| Public Health Service Food and Drug Administration |
| 10903 New Hampshire Avenue Silver Spring, MD 20993 |
Department of Health and Human ServicesWARNING LETTER
AUG 04 2010
VIA United Parcel Services
Jan I. Stalemark
CEO
Neoventa Medical AB
Agatan 32
SE-431 35 Molndal, Sweden
Dear Mr. Stalemark:
During an inspection of your firm located in Molndal, Sweden on March 29, 2010 through April 1, 2010, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures fetal heart monitors. 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 are intended 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 (CGMP) requirements of the Quality System (QS) regulation found at Title 21, Code of Federal Regulations (CFR), Part 820. We received a response from Mr. Jan I. Stalemark, Chief Executive Officer dated April 20, 2010 concerning our investigator's observations noted on the Form FDA 483, List of Inspectional Observations that was issued to you. 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 implementing corrective and preventive action that include requirements for verifying or validating the corrective and preventive action to ensure that such action is effective and does not adversely affect the finished device and that all activities required under this section and their results be documented, as required by 21 CFR 820.100(a)(4) and (b).
For example: your Corrective and Preventive Actions 33/S0P-2 Revision H does not address verification or validation of corrective and preventive actions to ensure such action is effective and does not adversely affect the product or process. In addition your procedure, Corrective and Preventive Actions 33/S0P-2 Revision H, does not include requirements to document verification/validation activities when these activities are necessary. Your Template for CAPA reports, Document number 3/RPT-4 Revision A does not include requirements to complete and document verification/validation activities.
We have reviewed your response and have concluded that it is inadequate. You provided documentation and indicated that you only reviewed 10 CAPAs. You provided documentation that you modified the Corrective and Preventive Action SOP to incorporate a step to ensure that the corrective action is effective and does not adversely affect the finished device and that training was conducted on this revised SOP. However, you did not provide a description and evidence of any systemic corrective action to include reviewing all CAPAs to ensure that verification/validation activities were taken effectively and that the verification/validation activities were now documented appropriately.
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:
a. Your Complaint Handling 13/S0P-2 Revision J does not ensure that all instances of written, electronic or oral communications are considered and handled as complaints because the procedure does not include consideration of communications that allege deficiencies of the device and it does not include consideration of communications that address deficiencies related to the effectiveness of the device; thus the Complaint Handling 13/S0P-2 Revision J procedure does not ensure that all complaints as defined by 21 CFR 820.3(b) are processed.
We have reviewed your response and have concluded that it is inadequate. You provided a copy of the revised Complaint Handling 13/S0P-2 Revision K and documentation of training on these revised procedures. However, you did not provide a description and evidence of implementation of systemic corrective action or performing a retrospective review of previous data according to the new procedure and definition.
b. Your Complaint Handling Procedure 13/S0P-2 Revision J requires any documents associated with a complaint to be identified with the complaint number; however, of the nineteen complaints reviewed, all had documents which had not been identified by the complaint number and all complaint files reviewed were missing documents; these complaints were not processed in a uniform manner as required. For example, complaints (b)(4) and (b)(4) included reports, event log and monitor printout and emails, respectively which were not identified with the Complaint No. as required by the firm's Complaint Handling procedure 13/S0P-2 Revision 1.
We have reviewed your response and have concluded that it is inadequate. Although the modified Complaint Handling Template and Procedures incorporated a space for "Complaint TD", TD numbers on all of the documents related to each complaint. In addition, evidence of implementation of a corrective action and consideration of a systemic corrective action were not provided for having missing documents
within complaint files.
c. Of the nineteen complaint files reviewed, all were missing documentation. For example, the complaint files for Complaints (b)(4) and (b)(4) did not include documentation of the initial oral conversations regarding the complaint information originally received from the complainants as required by the firm's Complaint Handling Template and procedure. Written documentation referencing (b)(4) and (b)(4) indicated oral conversations were conducted that provided information that led to filing these complaints.
We have reviewed your response and have concluded that it is inadequate. You provided a copy of the modified Complaint Handling Template and Procedures which included developed steps that ensure each complaint is being evaluated and documented in the complaint file and documentation of the training on the revised procedure. You did not provide a description and evidence of implementation of a correction to having missing documentation in complaint files; evidence that the information received orally was included in the complaint was not provided. In addition evidence of consideration of a systemic corrective action was not provided for a retrospective review and analysis of other improperly documented oral complaints.
3. Failure to include the date the complaint was received in the record of investigation when an investigation is made, as required by 21 CFR 820.198(e)(2).
For example: all nineteen complaint files reviewed did not include the date the complaint was received. The complaint files included the complaint registration date, but not the date the complaint was initially received. Complaints (b)(4) and (b)(4) do not contain the date the complaint was received.
