[Code of Federal Regulations]
 [Title 21, Volume 1 ]
 [Revised as of April 1 , 2002]
 From the U.S. Government Printing Office via GPO Access
 [CITE: 21CFR50.1]
 
 [Page 285-286]
 
                         TITLE 21--FOOD AND DRUGS
 
 CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN
                                 SERVICES
 
 PART 50--PROTECTION OF HUMAN SUBJECTS--Table of Contents
 
                       Subpart A--General Provisions
 
 Sec. 50.1  Scope.
 
     (a) This part applies to all clinical investigations regulated by
 the Food and Drug Administration under sections 505(i) and 520(g) of the
 Federal Food, Drug, and Cosmetic Act, as well as clinical investigations
 that support applications for research or marketing permits for products
 regulated by the Food and Drug Administration, including foods,
 including dietary supplements, that bear a nutrient content claim or a
 health claim, infant formulas, food and color additives, drugs for human
 use, medical devices for human use, biological products for human use,
 and electronic products. Additional specific obligations and commitments
 of, and standards of conduct for, persons who sponsor or monitor
 clinical investigations involving particular test articles may also be
 found in other parts (e.g., parts 312 and 812). Compliance with these
 parts is intended to protect the rights and safety of subjects involved
 in investigations filed with the Food and Drug Administration pursuant
 to sections 403, 406, 409, 412, 413, 502, 503, 505, 510, 513-516, 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.
     (b) References in this part to regulatory sections of the Code of
 Federal
 
 [[Page 286]]
 
 Regulations are to chapter I of title 21, unless otherwise noted.
 
 [45 FR 36390, May 30, 1980; 46 FR 8979, Jan. 27, 1981, as amended at 63
 FR 26697, May 13, 1998; 64 FR 399, Jan. 5, 1999; 66 FR 20597, Apr. 24,
 2001]
 
 
 
 [Code of Federal Regulations]
 [Title 21, Volume 1]
 [Revised as of April 1, 2002]
 From the U.S. Government Printing Office via GPO Access
 [CITE: 21CFR50.3]
 
 [Page 286-288]
 
                         TITLE 21--FOOD AND DRUGS
 
 CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN
                                 SERVICES
 
 PART 50--PROTECTION OF HUMAN SUBJECTS--Table of Contents
 
                       Subpart A--General Provisions
 
 Sec. 50.3  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 marketing permit includes:
     (1) A color additive petition, described in part 71.
     (2) A food additive petition, described in parts 171 and 571.
     ( 3 ) Data and information about a substance submitted as part of the
 procedures for establishing that the substance is generally recognized
 as safe for use that 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 Secs. 170.30 and
 570.30.
     (4) Data and information about a food additive submitted as part of
 the procedures for food additives permitted to be used on an interim
 basis pending additional study, described in Sec. 180.1.
     (5) 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 section 406 of the act.
     (6) An investigational new drug application, described in part 312
 of this chapter.
     (7) A new drug application, described in part 314.
     (8) Data and information about the bioavailability or bioequivalence
 of drugs for human use submitted as part of the procedures for issuing,
 amending, or repealing a bioequivalence requirement, described in part
 320.
     (9) Data and information about an over-the-counter drug for human
 use submitted as part of the procedures for classifying these drugs as
 generally recognized as safe and effective and not misbranded, described
 in part 330.
     (10) Data and information about a prescription drug for human use
 submitted as part of the procedures for classifying these drugs as
 generally recognized as safe and effective and not misbranded, described
 in this chapter.
     (11) [Reserved]
     (12) An application for a biologics license, described in part 601
 of this chapter.
     (13) Data and information about a biological product submitted as
 part of the procedures for determining that licensed biological products
 are safe and effective and not misbranded, described in part 601.
     (14) Data and information about an in vitro diagnostic product
 submitted as part of the procedures for establishing, amending, or
 repealing a standard for these products, described in part 809.
     (15) An Application for an Investigational Device Exemption,
 described in part 812.
     (16) Data and information about a medical device submitted as part
 of the procedures for classifying these devices, described in section
 513.
     (17) Data and information about a medical device submitted as part
 of the procedures for establishing, amending, or repealing a standard
 for these devices, described in section 514.
     (18) An application for premarket approval of a medical device,
 described in section 515.
     (19) A product development protocol for a medical device, described
 in section 515.
     (20) Data and information about an electronic product submitted as
 part of the procedures for establishing, amending, or repealing a
 standard for these products, described in section 358 of the Public
 Health Service Act.
     (21) Data and information about an electronic product submitted as
 part of the procedures for obtaining a variance from any electronic
 product performance standard, as described in Sec. 1010.4.
     (22) Data and information about 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
 Sec. 1010.5.
     (23) Data and information about a clinical study of an infant
 formula when submitted as part of an infant formula notification under
 section
 
 [[Page 287]]
 
