Pu period of funding, but definite plans would not normally be set forth in the application or proposal. These include activities such as institutional type grants (including bloc grants) where selection of specific projects is ihe institution's responsibility; research training grants where the activities involving subjects remain to he selected; and projects in which human subjects’ involvement will depend upon completion of instruments, prior animal studies, or purification of compounds. These applications need not be reviewed by an IRB before an award may be made. However, except for research described in § 46.101(b}, no human subjects may be involved in any Project supported by these awards until the project has been reviewed and approved by the IRB, as provided in these regulations, and certification submitted to the Department. § 46.119 Research undertaken without the intention of involving human subjects, In the eveat research (conducted or funded by the Department) is undertaken without the intention of involving human subjects, but it is later proposed to use human subjects in the research, the research shall first be reviewed and approved by an IRB, a» provided in these regulations, 4 cerufication submitted to the Depacunent, and final approval given to the proposed change by the Department. $46,120 Evaluation and disposition af applications and proposals, (ai The Secretary will evaluate all applications and proposals involving human subjects submitted to the Department through such officers and employees of the Department and such experts and consultants as the Secretary determines to be appropriate. This evaluation will take into consideration the risks to the subjeets, the adequacy of protection against these risks, the potential benefits of the proposed research to PARC SS pS abit Ee the subjects and others, and the importance of the knowledge to be gained. (b) On the basis of this evaluation, the Secretary may approve or disapprove the application or Proposal, or enter into negotiations to develoy an approvable one. $46,121 Investigational new drug or device 3-day delay requirement. When an institution is required to Prepare or to submit a certification with an application or Proposal under these regulations, and the application OF proposal involves an investigational new drug (within the meaning of 21 U.S.C. 355(i) or 357(d)) of a significant risk device (as defined in 21 CFR 812.3(m)), the institution shall identify the drug or device in the certification. The institution shall also state whether the 30-day interval required for investigational new drugs by 21 CFR 312. ta) and for significant risk devices by 71 CFR 812.30 has elapsed, or whether the Food and Drug Adininistration has waived that requirement. If the 30-day interval has expired, the institution shall tute whether the Food and Drug Administration has requested that the Sponsor Continue to withhold or restrict the use of the drug or device in human subjects. [f the 30-day interval has not expired, and a waiver has not been received, the institution shall send a statement to the Department upon expiration of the interval, The Department will not consider a certification acceptable anti the institution has submitted a Statement that the 30-day interval has elapsed, and the Food and Drug Administration has not requested it to limit the use of the drug or device, or that the Food and Druw Administration has waived the 30-day interval. § 40.122 Use of Federal funds, Federal funds administered by the Department May Not be expended for research involving human subjects unless the requirement of these Sd lla ali aia FE IEE 8 BERS SEP SESAME EE IES ORE IRE AGE AD SIRS SEE AAR EN ESE BO A SRE NT) A PD PAI lial A PO SOE regulations, including all subparts of these regulations, have been satisfied. § 46.123 Early termination of research funding; evatuation of subsequent applications and proposals. (a) The Secretary may require that Department funding for any project be terminated or suspended in the manner prescribed in applicable Program requirements, when the Secretary finds an institution has materially failed to comply with the terms of these regulations. (b) In making decisions about funding applications or proposals covered by these regulations the Secretary may take into account, in addition to all other cligibility requirements and program criteria, factors such as whether ihe applicant has been subject to a termination or suspension under paragraph (a) of this section and whether the applicant or the person who would direct the scientific and technical aspects of an activity has in the judgment of the Secretary materially failed to discharge responsibility for the protection of the rights and welfare of human subjects (whether or not Department funds were involved). } 46.124 Conditions. With respect to any research Pruject or any class of research projecis the Secretary may impose additional conditions prior to or at the lime of funding when in the Secretary's judgment additional conditions are necessary for the Protection of human subjects. Subpart B--- Additional Protections Pertaining to Research Development, and Related “Activitles Involving Fetuses, * Pregnant Women, and Human tn Vitro Fertilization’ Souwcn: 40 FR W358, Aup 8, 1974. 49 FR (758, Januare ff, 1978, 42 ER SESS9, November 3, [u7K § 46.201 Applicability, (a) The regulations in this subpart are applicable to all Departmen: of Health, Education, and Welfare Approved For Release 2000/08/08 : CIA-RDP96-00788R001500140003-9