We have reviewed your response and have concluded that it is inadequate. You indicated that you modified the Complaint Handling Process to ensure that the complaint awareness date is correctly documented and that training on the revised procedure was completed. However, you did not provide evidence that the date the complaint was made was now included in the complaints. In addition evidence of consideration of a systemic corrective action was not provided nor a retrospective review and analysis of other improperly documented complaints.
4. Failure to establish and maintain adequate procedures for rework, to include retesting and reevaluation of the nonconforming product after rework, to ensure that the product meets its current approved specifications; rework and reevaluation activities, including a determination of any adverse effect from the rework upon the product shall be documented in the Device History Record (DHR), as required by 21 CFR 20.90(b)(2).
For example: documentation of the rework conducted on SIN (b)(4) under (b)(4) was not recorded in the DHR as required under Section 4.3.3 Documentation and release in Document number 3/INS-SBS 101 003 EN Revision L, "STAN S31 Safety and Basic Function Test".
We have reviewed your response and have concluded that it is inadequate. You upgraded the SOP for Corrective and Preventive Actions to address this failure. Specifically, both non-conformity/rework records and the DHR now have fields for reference to each other. Employee training on these revised SOP has been completed and documentation was provided. However, you did not provide evidence of implementation of the correction and you did not provide documentation that you reviewed other rework activity conducted to ensure information was appropriately included and recorded.
Our inspection also revealed that your devices are misbranded under section 502(t)(2) of the Act 21 U.S.C. 352(t)(2), in that your firm failed or refused to furnish material or information respecting the device that is required by or under section 519 of the Act, 21 U.S.C. 360i, and 21 CFR Part 803 - Medical Device Reporting (MDR) regulation. Significant deviations include, but are not limited to, the following:
1. Failure to report to the FDA no later than 30 calendar days after the day you receive or otherwise became aware of information, from any source, that reasonably suggests that a device that you market may have caused or contributed to a death or serious injury, as required by 21 CFR 803.50(a)(1).
For example:
a. Your Complaint (b)(4) involved an event that occurred on September 18, 2007. This event resulted in a poor outcome involving a baby (death) and it was known that a STA S31 monitor was in use during the delivery. While the complaint was registered in the firm's complaint system on May 19, 2008, the date you became aware of the incident was not documented in the compliant file. Manufacturers Incident Report Form which is a follow-up report regarding the death of newborn, lists an event date of September 18, 2007. You did not file an MDR Report with FDA and neither established a decision for filing the report with the FDA.
b. Your Complaint (b)(4) involved an event that occurred on June 1, 2007. This event also resulted in a poor outcome involving a baby and it was known that a STAN S31 monitor was used. The date that you became aware of the event was not documented in your complaint file. You concluded the device was not alleged to have caused or contributed to the poor outcome of the baby since the clinic where the event occurred did not report the incident to the firm. An employee of your firm read about the incident in a newspaper article which indicated that a complaint of medical negligence was filed with the local regulatory authorities presumably by the patient. You subsequently initiated an investigation, but the clinic involved declined to provide additional information about the event until the medical negligence case was resolved and closed. You determined the event is reportable and reported it to the Swedish authorities, but you failed to report it to the FDA.
c. Your Complaint (b)(4) includes an evaluation for MDR reportability of an adverse event involving the STAN S31 monitor. The evaluation indicated that the event was not MDR reportable, but it was reported to Swedish regulatory authorities. The investigator indicated that an MDR should have been filed with the FDA.
We have reviewed your response and have concluded that it is inadequate. You upgraded your SOP for Complaint Handling and Medical Device Reporting and established a new Reportable Events Decision Tree template that will be used to document the decisions for not reportable. However, you did not provide documentation that you filed the events that may have caused or contributed to death or serious injury involving a baby as MDRs with the FDA.
2. Failure to develop, maintain, and implement adequate written MDR procedures for internal systems that provide for timely and effective identification, communication, and evaluation of events that may be subject to MDR requirements as required by 21 CFR Part 803.17(a)(1).
For example: your Medical Device Reporting Procedure, 30/S0P-2/INT 000 001 EN, Revision G, dated 2007-10-09, does not adequately describe how you will provide for timely and effective identification, communication, and evaluation of events that may be subject to the MDR requirements in 21 CFR §803. The procedure provides references to the Complaint Handling 13/S0P-2 and other documents that should be utilized when determining MDR reportability. The Complaint Handling procedure does not include a determination to be reportable to FDA for instances where a device may have caused or contributed to a serious injury. Therefore some events may not be identified and evaluated timely and effectively. Specifically, the MDR procedure does not address how the firm will assess events that may be subject to the MDR reporting requirements. The "Reportable events" section on page 1 of 10 uses terminology and/or definitions, such as "serious deterioration in state of health", that is not consistent with the terminology and definitions in 21 CFR Part 803.3. The procedure includes "Exceptions" to reportable events, for example, under "death [5]=", it lists two "Exceptions" where a death would not be reportable to FDA. You need to clarify that the "Exceptions" will only be applicable if documentation is available to support the decision not to file an MDR for the various scenarios listed. The Decision Chart on page 5 of 10 is illegible in places, but for areas that are visible, the firm has combined terminology and definitions from the MDR regulation with terminology and definitions for European Medical Device Vigilance reporting (MDV). The chart is difficult to follow if evaluating for MDR decision making purposes.