 412(c) of the Federal Food, Drug, and Cosmetic Act.
     (24) Data and information submitted in a petition for a nutrient
 content claim, described in Sec. 101.69 of this chapter, or for a health
 claim, described in Sec. 101.70 of this chapter.
     (25) Data and information from investigations involving children
 submitted in a new dietary ingredient notification, described in
 Sec. 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 is subject to
 requirements for prior submission to the Food and Drug Administration
 under section 505(i) or 520(g) of the act, or is not subject to
 requirements for prior submission to the Food and Drug Administration
 under these sections of the act, but the results of which are intended
 to be submitted later to, or held for inspection by, the Food and Drug
 Administration as part of an application for a research or marketing
 permit. The term does not include experiments that are subject to the
 provisions of part 58 of this chapter, regarding nonclinical laboratory
 studies.
     (d) Investigator means an individual who actually conducts a
 clinical investigation, i.e., under whose immediate direction the test
 article is administered or dispensed to, or used involving, a subject,
 or, in the event of an investigation conducted by a team of individuals,
 is the responsible leader of that team.
     (e) Sponsor means a person who initiates a clinical investigation,
 but who 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 individual. A person other than
 an individual (e.g., corporation or agency) that uses one or more of its
 own employees to conduct a clinical investigation it has initiated is
 considered to be a sponsor (not a sponsor-investigator), and the
 employees are considered to be investigators.
     (f) Sponsor-investigator means an individual who both initiates and
 actually 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 individual, e.g., corporation or agency.
     (g) Human subject means an individual 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 human or a patient.
     (h) Institution means any public or private entity or agency
 (including Federal, State, and other agencies). The word facility as
 used in section 520(g) of the act is deemed to be synonymous with the
 term institution for purposes of this part.
     (i) Institutional review board (IRB) means any board, committee, or
 other group formally designated by an institution to review biomedical
 research involving humans as subjects, to approve the initiation of and
 conduct periodic review of such research. The term has the same meaning
 as the phrase institutional review committee as used in section 520(g)
 of the act.
     (j) Test article means any drug (including a biological product for
 human use), medical device for human use, human food additive, color
 additive, electronic product, or any other article subject to regulation
 under the act or under sections 351 and 354-360F of the Public Health
 Service Act (42 U.S.C. 262 and 263b-263n).
     (k) Minimal risk means that the probability and magnitude of harm or
 discomfort anticipated in the research are not greater in and of
 themselves than those ordinarily encountered in daily life or during the
 performance of routine physical or psychological examinations or tests.
     (l) Legally authorized representative means an individual or
 judicial or other body authorized under applicable law to consent on
 behalf of a prospective subject to the subject's particpation in the
 procedure(s) involved in the research.
     (m) Family member means any one of the following legally competent
 persons: Spouse; parents; children (including adopted children);
 brothers, sisters, and spouses of brothers and sisters; and any
 individual related by blood or affinity whose close association with the
 subject is the equivalent of a family relationship.
 
 [[Page 288]]
 
     (n) Assent means a child's affirmative agreement to participate in a
 clinical investigation. Mere failure to object may not, absent
 affirmative agreement, be construed as assent.
     (o) Children means persons who have not attained the legal age for
 consent to treatments or procedures involved in clinical investigations,
 under the applicable law of the jurisdiction in which the clinical
 investigation will be conducted.
     (p) Parent means a child's biological or adoptive parent.
     (q) Ward means a child who is placed in the legal custody of the
 State or other agency, institution, or entity, consistent with
 applicable Federal, State, or local law.
     (r) Permission means the agreement of parent(s) or guardian to the
 participation of their child or ward in a clinical investigation.
 Permission must be obtained in compliance with subpart B of this part
 and must include the elements of informed consent described in
 Sec. 50.25.
     (s) Guardian means an individual who is authorized under applicable
 State or local law to consent on behalf of a child to general medical
 care when general medical care includes participation in research. For
 purposes of subpart D of this part, a guardian also means an individual
 who is authorized to consent on behalf of a child to participate in
 research.
 
 [45 FR 36390, May 30, 1980, as amended at 46 FR 8950, Jan. 27, 1981; 54
 FR 9038, Mar. 3 , 1989; 56 FR 28028, June 18, 1991; 61 FR 51528, Oct. 2,
 1996; 62 FR 39440, July 23, 1997; 64 FR 399, Jan. 5, 1999; 64 FR 56448,
 Oct. 20, 1999; 66 FR 20597, Apr. 24, 2001]
 
 
 
 [Code of Federal Regulations]
 [Title 21, Volume 1]
 [Revised as of April 1, 2002]
 From the U.S. Government Printing Office via GPO Access
 [CITE: 21CFR50.20]
 
 [Page 288]
 
                         TITLE 21--FOOD AND DRUGS
 
 CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN
                                 SERVICES
 
 PART 50--PROTECTION OF HUMAN SUBJECTS--Table of Contents
 
               Subpart B--Informed Consent of Human Subjects
 
 Sec. 50.20  General requirements for informed consent.
 
     Source: 46 FR 8951, Jan. 27, 1981, unless otherwise noted.
 
     Except as provided in Secs. 50.23 and 50.24, no investigator may
 involve a human being as a subject in research covered by these
 regulations unless the investigator has obtained the legally effective
 informed consent of the subject or the subject's legally authorized
 representative. An investigator shall seek such consent only under
 circumstances that provide the prospective subject or the representative
 sufficient opportunity to consider whether or not to participate and
 that minimize the possibility of coercion or undue influence. The
 information that is given to the subject or the representative shall be
 in language understandable to the subject or the representative. No
 informed consent, whether oral or written, may include any exculpatory
 language through which the subject or the representative is made to
 waive or appear to waive any of the subject's legal rights, or releases
 or appears to release the investigator, the sponsor, the institution, or
 its agents from liability for negligence.
 