a HEGLas. deve) LRM RE FUR das ta PEF a TR ts HIROTA Rae SB atl TT RSE © Fa Ee OR Sa ee TE Approved For Release 2000/08/08 : CIA-RDP96-00788R001500140003-9 _ Page 2 hae emreran A en ean etree en prants and contract supporting research, development, and related actividies involving: (1) The fetus, (2) pregnant women, and (3) human iv vitro ferulization, (b) Nothing in this subpart shall be construed as indicating that compliance with the procedures set forth herein will in any way render inapplicable pertinent State or local liws bearing upon activities covered by this subpart. (c) The requirements of this subpart are in addition to those imposed under the other subparts of this part. § 46.202 Purpose. It is the purpose of this subpart to provide additional safeguards in reviewing activities to which this subpart is applicable to assure that they conform to appropriate ethical standards and relate to important societal needs. 446.203 Definitions. AS used in this subpart: (a) ‘*Secretary'' means the Secretary of Health, Education, and Welfare and any other officer or employee of the Department of Health, Education, and Welfare to whom authority has been delegated. (b} *‘Pregnancy’" encompasses the period of time from confirmation of inplantatton (through any of the presumptive signs of pregnancy, such ts missed menses, or by a medically acceptable pregnancy test), until expulsion or extraction of the fetus. (c) **Fetus"’ means the product of conception from the time of implantation (as evidenced by any of the presumptive signs of pregnancy, such as missed menses, of a medically acceptable pregnancy test), until a determination is made, tollowing explusion or extraction of the fetus, that itis viable. (d) ‘Viable’ as it pertains to the te‘us means betng able, after either spontaneous or induced delivery, to survive (given the benefit of available medical therapy) to the point of independently maintaining heart beat and respiration. The Secretary may fron: time to time, taking into account medical advances, publish in the PENERAL REGISTER puidelines to assist in determining whether a fetus is viable for purposes of this subpart. If a fetus is viable after delivery, it is a premature infant. (e) ‘‘Nonviable fetus’ means a Fetus ex uiero which, although living, is not viable, () “Dead fetus’' means a fetus ex utere which exhibits neither heartbeat, spontaneous respiratory activity, spomtaneous movement of voluntary muscles, nor pulsation of the umbilical cord (if still attached). (2) ‘dn vitro fertilization” means any fertilization of human ova which occurs outside the body of a female, either through admixture of donor human sperm and ova or by any other means, - § 46.204 “Ethical Advisory” Boards. | (a) One of more Ethical Advisory Boards shall be established by the Secretary. Members of these board(s) shali be so selected that the board(s) will be competent to deal with medical, legal, social, ethical, and related issues and may inctude, for example, research scientists, physicians, psychologists, sociologists, educators, lawyers, and ethicists, as well as represcntatives of the general public. No board member may be a repular, full-time employee of the Department of Health, Education, and Welfare. (b) At the request of the Secretary, the Ethical Advisory Board shall render advice consistent wiih the policies and requirements of this Part as to ethical issues, involving activities covered by this subpart, raised by individual applications or proposals. In addition, upon request by the Secretary, the Board shall render advice as to classes of applications or proposals and veneral polictes, guidelines, and procedures. (c) A Board may establish, with the approval of the Secretary, classes of applications or proposals which: 45 CFR 46 etn ma PROS ota met eeu nce mete env eS the ET eck eh eR toa ema re aero pep (13 Must be submitted to the Board, or (2) need not be submitted to the Board, Where the Board so establishes a class of applications or proposals which must be submitted, no application or proposal within the class may be funded by the Department or any component thereof until the application or proposal has been reviewed by the Board and the Board has rendered advice as to its acceptability from an ethical standpoint. (d) No application or proposai involving human in vitro fertilization may be funded by the Department or any component thercof until the application or proposal has been reviewed by the Ethical Advisory Board and the Board has rendered advice ag to its acceptability from an ethical standpoint. §46.205 Additional duties of the Institutional Review Boards in connection with activities involving fetuses, pregnant women, or human in vitro fertilization, (a) In addition to the responsibilities prescnbed for Institutional Review Boards under Subpart A of this part, the applicant's or offeror's Board shall, with respect to activities covered by this subpart, carry aut the following additional duties: (1) Determine that all aspects of the activity meet the requirements of thts subpari: (2) Determine that adequate consideration has been given to the manner in which potential subjects will be selected, and adequate provision has been made by the _ applicant or offeror for monitoring the actual informed consent process (e.g., through such mechanisms, when appropriate, as participation by the Institutional Review Board ar subject advocates int (i) Oversecing the actual process by which individual consents required by this subpart are secured cither by approving induction of each individual into the activity or Approved For Release 2000/08/08 : CIA-RDP96-00788R001500140003-9 © =
