testing facility management. 58.33 Study director. 58.35 Quality assurance unit. Subpart C—Facilities 58.41 General. 58.43 Animal care facilities. 58.45 Animal supply facilities. 58.47 Facilities for handling test and con trol articles. 58.49 Laboratory operation areas. 58.51 Specimen and data storage facilities. Subpart D—Equipment 58.61 Equipment design. 58.63 Maintenance and calibration of equip ment. Subpart E—Testing Facilities Operation 58.81 Standard operating procedures. 58.83 Reagents and solutions. 58.90 Animal care. Subpart F—Test and Control Articles 58.105 Test and control article characteriza tion. 58.107 Test and control article handling. 58.113 Mixture of articles with carriers. Subpart G—Protocol for and Conduct of a Nonclinical Laboratory Study 58.120 Protocol. 58.130 Conduct of a nonclinical laboratory study. Subparts H–I [Reserved] Subpart J—Records and Reports 58.185 Reporting of nonclinical laboratory study results. 58.190 Storage and retrieval of records and data. 58.195 Retention of records. Subpart K—Disqualification of Testing Facilities 58.200 Purpose. 58.202 Grounds for disqualification. 58.204 Notice of and opportunity for hearing on proposed disqualification. 58.206 Final order on disqualification. 58.210 Actions upon disqualification. 58.213 Public disclosure of information re garding disqualification. 58.215 Alternative or additional actions to disqualification. 58.217 Suspension or termination of a test ing facility by a sponsor. 58.219 Reinstatement of a disqualified test ing facility. AUTHORITY: 21 U.S.C. 342, 346, 346a, 348, 351, 352, 353, 355, 360, 360b–360f, 360h–360j, 371, 379e, 381; 42 U.S.C. 216, 262, 263b–263n. SOURCE: 43 FR 60013, Dec. 22, 1978, unless otherwise noted. Subpart A—General Provisions § 58.1 Scope. (a) This part prescribes good labora tory practices for conducting nonclin ical 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 addi tives, human and animal drugs, med ical 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 sec tions 406, 408, 409, 502, 503, 505, 506, 510, 512–516, 518–520, 721, and 801 of the Fed eral Food, Drug, and Cosmetic Act and sections 351 and 354–360F of the Public Health Service Act. (b) References in this part to regu latory sections of the Code of Federal Regulations are to chapter I of title 21, unless otherwise noted. [43 FR 60013, Dec. 22, 1978, as amended at 52 FR 33779, Sept. 4, 1987; 64 FR 399, Jan. 5, 1999] § 58.3 Definitions. As used in this part, the following terms shall have the meanings speci fied: (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)). VerDate Sep<11>2014 14:18 Apr 18, 2016 Jkt 238070 PO 00000 Frm 00376 Fmt 8010 Sfmt 8010 Q:\21\21V1.TXT 31lp o w e ll o n D S K 5 4 D X V N 1 O F R w ith $ $ JO B