 [46 FR 8951, Jan. 27, 1981, as amended at 64 FR 10942, Mar. 8, 1999]
 
 
 
 [Code of Federal Regulations]
 [Title 21, Volume 1]
 [Revised as of April 1, 2002]
 From the U.S. Government Printing Office via GPO Access
 [ CITE :21CFR50.23]
 
 [Page 288-290]
 
                         TITLE 21--FOOD AND DRUGS
 
 CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN
                                 SERVICES
 
 PART 50--PROTECTION OF HUMAN SUBJECTS--Table of Contents
 
               Subpart B--Informed Consent of Human Subjects
 
 Sec. 50.23  Exception from general requirements.
 
     (a) The obtaining of informed consent shall be deemed feasible
 unless, before use of the test article (except as provided in paragraph
 (b) of this section), both the investigator and a physician who is not
 otherwise participating in the clinical investigation certify in writing
 all of the following:
     (1) The human subject is confronted by a life-threatening situation
 necessitating the use of the test article.
     (2) Informed consent cannot be obtained from the subject because of
 an inability to communicate with, or obtain legally effective consent
 from, the subject.
     (3) Time is not sufficient to obtain consent from the subject's
 legal representative.
     (4) There is available no alternative method of approved or
 generally recognized therapy that provides an equal or greater
 likelihood of saving the life of the subject.
     (b) If immediate use of the test article is, in the investigator's
 opinion, required to preserve the life of the subject, and time is not
 sufficient to obtain the independent determination required in paragraph
 (a) of this section in advance of using the test article, the
 determinations of the clinical investigator shall be made and, within 5
 working days after the use of the article, be
 
 [[Page 289]]
 
 reviewed and evaluated in writing by a physician who is not
 participating in the clinical investigation.
     (c) The documentation required in paragraph (a) or (b) of this
 section shall be submitted to the IRB within 5 working days after the
 use of the test article.
     (d)(1) Under 10 U.S.C. 1107(f) the President may waive the prior
 consent requirement for the administration of an investigational new
 drug to a member of the armed forces in connection with the member's
 participation in a particular military operation. The statute specifies
 that only the President may waive informed consent in this connection
 and the President may grant such a waiver only if the President
 determines in writing that obtaining consent: Is not feasible; is
 contrary to the best interests of the military member; or is not in the
 interests of national security. The statute further provides that in
 making a determination to waive prior informed consent on the ground
 that it is not feasible or the ground that it is contrary to the best
 interests of the military members involved, the President shall apply
 the standards and criteria that are set forth in the relevant FDA
 regulations for a waiver of the prior informed consent requirements of
 section 505(i)(4) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C.
 355(i)(4)). Before such a determination may be made that obtaining
 informed consent from military personnel prior to the use of an
 investigational drug (including an antibiotic or biological product) in
 a specific protocol under an investigational new drug application (IND)
 sponsored by the Department of Defense (DOD) and limited to specific
 military personnel involved in a particular military operation is not
 feasible or is contrary to the best interests of the military members
 involved the Secretary of Defense must first request such a
 determination from the President, and certify and document to the
 President that the following standards and criteria contained in
 paragraphs (d)(1) through (d)(4) of this section have been met.
     (i) The extent and strength of evidence of the safety and
 effectiveness of the investigational new drug in relation to the medical
 risk that could be encountered during the military operation supports
 the drug's administration under an IND.
     (ii) The military operation presents a substantial risk that
 military personnel may be subject to a chemical, biological, nuclear, or
 other exposure likely to produce death or serious or life-threatening
 injury or illness.
     (iii) There is no available satisfactory alternative therapeutic or
 preventive treatment in relation to the intended use of the
 investigational new drug.
     (iv) Conditioning use of the investigational new drug on the
 voluntary participation of each member could significantly risk the
 safety and health of any individual member who would decline its use,
 the safety of other military personnel, and the accomplishment of the
 military mission.
     (v) A duly constituted institutional review board (IRB) established
 and operated in accordance with the requirements of paragraphs (d)(2)
 and (d)(3) of this section, responsible for review of the study, has
 reviewed and approved the investigational new drug protocol and the
 administration of the investigational new drug without informed consent.
 DOD's request is to include the documentation required by
 Sec. 56.115(a)(2) of this chapter.
     (vi) DOD has explained:
     (A) The context in which the investigational drug will be
 administered, e.g., the setting or whether it will be self-administered
 or it will be administered by a health professional;
     (B) The nature of the disease or condition for which the preventive
 or therapeutic treatment is intended; and
     (C) To the extent there are existing data or information available,
 information on conditions that could alter the effects of the
 investigational drug.
     (vii) DOD's recordkeeping system is capable of tracking and will be
 used to track the proposed treatment from supplier to the individual
 recipient.
     (viii) Each member involved in the military operation will be given,
 prior to the administration of the investigational new drug, a specific
 written information sheet (including information required by 10 U.S.C.
 1107(d)) concerning the investigational new drug,
 