4s‘ CNpproved For Release 2000/08/08 : CIA-RDP96-00788R001500140003-9 cect de AAU ct AAR ee MERTEN! hE tN SRNR IA fl dats nia pore te rE Prenat ein deen lL verifying, perhaps through sampling, _that approved procedures for induction of individuals into the activily are being followed, and (ii) monitoring the progress of the activity and intervening as necessary through such steps as visits to the activity site and continuing evaluation to determine if any unanticipated risks have arisen), (3) Carry out such other responsibilities as may be assigned by the Secretary. (b) No award may be issued until the applicant or offeror has certified to the Secretary that the Institutional Review Board has made the deterniinations required under paragraph (a) of this section and the Secretary has approved these determinations, as provided in § 46.120 of Subpart A of this pari. ic) Applicants or offerors seeking support for activities covered by this subpart must provide for the designation of an (nstitutional Review Board, subject to approval by the Secretary, where no such Board has heen established under Subpart A of this part, § 46.206 General limitations. (a} No activity to which this subpart is applicable may be undertaken unless: (1) Appropriate studies on animals end nonpregnant individuals have heen completed; (2) Excepi where the purpose of the activity is to meet the health needs of the mother or the particular fetus, the risk to the fetus is minimal and. in all cases, is the least possible risk for achieving the objectives of the activity, (3) Individuals engaged in the acuity will have ao part int (i) Any decisions as to the timing, method, ang procedures used to terminate the pregnancy, and (ii) determining the viability of the fetus at the tenmination of the pregnancy; and (4) No procedural changes which may cause greater (han minimal risk to the fetus or the pregnant woman will he introduced into the procedure for terminating the pregnancy solely in the interest of the activity. (b) No inducements, monetary or otherwise, may be offered to terminate pregnancy for purposes of the activity, 140 FR 33528, Aug. 8. 1975, as amended at 40 FR 51638. Nov. 6, 1975] § 46.207 Activities directed toward pregnant women as subjects. (a) No pregnant woman may be involved as a subject in an activity covered by this subpart unless: (1) The purpose of the activity is to meet the health needs of the mother and the fetus will be placed at risk only to the minimum exient necessary to meet such needs, or (2) the risk to the fetus is minimal. (b) An activity permitted under Paragraph (a) of this section may be conducted only if the mother and father are legally competent and have given their informed consent after having heen fully informed regarding possible imipact on the fetus, except that the father's informed consent need not be secured if: (1) The purpose of the activity is to meet the health needs of the mother; (2) his identity or whereabouts cannot reasonably be ascertained: (3) he is not reasonably available: or (4) the pregnancy resulted from rape. § 46.208 Activities directed toward fetuses in utero as subjects. (a) No fetus in utero may be involved as a subject in any activity covered by this subpart unless: (1) The purpose of the activity is to meet the health needs of the particular fetus and the fetus will be placed at risk only to the minimum extent necessary to meet such needs, or (2) the risk to the fetus imposed by the research is minimal and the purpose of the activily is the development of important biomedical knowledge which cannot be obtained by other means, (b) An activity permitted under paragraph (2) of this section may be conducted only if the mother and co Raa ber Te ne a cae Se Ck Se eM Mm A RAPE te ire se oR Pe RB ae Page 13 father are legally competent and have given their informed consent, except that the father’s consent need not be secured if: (1) His identity or whereabouts cannot reasonably be ascertained, (2) he is not reasonably available, or (3) the pregnancy resulted from rape. § 46.209 Activities directed toward fetuses ex utero, including nonviable fetuses, as subjects. (a) Until it has been ascertained whether or not a fetus ex utero is Viable, a fetus ex utero may not be involved as a subject in an activity covered by this subpart unless: (1) There will be no added risk to the fetus resulting from the activity, and the purpose of the activity is the development of important biomedical knowledge which cannot be obtained by other means, of (2) The purpose of the activity is to enhance the possibility of survival of the particular fetus to the point of viability. (b) No nonviable fetus may be involved as a subject in an activity covered by this subpart unless: (1) Vital fuactions of the fetus will not be artificially maintained, (2) Experimenta! activities which of themselves would terminate the hearibeat or respiration of the fetus will not be employed, and (3) The purpose of the activity is the development of important biomedical knowledge which cannot be obtained by other means. (c) In the event the fetus ex utero is found to be viable, it may be included as a subject in the activity only fo the extent permitted by and in accordance with the requirements of others subparts of this part. (d) An activity permitted under paragraph (a) or (b) of this section may be conducted only if the mother and tather are legally competent and have given their informed consent, except that the father’s informed consent need nat be secured if: (1) his idenuty or whereabouts cannot reasonably be ascertained, (2) he is Approved For Release 2000/08/08 : CIA-RDP96-00788R001500140003-9
