Authority: 21 U.S.C 321, 343, 346, 346a, 348, 350a, 350b, 352, 353, 355, 360, 360c-360f, 360h-360j, 371, 379e, 381; 42 U.S.C. 216, 241, 262, 263b-263n. Source: 45 FR 36390, May 30, 1980, unless otherwise noted. [Includes interim rule on Additional Safeguards for Children in Clinical Investigations of FDA -Regulated Products]
	Subpart A General Provisions

50.1 Scope	Sec. 50.1 Scope.
50.1(a) Applies to all research regulated by FDA and undertaken to support permit applications	(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.
50.1(b) References are to Chapter I, Title 21 CFR	(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]

50.3 Defnitions	Sec. 50.3 Definitions. As used in this part:
50.3(a) Act	(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)).
50.3(b) Application for research or marketing permit includes:	(b) Application for research or marketing permit includes:
50.3(b)(1) Color additive petition	(1) A color additive petition, described in part 71.
50.3(b)(2) Food additive petition	(2) A food additive petition, described in parts 171 and 571.
50.3(b)(3) Data about safety of food components	(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.
50.3(b)(4) Data about food additives used pending further study	(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.
50.3(b)(5) Data about tolerance for food contaminants	(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.
50.3(b)(6) Investigational new drug application	(6) An investigational new drug application, described in part 312 of this chapter.
50.3(b)(7) New drug application	(7) A new drug application, described in part 314.
50.3(b)(8) Data about bioavailability or bioequivalence	(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.
50.3(b)(9) Data about safety and effectiveness of over-the-counter drugs	(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.
50.3(b)(10) Data about safety and effectiveness of prescription drugs	(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.
50.3(b)(11) Data about antibiotic drugs pertaining to their regulation	(11) Data and information about an antibiotic drug submitted as part of the procedures for issuing, amending, or repealing regulations for these drugs, described in Sec. 314.300 of this chapter.
50.3(b)(12) Application for biological product license	(12) An application for a biologics license, described in part 601 of this chapter.
50.3(b)(13) Data about safety and effectiveness of biological products	(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.
50.3(b)(14) Data pertaining to standards for in vitro diagnostic products	(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.
50.3(b)(15) Application for an Investigational Device Exemption	(15) An Application for an Investigational Device Exemption, described in part 812.
50.3(b)(16) Data pertaining to classification of medical devices	(16) Data and information about a medical device submitted as part of the procedures for classifying these devices, described in section 513.
50.3(b)(17) Data pertaining to standards for medical devices	(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.
50.3(b)(18) Application for premarket approval of a medical device	(18) An application for premarket approval of a medical device, described in section 515.
50.3(b)(19) Medical device product development protocol	(19) A product development protocol for a medical device, described in section 515.
50.3(b)(20) Data pertaining to standards for electronic products	(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.
50.3(b)(21) Data used to apply for variance for an electronic product	(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.
50.3(b)(22) Data used to apply for exemption for an electronic product	(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.
50.3(b)(23) Data about clinical study of infant formula	(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.
50.3(b)(24) Data to support a nutrient content or health claim	(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.
50.3(b)(25) Data from investigations involving children for a new dietary ingredient	(25) Data and information from investigations involving children submitted in a new dietary ingredient notification, described in Sec. 190.6 of this chapter.
50.3(c) Clinical Investigation	(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.
50.3(d) Investigator	(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.
50.3(e) Sponsor	(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.
50.3(f) Sponsor-investigator	(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.
50.3(g) Human Subject	(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.
50.3(h) Institution	(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.
50.3(i) IRB	(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.
50.3(j) Test article	(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).
50.3(k) Minimal risk	(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.
50.3(l) Legally authorized representative	(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.
50.3(m) Family member	(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.
50.3(n) Assent	(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.
50.3(o) Children	(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.
50.3(p) Parent	(p) Parent means a child's biological or adoptive parent.
50.3(q) Ward	(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.
50.3(r) Permission	(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.
50.3(s) Guardian	(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.

	Subpart B Informed Consent of Human Subjects

	Section 50.20 General requirements for informed consent
50.20 Informed consent is required for covered research	Except as provided in section 50.23, 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.

50.21 Effective July 27, 1981	Section 50.21 Effective date
	The requirements for informed consent set out in this part apply to all human subjects entering a clinical investigation that commences on or after July 27, 1981.