 [[Page 290]]
 
 the risks and benefits of its use, potential side effects, and other
 pertinent information about the appropriate use of the product.
     (ix) Medical records of members involved in the military operation
 will accurately document the receipt by members of the notification
 required by paragraph (d)(1)(viii) of this section.
     (x) Medical records of members involved in the military operation
 will accurately document the receipt by members of any investigational
 new drugs in accordance with FDA regulations including part 312 of this
 chapter.
     (xi) DOD will provide adequate followup to assess whether there are
 beneficial or adverse health consequences that result from the use of
 the investigational product.
     (xii) DOD is pursuing drug development, including a time line, and
 marketing approval with due diligence.
     (xiii) FDA has concluded that the investigational new drug protocol
 may proceed subject to a decision by the President on the informed
 consent waiver request.
     (xiv) DOD will provide training to the appropriate medical personnel
 and potential recipients on the specific investigational new drug to be
 administered prior to its use.
     (xv) DOD has stated and justified the time period for which the
 waiver is needed, not to exceed one year, unless separately renewed
 under these standards and criteria.
     (xvi) DOD shall have a continuing obligation to report to the FDA
 and to the President any changed circumstances relating to these
 standards and criteria (including the time period referred to in
 paragraph (d)(1)(xv) of this section) or that otherwise might affect the
 determination to use an investigational new drug without informed
 consent.
     (xvii) DOD is to provide public notice as soon as practicable and
 consistent with classification requirements through notice in the
 Federal Register describing each waiver of informed consent
 determination, a summary of the most updated scientific information on
 the products used, and other pertinent information.
     (xviii) Use of the investigational drug without informed consent
 otherwise conforms with applicable law.
     (2) The duly constituted institutional review board, described in
 paragraph (d)(1)(v) of this section, must include at least 3
 nonaffiliated members who shall not be employees or officers of the
 Federal Government (other than for purposes of membership on the IRB)
 and shall be required to obtain any necessary security clearances. This
 IRB shall review the proposed IND protocol at a convened meeting at
 which a majority of the members are present including at least one
 member whose primary concerns are in nonscientific areas and, if
 feasible, including a majority of the nonaffiliated members. The
 information required by Sec. 56.115(a)(2) of this chapter is to be
 provided to the Secretary of Defense for further review.
     (3) The duly constituted institutional review board, described in
 paragraph (d)(1)(v) of this section, must review and approve:
     (i) The required information sheet;
     (ii) The adequacy of the plan to disseminate information, including
 distribution of the information sheet to potential recipients, on the
 investigational product (e.g., in forms other than written);
     (iii) The adequacy of the information and plans for its
 dissemination to health care providers, including potential side
 effects, contraindications, potential interactions, and other pertinent
 considerations; and
     (iv) An informed consent form as required by part 50 of this
 chapter, in those circumstances in which DOD determines that informed
 consent may be obtained from some or all personnel involved.
     (4) DOD is to submit to FDA summaries of institutional review board
 meetings at which the proposed protocol has been reviewed.
     (5) Nothing in these criteria or standards is intended to preempt or
 limit FDA's and DOD's authority or obligations under applicable statutes
 and regulations.
 
 [46 FR 8951, Jan. 27, 1981, as amended at 55 FR 52817, Dec. 21, 1990; 64
 FR 399, Jan. 5, 1999; 64 FR 54188, Oct. 5, 1999]
 
 [[Page 291]]
 
 
 
 [Code of Federal Regulations]
 [Title 21, Volume 1]
 [Revised as of April 1, 2002]
 From the U.S. Government Printing Office via GPO Access
 [CITE: 21CFR50.24]
 
 [Page 291-292]
 
                         TITLE 21--FOOD AND DRUGS
 
 CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN
                                 SERVICES
 
 PART 50--PROTECTION OF HUMAN SUBJECTS--Table of Contents
 
               Subpart B--Informed Consent of Human Subjects
 
 Sec. 50.24  Exception from informed consent requirements for emergency research.
 