"Pog bproved For Release 2000/08/08 : CIA-RDP96-00788R001500140003-9 ser not reasonably available, or (3) the pregnancy resulted from rape. § 46.210 Activities invoiving the dead fetus, fetal material, or the placenta, Activities involving the dead fetus, mascerated fetal material, or cells, iissue, oF organs excised from a dead fetus shall be conducted only in accordance with any applicable Strate or local laws regarding such activities. $46.21 Modification or waiver of specific requirements. Upon the request of an applicant or offeror (with the approval of its Institutional Review Board), the Secretary may modify or waive specific requirements of this subpart, with the approval of the Ethical Advisory Board after such opportunity for public comment as the Ethical Advisory Board considers appropriate in the particular instance. in making such decisions, the Secretary will consider whether the risks to the subject are so outweighed by the sum of the benefit to the subject and the importance of the hnowdedee to be gained as to warrant such modification of waiver und that such benefits cannot be gained except through a modification or waiver. : Any such modifications or waivers wil be published as nutices in the FrDERAL REGISTER Subpart C—Additional Protections Pertaining to Biomedical and Behavioral Research Involving Prisoners as Subjects : Sairce: 43 FR $3655, Nov La, 4 46.301 Applicability. (a) The regulations in this subpart are applicable to all biomedical and behavioral research conducted or supported by the Department of Health, Educanon, and Welfare Involving prisoners as subjects. (b) Nothing in this subpart shall be cunstrued as indicating that cormpliance with the procedures set forth herein will authorize research involving prisoners as subjects, to the eatene such research is limited or [97s barred by applicable State or local law, (c) The requirements of this subpart are in addition to those imposed under the other subparts of this part, § 46.302 Purpose. Inasmuch as prisoners may be under constraints because of their incarceration which could affect their ability to make a truly voluntary and uncoerced decision whether or not to Participate as subjects in research, it is the purpose of this subpart to provide additional safeguards for the protection of prisoners involved in acttvitics to which this subpart is applicable. § 46.303 Definitions. As used in this subpart: (a) “*‘Seeretary'* means the Secretary of Health, Education, and Welfare and any other officer or employee of the Department of Health, Education, and Welfare to whom authority has been deleyated. (>) “DHEW"' means the Department of Health, Education, and Welfare. (c) ‘*Prisoner’’ means any ‘hidividual involuntarily confined of detained | in a penal institution. The term is intended ‘to enconipass © individuals sentenced to such an institution under a criminal or civil “statute, individuals ‘detained i in other fac ilities by virtue of statutes or | ‘commitment, procedures which ‘Provide: alternatives to crirainal: prosecution, or incarceration in’a >penal institution, and individuals detained pending arraignment, trial, OF sentencing. (d) ° ‘Minimal risk" is the probability and magnitude of physical or psychological hurm that is normally encountered in the daily lives, or in the routine medical, dental, oF Psychological examination of healthy persons. § 46.304 Composition of Institutional Review Boards where prisoners are involved, In addition to satisfying the : CORRES SNS A | TR ee YS 45 CFR 46 Send SADR cai amromeemi requirements in § 46.107 of this part, an Institutional Review Board, carrying out responsibilities under this part with respect to research covered by this subpart, shal! aiso meet the following specific requiremenis: (a) A majority of the Board... or (exclusive. of j (Prisoner members) shai? have no association with the prison(y involved, apart from their” membership on the Board! og) (b) At least one e member of the4 Board shall be a prisoner , OF re pridoaer, fepresentative with! a appropriate background and ing experience to serve in that capacity, except that where a particular research project is reviewed by more than one Board caly one Board need satisfy this requirement. a § 46.305 Addliional duties of the Institutional Keview Hoards where prisoners are involved, (a) In addition to all other responsibilities prescribed for Institutional Review Boards under this part, the Board shall review research covered by this subpart and approve such research only if it finds that: (1) The research under review represents one of the categories of research permissible under § 46.306(a)(2), (2) Ay possible advantages accruing to the prisoner through his or her participation in the research, when compared to the general living conditions, medical care, quality of food, amenities and opportunity for earnings in the prison, are not of such @ Magnitude that bis or her ability to, . weigh the risks of the research against., the value of such advantages i in the limited choice environment of the prison is impaired; (3) The risks involved in the research are commensurate with risks that would be accepted by nonprisoner volunteers: @0 (4) Procedures for the selection of subjects within the prison are fair to ® Approved For Release 2000/08/08 : CIA-RDP96-00788R001500140003-9