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U.S. Department of Health and Human Services

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Enforcement Actions

Amplivox Ltd 5/2/12

  

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 UNITED PARCEL SERVICE
 
Mr. Arne Boye Nielsen
General Manager and President, Diagnostic Instruments
William Demant Holdings A/S
(Amplivox Limited)
Kongebakken 9
Smorum
Denmark, DK-2765
 
Dear Mr. Nielsen:
 
During an inspection of your firm, Amplivox Limited, located in Oxford, United Kingdom, on December 12 through December 15, 2011, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures tympanometers and audiometers.  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 (b)(6), Quality Manager, Amplivox Limited, dated December 21, 2012, concerning our investigator’s observations noted on the Form FDA 483 (FDA 483), List of Inspectional Observations, that 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 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, your firm’s procedure, (b)(4), dated 01/10/2011, states that design changes are controlled by the (b)(4), dated 01/10/2011. However, the design change section of the (b)(4) does not contain requirements for validating or, where appropriate, verifying the design change before implementation. Specifically, on August 8, 2011, engineering design change note 107 was made to the Otowave 102 without being validated.

We reviewed your firm’s response and conclude that it is not adequate. Your firm did not submit supporting documentation indicating that it will revise the design change control procedure to include the requirements found in 21 CFR 820.30(i). Your firm’s response did not include evidence to indicate that a correction and corrective action (including evidence that your firm has validated or verified, where appropriate, design change note 107) were implemented or that a systemic corrective action was considered.
 
2.    Failure to establish and maintain adequate procedures for validating the device design. Design validation shall include risk analysis, where appropriate, as required by 21 CFR 820.30(g).
 
For example, your firm’s procedure, (b)(4), dated 01/10/2011, does not include or refer to the process to be used when conducting a risk analysis. Specifically, the design history file (DHF) for the Otowave102 Hand Held Tympanometer device included a risk management file document that stated your firm (b)(4). However, your firm did not establish a process for identifying the potential hazards of the design project as required by the standard being used (b)(4).  
 
We reviewed your firm’s response and conclude that it is not adequate.  Your firm did not submit supporting documentation indicating that it will revise the Design and Development Procedure to include adequate requirements for conducting risk analysis. Your firm did not provide any information about developing a new risk analysis procedure.  Your firm’s response did not include evidence to indicate that a correction and corrective action (including identifying the potential hazards for the Otowave102 Hand Held Tympanometer device, as required by the standard being used to conduct risk analysis, and reviewing other validation activities to ensure that risk analysis was conducted as required) were implemented or that a systemic corrective action was considered.
 
Failure to establish and maintain adequate procedures for verifying the device design. Design verification shall confirm that the design output meets the design input requirements. The results of the design verification, including identification of the design, methods, the date, and the individuals performing the verification, shall be documented in the Design History File (DHF), as required by 21 CFR 820.30(f).
 
 
For example, your firm’s procedure, (b)(4), dated 01/10/2011, does not require that design outputs meet design input requirements. Specifically, the (b)(4)
 
We reviewed your firm’s response and conclude that it is not adequate.  Your firm did not submit supporting documentation indicating that it will revise the design verification procedure to include a requirement that the design outputs meet the design input requirements. Your firm did not provide any documentation to indicate that the design outputs met the design input requirements for the Otowave 102 Tympanometer. Your firm’s response also did not include evidence to indicate that a corrective action was implemented or that a systemic corrective action was considered.
 
3.    Failure to establish and maintain adequate procedures for defining and documenting design output in terms that allow an adequate evaluation of conformances to design input requirements. Design output shall be documented, reviewed, and approved before release, as required by 21 CFR 820.30(d).
 
For example, your firm’s procedure, (b)(4), 01/10/2011, does not contain requirements for defining and documenting design outputs in a form that would allow it to be adequately compared to design input requirements. Specifically, the design record, (b)(4) for the Otowave 102 Tympanometer does not contain documentation of design outputs in a form that would allow it to be compared to design inputs.
 
We reviewed your firm’s response and conclude that it is not adequate. Your firm did not submit supporting documentation indicating that it has revised the design control procedure to include a requirement (b)(4). For the Otowave 102 Tympanometer, your firm did not provide documentation comparing the design outputs and design inputs. Your firm’s response did not include evidence to indicate that a corrective action was implemented or that a systemic corrective action was considered. 
 
4.    Failure to establish and maintain adequate procedures for receiving, reviewing, and evaluating complaints by a formally designated unit. Such procedures shall ensure that complaints are evaluated to determine whether the complaint represents an event that is required to be reported to FDA under 21 CFR Part 803 or 804, as required by 21 CFR and 820.198(a)(3).
 
For example, your firm’s complaint procedure, (b)(4), dated 01/11/2011, does not include a requirement that complaints be evaluated to determine whether or not the complaint should be submitted to FDA as a medical device report. Specifically, the record for complaint (b)(6) did not contain objective evidence to indicate that it was evaluated to determine whether the complaint represented an event which is required to be reported to FDA.
 
We reviewed your firm’s response and conclude that it is not adequate.  Your firm did not submit supporting documentation indicating that it will revise the complaint handling procedure to include adequate requirements for evaluating complaints and for documenting if a medical device report needs to be filed. No documentation verifying that Complaint (b)(6) was reviewed to determine if it represented an event that is reportable to FDA was provided. Your firm’s response did not include evidence to indicate that a correction and corrective action (including reviewing all complaints to ensure that an evaluation to determine whether the complaint was required to be reported to FDA occurred) were implemented or that a systemic corrective action was considered. 
 