     (a) The IRB responsible for the review, approval, and continuing
 review of the clinical investigation described in this section may
 approve that investigation without requiring that informed consent of
 all research subjects be obtained if the IRB (with the concurrence of a
 licensed physician who is a member of or consultant to the IRB and who
 is not otherwise participating in the clinical investigation) finds and
 documents each of the following:
     (1) The human subjects are in a life-threatening situation,
 available treatments are unproven or unsatisfactory, and the collection
 of valid scientific evidence, which may include evidence obtained
 through randomized placebo-controlled investigations, is necessary to
 determine the safety and effectiveness of particular interventions.
     (2) Obtaining informed consent is not feasible because:
     (i) The subjects will not be able to give their informed consent as
 a result of their medical condition;
     (ii) The intervention under investigation must be administered
 before consent from the subjects' legally authorized representatives is
 feasible; and
     (iii) There is no reasonable way to identify prospectively the
 individuals likely to become eligible for participation in the clinical
 investigation.
     (3) Participation in the research holds out the prospect of direct
 benefit to the subjects because:
     (i) Subjects are facing a life-threatening situation that
 necessitates intervention;
     (ii) Appropriate animal and other preclinical studies have been
 conducted, and the information derived from those studies and related
 evidence support the potential for the intervention to provide a direct
 benefit to the individual subjects; and
     (iii) Risks associated with the investigation are reasonable in
 relation to what is known about the medical condition of the potential
 class of subjects, the risks and benefits of standard therapy, if any,
 and what is known about the risks and benefits of the proposed
 intervention or activity.
     (4) The clinical investigation could not practicably be carried out
 without the waiver.
     (5) The proposed investigational plan defines the length of the
 potential therapeutic window based on scientific evidence, and the
 investigator has committed to attempting to contact a legally authorized
 representative for each subject within that window of time and, if
 feasible, to asking the legally authorized representative contacted for
 consent within that window rather than proceeding without consent. The
 investigator will summarize efforts made to contact legally authorized
 representatives and make this information available to the IRB at the
 time of continuing review.
     (6) The IRB has reviewed and approved informed consent procedures
 and an informed consent document consistent with Sec. 50.25. These
 procedures and the informed consent document are to be used with
 subjects or their legally authorized representatives in situations where
 use of such procedures and documents is feasible. The IRB has reviewed
 and approved procedures and information to be used when providing an
 opportunity for a family member to object to a subject's participation
 in the clinical investigation consistent with paragraph (a)(7)(v) of
 this section.
     (7) Additional protections of the rights and welfare of the subjects
 will be provided, including, at least:
     (i) Consultation (including, where appropriate, consultation carried
 out by the IRB) with representatives of the communities in which the
 clinical investigation will be conducted and from which the subjects
 will be drawn;
     (ii) Public disclosure to the communities in which the clinical
 investigation will be conducted and from which the subjects will be
 drawn, prior to initiation of the clinical investigation, of plans for
 the investigation and its risks and expected benefits;
     (iii) Public disclosure of sufficient information following
 completion of the clinical investigation to apprise the community and
 researchers of the study, including the demographic characteristics of
 the research population, and its results;
 
 [[Page 292]]
 
     (iv) Establishment of an independent data monitoring committee to
 exercise oversight of the clinical investigation; and
     (v) If obtaining informed consent is not feasible and a legally
 authorized representative is not reasonably available, the investigator
 has committed, if feasible, to attempting to contact within the
 therapeutic window the subject's family member who is not a legally
 authorized representative, and asking whether he or she objects to the
 subject's participation in the clinical investigation. The investigator
 will summarize efforts made to contact family members and make this
 information available to the IRB at the time of continuing review.
     (b) The IRB is responsible for ensuring that procedures are in place
 to inform, at the earliest feasible opportunity, each subject, or if the
 subject remains incapacitated, a legally authorized representative of
 the subject, or if such a representative is not reasonably available, a
 family member, of the subject's inclusion in the clinical investigation,
 the details of the investigation and other information contained in the
 informed consent document. The IRB shall also ensure that there is a
 procedure to inform the subject, or if the subject remains
 incapacitated, a legally authorized representative of the subject, or if
 such a representative is not reasonably available, a family member, that
 he or she may discontinue the subject's participation at any time
 without penalty or loss of benefits to which the subject is otherwise
 entitled. If a legally authorized representative or family member is
 told about the clinical investigation and the subject's condition
 improves, the subject is also to be informed as soon as feasible. If a
 subject is entered into a clinical investigation with waived consent and
 the subject dies before a legally authorized representative or family
 member can be contacted, information about the clinical investigation is
 to be provided to the subject's legally authorized representative or
 family member, if feasible.
     (c) The IRB determinations required by paragraph (a) of this section
 and the documentation required by paragraph (e) of this section are to
 be retained by the IRB for at least 3 years after completion of the
 clinical investigation, and the records shall be accessible for
 inspection and copying by FDA in accordance with Sec. 56.115(b) of this
 chapter.
     (d) Protocols involving an exception to the informed consent
 requirement under this section must be performed under a separate
 investigational new drug application (IND) or investigational device
 exemption (IDE) that clearly identifies such protocols as protocols that
 may include subjects who are unable to consent. The submission of those
 protocols in a separate IND/IDE is required even if an IND for the same
 drug product or an IDE for the same device already exists. Applications
 for investigations under this section may not be submitted as amendments
 under Secs. 312.30 or 812.35 of this chapter.
     (e) If an IRB determines that it cannot approve a clinical
 investigation because the investigation does not meet the criteria in
 the exception provided under paragraph (a) of this section or because of
 other relevant ethical concerns, the IRB must document its findings and
 provide these findings promptly in writing to the clinical investigator
 and to the sponsor of the clinical investigation. The sponsor of the
 clinical investigation must promptly disclose this information to FDA
 and to the sponsor's clinical investigators who are participating or are
 asked to participate in this or a substantially equivalent clinical
 investigation of the sponsor, and to other IRB's that have been, or are,
 asked to review this or a substantially equivalent investigation by that
 sponsor.
 
 [61 FR 51528, Oct. 2, 1996]
 
 
 
 [Code of Federal Regulations]
 [Title 21, Volume 1]
 [Revised as of April 1, 2002]
 From the U.S. Government Printing Office via GPO Access
 [CITE: 21CFR50.25]
 
 [Page 292-293]
 
                         TITLE 21--FOOD AND DRUGS
 
 CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN
                                 SERVICES
 
 PART 50--PROTECTION OF HUMAN SUBJECTS--Table of Contents
 
               Subpart B--Informed Consent of Human Subjects
 
 Sec. 50.25  Elements of informed consent.
 
