CFR part 56 Institutional review boards

8/7/2019 CFR part 56 Institutional review boards

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2358 Federal Register / Vol. 74, No. 10/ Thursday, January 15, 2009 / Rules and Regulations

party listed in Appendix A to 31 CFRChapter V with the bracketed suffix[NPWMD] of an item subject to the EAR.If OFAC authorizes an export from theUnited States or an export or reexportby a U.S. person to a party listed inAppendix A to 31 CFR Chapter V withthe bracketed suffix [NPWMD], suchauthorization constitutes authorization

for purposes of the EAR as well.(ii) U.S. persons must seek

authorization from BIS for the export orreexport to a party listed in AppendixA to 31 CFR Chapter V with thebracketed suffix [NPWMD] of any itemsubject to the EAR that is not subject toOFACs regulatory authority pursuant toExecutive Order 13382.

(iii) Non-U.S. persons must seekauthorization from BIS for any exportfrom abroad or reexport to a party listedin Appendix A to 31 CFR Chapter Vwith the bracketed suffix [NPWMD] ofany item subject to the EAR.

(iv) Any export or reexport to a partylisted in Appendix A to 31 CFR ChapterV with the bracketed suffix [NPWMD] ofany item subject to the EAR and notauthorized by OFAC is a violation of theEAR.

(v) Any export or reexport by a U.S.person to a party listed in Appendix Ato 31 CFR Chapter V with the bracketedsuffix [NPWMD] of any item subject tothe EAR that is not subject to regulationby OFAC and not authorized by BIS isa violation of the EAR. Any export fromabroad or reexport by a non-U.S. personto a party listed in Appendix A to 31CFR Chapter V with the bracketed suffix[NPWMD] of any item subject to theEAR and not authorized by BIS is aviolation of the EAR.

(3) Relation to other EAR licenserequirements. The license requirementsin this section supplement any otherrequirements set forth elsewhere in theEAR.

(b) License exceptions. No licenseexceptions are available for the EARlicense requirements imposed in thissection.

(c) Licensing policy. Applications forEAR licenses required by this sectiongenerally will be denied. You should

consult with OFAC concerningtransactions subject to OFAC licensingrequirements.

(d) Contract sanctity. Contractsanctity provisions are not available forlicense applications reviewed under thissection.

PART 746[AMENDED]

7. The authority citation for part 746continues to read as follows:

Authority: 50 U.S.C. app. 2401 et seq.; 50U.S.C. 1701 et seq.; 22 U.S.C. 287c; Sec 1503,

Public Law 10811, 117 Stat. 559; 22 U.S.C.6004; 22 U.S.C. 7201 et seq.; 22 U.S.C. 7210;E.O. 12854, 58 FR 36587, 3 CFR, 1993 Comp.,p. 614; E.O. 12918, 59 FR 28205, 3 CFR, 1994Comp., p. 899; E.O. 13222, 3 CFR, 2001Comp., p. 783; Presidential Determination200323 of May 7, 2003, 68 FR 26459, May16, 2003; Presidential Determination 20077of December 7, 2006, 72 FR 1899 (January 16,2007); Notice of July 23, 2008, 73 FR 43603

(July 25, 2008).

8. Revise 746.7 to read as follows:

746.7 Iran.

The Treasury Departments Office ofForeign Assets Control (OFAC)administers a comprehensive trade andinvestment embargo against Iran. Thisembargo includes prohibitions onexports and certain reexporttransactions involving Iran, includingtransactions dealing with items subjectto the EAR. These prohibitions are setforth in OFACs Iranian TransactionsRegulations (31 CFR part 560). Inaddition, BIS maintains licensingrequirements on exports and reexportsto Iran under the EAR as described inparagraph (a)(1) of this section orelsewhere in the EAR (See, e.g., 742.8Anti-terrorism: Iran).

(a) License requirements.

(1) EAR license requirements. Alicense is required under the EAR toexport or reexport to Iran any item onthe CCL containing a CB Column 1, CBColumn 2, CB Column 3, NP Column 1,NP Column 2, NS Column 1, NSColumn 2, MT Column 1, RS Column 1,

RS Column 2, CC Column 1, CC Column2, CC Column 3, AT Column 1 or ATColumn 2 in the Country Chart Columnof the License Requirements section ofan ECCN or classified under ECCNs0A980, 0A982, 0A983, 0A985, 0E982,1C355, 1C395, 1C980, 1C981, 1C982,1C983, 1C984, 2A994, 2D994, 2E994,5A980, 5D980, or 5E980.

(2) BIS authorization. To avoidduplication, exporters or reexporters arenot required to seek separateauthorization from BIS for an export orreexport subject both to the EAR and toOFACs Iranian TransactionsRegulations. Therefore, if OFACauthorizes an export or reexport, suchauthorization is consideredauthorization for purposes of the EAR aswell. Transactions that are not subject toOFAC regulatory authority may requireBIS authorization.

(b) Licensing Policy. Applications forlicenses for transactions forhumanitarian reasons or for the safety ofcivil aviation and safe operation of U.S-origin aircraft will be considered on acase-by-case basis. Licenses for otherpurposes generally will be denied.

(c) License Exceptions. No licenseexceptions may be used for exports orreexports to Iran.

(d) EAR Anti-terrorism controls. TheSecretary of State has designated Iran asa country that has repeatedly providedsupport for acts of internationalterrorism. Anti-terrorism licenserequirements and licensing policy

regarding Iran are set forth in 742.8 ofthe EAR.

(e) Prohibition on exporting orreexporting EAR items without requiredOFAC authorization. No person mayexport or reexport any item that issubject to the EAR if such transaction isprohibited by the Iranian TransactionsRegulations (31 CFR part 560) and notauthorized by OFAC. The prohibition ofthis paragraph (e) applies whether ornot the EAR requires a license for theexport or reexport.

Dated: January 9, 2009.

Christopher R. Wall,

Assistant Secretary for ExportAdministration.

[FR Doc. E9726 Filed 11409; 8:45 am]

BILLING CODE 351033P

DEPARTMENT OF HEALTH ANDHUMAN SERVICES

Food and Drug Administration

21 CFR Part 56

[Docket No. FDA2004N0117] (formerlyDocket No. 2004N0242)

RIN 0910AB88

Institutional Review Boards;Registration Requirements

AGENCY: Food and Drug Administration,HHS.

ACTION: Final rule.

SUMMARY: The Food and DrugAdministration (FDA, we) is issuing afinal rule to require institutional reviewboards (IRBs) to register through asystem maintained by the Department ofHealth and Human Services (HHS). Theregistration information includescontact information (such as addressesand telephone numbers), the number ofactive protocols involving FDA-regulated products reviewed during thepreceding 12 months, and a descriptionof the types of FDA-regulated productsinvolved in the protocols reviewed. TheIRB registration requirements will makeit easier for FDA to inspect IRBs and toconvey information to IRBs.

DATES: This rule is effective July 14,2009. This effective date is necessary toallow refinement of the electronic

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registration system so that itcorresponds to this final rule. All IRBsmust comply with the initial registrationrequirement and, if necessary, makerequired revisions to their registrationsby September 14, 2009.

FOR FURTHER INFORMATION CONTACT: ErikMettler, Office of Policy, Planning andPreparedness, Food and DrugAdministration, WO1, rm. 4324, SilverSpring, MD 209930002, 3017964830.

SUPPLEMENTARY INFORMATION:

I. Introduction

What Led Us to Issue This Rule?IRBs are boards, committees, or

groups formally designated by aninstitution to review, to approve theinitiation of, and to conduct periodicreview of, biomedical researchinvolving human subjects (see 21 CFR56.102(g)). An IRBs primary purposeduring such reviews is to assure theprotection of the rights and welfare of

human subjects (id.). FDAs generalregulations pertaining to IRBs are at part56 (21 CFR part 56). (While section520(g) of the Federal Food, Drug, andCosmetic Act (the act) (21 U.S.C.360j(g)) refers to institutional reviewcommittees rather than IRBs, FDAconsiders institutional reviewcommittees to be IRBs and to be subjectto the IRB regulations.)

