[Federal Register Volume 62, Number 217 (Monday, November 10, 1997)]
[Notices]
[Pages 60604-60607]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-29651]



[[Page 60603]]

_______________________________________________________________________

Part III





Department of Health and Human Services





_______________________________________________________________________



Food and Drug Administration



National Institutes of Health



_______________________________________________________________________



Protection of Human Subjects: Suggested Revisions to the Institutional 
Review Board (IRB) Expedited Review List; Request for Comments; Notice

Federal Register / Vol. 62, No. 217 / Monday, November 10, 1997 / 
Notices

[[Page 60604]]



DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration
[Docket No. 97N-0447]


Protection of Human Subjects: Suggested Revisions to the 
Institutional Review Board (IRB) Expedited Review List; Request for 
Comments

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA), in consultation with 
the Office for Protection from Research Risks (OPRR), is requesting 
written comments relating to the proposed republication of the 
Expedited Review List that identifies certain research involving human 
subjects that may be reviewed by the Institutional Review Board (IRB) 
through the expedited review procedures authorized in FDA's 
regulations. Since the list was created, significant advances have been 
made in medicine and biological technology such that it is appropriate 
to consider revising this list to include additional categories of 
research. FDA seeks information and suggestions from the research 
community and the public on possible revisions to the Expedited Review 
List. The proposed list included in this notice is for discussion 
purposes only. FDA and OPRR will consider the comments received in 
deciding whether to revise the list.

DATES: Submit written comments on or before March 10, 1998.
ADDRESSES: Submit written comments to Dockets Management Branch (HFA-
305), Food and Drug Administration, 12420 Parklawn Dr., rm. 1-23, 
Rockville, MD 20857. Because FDA and OPRR are simultaneously publishing 
identical lists, comments need not be sent to both agencies.

FOR FURTHER INFORMATION CONTACT: Paul W. Goebel, Office of Health 
Affairs (HFY-20), Food and Drug Administration, 5600 Fishers Lane, 
Rockville, MD 20857, 301-827-1685.

SUPPLEMENTARY INFORMATION: FDA's regulations for protection of human 
subjects can be found under part 50 (21 CFR part 50), and the 
regulations for IRB's under part 56 (21 CFR part 56). The regulations 
require, with limited exceptions, review of research involving human 
subjects by an IRB and obtaining and documenting legally effective 
informed consent for all human subjects of research.
    Section 56.110 provides for expedited review procedures for certain 
kinds of research involving no more than minimal risk, and for minor 
changes in previously approved research during the period for which 
approval is authorized. In the Federal Register of January 26, 1981 (46 
FR 8392), FDA published the Expedited Review List that is referenced in 
Sec. 56.110(a), which is a list of categories of research that could be 
reviewed by an IRB through the expedited review procedures set forth in 
FDA's regulations. In the Federal Register of January 27, 1981 (46 FR 
8980), a separate Expedited Review List is referenced in 45 CFR part 46 
that applies to matters under the Department of Health and Human 
Services' (HHS) jurisdiction was published. The HHS and FDA lists that 
published in 1981 differ slightly, in that item 9 on the 1981 HHS list 
pertains only to 45 CFR 46.110. Because behavioral research was not 
regulated by FDA, that category was not included in the list published 
by FDA in 1981, which is reproduced here to facilitate comparison with 
the proposed list.