     (a) Basic elements of informed consent. In seeking informed consent,
 the following information shall be provided to each subject:
     (1) A statement that the study involves research, an explanation of
 the purposes of the research and the expected duration of the subject's
 participation, a description of the procedures to be followed, and
 identification of any procedures which are experimental.
 
 [[Page 293]]
 
     (2) A description of any reasonably foreseeable risks or discomforts
 to the subject.
     (3) A description of any benefits to the subject or to others which
 may reasonably be expected from the research.
     (4) A disclosure of appropriate alternative procedures or courses of
 treatment, if any, that might be advantageous to the subject.
     (5) A statement describing the extent, if any, to which
 confidentiality of records identifying the subject will be maintained
 and that notes the possibility that the Food and Drug Administration may
 inspect the records.
     (6) For research involving more than minimal risk, an explanation as
 to whether any compensation and an explanation as to whether any medical
 treatments are available if injury occurs and, if so, what they consist
 of, or where further information may be obtained.
     (7) An explanation of whom to contact for answers to pertinent
 questions about the research and research subjects' rights, and whom to
 contact in the event of a research-related injury to the subject.
     (8) A statement that participation is voluntary, that refusal to
 participate will involve no penalty or loss of benefits to which the
 subject is otherwise entitled, and that the subject may discontinue
 participation at any time without penalty or loss of benefits to which
 the subject is otherwise entitled.
     (b) Additional elements of informed consent. When appropriate, one
 or more of the following elements of information shall also be provided
 to each subject:
     (1) A statement that the particular treatment or procedure may
 involve risks to the subject (or to the embryo or fetus, if the subject
 is or may become pregnant) which are currently unforeseeable.
     (2) Anticipated circumstances under which the subject's
 participation may be terminated by the investigator without regard to
 the subject's consent.
     (3) Any additional costs to the subject that may result from
 participation in the research.
     (4) The consequences of a subject's decision to withdraw from the
 research and procedures for orderly termination of participation by the
 subject.
     (5) A statement that significant new findings developed during the
 course of the research which may relate to the subject's willingness to
 continue participation will be provided to the subject.
     (6) The approximate number of subjects involved in the study.
     (c) The informed consent requirements in these regulations are not
 intended to preempt any applicable Federal, State, or local laws which
 require additional information to be disclosed for informed consent to
 be legally effective.
     (d) Nothing in these regulations is intended to limit the authority
 of a physician to provide emergency medical care to the extent the
 physician is permitted to do so under applicable Federal, State, or
 local law.
 
 
 
 [Code of Federal Regulations]
 [Title 21, Volume 1]
 [Revised as of April 1, 2002]
 From the U.S. Government Printing Office via GPO Access
 [CITE: 21CFR50.27]
 
 [Page 293-294]
 
                         TITLE 21--FOOD AND DRUGS
 
 CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN
                                 SERVICES
 
 PART 50--PROTECTION OF HUMAN SUBJECTS--Table of Contents
 
               Subpart B--Informed Consent of Human Subjects
 
 Sec. 50.27  Documentation of informed consent.
 
     (a) Except as provided in Sec. 56.109(c), informed consent shall be
 documented by the use of a written consent form approved by the IRB and
 signed and dated by the subject or the subject's legally authorized
 representative at the time of consent. A copy shall be given to the
 person signing the form.
     (b) Except as provided in Sec. 56.109(c), the consent form may be
 either of the following:
     (1) A written consent document that embodies the elements of
 informed consent required by Sec. 50.25. This form may be read to the
 subject or the subject's legally authorized representative, but, in any
 event, the investigator shall give either the subject or the
 representative adequate opportunity to read it before it is signed.
     (2) A short form written consent document stating that the elements
 of informed consent required by Sec. 50.25 have been presented orally to
 the subject or the subject's legally authorized representative. When
 this method is used, there shall be a witness to the oral presentation.
 Also, the IRB shall approve a written summary of what is to be said to
 the subject or the representative. Only the short form itself is to be
 signed by the subject or the representative. However, the witness shall
 
 [[Page 294]]
 
 sign both the short form and a copy of the summary, and the person
 actually obtaining the consent shall sign a copy of the summary. A copy
 of the summary shall be given to the subject or the representative in
 addition to a copy of the short form.
 
 [46 FR 8951, Jan. 27 , 1981, as amended at 61 FR 57280, Nov. 5, 1996]
 
 Subpart C [Reserved]
 
 
 
 [Code of Federal Regulations]
 [Title 21, Volume 1]
 [Revised as of April 1, 2002]
 From the U.S. Government Printing Office via GPO Access
 [CITE :21CFR50.50]
 
 [Page 294]
 
                         TITLE 21--FOOD AND DRUGS
 
 CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN
                                 SERVICES
 
 PART 50 --PROTECTION OF HUMAN SUBJECTS--Table of Contents
 
 Subpart D--Additional Safeguards for Children in Clinical Investigations
 
 Sec. 50.50  IRB duties.
 
