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U.S. Department of Health and Human Services

Inspections, Compliance, Enforcement, and Criminal Investigations

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John Joseph Hewett, M.D. 9/5/12

  

Department of Health and Human Services logoDepartment of Health and Human Services

Public Health Service
Food and Drug Administration
 10903 New Hampshire Ave.
Silver Spring, MD 20993-0002 

 

WARNING LETTER
 
 
September 5, 2012
 
 
 
VIA UNITED PARCEL SERVICE
 
John Joseph Hewett, M.D.
Synergy Health Concepts, Inc.
4501 Birch Street
Ste B
Newport Beach CA 92660
 
Dear Dr. Hewett:
 
This Warning Letter is to inform you of objectionable conditions observed during the Food and Drug Administration (FDA) inspection of your clinical site from March 23, 2012, to May 15, 2012, by an investigator from the FDA Los Angeles District Office. This inspection was conducted to determine whether activities and procedures related to you as clinical investigator in the clinical studies: Venous Obstruction in Neurodegenerative Disorders Research Registry Study (Registry study) and Venous Irregularities, Flow and Perfusion in MS Study (VERIFY MS study) complied with applicable federal regulations.  The percutaneous transluminal angioplasty balloon dilation catheters and stents used in the Registry and VERIFY MS studies are devices as that term is defined in section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. § 321(h), because they are intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or to affect the structure or function of the body. This letter also requests prompt corrective action to address the violations cited and discusses the written response, dated June 5, 2012, to the noted violations.
 
The inspection was conducted under a program designed to ensure that data and information contained in requests for Investigational Device Exemption (IDE), Premarket Approval (PMA) applications, and Premarket Notification submissions are scientifically valid and accurate. Another objective of the program is to ensure that human subjects are protected from undue hazard or risk during the course of scientific investigations. 
 
Our review of the inspection report prepared by the district office revealed several serious violations of Title 21, Code of Federal Regulations (CFR) Part 812-Investigational Device Exemptions, and Part 50-Protection of Human Subjects, which concerns requirements prescribed under section 520(g) of the Act,21 U.S.C. § 360j(g). At the close of the inspection, the FDA investigator presented an inspectional observations Form FDA 483 for your review and discussed the observations listed on the form with you. The deviations noted on the Form FDA 483, your written response, and our subsequent review of the inspection report are discussed below:
 
1.    Failure to ensure that an investigation is conducted according to the signed agreement, the investigational plan, and applicable regulations. [21 CFR 812.100] 
 
A clinical investigator is responsible for ensuring that an investigation is conducted according to the signed agreement, the investigational plan, and applicable FDA regulations, for protecting the rights, safety, and welfare of subjects under the investigator’s care, and for the control of devices under investigation.  Specifically, you failed to check pre-procedure creatinine levels in at least (b)(4) subjects to confirm that subjects did not have a creatinine level greater than 1.8 mg/dl.  According to the VERIFY MS study protocol, subjects with a creatinine level greater than 1.8 mg/dl would not receive magnetic resonance imaging (MRI) contrast agents due to the increased risk of complications.  Conducting creatinine laboratory tests pre‑procedure is important to confirm that subjects will not be at increased risk of serious medical complications, such as kidney disease, associated with MRI contrast agents.
 
Adherence to the investigational protocol assures that research subjects will not be exposed to known hazards that would place them in jeopardy or invalidate the outcome of the research.
 
2.    Failure to obtain informed consent by the use of a written consent form approved by the IRB and signed and dated by the subject or the subject’s legally authorized representative at the time of the consent. [21 CFR 50.27(a)]
 
Informed consent shall be documented by the use of a written consent form approved by the Institutional Review Board (IRB) and signed and dated by the subject or the subject’s legally authorized representative at the time of consent. You failed to ensure that informed consent was obtained from subjects and documented in accordance with 21 CFR Parts 50 and 56. Examples of these failures include, but are not limited to, the following: 
 
  • At least (b)(4) subjects in the VERIFY MS study signed an unapproved informed consent document after the IRB approved an informed consent document indicating they would receive (b)(4).
 
  • You failed to use the approved informed consent document for at least (b)(4) subjects for the Registry study from July 27, 2011, to December 27, 2011. 
 
  • You used an unapproved informed consent document for at least (b)(4)  subjects in the Registry study after the IRB rescinded the use of the informed consent document on January 5, 2012. 
 
  • A research subject in the VERIFY MS study signed the informed consent document (b)(4) after undergoing the procedure. 
 
A valid informed consent process ensures that research subjects have a clear understanding of risks of participation in a research protocol, have sufficient opportunity to consider whether to participate in the study, and make an informed decision if they decide to participate.
 