	Section 50.23 Exception from general requirements.
50.23(a) Informed consent is required unless both investigator and another physician certify that:	(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:
50.23(a)(1) Life-threatening situation require use of the article	(1) The human subject is confronted by a life-threatening situation necessitating the use of the test article.
50.23(a)(2) Subject unable to give consent	(2) Informed consent cannot be obtained from the subject because of an inability to communicate with, or obtain legally effective consent from, the subject.
50.23(a)(3) There is not enough time to obtain consent form legal representative	(3) Time is not sufficient to obtain consent from the subject's legal representative.
50.23(a)(4) No alternative treatment is available	(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.
50.23(b) If time does not allow certification by other physician, a review must be made within 5 days	(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.
50.23(c) Report must be made to IRB within 5 days	(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 thetest article.
50.23(d)(1) President may waive prior consent of use of investigational drug in connection with a military operation; Secretary of Defense must document that:	(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.
50.23(d)(1)(i) Evidence of safety and effectiveness of drug supports administration	(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.
50.23(d)(1)(ii) Military operation presents substantial risk	(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.
50.23(d)(1)(iii) No alternative treatment available	(iii) There is no available satisfactory alternative therapeutic or preventive treatment in relation to the intended use of the investigational new drug.
50.23(d)(1)(iv) Requiring consent could put personnel significantly at risk	(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.
50.23(d)(1)(v) A duly constituted IRB has approved the protocol	(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.
50.23(d)(1)(vi) DOD has explained context for administration, nature of disease or condition, conditions that may alter effects of the drug	(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.
50.23(d)(1)(vii) Records will track treatment	(vii) DOD's recordkeeping system is capable of tracking and will be used to track the proposed treatment from supplier to the individual recipient.
50.23(d)(1)(viii) A written information sheet will be provided	(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.
50.23(d)(1)(ix) Medical records will document this notification	(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.
50.23(d)(1)(x) Medical records will document receipt of drug	(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.
50.23(d)(1)(xi) Adequate follow up will be provided	(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.
50.23(d)(1)(xii) DOD is pursuing drug development with due diligence	(xii) DOD is pursuing drug development, including a time line, and marketing approval with due diligence.
50.23(d)(1)(xiii) FDA has approved subject to Presidential waiver	(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.
50.23(d)(1)(xiv) DOD will train medical personnel and recipients about drug	(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.
50.23(d)(1)(xv) DOD has set a time period, not to exceed one year	(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.
50.23(d)(1)(xvi) DOD must report changes to FDA and President	(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.
50.23(d)(1)(xvii) DOD will provide public notice	(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.
50.23(d)(1)(xviii) Use of the drug otherwise conforms to law	(xviii) Use of the investigational drug without informed consent otherwise conforms with applicable law.
50.23(d)(2) The IRB will include 3 members who are unaffiliated and not federal employees; a majority of unaffiliated members is preferable for quorum	(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.
50.23(d)(3) IRB must review and approve:	(3) The duly constituted institutional review board, described in paragraph (d)(1)(v) of this section, must review and approve:
50.23(d)(3)(i) The information sheet	(i) The required information sheet;
50.23(d)(3)(ii) Adequacy of plan to disseminate information	(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);
50.23(d)(3)(iii) Adequacy of information disseminated to providers	(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
50.23(d)(3)(iv) A consent form to be used if appropriate	(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.
50.23(d)(4) Summaries of IRB meetings to be submitted to FDA	(4) DOD is to submit to FDA summaries of institutional review board meetings at which the proposed protocol has been reviewed.
50.23(d)(5) FDA and DOD authority and obligations not preempted	(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]

50.24 Exception from informed consent requirements for emergency research.

	Section 50.25 Elements of informed consent.
50.25(a) Elements of consent:	(a) Basic elements of informed consent. In seeking informed consent, the following information shall be provided to each subject:
50.25(a)(1) Explanation of research	(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.
50.25(a)(2) Description of risks	(2) A description of any reasonably foreseeable risks or discomforts to the subject.
50.25(a)(3) Description of benefits	(3) A description of any benefits to the subject or to others which may reasonably be expected from the research.
50.25(a)(4) Alternative treatments	(4) A disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject.
50.25(a)(5) How confidential records will be maintained, FDA may inspect	(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.
50.25(a)(6) Compensation for injury (research involving more than minimal risk)	(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.
50.25 (a)(7) Whom to contact	(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.
50.25(a)(8) No penalty for refusal to participate	(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.
50.25(b) Additional elements may be required	(b) Additional elements of informed consent. When appropriate one or more of the following elements of information shall also be provided to each subject:
50.25(b)(1) Unforeseeable risks	(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.
50.25(b)(2) When investigator may terminate participation	(2) Anticipated circumstances under which the subject's participation may be terminated by the investigator without regard to the subject's consent.
50.25(b)(3) Additional costs	(3) Any additional costs to the subject that may result from participation in the research.
50.25(b)(4) Consequences of withdrawal	(4) The consequences of a subject's decision to withdraw from the research and procedures for orderly termination of participation by the subject.
50.25(b)(5) New findings will be provided	(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.
50.25(b)(6) Number of subjects in study	(6) The approximate number of subjects involved in the study.
50.25(c) Other laws may also apply	(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.
50.25(d) Physician’s authority to provide emergency medical care is not limited	(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.

