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U.S. Department of Health and Human Services

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Enforcement Actions

Vision RT Ltd 8/16/13

  

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

Public Health Service
Food and Drug Administration
 
10903 New Hampshire Avenue
Silver Spring, MD 20993 

 

WARNING LETTER
VIA UPS
                                                                                                            August 16, 2013
Norman Smith, PhD
Chief Executive Officer
Vision RT Ltd., Dove House
Arcadia Avenue
London, N3 2JU, UK
 
Re: FDA Reference Number: CMS# 408780
 
Dear Dr. Smith:
 
During an inspection of your firm located in London, United Kingdomon April 15-17, 2013, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures the AlignRT® and AlignRT® Plus light beam patient position indicators, which FDA has classified as accessories to medical linear accelerators.  Under section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. § 321(h), these products are devices 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 inspection revealed that these devices are adulterated within the meaning of section 501(h) of the Act, 21 U.S.C. § 351(h), in that the methods used in, or the facilities or controls used for, their manufacture, packing, storage, or installation are not in conformity with the current good manufacturing practice requirements of the Quality System regulation found at Title 21, Code of Federal Regulations (CFR), Part 820.
 
We received a response from you dated May 7, 2013 concerning our investigator’s observations noted on the Form FDA 483 (FDA 483), List of Inspectional Observations, which was issued to your firm. We address this response below, in relation to each of the noted violations. These violations include, but are not limited to, the following:
 
1.    Failure to establish and maintain adequate procedures for corrective and preventive action, as required by 21 CFR 820.100(a).
 
For example:
  1. SOP 014 Issue No. 4.0 "Corrective & Preventative Action" dated August 1, 2012:
 
i.    Does not include the requirement for analyzing sources of quality data to identify existing and potential causes of nonconforming product, or other quality problems.
 
ii.    Does not include the requirements for verifying or validating the corrective and preventive action to ensure that such action does not adversely affect the finished device.
 
iii.    Does not include the requirement for ensuring that information related to quality problems or nonconforming product is disseminated to those directly responsible for assuring the quality of such product or the prevention of such problems.
 
The adequacy of your response dated May 7, 2013, cannot be determined at this time since the supporting documentation was not provided for our review. You have created a compliance matrix to make sure the revised work instructions and procedures, including the CAPA procedures, comply with the corresponding requirements of the Quality System regulation. These changes will be documented per the document control process. The anticipated completion date is June 21, 2013.
 
  1. CAPA No. 000 1923 submitted on September 12, 2011 was opened to review and update the Quality Management System for IEC 60601-1 3rd edition. The investigation identified a list of procedures, which needed to be revised. Although (b)(4) procedures were identified, only (b)(4) were documented as being revised. The CAPA record incorrectly indicates that "All the SOPs have been revised and issued." Also, the CAPA record incorrectly indicates that "The changes have been verified."
 
The adequacy of your response dated May 7, 2013, cannot be determined at this time since the supporting documentation was not provided for our review. All CAPAs from January 1, 2011 shall be reviewed and checked for accuracy, completeness, verification of effectiveness and appropriately closed. CAPAs that are incomplete will be reopened. The anticipated completion date is August 2, 2013. Updated CAPA will be provided to the FDA along with the revised SOPs and records of any required training as evidence of completion of the CAPAs.
 
  1. CAPA No. 0001926 submitted on June 25, 2012 was opened to revise SOP 030 to include the new HD Cameras. The original nonconformity that resulted in the submission of this CAPA was a discrepancy in results, which led to an investigation. The identified action needed to correct and prevent recurrence of the discrepancy was to create the (b)(4). However, these CAPA activities were not documented in your CAPA system.
 
The adequacy of your response dated May 7, 2013, cannot be determined at this time since the supporting documentation was not provided for our review. The CAPA procedure, SOP 14, will be revised in order to provide clear instructions on completing a CAPA such that corrective actions are not anticipated from the outset. The revised CAPA procedure was not provided for review. CAPA 1926 will be reopened to clarify the wording and properly closed. The anticipated completion date is August 2, 2013.
 
  d.  CAPA records are closed by referencing previously closed CAPAs.   However, the referenced CAPAs do not involve the same issue or problem.
 
      For example,
 
i.    CAPA No. 0001969 submitted on March 13, 2013 was opened to address training files. This CAPA was closed and referenced CAPA No. 0001995, which doesn't involve any training issues. As such, CAPA No. 0001969 was prematurely closed.
 
ii.    CAPA No. 000 1951 submitted on February 8, 2013 was opened to address the lack of manufacturing procedures. The CAPA record also contains information on design controls, which is associated with a different CAPA. Due to other CAPA information contained in this CAPA record, the CAPA is identified as being resolved. However, the firm has yet to establish manufacturing procedures.
 