Current List: Items Included in the List Published in 1981

    The current (1981) list allows an IRB to utilize the expedited 
review procedure for research activities involving no more than minimal 
risk and in which the only involvement of human subjects will be in one 
or more of the following categories (carried out through standard 
methods):
    (1) Collection of hair and nail clippings, in a non-disfiguring 
manner; deciduous teeth; and permanent teeth if patient care 
indicates a need for extraction.
    (2) Collection of excreta and external secretions including 
sweat, uncannulated saliva, placenta at delivery, and amniotic fluid 
at the time of rupture of the membrane prior to or during labor.
    (3) Recording of data from subjects who are 18 years of age [of] 
older using noninvasive procedures routinely employed in clinical 
practice. This includes the use of physical sensors that are applied 
either to the surface of the body or at a distance and do not 
involve input of matter or significant amounts of energy into the 
subject or an invasion of the subject's privacy. It also includes 
such procedures as weighting, electrocardiography, 
electroencephalography, thermography, detection of naturally 
occurring radioactivity, diagnostic echography, and 
electroretinography. This category does not include exposure to 
electromagnetic radiation outside the visible range (for example, x-
rays, microwaves).
    (4) Collection of blood samples by venipuncture, in amounts not 
exceeding 450 milliliters in an eight-week period and no more often 
than two times per week, from subjects who are 18 years of age or 
older and who are in good health and not pregnant.
    (5) Collection of both supra- and subgingival dental plaque and 
calculus, provided the procedure is not more invasive than routine 
prophylactic scaling of the teeth and the process is accomplished in 
accordance with accepted prophylactic techniques.
    (6) Voice recordings made for research purposes such as 
investigations of speech defects.
    (7) Moderate exercise by healthy volunteers.
    (8) The study of existing data, documents, records, pathological 
specimens, or diagnostic specimens.
    (9) Research on drugs or devices for which an investigational 
new drug exemption or an investigational device exemption is not 
required.
    FDA, in consultation with OPRR, is proposing to revise the current 
Expedited Review List to include additional procedures or categories of 
research that may be reviewed under the expedited review procedure. FDA 
seeks comments from the public on procedures or categories of research 
involving human subjects that may be amenable to expedited review in 
accordance with the procedures outlined in Sec. 56.110(b), instead of 
review at a convened meeting of the IRB. The proposed list is being 
published for discussion purposes only. FDA and OPRR intend to 
determine, after review of comments received, whether any changes 
should be made to the current list. FDA and OPRR have not determined 
that the suggested additional categories of research in the proposed 
list are appropriate for expedited review procedures. The proposed list 
does not bind FDA or OPRR to include any of the suggested categories in 
a list that is expected to be published after review of comments.
    The following is a proposed revision of the current Expedited 
Review Lists published in the Federal Register of January 26, 1981 (46 
FR 8392), and January 27, 1981 (46 FR 8980). In order to simplify 
review, the proposed revision is identical to the list published 
elsewhere in this issue of the Federal Register by OPRR. Judgment is 
reserved on whether FDA and OPRR will publish identical lists after 
comments are received and reviewed. FDA welcomes and encourages 
comments from the research community and the public.

Proposed List: Research Activities Which May Be Reviewed Through 
Expedited Review Procedures \1\
---------------------------------------------------------------------------

    \1\ The expedited review procedure consists of a review of 
research involving human subjects by the IRB chairperson or by one 
or more experienced reviewers designated by the chairperson from 
among members of the IRB in accordance with the requirements set 
forth in Sec. 56.110.
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    Research activities (carried out through standard methods) that: 
(1) Involve no more than minimal risk, and

[[Page 60605]]

(2) appear in one or more of the following categories may be reviewed 
by the IRB through the expedited review procedure authorized in 45 CFR 
46.110 and Sec. 56.110. The activities that appear on this list should 
not be deemed to be of minimal risk simply because they are included on 
this list. Appearance on this list merely means that the activity is 
eligible for review through the expedited process when the specific 
circumstances of the proposed research involve no more than minimal 
risk to the human subjects. The categories in this list apply 
regardless of the age of subjects, except as noted.
(1) Research on drugs or devices for which an investigational new drug 
exemption or an investigational device exemption is not required.
(2) Collection of blood samples by finger stick or venipuncture as 
follows:
    (a) From healthy, nonpregnant adults \2\ who weigh at least 110 
pounds (lb), in amounts not exceeding 550 milliliters (mL) in an 8-week 
period and no more than 2 times per week.
---------------------------------------------------------------------------

    \2\ Throughout this document, when FDA refers to ``adult,'' FDA 
defers to state law for determining the age of majority.
---------------------------------------------------------------------------