Even though IRBs play an importantrole in the conduct of clinicalinvestigations regulated by FDA, wehave never compiled a comprehensivelist of IRBs involved in reviewing

clinical investigations regulated byFDA. Existing FDA regulations haverequired some, but not all, clinicalinvestigators or sponsors of clinicalinvestigations to provide IRB names andaddresses to FDA, and the requirementsdiffer slightly among the different typesof products regulated by FDA. Forexample, for human drug products, thesponsor must disclose the name andaddress of each reviewing IRB (see 21CFR 312.23(a)(6)(iii)(b)). For medicaldevices, the sponsor must disclose thenames and addresses of IRBs that havebeen asked or will be asked to review

the investigation (see 21 CFR812.20(b)(7)) (emphasis added). Forother types of clinical investigationsregulated by FDA (such as food additivestudies involving human subjects), theregulations do not expressly require thesponsor or the clinical investigator todisclose or keep records showing anIRBs name and address, and they makeno distinction between reviewingIRBs and IRBs that have been asked orwill be asked to review a study.

In 1998, the Department of Health andHuman Services Office of the Inspector

General (OIG) issued several reports onIRBs. The OIG sought to identify thechallenges facing IRBs and to makerecommendations on improving Federaloversight of IRBs. One recommendationwas that all IRBs should register withthe Federal Government on a regularbasis as part of an effort to develop morestreamlined, coordinated, and probing

means of assessing IRB performance andto enhance the Federal Governmentsability to identify and respond toemerging problems before they result inserious transgressions (see Office ofthe Inspector General, Department ofHealth and Human Services,Institutional Review Boards: a Time forReform, pages 20 and 21, June 1998).

After reviewing the OIGsrecommendation, we concluded thatIRB registration would serve severalimportant goals. IRB registration would:

Enable us to identify more preciselythose IRBs reviewing clinicalinvestigations regulated by FDA. Atpresent, much of our knowledge aboutthe identities and numbers of IRBsreviewing clinical investigationsregulated by FDA is based oninformation from persons conducting orsponsoring clinical investigations ratherthan from IRBs themselves. Thisinformation may be obsolete (becausethere may be no obligation to update theinformation) or incomplete (because therequirements to report the names andaddresses of IRBs are not uniform acrossall FDA-regulated products);

Enable us to send educationalinformation and other information to

IRBs. Because we lack an accurate listof IRBs, our outreach and educationalefforts are not as efficient as they mightbe. Changes in IRB addresses result inreturned mail, and newly formed IRBsmay not appear in FDAs mailing lists;and

Help us identify IRBs forinspection, because we would have amore accurate list of IRBs.

Consequently, FDA, in consultationwith the Department of Health andHuman Services, Office for HumanResearch Protections (OHRP), publisheda proposed rule in the Federal Register

of July 6, 2004 (69 FR 40556), thatwould require IRB registration for IRBsreviewing clinical investigationsinvolving FDA-regulated products.OHRP issued a companion proposedrule which appeared in the FederalRegister of July 6, 2004 (69 FR 40584)that would require registration for IRBsreviewing federally supported research.The final OHRP IRB registration rule ispublished elsewhere in this issue of theFederal Register.

The goal of the two rules is to createa simple, electronic registration system

that all IRBs, regardless of whether theyreview clinical investigations regulatedby FDA or federally supported research,can use.

II. What Comments Did We Receive?

A. How Many Comments Did WeReceive, and Who SubmittedComments?

We received over 15 comments inresponse to the proposed rule.Individuals, IRB members, IRBassociations, an IRB accreditationassociation, government, health,academic or trade associations, auniversity system, and drug companiessubmitted comments. In general, thecomments supported IRB registration,although some disagreed with specificaspects of the proposal or with otherissues that were discussed in thepreamble to the proposed rule. To makeit easier to identify comments and ourresponses, the word Comment, in

parentheses, will appear before thecomments description, and the wordResponse, in parentheses, will appearbefore our response. We have alsonumbered each comment to helpdistinguish between differentcomments. The number assigned to eachcomment is purely for organizationalpurposes and does not signify thecomments value or importance or theorder in which it was received.

B. Who Must Register? (Section56.106(a))

Proposed 56.106(a) would require

the following IRBs to register: Each IRB in the United States that

reviews clinical investigations regulatedby FDA under sections 505(i) (21 U.S.C.355(i)) or 520(g) of the act; and

Each IRB in the United States thatreviews clinical investigations that areintended to support applications forresearch or marketing permits for FDA-regulated products.

The preamble to the proposed ruleinvited comment on whether there arecircumstances in which foreign IRBsshould be required or invited to register(see 69 FR 40556 at 40558).

(Comment 1) One comment statedthat foreign IRBs are not needed inAmerica.

(Response) The comment may havemisinterpreted the preamble. The issueis not whether foreign IRBs should orshould not review studies, but ratherwhether foreign IRBs should beincluded in the IRB registration system.

(Comment 2) Several commentsdiffered as to whether foreign IRBsshould have to register. One commentwould require foreign IRBs to register ifthey review research conducted in the



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United States; the same comment wouldgive foreign IRBs the option to registerif they review research conductedoutside the United States that may beused to support a future marketingapplication in the United States.

Several comments would allow forvoluntary registration of foreign IRBs orethical review committees. Two

comments explained that registeringforeign IRBs would enable them to haveaccess to educational materials andother information. However, onecomment would limit such registrationto foreign IRBs reviewing researchconducted in the United States, andanother comment noted that localprivacy laws in foreign countries mightaffect a foreign IRBs ability to providecertain registration information.

In contrast, one comment said that weshould respect oversight of ethicalreview committees by foreignauthorities and that we should notimpose additional bureaucracy.Similarly, another comment opposedregistering foreign IRBs, stating thatsuch registration could pose significantdifficulties for clinical investigatorsand sponsors and that foreign laws andregulations might make it difficult forforeign IRBs to register.

(Response) We agree in part with thecomments. We agree that foreign IRBswould benefit from educational andother materials that would be sent toregistered IRBs. Therefore, we haverevised 56.106(a) to allow forvoluntary registration by foreign IRBsand by any domestic IRB that is not

otherwise required to register.We decline to require registration by

foreign IRBs that review research to beconducted in the United States. We donot believe a significant number offoreign IRBs review research that is tobe conducted in the United States.Furthermore, requiring registration byforeign IRBs that review researchconducted in the United States couldlead to arguments over the validity ofour regulatory authority when appliedto actions occurring in a foreigncountry.

As for possible problems foreign IRBs

might encounter in registeringinformation due to foreign laws andregulations, the comments did notidentify specific registration elementsthat would be a problem. Consequently,we lack sufficient information todetermine whether we should modifycertain IRB registration elements toaccommodate foreign IRBs.

(Comment 3) One comment asked usto clarify whether the reference tosection 520(g) of the act was limited toresearch done under an investigationaldevice exemption (IDE) or encompassed

all investigational devices in a clinicalinvestigation.

(Response) The reference to section520(g) of the act encompasses allinvestigational devices in a clinicalinvestigation, regardless of whetherFDA approval of an IDE is needed inaccordance with 21 CFR part 812 for theclinical investigation.

(Comment 4) One comment asked usto clarify whether the rule applied tonon-local or commercial IRBs.

(Response) The comment did notexplain what it meant by the termsnon-local or commercial IRB. Forpurposes of this response, we willassume that a non-local IRB is onethat is physically located away from theclinical trial site(s) and that acommercial IRB is one that is paid toreview research.

If the non-local or commercialIRB is located in the United States and:

Reviews clinical investigationsregulated by FDA under sections 505(i)or 520(g) of the act; or

Reviews clinical investigations thatare intended to support applications forresearch or marketing permits for FDA-regulated products, then the non-localor commercial IRB must register under 56.106(a). If the non-local orcommercial IRB does not perform any ofthe reviews described immediatelyabove or is outside the United States,then it may register voluntarily.

C. What Information Must an IRBRegister? (Section 56.106(b))

Proposed 56.106(b) would describe

the information that IRBs would provideas part of the registration process. Forexample, proposed 56.106(b)(1) wouldrequire the name and mailing address ofthe institution operating the IRB and thename, mailing address, phone number,facsimile number, and electronic mailaddress of the senior officer of thatinstitution who is responsible foroverseeing the IRBs activities. (Afacsimile number also is known morecommonly as a fax number.)