We have reviewed your response and have concluded that it is inadequate because your Evaluation of Potential MDR Reportable, 30/INS-3/INT 000 001 EN, Revision A, dated April 19, 2001 is inadequate. You noted that the guideline is to be used primarily for events involving electronic fetal/maternal monitors, but may also apply to other devices. In the chart, specific event scenarios are defined, such as "loss of signal," and it provides definitions, MDR reporting and non-reporting rationale. The chart, as written may not capture all situations where an event may be reportable. For example, in the "loss of signal" section, an MDR reportable event is described as one in which the loss of signal
may have required significant or unnecessary medical intervention. This is incorrect. The definition of an MDR reportable event is one in which the information reasonably suggests that a marketed device may have caused or contributed to a reportable death or serious injury. The definition of a serious injury is: an injury or illness that: 1) is life-threatening; 2) results in permanent impairment of a body function or permanent damage to a body structure; or 3) necessitates medical or surgical intervention to preclude permanent impairment of a body function or permanent damage to a body structure. As written, the document does not provide timely and effective identification of events that may be subject to the MDR regulation.
Your Medical Device Reporting Procedure, 30/S0P-2/INT 000 0001 EN, Revision H, dated April 19, 2010 I, is inadequate because the document provides references to other documents. The problem is that these documents are listed only as references. They should be identified as companion documents for decision making for MDR reportability.
The procedure also contains an incorrect reference in Section 4.3.2 to Annual Certification using FDA Form 3381. The FDA Modernization Act of 1997 repealed the requirement for manufacturers to submit annual certification reports to FDA. The requirement to submit annual certification reports to FDA was removed from the MDR regulation in February 2010. You may remove this reference.
3. Failure to establish and maintain adequate MDR event files, as required by CFR 21 803.18(a).
For Example:
a. The Complaint file for (b)(4) which was reported as an MDR, did not include documentation of the investigation results and the date laboratory results were obtained for the patient's pH levels and blood results which were reported in the MDR file. General instructions for completing the MDR require the date the laboratory test was completed and results obtained.
b. The Complaint file for the (b)(4) which was reported as an MDR, did not include documentation of the investigation results and the date laboratory results were obtained for the patient blood results and diagnosis. General instructions for completing the MDR require the date the laboratory test was completed and results obtained.
We have reviewed your response and have concluded that it is inadequate. You provided a new template for Compliant Evaluation Report which will be developed for every complaint received. However, you did not provide documentation that you included the missing information in the MDR file.
Given the serious nature of the violation(s) of the Act, fetal heart monitors manufactured by your firm are subject to refusal of admission under section 801(a) of the Act, 21 U.S.C. § 381(a), in that they appear to be adulterated. As a result, FDA may take steps to refuse these products, known as "detention without physical examination," until these violations are corrected. In order to remove the devices from detention, you should provide a written response to this Warning Letter as described below and correct the violation(s) described in this letter. We will notify you if your response is adequate, and we may need to re-inspect your facility to verify that the appropriate corrections have been made.
Also, U.S. federal agencies are advised of the issuance of all 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 (15) working days from the date you receive this letter of the specific steps you have taken to correct the noted violations, including an explanation of how you plan to prevent these violation(s), or similar violation(s), from occurring again. Include documentation of the corrective action you have taken. If your planned corrections will occur over time, please include a timetable for implementation of those corrections. If corrective action cannot be completed within 15 working days, state the reason for the delay and the time within which the corrections will be completed. Please provide a translation of documentation not in English to facilitate our review.
Your response should be sent to: Mr. Paul F. Tilton, Chief, OB/GYN, Gastroenterology, and Urology Devices Branch, 10903 New Hampshire Avenue, Silver Spring, MD 20993. If you have any questions about the content of this letter please contact: Ms. Leslie E. Caster at 301-796-5770 or by fax at 301-847-8137.
Finally, you should know that this letter is not intended to be an all-inclusive list of the violations at your facility. It is your responsibility to ensure compliance with applicable laws and regulations administered by FDA. The specific violations noted in this letter and in the Inspectional Observations, Form FDA 483 (FDA 483), issued at the closeout of the inspection may be symptomatic of serious problems in your firm's manufacturing and quality assurance systems. You should investigate and determine the causes of the violations, and take prompt actions to correct the violations and to bring your products into compliance.
Sincerely yours,
/s/
Timothy A. Ultaowski
Director
Office of Compliance
Center for Devices and
Radiological Health
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