    (b) From healthy, pregnant adults who weigh at least 110 lb, in 
amounts not exceeding 100 mL in an 8-week period and no more than 2 
times per week.
    (c) From healthy children, in amounts not exceeding 3 mL/kilograms 
(kg) in an 8-week period and no more than 2 times per week.
    (d) From medically vulnerable adults who weigh at least 110 lb, in 
amounts not exceeding 50 mL in an 8-week period and no more than 2 
times per week.
(3) Prospective collection for research purposes of the following 
biological specimens:
    (a) Hair and nail clippings in a nondisfiguring manner.
    (b) Deciduous teeth at time of exfoliation, or if routine patient 
care indicates a need for extraction.
    (c) Permanent teeth if routine patient care indicates a need for 
extraction.
    (d) Excreta and external secretions (including sweat).
    (e) Uncannulated saliva collected either in an unstimulated fashion 
or stimulated by chewing gumbase or wax or by applying a dilute citric 
solution to the tongue.
    (f) Placenta removed at delivery.
    (g) Amniotic fluid obtained at the time of rupture of the membrane 
prior to or during labor.
    (h) Supra-and subgingival dental plaque and calculus, provided the 
collection procedure is not more invasive than routine prophylactic 
scaling of the teeth and the process is accomplished in accordance with 
accepted prophylactic techniques.
    (i) Stool cultures obtained by rectal swab.
    (j) Mucosal and skin cells collected by buccal scraping or swab, 
skin swab, or mouth washings.
    (k) Sputum collected after saline mist nebulization.
(4) Research involving existing identifiable data, documents, records, 
or biological specimens (including pathological or diagnostic 
specimens) where these materials, in their entirety, have been 
collected prior to the research, for a purpose other than the proposed 
research.
(5) Research involving solely (a) prospectively collected identifiable 
residual or discarded specimens, or (b) prospectively collected 
identifiable data, documents, or records, where (a) or (b) has been 
generated for nonresearch purposes.
(6) Collection of data through use of the following procedures:
    (a) Noninvasive procedures routinely employed in clinical practice 
and not involving exposure to electromagnetic radiation outside the 
visible range (i.e., not involving x-rays, microwaves, etc.).
    (b) Physical sensors that are applied either to the surface of the 
body or at a distance and do not involve input of significant amounts 
of energy into the subject or an invasion of the subject's privacy.
    (c) Weighing, testing sensory acuity, electrocardiography, 
electroencephalography, thermography, detection of naturally occurring 
radioactivity, electroretinography, echography, sonography, ultrasound, 
magnetic resonance imaging (MRI), diagnostic infrared imaging, doppler 
blood flow, and echocardiography.
    (d) Moderate exercise, muscular strength testing, body composition 
assessment, and flexibility testing involving healthy subjects.
(7) Collection of data from voice, video, or image recordings made for 
research purposes where identification of the subjects and/or their 
responses would not reasonably place them at risk of criminal or civil 
liability or be damaging to the subjects' financial standing, 
employability, or reputation.
(8) Research on individual or group characteristics or behavior 
(including but not limited to research involving perception, cognition, 
surveys, interviews, and focus groups) as follows:
    (a) Involving adults, where (i) the research does not involve 
stress to subjects, and (ii) identification of the subjects and/or 
their responses would not reasonably place them at risk of criminal or 
civil liability or be damaging to the subjects' financial standing, 
employability, or reputation.
    (b) Involving children, where (i) the research involves neither 
stress to subjects nor sensitive information about themselves, or their 
family; (ii) no alteration or waiver of regulatory requirements for 
parental permission has been proposed; and (iii) identification of the 
subjects and/or their responses would not reasonably place them or 
their family members at risk of criminal or civil liability or be 
damaging to the financial standing, employability, or reputation of 
themselves or their family members.
(9) Research previously approved by the convened IRB as follows:
    (a) Where (i) the research is permanently closed to the enrollment 
of new subjects; (ii) all subjects have completed all research-related 
interventions; and (iii) the research remains active only for long-term 
follow-up of subjects; or
    (b) Where the research remains active only for the purposes of data 
analysis; or
    (c) Where the IRB has determined that the research involves no 
greater than minimal risk and no additional risks have been identified; 
or
    (d) Where no subjects have been enrolled and no additional risks 
have been identified.
    The following tabulation of changes is included to enable readers 
to more easily compare the categories of research included in both 
lists.