(Comment 5) Several commentsaddressed the registration informationin proposed 56.106(b) generally. Two

comments said that the registrationinformation that OHRP and FDA wouldrequire should either be the same or thatinformation required by OHRP, but notby FDA, should be clearly delineatedand marked as optional for IRBs that aresubject to FDA regulation. Similarly,one comment said that questionsrelating to research funded by HHS,which were part of OHRPs proposedregistration system, should be identifiedclearly so IRBs that do not review HHS-funded research are not obliged toanswer those questions.

Another comment said the proposedregistration information is appropriate.

One comment urged us to reexaminethe registration information to assurethat the information is necessary tosupport the rules stated goals.

(Response) We coordinated our rulewith OHRP and tailored our respectiveregistration information elements to be

as consistent as possible and to use thesame internet-based registration system.

We agree that the IRB registrationsystem should specify whether certainregistration information is optional ornot required for IRBs subject only to ourjurisdiction. The preamble to theproposed rule stated that, In thoseinstances where the Internet registrationsite would seek more information thanFDA would require under this proposal,the site would clarify that IRBsregulated solely by FDA may, but arenot required to, provide the additionalinformation (69 FR 40556 at 40558).The Internet registration site will bestructured so that required informationwill be identified or marked as such,and IRBs indicating that they areregistering pursuant to FDAs regulationalso will be directed to questionsrequesting information required onlyunder FDAs regulation.

(Comment 6) Proposed 56.106(b)(1)would require IRBs to provide the nameand mailing address of the institutionoperating the IRB and the name, mailingaddress, phone number, facsimilenumber, and electronic mail address ofthe senior officer of that institutionwho is responsible for overseeing

activities performed by the IRB. Thepreamble to the proposed rule explainedthat the senior officer must not be anIRB member, IRB staff, or a sponsor orinvestigator participating in aninvestigation under review by that IRB(see 69 FR 40556 at 40558).

Several comments addressed thisprovision. Two comments supported theproposed requirement, but two othercomments stated that our interpretationof senior officer was too prohibitiveor too restrictive. These comments saidthat if a senior officer is on the IRB, hisor her membership should not

invalidate registration or subject the IRBto enforcement action.Another comment questioned what

we meant when we referred to IRBstaff. The comment said that some IRBsdistinguish staff from IRB members toensure the IRBs integrity andindependence. The comment suggestedthat we list persons who cannot be asenior officer and that we delete IRBstaff from that list.

(Response) We agree, in part, with thecomments. We recognize that, in somecases, it may not be feasible to identify



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meeting or under an expedited reviewprocedure during the preceding 12months. We have made this change tobe consistent with changes made byOHRP in its final rule.

With respect to the proposalsnumerical ranges and their usefulness tous, we reiterate that our intent was toget a generalrather than a precise

sense of how active IRBs are and toassign our limited inspectionalresources more efficiently andeffectively. We recognize that there aredifferent types of IRB review and thatchanges in an IRBs workload couldmake an IRBs protocol estimateoutdated or obsolete at a later point intime. However, given the protocolranges were created simply to give us anidea about an IRBs activity, we haverevised the rule to eliminate thesmall, medium, and large ranges.Instead, the final rule requires anapproximate number of active protocols

reviewed, but we neither expect norwant IRBs to constantly change orupdate their protocol numberswhenever their protocol numbersfluctuate. If the approximate number ofprotocols changes after initial IRBregistration, the IRB should report thenew protocol number as part of the re-registration process which takes placeevery 3 years.

As for compliance activities, webelieve the comment may havemisinterpreted the preamble to theproposed rule. We did not state that wewould base inspections solely on anIRBs self-reported level of small,

medium, or large numbers ofprotocols reviewed. We simply said thatthe information would help us assigninspection resources based on IRBactivity levels.

To put it another way, we havelimited inspectional resources, and ourfield staffs that inspect IRBs are alsoresponsible for many other types ofinspections and activities. We mustprioritize our routine IRB inspections insome manner to make the most efficientuse of our resources. Such prioritizationof IRB inspections is not tantamount todeclaring, as the comment suggests, that

IRBs reviewing small or mediumnumbers of protocols do not have tocomply with FDA regulations or that weenforce our requirements differentlydepending on whether an IRB reviews asmall, medium, or large numberof protocols. Nevertheless, given thatthe final rule does not contain thesmall, medium, or large protocolranges, the issue is largely moot.

(Comment 10) Proposed 56.106(b)(4)would require IRBs to describe the typesof FDA-regulated products, such asbiological products, color additives,

food additives, human drugs, or medicaldevices, involved in the protocols thatthey review.

Two comments addressed thisprovision. One comment stated that ithad no objection to the requirementprovided that the description could besimple or generic without numericalranges associated with each product

type. Another comment said thedescriptions would be appropriate onlyif we used the information for purposesof sending useful and targetedinformation to IRBs. The comment alsosaid that the description should begeneric and without numerical rangesassociated with product types.

(Response) We agree with thecomments. Section 56.106(b)(4) merelyseeks a generic description of the FDA-regulated products in the protocolsreviewed by the IRB. So, for example, ifthe IRB reviews protocols for humandrug studies, the description, to satisfy 56.106(b)(4), could simply be humandrugs. If the IRB reviews protocols forhuman drug and medical device studies,the description would be humandrugs and medical devices. We alsonote that the electronic registrationsystem will list the types of FDA-regulated products and allowindividuals to check the appropriateboxes relating to those products and tocheck other and explain what theother FDA-regulated products are.

Furthermore, 56.106(b)(4) does notrequire IRBs to assign numerical valuesto the FDA-regulated product types. Asthe comments noted, our intent is to use

this information to send product-specific information to IRBs, and we cando so with a simple description ofproduct types.

(Comment 11) Proposed 56.106(b)(5)would require an indication whether theIRB is accredited and, if so, the date ofthe last accreditation and the name ofthe accrediting body or organization.The preamble to the proposed rulestated that we recognized that IRBaccreditation is a developing conceptand invited comment on the perceivedvalue of collecting information on theaccreditation status of IRBs (see 69 FR

40556 at 40558).We received more than 10 commentson IRB accreditation issues, and thecomments reflected a considerabledifference of opinion regarding IRBaccreditation and whether we shouldrequire information about suchaccreditation. In brief, the commentsstated:

IRB accreditation information maygive FDA useful information in decidingwhich IRBs to inspect and may help usdecide whether to focus educationalactivities on certain areas. One comment

added that accreditation informationwould help us evaluate the value of IRBaccreditation. In contrast, one commentsaid that IRB accreditation informationwill not give FDA new information thatwill be useful in assessingaccreditations value;

FDA should refer to accreditation ofhuman research protection programs

rather than accreditation of IRBs; FDA should require information

about the name of the accreditingorganization under which the IRBfunctions or collect information aboutaccreditation type or level. Onecomment explained that one body hastwo different accreditation categories;

The additional reporting burdenshould not be passed on to theinstitution;

FDA should delete the provisionbecause accreditation information canbe collected without the need for aregulation or is publicly available from

accrediting organizations. One commentadded that accreditation information, ifit were part of the IRB registrationrequirement, might be unreliablebecause our rule would require re-registration every 3 years; and

Accreditation does not accuratelyrepresent a measure of compliance withhuman subject protection requirements.Similarly, an IRBs lack of accreditationcould be misconstrued as reflecting onthe quality of the IRBs human subjectprotection program. In contrast, onecomment strongly encouraged IRBs tobecome accredited, and another

comment said that accreditation impliesthat a certain standard has beenachieved.

(Response) The final rule omitsaccreditation information from the IRBregistration requirements. We agree that,if necessary, we can obtain accreditationinformation from the accreditationorganizations themselves and that theresulting information may be morereliable or accurate, given that the ruledoes not require certain registrationinformation to be updated until re-registration. We also agree that, as ageneral matter, accreditation does notensure or demonstrate that a particularaction was done correctly; instead,accreditation may increase onesconfidence that the accredited body iscapable of performing a particularaction correctly.