3.    Failure to maintain accurate, complete, and current records related to your participation in the investigation. [21 CFR 812.140(a)(2) and 21 CFR 812.140(d)]
 
As a clinical investigator, you are responsible for maintaining accurate, complete, and current records of study-related matters that include receipt and use of each device with specifics about the type and quantity of the device, dates of receipt, and batch number or code mark. 21 CFR 812.140(a)(2).  All records required by 21 CFR 812.140(a) must be maintained during the investigation and 2 years after the date on which the investigation is terminated or completed, or the date that the records are no longer required for purposes of supporting a PMA application, whichever is later. 21 CFR 812.140(d). Specifically, you failed to maintain and so could not produce during the inspection the device accountability records, as described above, in the Registry study for at least (b)(4) subjects because, as you state in your affidavit of (b)(4), you are (b)(4).
 
These records are necessary to document that the use of the angioplasty balloon dilation catheters and stents, which are investigational devices, is limited to the clinical studies you are conducting and to ensure that subjects can be notified in the event of any need for additional follow up, e.g., exposure to an unanticipated risk. 
 
The response submitted June 5, 2012 on your behalf by C. Humphrey and Associates P.A., states that FDA has no jurisdiction to inspect or review Synergy Health’s IRB studies for which you are a clinical investigator. This is incorrect.  The Registry and VERIFY MS studies are subject to FDA jurisdiction because they involve the investigational use of medical devices by experts qualified by scientific training and experience to investigate the safety and effectiveness of such devices (see section 520(g) of the Act, 21 U.S.C. § 360j(g)).  Synergy Health must apply for an IDE in accordance with the regulations in 21 CFR Part 812 to conduct these studies.  As a clinical investigator, if Synergy Health obtains an IDE, it is your responsibility to follow the applicable regulations in 21 CFR Parts 50, 56, and 812 when conducting the study.  The June 25, 2012, response is inadequate in that: 

1.    it does not address how you will ensure that creatinine levels are tested pre‑procedure to avoid exposing research subjects to MRI contrast agents associated with the risk of serious medical complications;

2.    it does not acknowledge that research subjects in a clinical research study must be consented with the use of an IRB-approved informed consent document, which ensures that subject risks are outweighed by anticipated benefits, as required by 21 CFR 50.27; and

3.    it does not address how you will correct the failure to maintain adequate device shipment records and records related to your participation as a clinical investigator in these studies.  

 
The violations described above are not intended to be an all-inclusive list of problems that may exist with your clinical study. It is your responsibility as a clinical investigator to ensure compliance with the Act and applicable regulations.  
 
Within 15 working days of receiving this letter, please provide documentation of the actions that you have taken or will take to correct these violations and to prevent the recurrence of similar violations in current or future studies for which you are the clinical investigator. Any submitted corrective action plan must include projected completion dates for each action to be accomplished and a plan for monitoring the effectiveness of your corrective actions. Failure to respond to this letter and take appropriate corrective action could result in the FDA taking regulatory action without further notice to you. In addition, FDA could initiate disqualification proceedings against you in accordance with 21 CFR 812.119.
 
You will find information to assist you in understanding your responsibilities and planning your corrective actions in the FDA Information Sheets Guidance for Institutional Review Boards and Clinical Investigators, which can be found at http://www.fda.gov/oc/ohrt/irbs/.   
 
Your response should reference “CTS  EC120259/E001 and be sent to:    
 
Attention: Anne Hawthorn
Food and Drug Administration
Center for Devices and Radiological Health
Office of Compliance
Division of Bioresearch Monitoring
10903 New Hampshire Avenue
Building 66, Room 3504
Silver Spring, Maryland 20993-0002.
                       
A copy of this letter has been sent to FDA’s Los Angeles District Office, 19701 Fairchild, Irvine, CA 92612. Please send a copy of your response to that office.
 
The Division of Bioresearch Monitoring has developed introductory training modules in FDA-regulated device clinical research practices, which are available on the FDA website. The modules are for persons involved in FDA-regulated device clinical research activities. These modules are located at the following website address: http://www.fda.gov/Training/CDRHLearn/ucm162015.htm.
 
If you have any questions, please contact Anne T. Hawthorn at (301) 796-6561 or Anne.Hawthorn@fda.hhs.gov.
 
Sincerely yours,
/S/ 
Steven D. Silverman
Director
Office of Compliance
Center for Devices and
    Radiological Health
 
cc:
Synergy Health Concepts, Inc.
Dr. Michael A. Arata, CEO
4501 Birch Street
Ste B
Newport Beach CA 92660
 
Biomedical Research Institute of America
2525 Camino del Rio South
Suite 300
San Diego, CA 92108