[[Page 60606]]



          Comparison of the Proposed List With the Current List         
------------------------------------------------------------------------
                                       1981 (Current) Expedited Review  
   Proposed Expedited Review List                    List               
------------------------------------------------------------------------
1. Research on drugs or devices for  Unchanged; currently number 9.     
 which an investigational new drug                                      
 exemption or an investigational                                        
 device exemption is not required.                                      
                                                                        
2. Collection of blood samples by    Currently number 4, limited to     
 finger stick or venipuncture as      venipuncture; ``finger stick'' not
 follows:                             included.                         
                                                                        
(a) From healthy, nonpregnant        Amounts currently limited to 450   
 adults, in amounts not exceeding     ml.                               
 550 mL in an 8-week period and no                                      
 more than 2 times per week.                                            
                                                                        
(b) From healthy, pregnant adults,   Not included.                      
 in amounts not exceeding 100 mL in                                     
 an 8-week period and no more than                                      
 2 times per week.                                                      
                                                                        
(c) From healthy children, in        Not included.                      
 amounts not exceeding 3 mL/kg in                                       
 an 8-week period and no more than                                      
 2 times per week.                                                      
                                                                        
(d) From medically vulnerable        Not included.                      
 adults, in amounts not exceeding                                       
 50 mL in an 8-week period and no                                       
 more than 2 times per week.                                            
                                                                        
3. Prospective collection for        ``Prospective'' and ``for research 
 research purposes of the following   purposes'' currently not included.
 biological specimens:                                                  
                                                                        
(a) Hair and nail clippings in a     Currently part of number 1;        
 nondisfiguring manner.               unchanged.                        
                                                                        
(b) Deciduous teeth at time of       Currently part of number 1;        
 exfoliation, or if routine patient   ``deciduous teeth'' included      
 care indicates a need for            without qualifiers.               
 extraction.                                                            
                                                                        
(c) Permanent teeth if routine       Currently part of number 1;        
 patient care indicates a need for    ``routine'' not included.         
 extraction.                                                            
                                                                        
(d) Excreta and external secretions  Currently part of number 2;        
 (including sweat).                   unchanged.                        
                                                                        
(e) Uncannulated saliva collected    Currently part of number 2;        
 either in an unstimulated fashion    ``uncannulated saliva'' included  
 or stimulated by chewing gumbase     without qualifiers.               
 or wax or by applying a dilute                                         
 citric solution to the tongue.                                         
                                                                        
(f) Placenta removed at delivery.    Currently part of number 2;        
                                      unchanged.                        
                                                                        
(g) Amniotic fluid obtained at the   Currently part of number 2;        
 time of rupture of the membrane      unchanged.                        
 prior to or during labor.                                              
                                                                        
(h) Supra- and subgingival dental    Currently number 5; ``procedure''  
 plaque and calculus, provided the    is not qualified with the word    
 collection procedure is not more     ``collection.''                   
 invasive than routine prophylactic                                     
 scaling of the teeth and the                                           
 process is accomplished in                                             
 accordance with accepted                                               
 prophylactic techniques.                                               
                                                                        
(i) Stool cultures obtained by       Not included.                      
 rectal swab.                                                           
                                                                        
(j) Mucosal and skin cells           Not included.                      
 collected by buccal scraping or                                        
 swab, skin swab, or mouth                                              
 washings.                                                              
                                                                        
(k) Sputum collected after saline    Not Included.                      
 mist nebulization.                                                     
                                                                        
4. Research involving existing       Currently number 8; stated as:     
 identifiable data, documents,        ``The study of existing data,     
 records, or biological specimens     documents, records, pathological  
 (including pathological or           specimens, or diagnostic          
 diagnostic specimens) where these    specimens.``                      
 materials, in their entirety, have                                     
 been collected prior to the                                            
 research, for a purpose other than                                     
 the proposed research.                                                 
                                                                        
5. Research involving solely (a)     Not included.                      
 prospectively collected                                                
 identifiable residual or discarded                                     
 specimens, or (b) prospectively                                        
 collected identifiable data,                                           
 documents, or records, where (a)                                       
 or (b) has been generated for                                          
 nonresearch purposes.                                                  
                                                                        
6. Collection of data through use    Currently number 3; ``recording''  
 of the following procedures:         instead of ``collection.''        
                                                                        