Furthermore, we continue to believethat accreditation, insofar as humansubject protection is concerned, is stilla developing concept. Consequently, wewill continue to follow suchaccreditation activities, but will notrequire accreditation information as partof IRB registration.



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Finally, because the final rule doesnot require accreditation information,the comment regarding reportingburdens is moot.

D. When Must an IRB Register? (Section56.106(c))

Proposed 56.106(c) would have IRBsregister once and to renew their

registrations every 3 years. Initial IRBregistration would occur within 30 daysbefore the date when the IRB intends toreview clinical investigations regulatedby FDA. IRB registration would becomeeffective upon HHS posting of theregistration information on its Web site.

(Comment 12) One comment wouldhave us consider IRBs to be registeredas soon as they complete submitting theregistration information regardless ofwhether the IRB submitted theinformation electronically or in writing.Another comment suggested that theelectronic registration systemacknowledge or document that the IRBhas registered. Another comment statedthat, if IRB registration is to identifyIRBs for future inspections, there is noneed for a 30-day waiting period.

A different comment said that the 30-day time period might interfere withIRB review, particularly expeditedreviews and full IRB reviews that takeless than 30 days. The commentsuggested that we revise the rule so thatIRBs may not issue a determination onFDA-regulated research until they haveregistered.

Another comment asked us to clarifywhen IRBs must register. The comment

explained that the codified provisiondirected IRBs to submit an initialregistration within 30 days before thedate when the IRB intends to reviewclinical investigations regulated byFDA. The comment said that the wordwithin could mean that an IRB couldregister anytime between one and 30days before reviewing a protocol, butthat the preamble to the proposed ruleinterpreted proposed 56.106(c) asrequiring registration at least 30 daysbefore reviewing the protocol. Thecomment preferred giving IRBs theability to register any time between 1

and 30 days before reviewing protocolsin FDA-regulated research.(Response) We agree, in part, with the

comments. For IRBs that registerelectronically, the registration systemwill notify them that they are registered.This notification will be sent to theelectronic mail address that the IRBprovides as part of the registrationprocess. The IRBs registration will beeffective after review and acceptance byHHS. We have amended 56.106(c)regarding the time at which IRBregistration becomes effective to

correspond to changes made by OHRPin its final rule which is publishedelsewhere in this issue of the FederalRegister. OHRP revised a comparableprovision in its rule to clarify when IRBregistration would become effective.

For IRBs that submit their registrationinformation in writing, our experiencewith written forms in other contexts

suggests that some individuals will notcomplete the forms or omit requiredinformation. As a result, we may needto contact individuals to obtain themissing information. Therefore, itwould be more practical for us toconsider IRBs who submit theirregistration information in writing to beregistered only after they havesubmitted all required registrationinformation, we have entered thatinformation into the electronicregistration system, and the informationis reviewed and accepted by HHS.

As for the comments concerning the

30-day timeframe and the suggestionthat we amend the rule so that IRBscannot issue decisions on FDA-regulated research until they haveregistered, we have decided to eliminatethe 30-day timeframe from the finalrule. We note that IRB registration,alone, does not address issues regardingan IRBs competence or expertise, nordoes it require IRBs to meet a particularstandard in order to conduct a review.However, because it is important to FDAto assemble an accurate IRB database,we have revised 56.106(c) to state that:Each IRB must submit an initial

registration. The initial registration mustoccur before the IRB begins to review aclinical investigation described inparagraph (a) of this section. Each IRBmust renew its registration every 3years. IRB registration becomes effectiveafter review and acceptance by HHS.

(Comment 13) One comment wouldrequire IRBs to renew their registrationevery year instead of every 3 years. Thecomment said that 3 years would be toolong a time period.

(Response) We decline to revise therule as suggested by the comment. IRBregistration does not confer any

particular status on IRBs, nor doesregistration, alone, reflect upon an IRBscompetence or capabilities. Moreover,given that the information we seekthrough IRB registration is quite basic(as in names and addresses) and that 56.106(e) describes how and whenIRBs are to revise their registrationinformation, annual registration wouldnot appear to confer any advantages ormake registration information moreaccurate or reliable. Consequently, wedecline to require IRBs to registerannually.

E. Where Can an IRB Register? (Section56.106(e))

Proposed 56.106(e) would directIRBs to register at a specific Internetaddress or, if an IRB lacked the abilityto register electronically, to send itsregistration information to a specificmail address. We indicated that we

would provide the Internet address andmail address in the final rule. We alsoinvited comment on whether we shoulddiscontinue written IRB registrationprocedures after some time period haselapsed, because we did not know howwidespread Internet access is amongIRBs (see 69 FR 40556 at 40558).

(Comment 14) Several commentspertained to the registration site(s). Onecomment said we should maintain onecommon registration site with OHRPand that the registration system shouldautomatically include currentlyregistered IRBs. The comment said theregistration system should also allow

such IRBs to retain their assignednumbers. The comment acknowledgedthe intent to create a single registrationsite, but implied that the proposedrules omission of a specific Internetaddress created concern. Anothercomment supported creation of asimple, electronic registration system.

(Response) We agree that a singleInternet registration site should be usedfor electronic registrations and havealways worked with OHRP towards thatend. We were unable to provide aspecific Internet address at the time ofthe proposed rule because the electronic

registration system was still underdevelopment. The final rule now statesthat the Internet registration address ishttp://ohrp.cit.nih.gov/efile.

Additionally, as we stated in thepreamble to the proposed rule, OHRPwill continue to recognize previous IRBregistrations (see 69 FR 40556 at 40558).

(Comment 15) One comment askedwhether entities that have more thanone IRB at the same location need toregister more than once or whether theycould register once and providemultiple pieces of information inconnection with a single registration.

(Response) The electronic registrationsystem will assign an organizationnumber to each entity, and this willenable the entity to register several IRBswithout having to enter the same datarepeatedly for each IRB.

(Comment 16) Two commentsencouraged us to have the electronicregistration system consider IRBs to beregistered automatically once an IRBcompletes the electronic registrationprocess or to send acknowledgements tothe IRBs once they complete theelectronic registration process.

http://ohrp.cit.nih.gov/efilehttp://ohrp.cit.nih.gov/efilehttp://ohrp.cit.nih.gov/efile


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(Response) As we stated in ourresponse to comment 12 of thisdocument, when an IRB completes theelectronic registration process and HHShas reviewed and accepted theinformation, the electronic registrationsystem will notify IRBs that they areregistered.

(Comment 17) Several comments

responded to our question whether weshould discontinue written IRBregistrations after some time period haselapsed. One comment supportedconversion to electronic registration assoon as possible, but said it is importantto allow small organizations the time toacquire the necessary technology. Thecomment agreed that not all institutionshave electronic capabilities or Internetaccess.

Another comment supported givingIRBs the option to submit registrationinformation in writing for apredetermined period of time, but did

not suggest any time period. A differentcomment also supported the writtenregistration option, but suggested that itbe available only for 2 years.

Another comment opposeddiscontinuing written IRB registration.The comment said that there are adverseconsequences to both the IRB and anysponsor or investigator that might usean unregistered IRB (which appeared tobe a reference to a later discussion, inthe preamble to the proposed rule, aboutWhat Happens if an IRB Does NotRegister? (see 69 FR 40556 at 40559)),so we should continue to make written

IRB registration possible.(Response) While we continue tobelieve that most IRBs will use theelectronic registration system, we do notknow how many IRBs will use thewritten registration option, and theadministrative record for thisrulemaking does not give us sufficientbasis to set a deadline at which wewould end the written registrationoption. (We realize that one commentsuggested a 2-year period, but, giventhat IRBs have 3 years to renewregistrations, discontinuing writtenregistrations after 2 years would not give

IRBs the opportunity to renew theirregistrations in writing.) Consequently,until we become more experienced withIRB registrations, we will continue tooffer written registration as analternative to electronic registration, andthe final rule states that IRBs that lackthe ability to register electronically mustsend their registration information, inwriting, to the Good Clinical PracticeProgram (HF34), Office of Science andHealth Coordination, Food and DrugAdministration, 5600 Fishers Lane,Rockville, MD 20857.