     Source: 66 FR 20598, Apr. 24, 2001, unless otherwise noted.
 
     In addition to other responsibilities assigned to IRBs under this
 part and part 56 of this chapter, each IRB must review clinical
 investigations involving children as subjects covered by this subpart D
 and approve only those clinical investigations that satisfy the criteria
 described in Sec. 50 .51, Sec. 50 .52, or Sec. 50 .53 and the conditions of
 all other applicable sections of this subpart D.
 
 
 
 [Code of Federal Regulations]
 [Title 21, Volume 1]
 [Revised as of April 1, 2002]
 From the U.S. Government Printing Office via GPO Access
 [CITE: 21CFR50.51]
 
 [Page 294]
 
                         TITLE 21--FOOD AND DRUGS
 
 CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN
                                 SERVICES
 
 PART 50--PROTECTION OF HUMAN SUBJECTS--Table of Contents
 
 Subpart D--Additional Safeguards for Children in Clinical Investigations
 
 Sec. 50.51  Clinical investigations not involving greater than minimal risk.
 
     Any clinical investigation within the scope described in Secs. 50.1
 and 56.101 of this chapter in which no greater than minimal risk to
 children is presented may involve children as subjects only if the IRB
 finds and documents that adequate provisions are made for soliciting the
 assent of the children and the permission of their parents or guardians
 as set forth in Sec. 50.55.
 
 
 
 [Code of Federal Regulations]
 [Title 21, Volume 1]
 [Revised as of April 1, 2002]
 From the U.S. Government Printing Office via GPO Access
 [CITE: 21CFR50.52]
 
 [Page 294]
 
                         TITLE 21--FOOD AND DRUGS
 
 CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN
                                 SERVICES
 
 PART 50--PROTECTION OF HUMAN SUBJECTS--Table of Contents
 
 Subpart D--Additional Safeguards for Children in Clinical Investigations
 
 Sec. 50.52  Clinical investigations involving greater than minimal risk but presenting the prospect of dire
 
     Any clinical investigation within the scope described in Secs. 50.1
 and 56.101 of this chapter in which more than minimal risk to children
 is presented by an intervention or procedure that holds out the prospect
 of direct benefit for the individual subject, or by a monitoring
 procedure that is likely to contribute to the subject's well-being, may
 involve children as subjects only if the IRB finds and documents that:
     (a) The risk is justified by the anticipated benefit to the
 subjects;
     (b) The relation of the anticipated benefit to the risk is at least
 as favorable to the subjects as that presented by available alternative
 approaches; and
     (c) Adequate provisions are made for soliciting the assent of the
 children and permission of their parents or guardians as set forth in
 Sec. 50.55.
 
 
 
 [Code of Federal Regulations]
 [Title 21, Volume 1]
 [Revised as of April 1, 2002]
 From the U.S. Government Printing Office via GPO Access
 [CITE: 21CFR50.53]
 
 [Page 294]
 
                         TITLE 21--FOOD AND DRUGS
 
 CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN
                                 SERVICES
 
 PART 50--PROTECTION OF HUMAN SUBJECTS--Table of Contents
 
 Subpart D--Additional Safeguards for Children in Clinical Investigations
 
 Sec. 50.53   Clinical investigations involving greater than minimal risk and no prospect of direct benefit
           generalizable knowledge about the subjects' disorder or
           condition.
 
     Any clinical investigation within the scope described in Secs. 50.1
 and 56.101 of this chapter in which more than minimal risk to children
 is presented by an intervention or procedure that does not hold out the
 prospect of direct benefit for the individual subject, or by a
 monitoring procedure that is not likely to contribute to the well-being
 of the subject, may involve children as subjects only if the IRB finds
 and documents that:
     (a) The risk represents a minor increase over minimal risk;
     (b) The intervention or procedure presents experiences to subjects
 that are reasonably commensurate with those inherent in their actual or
 expected medical, dental, psychological, social, or educational
 situations;
     (c) The intervention or procedure is likely to yield generalizable
 knowledge about the subjects' disorder or condition that is of vital
 importance for the understanding or amelioration of the subjects'
 disorder or condition; and
     (d) Adequate provisions are made for soliciting the assent of the
 children and permission of their parents or guardians as set forth in
 Sec. 50.55.
 
 [[Page 295]]
 
 
 
 [Code of Federal Regulations]
 [Title 21, Volume 1]
 [Revised as of April 1, 2002]
 From the U.S. Government Printing Office via GPO Access
 [CITE: 21CFR50.54]
 
 [Page 295]
 
                         TITLE 21--FOOD AND DRUGS
 
 CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN
                                 SERVICES
 
 PART 50--PROTECTION OF HUMAN SUBJECTS--Table of Contents
 
 Subpart D--Additional Safeguards for Children in Clinical Investigations
 
 Sec. 50.54  Clinical investigations not otherwise approvable that present an opportunity to understand, pre
           health or welfare of children.
 