(a) Noninvasive procedures           Currently number 3; limited to     
 routinely employed in clinical       subects 18 years of age or older. 
 practice and not involving                                             
 exposure to electromagnetic                                            
 radiation outside the visible                                          
 range (i.e., not involving x-rays,                                     
 microwaves, etc.).                                                     
                                                                        
(b) Physical sensors that are        Currently number 3; limited to     
 applied either to the surface of     subjects 18 years of age or older.
 the body or at a distance and do                                       
 not involve input of significant                                       
 amounts of energy into the subject                                     
 or an invasion of the subject's                                        
 privacy.                                                               
                                                                        

[[Page 60607]]

                                                                        
(c) Weighing, testing sensory        Currently number 3; limited to     
 acuity, electrocardiography,         subjects 18 years of age or older;
 electroencephalography,              limited echography to ``diagnostic
 thermography, detection of           echography''; does not include    
 naturally occurring radioactivity,   ``sonography, ultrasound, magnetic
 electroretinography, echography,     resonance imaging (MRI),          
 sonography, ultrasound, magnetic     diagnostic infrared imaging,      
 resonance imaging (MRI),             doppler blood flow, and           
 diagnostic infrared imaging,         echocardiography.''               
 doppler blood flow, and                                                
 echocardiography.                                                      
                                                                        
(d) Moderate exercise, muscular      Currently number 7; limited to     
 strength testing, body composition   ``Moderate exercise by healthy    
 assessment, and flexibility          volunteers.''                     
 testing involving health subjects.                                     
                                                                        
7. Collection of data from voice,    Currently number 6; stated as:     
 video, or image recordings made      ``Voice recordings made for       
 for research purposes where          research purposes such as         
 identification of the subjects and/  investigations of speech          
 or their responses would not         defects.''                        
 reasonably place them at risk of                                       
 criminal or civil liability or be                                      
 damaging to the subjects'                                              
 financial standing, employability,                                     
 or reputation.                                                         
                                                                        
8. Research on individual or group   Not included.                      
 characteristics or behavior                                            
 (including but not limited to                                          
 research involving perception,                                         
 cognition, surveys, interviews,                                        
 and focus groups) as follows:                                          
                                                                        
(a) Involving adults, where (i) the                                     
 research does not involve stress                                       
 to subjects, and (ii)                                                  
 identification of the subjects and/                                    
 or their responses would not                                           
 reasonably place them at risk of                                       
 criminal or civil liability or be                                      
 damaging to the subjects'                                              
 financial standing, employability,                                     
 or reputation.                                                         
                                                                        
(b) Involving children, where (i)                                       
 the research involves neither                                          
 stress to subjects nor sensitive                                       
 information about themselves, or                                       
 their family; (ii) no alteration                                       
 or waiver of regulatory                                                
 requirements for parental                                              
 permission has been proposed; and                                      
 (iii) identification of the                                            
 subjects and/or their responses                                        
 would not reasonably place them or                                     
 their family members at risk of                                        
 criminal or civil liability or be                                      
 damaging to the financial                                              
 standing, employability, or                                            
 reputation of themselves or their                                      
 family members.                                                        
                                                                        
9. Research previously approved by   Not included.                      
 the convened IRB as follows:                                           
                                                                        
(a) Where (i) the research is                                           
 permanently closed to the                                              
 enrollment of new subjects; (ii)                                       
 all subjects have completed all                                        
 research-related interventions;                                        
 and (iii) the research remains                                         
 active only for long-term follow-                                      
 up of subjects; or                                                     
                                                                        
(b) Where the research remains                                          
 active only for the purposes of                                        
 data analysis; or                                                      
                                                                        
(c) Where the IRB has determined                                        
 that the research involves no                                          
 greater than minimal risk and no                                       
 additional risks have been                                             
 identified; or                                                         
                                                                        
(d) Where no subjects have been                                         
 enrolled and no additional risks                                       
 have been identified.                                                  
------------------------------------------------------------------------


    Dated: November 4, 1997.
William K. Hubbard,
Associate Commissioner for Policy Coordination.
[FR Doc. 97-29651 Filed 11-5-97; 3:51 pm]
BILLING CODE 4160-01-F