F. How Does an IRB Revise ItsRegistration Information? (Section56.106(e))

Proposed 56.106(e) would have IRBsrevise their registration informationwithin specific timeframes if certainchanges occurred. For example, if theIRBs contact or chair personinformation changes, proposed 56.106(e) would require the IRB tochange its registration informationwithin 90 days of the change. If the IRBdecided to disband or to discontinuereviewing FDA-regulated clinicalinvestigations, it would report thatchange within 30 days. All otherinformation changes would be reportedwhen the IRB renews its registration.

(Comment 18) Two comments pointedout a discrepancy between the proposedrule and its preamble. The commentsnoted that the preamble to the proposedrule said that if an IRB reviews newtypes of FDA-regulated products, it

would revise its registration informationwithin 30 days (see 69 FR 40556 at40559), yet proposed 56.106(e) wassilent regarding such changes. Thecomments suggested that we reconcilethe codified text with the preamble.

(Response) The comments werecorrect. We inadvertently omittedchanges in the IRBs review of FDA-regulated research from proposed 56.106(e), and we have revised therule so that IRBs must revise theirregistration information within 30 daysif they review new types of FDA-regulated products. Additionally, on our

own initiative, we have added aparenthetical phrase to clarify that adecision to review new types of FDA-regulated products should beinterpreted as a decision to review adifferent category of FDA-regulatedproducts, such as a decision to reviewstudies pertaining to food additiveswhen the IRB previously reviewedstudies pertaining to drug products. Wedo not want IRBs to revise theirregistration information if they decide toreview studies pertaining tosubcategories within the same class ofFDA-regulated products; for example, if

an IRB previously reviewed studiespertaining to drugs intended to treatcardiac conditions and then decided toreview studies pertaining to drugsintended to treat cancer, both types ofstudies would still pertain to drugproducts, so there would be no newtype of FDA-regulated product within 56.106(e).

(Comment 19) One commentaddressed IRBs that have decided todisband. The comment said that theprocess of closing an IRB may takelonger than 30 days, so requiring IRBs

to revise their registration informationwithin 30 days of a decision to disbandwould put an undue burden on IRBsand the institutions responsible for theIRBs.

(Response) We agree in part, anddisagree in part with the comment. Weagree that, in some cases, closing an IRBmay take more than 30 days, but, in

other cases, the process may take lesstime. In other words, IRBs vary in size,resources, organization, and complexity,and, as a result, different IRBs will takedifferent amounts of time to perform thesame or similar functions.

The comment also may havemisinterpreted the proposed rule.Proposed 56.106(e) stated that an IRBsdecision to disband or to discontinuereviewing FDA-regulated clinicalinvestigations is a change that must bereported within 30 days of that change;thus, the proposal would begin the timeperiod when IRB decides to close, not

when the IRB finally closes.Nevertheless, for consistency withOHRPs final rule (which appearselsewhere in this issue of the FederalRegister), we have revised 56.106(e) tostate that an IRBs decision to disbandis a change that must be reportedwithin 30 days of permanent cessationof the IRBs review of research. In thepreamble to the OHRP final rule, OHRPstates that the date of permanentcessation of the IRBs review of * * *research would occur on or after theIRBs decision to disband, but not beforethe IRBs decision to disband was

made.Furthermore, given the simplicity ofthe electronic registration system, we donot believe that IRBs or theirinstitutions will find it undulyburdensome to report the IRBs decisionto disband.

(Comment 20) One comment wouldshorten the time period for reportingchanges in the IRBs contact or chairperson information from 90 days to 60days.

(Response) We decline to revise therule as suggested by the comment. Thecomment did not identify any advantagein shortening the timeframe, and we do

not believe that reducing the timeframeby 30 days will confer any significantbenefit.

G. What Other Comments Did WeReceive?

1. What Information Will Be PubliclyAvailable?

The preamble to the proposed rulereferred to the OHRP proposal forinformation regarding public disclosureof IRB registration information, theFreedom of Information Act (FOIA), and



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the Privacy Act of 1974 (see 69 FR40556 at 40557). It also stated that,insofar as FDAs registration system wasconcerned, the name of the institutionoperating the IRB and the IRBs namewill be publicly accessible, and all otherIRB registration information would besubject to public disclosure under FOIAand our public information regulations

at part 20 (21 CFR part 20) (see id.).(Comment 21) One comment said

that, in addition to the institutionsname and the IRBs name, we shouldmake the following information publiclyavailable:

The name, address, and telephonenumber of the IRB contact; and

For accredited IRBs, informationrelating to that accreditation.

Another comment asked us to clarifywhat information would be publiclyavailable under FOIA.

(Response) All registrationinformation required under this rule

will be subject to FOIA and any otherapplicable statutes and regulationspertaining to public disclosure. Pleasenote that certain information may bewithheld from public disclosure or mayrequire an individuals consent topublic disclosure (see, e.g., 20.63(e)(stating that a request for all recordsrelating to a specific individual will bedenied as a clearly unwarrantedinvasion of personal privacy unlessaccompanied by the written consent ofthe individual named)).

As for accreditation information,accreditation status is not required

under the final rule, so that informationwill not be publicly available from us orfrom OHRP.

(Comment 22) One commentsuggested that sponsors andinvestigators have access to the IRBregistration database. The comment saidthat sponsors and investigatorscurrently have access to Federal-wideassurances data and suggested that, ifsponsors and investigators could nothave access to the IRB registrationdatabase, we or OHRP should issue areport of IRB registrations or issuecertificates to individual IRBs.

(Response) OHRP currently posts allregistered IRBs on its Web site,including the name and location of theorganization operating the IRB(s) andthe name and location of each IRB.

We decline to issue reports on IRBregistration or certificates to show thatan IRB is registered. As we stated in ourresponse to comment 12 of thisdocument, IRB registration, alone, doesnot address issues regarding an IRBscompetence or expertise, nor does itrequire IRBs to meet a particularstandard in order to conduct a review.

(Comment 23) One comment said weshould establish a link to the publiclyavailable IRB registration informationfrom the portion of our own Web sitethat pertains to Good Clinical Practicesin FDA-Regulated Clinical Trials,located at http://www.fda.gov/oc/gcp/default.htm.

(Response) We agree with the

comment and have modified our Website accordingly.

2. What Happens if an IRB Does NotRegister?

The preamble to the proposed rulestated that sponsors and investigatorswho used unregistered IRBs might beusing IRBs that would not have had thebenefit of receiving educationalmaterials from FDA and would not havebeen identified on an FDA IRBregistration list for future inspection(see 69 FR 40556 at 40559). Thus, thepreamble to the proposed rule addedthat, to the extent that any existingFDA regulation requires a sponsor orinvestigator to comply with [part 56] orto use an IRB that complies with part56, FDA will consider sponsors andinvestigators using an unregistered IRBto be in conflict with their regulatoryobligations (id.).

The preamble to the proposed rulealso noted how we considered otheroptions to require sponsors andinvestigators to use only registered IRBs,such as refusing to consider informationfrom an application for a researchpermit for a clinical investigation that isreviewed or is to be reviewed by an

unregistered IRB (id.). The preamble tothe proposed rule also invited commenton what sanctions or administrativemechanisms, if any, should or might beused against sponsors and investigatorswho use unregistered IRBs and whetherany additional changes to ourregulations were necessary.

(Comment 24) We received manycomments relating to sanctions, otherregulatory changes, and ensuring thatsponsors and investigators use onlyregistered IRBs. The comments reflecteda considerable difference of opinion. Forexample:

One comment said we shouldimpose and enforce high fines forfailure to follow human subjectprotection regulations;

Several comments said that theforms investigators currently use (FormFDA 1572) could be used to reinforce orotherwise highlight the need to use onlyregistered IRBs, but the commentsdiffered as to whether investigatorsshould be subject to any sanctions ifthey use an unregistered IRB. Forexample, one comment said failure touse a registered IRB should be treated

the same as any other breach of aninvestigators responsibilities, but otherssaid that IRBs, rather than sponsors orinvestigators, should be responsible forany failure to register. One commentalso opposed placing an investigationon clinical hold because, the commentargued, clinical holds are appropriatewhen the rights and/or safety of human

subjects are in jeopardy or othermaterial, noncompliance concerns areevident; the comment said that failure toregister does not mean improperoversight by the IRB or by the sponsor.Some comments argued that sponsorsand investigators should not be obligedto monitor an IRBs registration status.In contrast, one comment would have usamend the investigational new drug(IND) application regulations toauthorize us to place a study on clinicalhold if the sponsor or investigator usesan unregistered IRB. The same commentsuggested that we consider additional

enforcement options, such as refusingto consider information from anapplication for a research permit for aclinical investigation that is reviewed oris to be reviewed by an unregisteredIRB.