The adequacy of your response dated May 7, 2013, cannot be determined at this time since the supporting documentation was not provided for our review. The CAPA procedure, SOP 14, will be revised to ensure the CAPAs are accurate and complete and the CAPAs identified in Observation 1d will be corrected to ensure the information is correct. The revised CAPA procedure for ensuring the correction of the identified CAPAs was not provided for review. The anticipated completion date is August 2, 2013. 
 
2.    Failure to establish and maintain adequate procedures for receiving, reviewing, and evaluating complaints by a formally designated unit, as required by 21 CFR 820.198(a). 
 
For example:
 
  1. SOP 009 Issue No. 5.0"Complaints" dated February 26, 2013, "Complaint Handling Guide" Draft 1.1 dated 03/30/2013, and Form 079 Draft No. 1.2 "Complaint Evaluation and Review" dated March 30, 2013:
 
i.    Does not ensure that complaints are evaluated to determine whether the complaint represents an adverse event which is required to be reported to FDA under part 803; they do not appear to include evaluation of malfunction events.
 
ii.    Does not ensure that any complaint involving the possible failure of a device, labeling, or packaging to meet any of its specifications should be reviewed, evaluated, and investigated, unless such investigation has already been performed for a similar complaint and another investigation is not necessary.
 
iii.    Does not ensure that any complaint that represents an MDR-reportable event should be maintained in a separate portion of the complaint files or otherwise clearly identified.
 
The adequacy of your response dated May 7, 2013, cannot be determined at this time since the supporting documentation was not provided for our review. Complaint handling procedure, SOP 09, and complaint forms will be revised and checked to make sure they comply with the requirements of 21 CFR 820.198. Training on the updated procedure will be given to appropriate employees. The anticipated completion date is June 21, 2013.
 
  1. (b)(4) of (b)(4) complaints reviewed:
 
i.    Do not include the name of the device and any device identification(s) and control number(s) used.
 
ii.   (b)(4) of (b)(4) complaints do not meet the definition of a complaint. (#263       and #258).
 
iii.    One support ticket was not handled as a complaint even though it meets the definition of a complaint. (#235).
 
iv.    (b)(4) of (b)(4) complaints documented an evaluation and review date that precedes the receipt of the complaint (#258).
 
The adequacy of your response dated May 7, 2013, cannot be determined at this time since the supporting documentation was not provided for our review. As noted above, the revised complaint procedures and forms were not provided for review. The complaint procedures will be revised to clearly define what a complaint is. In addition, the firm is assessing all customer support tickets open since January 1, 2011, are completely and accurately completed and closed as well as reviewed if they should be reported per 21 CFR 803.The anticipated completion date is August 2, 2013. 
 
3.    Failure to establish and maintain adequate procedures for the identification, documentation, validation or where appropriate verification, review, and approval of design changes before their implementation, as required by 21 CFR 820.30(i).
 
For example:
 
  1. SOP 010 Issue No. 2.1 "Product Development Lifecycle" dated February 26, 2013 §6.9 "Control of Design and Development Changes", SOP 32 Issue No. 1.0 "Hardware Change Control Procedure" dated June 06, 2005, SOP 0 13 Issue No. 4.1 "Software Change Control" dated August 1, 2012, Form 024 Issue No. 1.0 "Software Change Request & Control" dated 0 January 27, 2010, and SOP 043 Issue No. 1. 1 "Software  Maintenance" dated August01, 2012 do not contain instructions for the validation or where appropriate verification of design changes before their implementation.
  2. Design changes were not implemented in accordance with design change procedures.
 
For example:
 
i.    The Align RT® software was changed from Build No. (b)(4) to Build No. (b)(4). However, Form 024 "Software Change Request & Control" was not used to document this pre-production design change.
 
ii.    The pre-production design change to (b)(4) was not implemented in accordance with SOP 32 Issue1.0.
 
iii.    Complaint #234 received on March 25, 2013 includes records of an investigation, which states "(b)(4). " This software change is not documented on Form 024 "Software Change Request Form" in accordance with SOP 013 Issue No. 4.1 §6.1.4.
 
The adequacy of your response dated May 7, 2013, cannot be determined at this time since the supporting documentation was not provided for our review. The design control procedures SOPs 010, 032, 013, 043 and the Software Change Request Form, form-024, are to be revised to ensure design changes are validated or where appropriate verified. All the design control procedures will also be reviewed to ensure they contain all the design control requirements (21 CFR 820.30). These procedures and form were not provided for review to determine their adequacy. Training on the revised procedures will also be provided to the appropriate personnel. Vision RT will also review all of the design changes for Align RT to make sure they have been validated or where appropriate verified. The anticipated completion date is June 21, 2013.
 