5.    Failure to establish and maintain procedures to control product that does not conform to specified requirements. The procedure shall address the identification, documentation, evaluation, segregation, and disposition of nonconforming product, as required by 21 CFR 820.90(a). 
 
For example, upon request from the investigator, your firm could not provide a procedure for control of non-conforming product. Also, your firm did not document the disposition of non-conforming product returned to the supplier (Note: 037819) on June 14, 2011.
 
We reviewed your firm’s response and conclude that it is not adequate.  Your firm did not submit supporting documentation indicating that it will establish a procedure for non-conforming product and that it will begin to maintain records of all non-conformances. Your firm did not provide any evidence to indicate that the product returned to the supplier on June 14, 2011, was subject to disposition. Your firm’s response did not include evidence to indicate that a corrective action was implemented or that a systemic corrective action was considered (including reviewing other non‑conformances to ensure proper disposition and that records were completed as required).  
 
6.    Failure to adequately maintain device history records (DHRs), as required by 21 CFR 820.184.
 
For example, according to your firm’s procedure, (b)(4) for each Pump Characteriser test, (b)(4)
 
We reviewed your firm’s response and conclude that it is not adequate. Your firm did not submit supporting documentation indicating (b)(4). Your firm did not provide any printouts of pump tests performed for route sheets 4788 and 4848. Your firm’s response did not include evidence to indicate that a corrective action (including reviewing other route sheets to ensure that the printouts for the pump tests performed were included) was implemented or that a systemic corrective action was considered. 
 
7.    Failure to adequately validate computer software for its intended use according to an established protocol, as required by 21 CFR 820.70(i).
 
For example, upon request for the protocol used during the validation of your firm’s software-controlled audiometer device calibration system, your firm stated that it did not have a pre-established protocol for conducting the validation. 
 
We reviewed your firm’s response and conclude that it is not adequate. Your firm did not submit supporting documentation indicating that it will create a requirement that protocols be used during future software validations. Your firm’s response did not address why no protocol was used during the validation of the audiometer testing equipment software. Your firm’s response also did not include evidence to indicate that a corrective action was implemented or that a systemic corrective action was considered (including reviewing all software validations to ensure that the validations were conducted as required).
 
8.    Failure to maintain adequate calibration procedures that include specific directions and limits for accuracy and precision, as required by 21 CFR 820.72(b).
 
For example, your firm’s calibration procedure, (b)(4) does not contain specification limits for accuracy and precision. Also, the testing records, (b)(4) do not contain specification limits or a record of the results of calibration testing.  Lastly, your firm’s process engineer, (b)(4), however, this specification is not established in your firm’s calibration procedure.
 
 
We reviewed your firm’s response and conclude that it is not adequate. Your firm did not submit evidence or supporting documentation to correct the issue of not documenting calibration specifications. Your firm did not provide documentation to indicate that it revised the testing procedure to include specification limits for finished product and that it will begin to maintain records of all calibration results that include specification limits. Your firm’s response did not include evidence to indicate that a corrective action was implemented or that a systemic corrective action was considered.
 
9.    Failure to establish adequate procedures for quality audits and conduct such audits to assure that the quality system is in compliance with the establish quality system requirements and to determine the effectiveness of the quality system. Quality audits shall be conducted by individuals who do not have direct responsibility for the matters being audited, as required by 21 CFR 820.22.
 
For example, your firm’s procedure for internal quality audits, (b)(4), dated 01/04/2009, does not require that audits be performed by someone not directly in authority over areas being audited.  Specifically, (b)(4).
 
We reviewed your firm’s response and conclude that it is not adequate. Your firm did not submit supporting documentation indicating that it will revise the internal quality audit procedure to include a requirement that audits be performed by someone who is not directly responsible for the area being audited. Your firm’s response did not include evidence to indicate that a correction (including ensuring that audits of management reviews and the Quality System were conducted as required) and corrective action were implemented or that a systemic corrective action was considered. 
 
10.    Failure to establish adequate procedures for training, identifying training needs, and ensuring that all personnel are trained to adequately perform their assigned duties. Training shall be documented, as required by 21 CFR 820.25(b).
 
For example, your firm’s training procedure, (b)(4), dated 01/04/2009, (b)(4). However, a review of training records for two production employees indicated that they were not trained in the areas of product testing and product calibration procedures for the product types listed above.

We reviewed your firm’s response and conclude that it is not adequate. Your firm did not submit supporting documentation indicating that it will revise the training procedure to include adequate requirements for training needs. Your firm’s response did not include evidence to demonstrate that the production employees were adequately trained. Your firm’s response did not include evidence to indicate that a corrective action (including reviewing training records of other employees to ensure that they were trained as required) was implemented or that a systemic corrective action was considered. 

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 action (including any systemic corrective actions) that your firm has taken.  If your firm’s planned corrections and/or corrective actions will occur over time, please include a timetable for implementation of those activities.  If corrections and/or corrective actions cannot be completed within fifteen business days, state the reason for the delay and the time within which these activities will be completed.  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, Office of Compliance, Field Operations Branch, White Oak Building 66, Rm 2609, 10903 New Hampshire Ave., Silver Spring, Maryland 20993. Refer to CMS case #290397 when replying. If you have any questions about the contents of this letter, please contact: Mr. Ron Swann at 301-796-5770 or 301-796-8173 (fax).
 
 
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/                                                           
Steven D. Silverman
Director
Office of Compliance
Center for Devices and
Radiological Health