Several comments, mostly frompharmaceutical firms or tradeassociations, opposed any changesoutside the IRB regulations. Thecomments, in general, felt that theexisting IND regulations were sufficientand clear regarding a sponsors orinvestigators obligation to use IRBs thatcomply with part 56. Some commentssaid we should not expend resources on

revising the IND regulations but shouldpromote awareness of the IRBregistration requirements instead.Another comment, from an associationof medical colleges, also opposedrevisions to the IND regulations, statingthat clinical holds would be unworkablebecause, if an unregistered IRB hadreviewed a clinical study and theclinical study had proceeded,retroactive review of the study would beimpermissible. The comment said weshould refuse to consider informationfrom an application for a researchpermit that is reviewed or is to be

reviewed by an unregistered IRB. One comment suggested aflexible approach whereby we wouldstart by sending a certified letter to anunregistered IRB regarding its failure toregister and include registrationinstructions. If the IRB remainedunregistered, the comment suggestedthat we inspect the IRB. The commentsaid that this approach would allow usto take appropriate action againstunregistered IRBs withoutunnecessarily penalizing sponsorsand investigators who have attempted to

http://www.fda.gov/oc/gcp/default.htmhttp://www.fda.gov/oc/gcp/default.htmhttp://www.fda.gov/oc/gcp/default.htmhttp://www.fda.gov/oc/gcp/default.htmhttp://www.fda.gov/oc/gcp/default.htm


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follow our regulations in good faith.Similarly, another comment advocatedsending letters to IRBs or notices tosponsors rather than imposingsanctions.

One comment agreed with us thatan IRBs failure to register would notjustify disqualification of the IRB under 56.121 absent the extreme

circumstances described in 56.121(b)(1) (the IRB has refused orrepeatedly failed to comply withregulatory requirements) or 56.121(b)(2) (the noncomplianceadversely affects the rights or welfare ofthe human subjects in a clinicalinvestigation).

(Response) We agree in part anddisagree in part with the comments. Weagree that the existing IND regulations,as well as the IDE regulations, aresufficient and clear regarding asponsors or investigators obligation touse IRBs that comply with part 56. We

also agree that an IRBs failure toregister, alone, should not lead todisqualification proceedings under 56.121 absent extreme circumstances.We intend to educate IRBs, sponsors,and investigators about the IRBregistration requirements and toencourage sponsors and investigators touse registered IRBs for the same reasonswe stated in the preamble to theproposed rule.

Given the existing IND and IDEregulations and our intent to pursueeducational efforts, we disagree withthose comments that would have us

impose fines or place clinicalinvestigations on clinical hold if thesponsor or investigator used anunregistered IRB. We believe that itwould be premature for us to considerthe use of such sanctions before we andthe regulated community have gainedsufficient experience with the IRBregistration program.

3. What Other Issues Did the CommentsRaise?

Several comments addressed issuesthat were either not part of therulemaking or not material to theproposed codified text.

(Comment 25) One commentdisagreed with the preamble to theproposed rule when we stated that ourknowledge about the identities andnumbers of IRBs reviewing FDA-regulated clinical research is obsolete orincomplete (see 69 FR 40556 at 40557).The comment said that we requiresponsors to identify IRBs and that, for20 years, OHRP has maintained a list ofIRBs that have filed assurances (under45 CFR part 46). The comment said thatsuch past practices were apparently

sufficient for purposes of conductinginspections.

(Response) We disagree with thecomment. As we stated in the preambleto the proposed rule, existing FDAregulations have required some, but notall, clinical investigators and sponsorsto provide IRB names and addresses tous, and those regulatory requirements

differ slightly (see 69 FR 40556 at40557). Consequently, because ofdifferences within our own regulations,we do not have a comprehensive list ofIRBs that review FDA-regulatedresearch. Additionally, because our pre-existing regulations do not requiresponsors and investigators to revise orupdate IRB information if and when theIRB changes its address, contact person,or chair person, or even, in some cases,to provide addresses, contactinformation, or chair person informationto us, the IRB information we do haveis not as detailed as the information we

seek under this rule.As for institutions that have filedassurances with OHRP under 45 CFRpart 46, the IRBs associated with suchinstitutions are not necessarily identicalto those that review FDA-regulatedresearch. OHRPs regulations apply toinstitutions that are engaged in humansubjects research conducted orsupported by HHS. In contrast, our IRBregulations apply to clinicalinvestigations regulated by us,regardless of whether thoseinvestigations are conducted orsupported by HHS. Thus, the fact thatOHRP has operated an assurance system

for decades does not necessarily meanthat the OHRP list of institutions thathave filed assurances can serve as a listof IRBs that review FDA-regulatedresearch.

(Comment 26) One comment said thatregistration and re-registration feesshould be set at $5,000 to cover costs.The comment said that taxpayers shouldnot have to pay the fees or fund thecosts of profiteers, and thatpharmaceutical companies should notget away with low fees when theycan pay their executives $150,000,000 atretirement.

(Response) We decline to revise therule as suggested by the comment. Wehave no express authority to imposeregistration or re-registration fees onIRBs. Additionally, the rule is directedat IRBs themselves rather thanpharmaceutical firms, so issues relatingto pharmaceutical executives salariesare not relevant to this rulemaking.

(Comment 27) One comment asked usto confirm that our IRB inspections willadhere to the guidelines described inthe Guidance for Institutional ReviewBoards and Clinical Investigators.

(Response) This rulemaking does notaffect how we conduct IRB inspections.We may, however, use IRB registrationinformation to help us prioritizeinspections. Additionally, our receipt ofmore accurate IRB addresses andcontact information due to IRBregistration should make it easier andmore efficient to schedule IRB

inspections.

H. What Other Amendment Did WePropose?

The proposal would also make a non-substantive amendment to part 56. Theproposal would revise the definition ofAn Application for an InvestigationalDevice Exemption, at 56.102(b)(12),to eliminate its reference to 21 CFR part813. The preamble to the proposed ruleexplained that this change is necessarybecause we removed the regulations atpart 813 (which had pertained tointraocular lenses) in 1997 (see 62 FR

4164, January 29, 1997).We received no comments on thisaspect of the proposal. Consequently,the final rule deletes a reference to part813.

III. Implementation

This rule is effective July 14, 2009.This protracted effective date isnecessary to allow refinement of theelectronic registration system so that itcorresponds to this final rule and toOHRPs final rule.

IV. Legal Authority

In general, the act authorizes us to

issue regulations pertaining toinvestigational uses of FDA-regulatedproducts (see, e.g., sections 409(j) (21U.S.C. 348(j)) (investigations involvingfood additives); 505(i) (investigationsinvolving human drugs); 520(g)(investigations involving devices); and721(f) (21 U.S.C. 379e(f)) of the act(investigations involving coloradditives)).

The act also requires the submissionof a petition or application to FDA (see,e.g., sections 409(b) (food additivepetitions); 505(b) (new drugapplications); 505(j) (abbreviated new

drug applications); 513(f) (premarketnotification for devices); 515(c)(premarket approval applications fordevices); 520(m) (humanitarian deviceexemption applications); and 721(b) ofthe act (color additive petitions)) beforemarketing begins.