     If an IRB does not believe that a clinical investigation within the
 scope described in Secs. 50.1 and 56.101 of this chapter and involving
 children as subjects meets the requirements of Sec. 50.51, Sec. 50.52,
 or Sec. 50.53, the clinical investigation may proceed only if:
     (a) The IRB finds and documents that the clinical investigation
 presents a reasonable opportunity to further the understanding,
 prevention, or alleviation of a serious problem affecting the health or
 welfare of children; and
     (b) The Commissioner of Food and Drugs, after consultation with a
 panel of experts in pertinent disciplines (for example: science,
 medicine, education, ethics, law) and following opportunity for public
 review and comment, determines either:
     (1) That the clinical investigation in fact satisfies the conditions
 of Sec. 50.51, Sec. 50.52, or Sec. 50.53, as applicable, or
     (2) That the following conditions are met:
     (i) The clinical investigation presents a reasonable opportunity to
 further the understanding, prevention, or alleviation of a serious
 problem affecting the health or welfare of children;
     (ii) The clinical investigation will be conducted in accordance with
 sound ethical principles; and
     (iii) Adequate provisions are made for soliciting the assent of
 children and the permission of their parents or guardians as set forth
 in Sec. 50.55.
 
 
 
 [Code of Federal Regulations]
 [Title 21, Volume 1]
 [Revised as of April 1, 2002]
 From the U.S. Government Printing Office via GPO Access
 [CITE: 21CFR50.55]
 
 [Page 295-296]
 
                         TITLE 21--FOOD AND DRUGS
 
 CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN
                                 SERVICES
 
 PART 50--PROTECTION OF HUMAN SUBJECTS--Table of Contents
 
 Subpart D--Additional Safeguards for Children in Clinical Investigations
 
 Sec. 50.55  Requirements for permission by parents or guardians and for assent by children.
 
     (a) In addition to the determinations required under other
 applicable sections of this subpart D, the IRB must determine that
 adequate provisions are made for soliciting the assent of the children
 when in the judgment of the IRB the children are capable of providing
 assent.
     (b) In determining whether children are capable of providing assent,
 the IRB must take into account the ages, maturity, and psychological
 state of the children involved. This judgment may be made for all
 children to be involved in clinical investigations under a particular
 protocol, or for each child, as the IRB deems appropriate.
     (c) The assent of the children is not a necessary condition for
 proceeding with the clinical investigation if the IRB determines:
     (1) That the capability of some or all of the children is so limited
 that they cannot reasonably be consulted, or
     (2) That the intervention or procedure involved in the clinical
 investigation holds out a prospect of direct benefit that is important
 to the health or well-being of the children and is available only in the
 context of the clinical investigation.
     (d) Even where the IRB determines that the subjects are capable of
 assenting, the IRB may still waive the assent requirement if it finds
 and documents that:
     (1) The clinical investigation involves no more than minimal risk to
 the subjects;
     (2) The waiver will not adversely affect the rights and welfare of
 the subjects;
     (3) The clinical investigation could not practicably be carried out
 without the waiver; and
     (4) Whenever appropriate, the subjects will be provided with
 additional pertinent information after participation.
     (e) In addition to the determinations required under other
 applicable sections of this subpart D, the IRB must determine that the
 permission of each child's parents or guardian is granted.
     (1) Where parental permission is to be obtained, the IRB may find
 that the permission of one parent is sufficient, if consistent with
 State law, for clinical investigations to be conducted under Sec. 50.51
 or Sec. 50.52.
     (2) Where clinical investigations are covered by Sec. 50.53 or
 Sec. 50.54 and permission is to be obtained from parents, both parents
 must give their permission unless one parent is deceased, unknown,
 incompetent, or not reasonably available, or when only one parent has
 legal responsibility for the care and custody of the child if consistent
 with State law.
 
 [[Page 296]]
 
     (f) Permission by parents or guardians must be documented in
 accordance with and to the extent required by Sec. 50.27.
     (g) When the IRB determines that assent is required, it must also
 determine whether and how assent must be documented.
 
 
 
 [Code of Federal Regulations]
 [Title 21, Volume 1]
 [Revised as of April 1, 2002]
 From the U.S. Government Printing Office via GPO Access
 [CITE: 21CFR50.56]
 
 [Page 296]
 
                         TITLE 21--FOOD AND DRUGS
 
 CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN
                                 SERVICES
 
 PART 50--PROTECTION OF HUMAN SUBJECTS--Table of Contents
 
 Subpart D--Additional Safeguards for Children in Clinical Investigations
 
 Sec. 50.56  Wards.
 
     (a) Children who are wards of the State or any other agency,
 institution, or entity can be included in clinical investigations
 approved under Sec. 50.53 or Sec. 50.54 only if such clinical
 investigations are:
     (1) Related to their status as wards; or
     (2) Conducted in schools, camps, hospitals, institutions, or similar
 settings in which the majority of children involved as subjects are not
 wards.
     (b) If the clinical investigation is approved under paragraph (a) of
 this section, the IRB must require appointment of an advocate for each
 child who is a ward.
     (1) The advocate will serve in addition to any other individual
 acting on behalf of the child as guardian or in loco parentis.
     (2) One individual may serve as advocate for more than one child.
     (3) The advocate must be an individual who has the background and
 experience to act in, and agrees to act in, the best interest of the
 child for the duration of the child's participation in the clinical
 investigation.
     (4) The advocate must not be associated in any way (except in the
 role as advocate or member of the IRB) with the clinical investigation,
 the investigator(s), or the guardian organization.