	Section 50.27 Documentation of informed consent.
50.27(a) Consent must be documented unless explicitly waived. Subject signature required. Subject must receive a copy.	(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.
50.27(b) Consent form may be either:	(b) Except as provided in Section 56.109(c), the consent form may be either of the following:
50.27(b)(1) Full written consent with all required elements	(1) A written consent document that embodies the elements of informed consent required by Section 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.
50.27(b)(2) Short form consent Requirement for witness, additional signatures and copies	(2) A short form written consent document stating that the elements of informed consent required by Section 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.

	Subpart C--[Reserved]

	Subpart D --Additional Safeguards for Children in Clinical Investigations
50.50 IRB duties	Sec. 50.50 IRB duties. 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 .

50.51 Clinical investigations not involving greater than minimal risk.	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.

50.52 For clinical investigations involving greater than minimal risk but presenting the prospect of direct benefit to individual subjects, IRB must find and document that	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:
50.52(a) Risk is justified by benefit	(a) The risk is justified by the anticipated benefit to the subjects;
50.52(b) Anticipated benefit at least as great as alternatives	(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
50.52(c) Provisions will be made for assent and permission	(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.

50.53 For 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, the IRB must find and document:	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:
50.53(a) Risk is minor increase over minimal	(a) The risk represents a minor increase over minimal risk;
50.53(b) Experience commensurate with actual experience	(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;
50.53(c) Intervention likely to yield vitally important information	(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
50.53(d) Provisions will be made for assent and permission	(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.

50.54 Clinical investigations not otherwise approvable may proceed if:	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:
50.54(a) IRB finds and documents that the Investigation presents opportunity for further understanding	(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
50.54(b) The Commissioner determines that:	(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:
50.54(b)(1) Condition under a previous section are met, or	(1) That the clinical investigation in fact satisfies the conditions of Sec. 50.51, Sec. 50.52, or Sec. 50.53, as applicable, or
50.54(b)(2) These conditions are met:	(2) That the following conditions are met:
50.54(b)(2)(i) Investigation presents opportunity for further understanding	(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 ;
50.54(b)(2)(ii) Sound ethical principles will be followed	(ii) The clinical investigation will be conducted in accordance with sound ethical principles; and
50.54(b)(2)(iii) Provisions will be made for assent and permission	(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.

50.55 Requirements for permission by parents or guardians and for assent by children	Sec. 50.55 Requirements for permission by parents or guardians and for assent by children.
50.55(a) IRB must determine that provision fro assent by children are adequate	(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.
50.55(b) Factors for determining if children can 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.
50.55(c) Assent may not be required if IRB determines:	(c) The assent of the children is not a necessary condition for proceeding with the clinical investigation if the IRB determines:
50.55(c)(1) Children’s capability too limited	(1) That the capability of some or all of the children is so limited that they cannot reasonably be consulted, or
50.55(c)(2) Intervention holds prospect of important direct benefit	(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.
50.55(d) IRB may waive assent requirement if	(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:
50.55(d)(1) Investigation is minimal risk	(1) The clinical investigation involves no more than minimal risk to the subjects;
50.55(d)(2) Waiver will not adversely affect rights and welfare	(2) The waiver will not adversely affect the rights and welfare of the subjects;
50.55(d)(3) Investigation not otherwise practicable	(3) The clinical investigation could not practicably be carried out without the waiver; and
50.55(d)(4) Additional information will be provided to subjects	(4) Whenever appropriate, the subjects will be provided with additional pertinent information after participation.
50.55(e) IRB must determine if parental permission will be obtained	(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.
50.55(e)(1) IRB may find that permission of one parent is sufficient	(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.
50.55(e)(2) For some studies both parents must give permission, with some exceptions	(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.
50.55(f) Permission must be documented	(f) Permission by parents or guardians must be documented in accordance with and to the extent required by Sec. 50.27.
50.55(g) IRB determines whether and how assent must be documented	(g) When the IRB determines that assent is required, it must also determine whether and how assent must be documented.

50.56 Wards	Sec. 50.56 Wards.
50.56(a) Wards may be included in studies if the study is:	(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:
50.56(a)(1) Related to their status as wards	(1) Related to their status as wards; or
50.56(a)(2) Conducted in settings in which the majority of children are not wards	(2) Conducted in schools, camps, hospitals, institutions, or similar settings in which the majority of children involved as subjects are not wards.
50.56(b) An advocate must be appointed	(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.
50.56(b)(1) Advocate is in addition to any other guardian	(1) The advocate will serve in addition to any other individual acting on behalf of the child as guardian or in loco parentis.
50.56(b)(2) One person may be advocate for more than one child	(2) One individual may serve as advocate for more than one child.
50.56(b)(3) Advocate must have relevant experience	(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.
50.56(b)(4) Advocate must be independent of the 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.