To implement these provisions of theact, section 701(a) of the act gives us theauthority to issue regulations for theefficient enforcement of the act. Byrequiring IRB registration, the final rulewill aid in the efficient enforcement ofthe acts provisions regarding the



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1Source: United States Department of Labor,Bureau of Labor Statistics; National CompensationSurvey, June 2005. Overall hourly rate in the United

States for administrators and officials, publicadministration, is $31.54. To account for benefits,the hourly rate was increased by 40 percent and

rounded to the nearest whole dollar. Data accessedon August 31, 2006, at http://data.bls.gov.

investigational use of various FDA-regulated products (because then wewould be able to conduct IRBinspections more efficiently) as well asthose provisions regarding marketingapplications (because marketingapplications usually depend on clinicalinvestigations involving humansubjects, and IRBs are supposed to

provide protections for the rights andwelfare of such human subjects).Moreover, by requiring IRBs to register,the final rule will enable FDA to contactIRBs more quickly and efficiently onvarious issues, such as adverse reactionsthat may be attributed to a particularproduct, new regulatory requirements orpolicies, or problems associated with aparticular protocol or clinicalinvestigator. Consequently, we concludethat we have sufficient legal authority toissue the final rule.

V. Economic Impact Analysis

We have examined the impacts of thefinal rule under Executive Order 12866,the Regulatory Flexibility Act (5 U.S.C.601612), and the Unfunded MandatesReform Act of 1995 (Public Law 1044).Executive Order 12866 directs agenciesto assess all costs and benefits ofavailable regulatory alternatives and,when regulation is necessary, to selectregulatory approaches that maximizenet benefits (including potentialeconomic, environmental, public healthand safety, and other advantages;distributive impacts; and equity). Theagency believes that this final rule is nota significant regulatory action as defined

by the Executive Order.The Regulatory Flexibility Act

requires agencies to analyze regulatoryoptions that would minimize anysignificant impact of a rule on smallentities. Because the requiredregistration information is minimal andthe costs associated with registration arelow, the agency certifies that the finalrule will not have a significanteconomic impact on a substantialnumber of small entities.

Section 202(a) of the UnfundedMandates Reform Act of 1995 requiresthat agencies prepare a writtenstatement, which includes an

assessment of anticipated costs andbenefits, before proposing any rule thatincludes any Federal mandate that mayresult in the expenditure by State, local,and tribal governments, in the aggregate,or by the private sector, of $100,000,000or more (adjusted annually for inflation)in any one year. The current thresholdafter adjustment for inflation is $127

million, using the most current (2006)Implicit Price Deflator for the GrossDomestic Product. FDA does not expectthis final rule to result in any 1-yearexpenditure that would meet or exceedthis amount.

The final rule requires most IRBs toregister with FDA. The informationsought through the registration processis minimal, consisting largely of namesand addresses for a contact person, theinstitution operating the IRB (if aninstitution exists), the head of theinstitution, the IRB, and the IRBchairperson. The registration would also

indicate the approximate number ofactive protocols reviewed and the typesof FDA-regulated products involved. Weestimate that initial IRB registration mayrequire 1 hour. The average loaded wagerate for administrators at publicinstitutions is about $44 per hour.1 Thismeans that each IRB would spend $44for an initial registration ($44 per hourx 1 hour per initial registration).

We estimate that re-registration wouldrequire less time, especially if the IRBverifies existing information. If re-registration requires 30 minutes, thenthe cost of re-registration to each IRB

would be approximately $22 ($44 perhour x 0.5 hours per re-registration).Revising an IRBs registration

information would probably involvecosts similar to re-registration costs. Ifthe revision requires 30 minutes, thenthe cost of revising an IRBs registrationinformation would be approximately$22 per IRB.

Given the minimal registrationinformation that would be required andthe low costs associated withregistration, this final rule is not asignificant regulatory action, and wecertify that the final rule does not havea significant economic impact on a

substantial number of small entities.Therefore, the rule is not a significantregulatory action under ExecutiveOrder 12866 and does not require aRegulatory Flexibility Act analysis.

Additionally, assuming that anestimated 5,000 IRBs would register, thefinal rule will result in a 1-yearexpenditure of $220,000 (5,000 IRBs x

$44 registration wage costs per IRB).Because the total expenditure under therule will not result in a 1-yearexpenditure of $100 million or more, weare not required to perform a cost-benefit analysis under the UnfundedMandates Reform Act.

VI. Environmental Impact

We have determined under 21 CFR25.30(h) that this action is of a type thatdoes not individually or cumulativelyhave a significant effect on the humanenvironment. Therefore, neither anenvironmental assessment nor an

environmental impact statement isrequired.

VII. Paperwork Reduction Act of 1990

This rule contains informationcollection requirements that are subjectto review by the Office of Managementand Budget (OMB) under the PaperworkReduction Act of 1995 (PRA) (44 U.S.C.35013520). The title, description, andrespondent description of theinformation collection provisions areshown below with an estimate of theannual reporting and recordkeepingburden. Included in the estimate is the

time for reviewing instructions,searching existing data sources,gathering and maintaining the dataneeded, and completing and reviewingeach collection of information.

Title: Institutional Review Boards:Registration Requirements.

Description: The final rule requiresIRBs to register with FDA.

Description of Respondents:Businesses and individuals.

The estimated burden associated withthe information collection requirementsof this rule is 8,750 hours.

We estimate the burden of thiscollection of information as follows:

TABLE 1.ESTIMATED ANNUAL REPORTING BURDEN1

21 CFR SectionNo. of

RespondentsAnnual Frequency

per ResponseTotal AnnualResponses

Hours perResponse

Total Hours

56.106(c) (initial registration) 5,000 1 5,000 1 5,000

56.106(c) (re-registration) 2,500 1 2,500 0.5 1,250

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TABLE 1.ESTIMATED ANNUAL REPORTING BURDEN1Continued

21 CFR SectionNo. of

RespondentsAnnual Frequency

per ResponseTotal AnnualResponses

Hours perResponse

Total Hours

56.106(e) 5,000 1 5,000 0.5 2,500

Total 8,750

1There are no capital costs or operating and maintenance costs associated with this collection of information.

Our estimates are based on thefollowing considerations. According to a1998 OIG report, there are 3,000 to 5,000IRBs in the United States, and most areassociated with hospitals and academiccenters (see Department of Health andHuman Services, Office of the InspectorGeneral, Institutional Review Boards: ATime for Reform, page 3, June 8, 1998).While not all IRBs are involved inclinical investigations regulated byFDA, for purposes of the PRA, we willuse 5,000 as the maximum number ofIRBs subject to the final rule.Additionally, because the final rulerequires basic information about an IRB(such as names and addresses) andbecause registration would, in mostcases, be done electronically, we willassume that registration will take only 1hour per IRB. Thus, the total burdenhours would be 5,000 hours (5,000 IRBsx 1 hour per IRB).

Re-registration and revisions toexisting registration information shouldrequire less time than initialregistration. We will assume that re-registration and revisions will take only30 minutes per IRB. We will also

assume, based on OHRPs experiencewith its IRB registration program, that50 percent of IRBs (2,500) will re-register and that all (5,000) will revisetheir registration information. Therefore,the total burden hours for re-registrationwill be 1,250 hours (2,500 IRBs x 0.5hours per IRB), and the total burdenhours for revisions will be 2,500 hours(5,000 IRBs x 0.5 hours per IRB).

Prior to the effective date of this finalrule, FDA will publish a notice in theFederal Register announcing OMBsdecision to approve, modify, ordisapprove the information collection

provisions in this final rule. Incompliance with the PRA (44 U.S.C.3507(d)), we have submitted theinformation collection requirements ofthis rule to OMB for review. An agencymay not conduct or sponsor, and aperson is not required to respond to, acollection of information unless itdisplays a currently valid OMB controlnumber.

VIII. Federalism

We have analyzed this final rule inaccordance with the principles set forth

in Executive Order 13132. We havedetermined that the rule does notcontain policies that have substantialdirect effects on the States, on therelationship between the NationalGovernment and the States, or on thedistribution of power andresponsibilities among the variouslevels of government. Accordingly, wehave concluded that the rule does notcontain policies that have federalismimplications as defined in the orderand, consequently, a federalismsummary impact statement isnot

required.

List of Subjects in 21 CFR Part 56

Human research subjects, Reportingand recordkeeping requirements, Safety. Therefore, under the Federal Food,Drug, and Cosmetic Act and underauthority delegated to theCommissioner, part 56 is amended asfollows:

PART 56INSTITUTIONAL REVIEWBOARDS

1. The authority citation for 21 CFRpart 10 continues to read as follows:

Authority: 21 U.S.C. 321, 343, 346, 346a,348, 350a, 350b, 351, 352, 353, 355, 360,360c360f, 360h360j, 371, 379e, 381; 42U.S.C. 216, 241, 262, 263b263n.