4.    Failure to establish and maintain adequate procedures for validating the device design, as required by 21 CFR 820.30(g).
 
For example:
 
  1. SOP 010 Issue No. 2.1 "Product Development Lifecycle" dated February 26, 2013 §6.7 "Design and Development Validation" and SOP 020 Issue No. 2.1 "System Validation Procedure" dated August 01, 2012:
 
i.    Does not assure that design validation shall be performed under defined operating conditions on initial production units, lots, or batches, or their equivalents.
 
ii.    Does not assure that testing of production units should be conducted under actual or simulated use conditions.
 
  1. Design validation activities for the AlignRT® Plus design project:
 
i.    Are not performed on initial production units.  It appears that the design validation activities were conducted on equivalents.  However, the design validation reports do not document how the device(s) were manufactured and do not include a comparison with initial production units.
 
ii.    Do not include the statistical justification of sample size.
 
The adequacy of your response dated May 7, 2013, cannot be determined at this time since the supporting documentation was not provided for our review. The design control procedures will include instructions for the involvement of users and volunteers in verification and validation activities and the application of statistical methods to justify any sample sizes used. The design control procedures will be reviewed to ensure they comply with the design control requirements in the Quality System regulation. However, these revised procedures were not provided for review in order to determine their adequacy. In addition, the firm intends to train all appropriate personnel. The anticipated completion date is June 21, 2013. 
 
5.    Failure to establish and maintain adequate procedures to ensure that all purchased or otherwise received product and services conform to specified requirements, as required by 21 CFR 820.50.
 
For example:
 
  1. SOP 003 Issue 2.1 "Purchasing" dated 0 1/ 10/2011:
 
i.    Does not define the procedures for evaluating and selecting potential suppliers, contractors, and consultants on the basis of their ability to meet specified requirements, including quality requirements. For example,supplier approval methods include (b)(4); however there are no procedures for conducting these approval methods.
 
ii.    Does not define the procedures for documenting supplier evaluation.
 
iii.    Does not define the supplier list codes identified in §5.1.2, which is used to determine the type of supplier approval method.
 
iv.    Does not define the type and extent of control to be exercised over the product, services, suppliers, contractors, and consultants, based on the evaluation results.
 
  1. Supplier approval documentation was not available for software that goes into the device and software that is used in the manufacturing of the device.
 
The adequacy of your response dated May 7, 2013, cannot be determined at this time since the supporting documentation was not provided for our review. Corrective actions have been opened to ensure the Purchasing Control procedure, SOP-003 is compliant with the purchasing control requirements in 21 CFR 820.50, reevaluate supplier approvals to make sure the necessary documents are present, and training will be conducted on the revised procedures. The revised procedures and reassessment of supplier approvals were not provided for review. The anticipated completion date is August 2, 2013.
 
6.    Failure to establish and maintain adequate procedures for verifying device design, as required by 21 CFR 820.30(f).
 
            For example:
 
  1. SOP 010 Issue No. 2.1 "Product Development Lifecycle" dated Febraury 26, 2013 §6.6 "Design and Development Verification" does not appear to define that the identification of the design, method(s), the date, and the individual(s) performing the verification will be documented in the DHF.
  1. Your firm was unable to provide approved methods for the AlignRT® Plus design project's design verification activities.
  2. 0022-00105 Issue No. 1.2 "Calibration Phantom Verification Tests" dated October 18, 2012 using Vision RT Calibration Phantom Part No. (b)(4) Serial No. (b)(4) "(b)(4) Validation Workflow" documents that the verification activities for the (b)(4) was not conducted. The verification report does not include any justification for this deviation from the method.
 
The adequacy of your response dated May 7, 2013, cannot be determined at this time since the supporting documentation was not provided for our review. The design verification procedure, SOP-010, will be revised and evaluated to ensure the procedure complies with the design control requirements in 21 CFR 820.30. All completed verification and validation tests completed within 2 years shall be reviewed against the revised SOP 010 to assure all requirements are met and training will be provided on the revised procedure. The anticipated completion date for all the corrective actions is August 2, 2013.
 
7.    Failure to establish and maintain adequate procedures for defining and documenting design output in terms that allow an adequate evaluation of conformance to design input requirements, as required by 21 CFR 820.30(d).
 
