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Public Health Service

                                                                                           Food and Drug Administration
                                                                                           Rockville  MD   20857
                                                        WARNING LETTER
                                                                                             JUL 22 1998
                   OVERNIGHT        MAIL
                    .                                                       Ref. No. : 98-HFD-340-0701
                   James A. Lane, J.D.
                   Kaiser Foundation Research Institute
                   1800 Harrison Street
                   Oakland, California 94612
                   Dear Mr. Lane:
                   On February 9-18 and March 2-3, 1998, Marie K. Kinkade and Cynthia L. Evitt,
                   investigators with the San Francisco District Office of the Food and Drug Administration
                  (FDA), conducted an inspection of the Kaiser Foundation Hospitals Northern California
                   Institutional Review Board (IRB). The purpose of this inspection was to determine
                  whether your procedures for the protection of human subjects complied with Title 21,
                  Code of Federal Regulations (CFR), Parts 50 and 56. These regulations apply to
                  clinical studies of products regulated by FDA.
                  At the conclusion of the inspection, Ms. Kinkade issued a Form FDA 483 [enclosure #1 ]
                  to Nancy R. King, M. Ed., M. P.A., Administrative Manager, Kaiser Foundation Research
                  Institute, which described the deviations from requirements specified under 21 CFR
                  Part 50 and 56 that she had identified during the inspection.
                 The Agency has reviewed the documents and records relating to the IRB’s
                 responsibilities for the protection of subjects of research contained in
                 Ms. Kinkade’s and Ms. Evitt’s inspection report and the objectionable conditions and
                 practices listed in the current Form FDA 483. The evidence shows that the IRB has
                 failed to adhere to pertinent federal regulations as contained in 21 CFR 50, 56 and
                 312. The Agency’s findings represent significant violations of the Federal Food, Drug,
                 and Cosmetic Act.
                 Summa ry of IRB Functions and Op erations Violations           r21 CFR 56.108(a~
                 56.~09(f}, 312.35.312.53      and 312.61]
                 1. The IRB has failed to assure that a licensed practitioner who receives an
                 investigational drug for treatment use under a treatment protocol, as directed by the
                 IRB procedure entitled “Regional Policy and Procedure 63G, Investigational Druas and
                 ~            [procedure 63 G], is an “investigator” under the protocol and meets all
                 applicable investigator responsibilities under 21 CFR Parts 50, 56 and 312 [see item #3
   Page 2- James A. Lane, J.D.
   in Form FDA 483]. We note that the agency rescinded a December 2, 1994
   suspension of the use of Procedure 63G by your IR13on January 25, 1996 [enclosure
  #2] based upon your lRB’s assurance that the use of Procedure 63G was to be
  conducted in compliance with FDA regulations governing research [enclosure #3].
   However, the inspection report shows that Procedure 63G has continued to be used by
  your IRB to permit physicians who are unqualified investigators under FDA regulations
  to receive and dispense investigational drugs for treatment use under treatment
  2. The inspection report shows that the IRB has failed to conduct continuing review of
  ongoing research at intervals not less than once per year [see item W in Form FDA
  Summarv of IRB Records Violation ~21 CFR 56.115(a)[fi~
  3. The inspection report shows that the IRB has failed to maintain copies of study
  protocols reviewed by the IRB [see item #1 in Form FDA 483].
  Summary of Informed Consent Violations             r21 CFR 50.20, 50.25 (a~2)       and (7)1
           . The last sentence in the first paragraph on page one of these consent forms
  states: “Its [drug or device] use is experimental until approved by the Food and Drug
  Administration”     Since this statement anticipates FDA approval of the test article, this
  statement is unduly influential within the meaning of 21 CFR 50.20.
           . The consent forms for Studies A, B and C fail to include a statement
  regarding the expected duration of the subject’s participation and a description of the
  procedures to be followed, and identification of any procedures that are experimental,
           . The   consent forms for Studies A, B and C fail to include the number and type
  of clinical test procedures that are performed during the study. Accordingly, these
  consent forms    fail to include an adequate description of reasonably foreseeable risks or
  discomforts to   the subject.
              These consent forms fail to include a person or office to contact in the event
  of a research-related     injury to the subject. Additionally, Study A also fails to include a
   Page 3- James A. Lane, J.D.
   person or office to contact for answers to pertinent questions about the research
  subjects’ rights.
  The above cited violations may not be all inclusive of the deficiencies  in your IRB
  Administrative      Restrictions
  We have no assurance that your procedures are adequately protecting the rights and
  welfare of human subjects of research. For this reason, in accordance with 27 CFR
  56. 120(b)(l) and (2),
             no new studies that are subject to Parts 50 and 56 of the FDA regulations
             are to be approved by your REI, and
             no new subjects are to be admitted to ongoing studies that are subject to 21
          CFR Parts 50 and 56 until you have received notification from this office that
          adequate corrections have been made.
  Please inform  this office, in writing, within fifteen (15) working days from the date of
  receipt of this letter, of the actions you have taken or plan to take to bring the
                   your IRB into compliance with FDA requirements. Please include a copy
  procedures of
  of any revised   documents, such as written procedures, with your response. Any plans
  of action must   include projected completion dates for each action to be accomplished.
  If you have any questions, please contact Ms. Mary Jo Zollo at (301 ) 594-1026,         Fax
  (301 ) 594-1204. Your written response should be addressed to:
                                  Mary Jo Zollo, Acting Team Leader
                                  Human Subject Protection Team, (HFI)-343)
                                  Division of Scientific Investigations
                                  Center for Drug Evaluation and Research
                                  7520 Standish Place
                                  Rockville, MD 20855
                                          Sincerely yours,
                                          David A. Lepay, M. D., Ph.D.
                                          Division of Scientific investigations
                                          Office of Compliance
                                          Center for Drug Evaluation and Research
   Page 4- James A. Lane, J.D.
  #1 - Form FDA 483
  #2 - January 25, 1996 letter from Paul W. Goebel, Jr., FDA to Glenda R. Marlow,
  Administrative Manager, Kaiser Foundation Research     Institute
  #3 - December 12, 1995 letter from Glenda R. Marlow,    Administrative Manager, Kaiser
        Foundation Research Institute to Paul W. Goebel,  Jr., FDA
  Nancy R. King, M.Ed., M.P.A.
  Administrative Manager
  Kaiser Foundation Research Institute
  1800 Harrison Street
  Oakland, California 94612
  Edmund E. VanBrunt, M. D., SC.D.
  Chairman, Institutional Review Board
  Kaiser Foundation Hospitals Northern California
  1800 Harrison Street
  Oakland, California 94612
  Stanley B. Watson, J.D.
  Kaiser Foundation Research Institute
  1800 Harrison Street
  Oakland, California 94612
  Susan Crandall, M.D.
  Chief, Compliance Oversight Branch
  Division of Human Subject Protection
  OPRR, OER, OD, MSC 7507
  National Institutes of Health
  6100 Executive Boulevard, Suite 3B01
  Rockville, MD 20892-7507




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