56.102 [Amended]

2. Amend 56.102 in paragraph(b)(12) by removing the phrase parts812 and 813 and by adding in its placethe phrase part 812. 3. Add 56.106 to subpart A to readas follows:

56.106 Registration.

(a) Who must register? Each IRB in the

United States that reviews clinicalinvestigations regulated by FDA undersections 505(i) or 520(g) of the act andeach IRB in the United States thatreviews clinical investigations that areintended to support applications forresearch or marketing permits for FDA-regulated products must register at a sitemaintained by the Department of Healthand Human Services (HHS). (A researchpermit under section 505(i) of the act isusually known as an investigationalnew drug application (IND), while aresearch permit under section 520(g) of

the act is usually known as aninvestigational device exemption (IDE).)An individual authorized to act on theIRBs behalf must submit theregistration information. All other IRBsmay register voluntarily.

(b) What information must an IRBregister? Each IRB must provide thefollowing information:

(1) The name, mailing address, andstreet address (if different from themailing address) of the institutionoperating the IRB and the name, mailingaddress, phone number, facsimile

number, and electronic mail address ofthe senior officer of that institution whois responsible for overseeing activitiesperformed by the IRB;

(2) The IRBs name, mailing address,street address (if different from themailing address), phone number,facsimile number, and electronic mailaddress; each IRB chairpersons name,phone number, and electronic mailaddress; and the name, mailing address,phone number, facsimile number, andelectronic mail address of the contactperson providing the registrationinformation.

(3) The approximate number of activeprotocols involving FDA-regulatedproducts reviewed. For purposes of thisrule, an active protocol is anyprotocol for which an IRB conducted aninitial review or a continuing review ata convened meeting or under anexpedited review procedure during thepreceding 12 months; and

(4) A description of the types of FDA-regulated products (such as biologicalproducts, color additives, foodadditives, human drugs, or medicaldevices) involved in the protocols thatthe IRB reviews.

(c) When must an IRB register? EachIRB must submit an initial registration.The initial registration must occurbefore the IRB begins to review aclinical investigation described inparagraph (a) of this section. Each IRBmust renew its registration every 3years. IRB registration becomes effectiveafter review and acceptance by HHS.

(d) Where can an IRB register? EachIRB may register electronically throughhttp://ohrp.cit.nih.gov/efile. If an IRBlacks the ability to registerelectronically, it must send its

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registration information, in writing, tothe Good Clinical Practice Program (HF34), Office of Science and HealthCoordination, Food and DrugAdministration, 5600 Fishers Lane,Rockville, MD 20857.

(e) How does an IRB revise itsregistration information? If an IRBscontact or chair person information

changes, the IRB must revise itsregistration information by submittingany changes in that information within90 days of the change. An IRBs decisionto review new types of FDA-regulatedproducts (such as a decision to reviewstudies pertaining to food additiveswhereas the IRB previously reviewedstudies pertaining to drug products), orto discontinue reviewing clinicalinvestigations regulated by FDA is achange that must be reported within 30days of the change. An IRBs decision todisband is a change that must bereported within 30 days of permanent

cessation of the IRBs review ofresearch. All other information changesmay be reported when the IRB renewsits registration. The revised informationmust be sent to FDA eitherelectronically or in writing inaccordance with paragraph (d) of thissection.


Jeffrey Shuren,

Associate Commissioner for Policy andPlanning.

[FR Doc. E9682 Filed 11409; 8:45 am]

BILLING CODE 416001S

DEPARTMENT OF STATE

22 CFR Part 42

[Public Notice: 6457]

RIN 1400AB84

Visas: Documentation of ImmigrantsUnder the Immigration and NationalityAct, as Amended: Electronic Petitionfor Diversity Immigrant Status

AGENCY: State Department.ACTION: Final rule.

SUMMARY:This rule makes final aninterim rule published in the Federal

Register on August 18, 2003, amendingthe Departments regulations pertainingto the manner in which aliens maypetition for the opportunity toparticipate in the Diversity VisaProgram. The rule changed the standardmail-in system previously used to anentirely electronic system for thepurpose of making the process lessprone to fraud, improve efficiency andsignificantly reduce the processing coststo the Government.

DATES: Effective Date: This rule iseffective on January 15, 2009.

FOR FURTHER INFORMATION CONTACT:Lauren Prosnik, Legislation andRegulations Division, Visa Services,Department of State, Washington, DC205200106, (202) 6631202, e-mail([email protected]).

SUPPLEMENTARY INFORMATION:

Why is the Department promulgatingthis rule?

The Department published an interimrule, Public Notice 4446 at 68 FR 49353,Aug. 18, 2003, with a request forcomments. The comment period expiredon October 17, 2003. No publiccomments were received during thecomment period.

What did the rule do?

The rule amended the Departments

regulations at 22 CFR 42.33 to establishan entirely electronic system utilizing aspecifically designated Internet Website, by which aliens can petition for theopportunity to participate in theDiversity Visa Program.

Why was the petitioning processchanged?

There are three main benefits tochanging the mail-in process to anelectronic format. First, it helpseliminate multiple applications,prohibited under INA Section

204(a)(1)(I). Secondly, it greatly reducesthe cost of administering the system.Finally, it benefits the petitioners byimmediately notifying them of thereceipt of the petition, impossible underthe mail-in system.

PART 42VISAS: DOCUMENTATIONOF IMMIGRANTS UNDER THEIMMIGRATION AND NATIONALITYACT, AS AMENDED

Accordingly, the interim ruleamending 22 CFR part 42 which waspublished at 68 FR 49353 on August 18,

2003, is adopted as final withoutchange.


Janice L. Jacobs,

Assistant Secretary for Consular Affairs,Department of State.

[FR Doc. E9698 Filed 11409; 8:45 am]

BILLING CODE 471006P

DEPARTMENT OF HOUSING ANDURBAN DEVELOPMENT

24 CFR Parts 203 and 3500

[Docket No. FR5180F04]

RIN 2502AI61

Real Estate Settlement Procedures Act

(RESPA): Rule To Simplify andImprove the Process of ObtainingMortgages and Reduce ConsumerSettlement Costs; DeferredApplicability Date for the RevisedDefinition of Required Use

AGENCY: Office of the AssistantSecretary for Housing-Federal HousingCommissioner, HUD.ACTION: Final rule.

SUMMARY: This final rule delays theeffective date of the definition ofrequired use as revised by HUDsNovember 17, 2008, final rule amending

its RESPA regulations. The November17, 2008, final rule provides that therevised definition is applicablecommencing January 16, 2009, theeffective date of the final rule. As aresult of recently initiated litigation,HUD has determined to delay theeffective date of the revised definition ofRequired use until April 16, 2009.DATES: This correction is effectiveJanuary 16, 2009, The definition ofRequired use in 3500.2, as revisedby HUDs final rule published onNovember 17, 2008, at 73 FR 68204, isdelayed until April 16, 2009.FOR FURTHER INFORMATION CONTACT

: IvyJackson, Director, or Barton Shapiro,Deputy Director, Office of RESPA andInterstate Land Sales, Office of Housing,Department of Housing and UrbanDevelopment, 451 7th Street, SW.,Room 9158, Washington, DC 204108000; telephone 2027080502 (this isnot a toll-free telephone number).Persons with hearing or speechimpairments may access this numberthrough TTY by calling the toll-freeFederal Information Relay Service at8008778339.SUPPLEMENTARY INFORMATION: On

November 17, 2008 (73 FR 68204), HUDpublished a final rule amending itsregulations to further the purposes ofthe Real Estate Settlement ProceduresAct (12 U.S.C. 26012617) by requiringmore timely and effective disclosuresrelated to mortgage settlement costs forfederally related mortgage loans toconsumers. The final rule followedpublication of a March 14, 2008,proposed rule (73 FR 14030) and madechanges in response to public commentand in further consideration of certainissues by HUD. Additional information
mailto:[email protected]:[email protected]:[email protected]

CFR part 56 Institutional review boards

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Transcript of CFR part 56 Institutional review boards