[Code of Federal Regulations]
[Title 21, Volume 1]
[Revised as of April 1, 2003]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR50]

                        TITLE 21--FOOD AND DRUGS
 
               CHAPTER I--FOOD AND DRUG ADMINISTRATION
               DEPARTMENT OF HEALTH AND HUMAN SERVICES
			   
PART 50--PROTECTION OF HUMAN SUBJECTS

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
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]




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
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.
    (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]




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]




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
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,
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]



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;
    (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]




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.
    (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.




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
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]




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.




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.




Subpart D--Additional Safeguards for Children in Clinical Investigations

Sec. 50.52 Clinical investigations involving greater than minimal risk but presenting the prospect of direct benefit to individual subjects.

    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.




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 to individual subjects, but likely to yield 
          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.



Subpart D--Additional Safeguards for Children in Clinical Investigations

Sec. 50.54 Clinical investigations not otherwise approvable that present an opportunity to understand, prevent, or alleviate a serious problem affecting the 
          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.




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.
    (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.




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.