For example:
 
  1. SOP 010 Issue No. 2.1 "Product Development Lifecycle" dated February 26, 2013 §6.4 "Design and Development Outputs" does not ensure that those design outputs that are essential for the proper functioning of the device are identified.
  1. The essential design outputs for the AlignRT® Plus design project were not identified.
 
The adequacy of your response dated May 7, 2013, cannot be determined at this time since the supporting documentation was not provided for our review. The design output procedures will be revised and evaluated to confirm they are in compliance with the design control requirements (21 CFR 820.30). The design outputs for the AlignRT® Plus design project will be reviewed to ensure they are complete and accurate and training on the revised procedures will be given and documented. The anticipated completion date is August 2, 2013.
 
8.    Failure to establish and maintain plans that describe or reference the design and development activities and define responsibility for implementation, as required by 21 CFR 820.30(b). 
 
For example:  A plan that describes or references the design and development activities and that defines responsibility for implementation was not established and maintained for the Align RT® Plus design project.
 
The adequacy of your response dated May 7, 2013, cannot be determined at this time since the supporting documentation was not provided for our review. The firm is creating a summary of the key steps and design resources used for the AlignRT® Plus design project. The design control procedures did not include a formal approval process for initiating a pre-product design project. Therefore procedure SOP 010 is being revised to include a pre-production approval process. The anticipated completion date for all the corrective actions is August 2, 2013.
 
9.    Failure to establish and maintain adequate procedures for quality audits, as required by 21 CFR 820.22. 
 
For example: SOP 024 Issue No. 4.0 "Internal Quality Audit" dated February 26, 2013:
 
  1. Does not define procedures for quality audits to assure that the quality system is in compliance with the established quality system requirements and to determine the effectiveness of the quality system. For example:
 
i.    SOP 024 Issue No. 4.0 does not define the frequency of quality audits.
 
ii.    SOP 024 Issue No. 4.0 does not define the elements of the quality system that should be audited.
 
  1. Does not define the conditions for when a reaudit of deficient matters should be taken.
 
The adequacy of your response dated May 7, 2013, cannot be determined at this time since the supporting documentation was not provided for our review. CAPAs 2018 and 2099 reveal the procedure will be revised to ensure the Internal Quality Audit procedure, SOP 014 complies with 21 CFR 820.22 and the appropriate personnel will be trained on the revised procedure. However there is no indication that any type of evaluation, such as a re-audit, will be conducted to ensure that all elements of the quality system will be evaluated. The current procedure did not ensure all elements of the quality system have been reviewed. Therefore it is unclear if all elements of the quality system have been assessed.
 
U.S. federal agencies may be advised of the issuance of Warning Letters about devices so that they may take this information into account when considering the award of contracts.  Additionally, premarket approval applications for Class III devices to which the Quality System regulation deviations are reasonably related will not be approved until the violations have been corrected.  Requests for Certificates to Foreign Governments will not be granted until the violations related to the subject devices have been corrected.
 
Please notify this office in writing within fifteen business days from the date you receive this letter of the specific steps your firm has taken to correct the noted violations, including an explanation of how your firm plans to prevent these violations, or similar violations, from occurring again.  Include documentation of the corrections and/or corrective actions (including any systemic corrective actions) that your firm has taken.    In your response letter dated May 7, 2013, you include a timetable for implementation of those activities, with some of the proposed CAPA to be completed by June 13, 2013 and the remainder to be completed by August 2, 2013.  Please provide a translation of documentation not in English to facilitate our review.
 
Your firm’s response should be sent to: Food and Drug Administration, Center for Devices and Radiological Health, Attention: Nuclear Medicine and Radiation Therapy Branch , Document Mail Center – W.O. 66 – G609, 10903 New Hampshire Avenue, Silver Spring, MD 20993-0002.   Refer to CMS case # 408780 and COR #13000136 when replying. If you have any questions about the contents of this letter, please contact: James L. Woods, Deputy Director for Patient Safety and Product Quality at 301-796-6225or fax at 301-847-8514.
 
Finally, you should know that this letter is not intended to be an all-inclusive list of the violations at your firm’s facility.  It is your firm’s responsibility to ensure compliance with applicable laws and regulations administered by FDA.  The specific violations noted in this letter and in the Inspectional Observations, FDA 483, issued at the close of the inspection may be symptomatic of serious problems in your firm’s manufacturing and quality management systems.  Your firm should investigate and determine the causes of the violations, and take prompt actions to correct the violations and bring the products into compliance. 
 
Sincerely yours,
/S/ 
Alberto Gutierrez, Ph.D.
Director
Office of In Vitro Diagnostics and
    Radiological Health
Center for Devices and Radiological Health