Inspections, Compliance, Enforcement, and Criminal Investigations
Zevex International, Inc. 4/20/11
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
Denver District Office
April 20, 2011
Mr. Robert T. Brady
CEO and President
300 Jamison Road
East Aurora, New York 14052
Dear Mr. Brady:
During an inspection of your firm, doing business as Zevex International, Inc., located at 4314 Zevex Park Lane, Salt Lake City, Utah, on December 7 – January 5, 2010, investigators from the United States Food and Drug Administration (FDA) determined that your firm manufactures Curlin 4000 and Curlin 6000 Infusion pump systems. 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. You can find these regulations on the FDA website at www.fda.gov
We received a response from Mike Henderson, Group Director for Operations/Management Representative dated January 20, 2011, concerning our investigators’ observations noted on the Form FDA 483, Inspectional Observations (FDA 483), that was issued to Mr. Luis O. Burgos, Group Director RA/QA, Zevex International, Inc. 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, as required by 21 CFR 820.100(a).
• (b)(4), Corrective and Preventive Action (CAPA) procedure specifies that CAPA activities need to be implemented in a “timely manner”; and that problems related to patient safety must be addressed with “all due haste” but does not define either of these terms. Corrective Action Plan (CAP) (b)(4) has been open since (b)(4). CAP (b)(4) has been open since (b)(4). CAPA (b)(4) was opened in (b)(4) , updated (b)(4), with a new due date of (b)(4).
• (b)(4) , Corrective and Preventive Action procedure does not specify the use of appropriate statistical methodology where necessary in the analysis of quality data to detect recurring quality problems such as the (b)(4).
• (b)(4), Corrective and Preventive Action Projects and Tasks, defines Corrective Action Tasks (CATs) as CAPA actions taken when the risk is undesirable. CAT (b)(4) was initiated for overrun complaints in the (b)(4). According to the QSP (b)(4), this CAT did not require verification of corrective actions despite the fact that complaints continued to be received regarding overruns and MDRs have been filed for this problem.
• CAPA (b)(4) was opened on (b)(4), under (b)(4). CAPA (b)(4) was initiated for (b)(4) errors on the (b)(4). The (b)(4) error causes (b)(4)]. The CAPA was closed on (b)(4), despite continued complaints related to (b)(4) prior to the completion (including the identification, validation, implementation, and verification of effectiveness) of a (b)(4) designed to address the problem.
• CAPA (b)(4) was opened on (b)(4), to address the failure of and evaluate Infinity Orange Enteral Feeding Pump complaints since the product was released to market. Corrective actions identified included (b)(4). This corrective action was not implemented.
The adequacy of your response cannot be determined at this time. You stated that you are aware of the importance of having a fully implemented and effective CAPA system addressing issues in a timely manner. You attempted to address the individual CAPAs mentioned in the observations but stated that the process to review and provide a complete and accurate response will require time. You contracted an outside auditor to assist in performing an in depth assessment of your Design Controls and Risk Management processes as well as to develop corrective action plans addressing all identified gaps. According to your submitted action plan, the assessment was to be completed (b)(4). The review of all CAPAs and CATs currently opened or initiated within the last 24 months will be completed within (b)(4). FDA cannot make an assessment with respect to the adequacy of your response without the results of the action plan and corrective actions documentation related to CAPAs and Risk Management.
2. 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).
• The Curlin 6000 infusion pump has undergone several software revisions to its original version (b)(4) in an attempt to eliminate (b)(4). These revisions were not adequately validated. Curlin 6000 infusion pumps containing versions of the (b)(4) software continue to experience (b)(4).
• Although the Curlin 6000 infusion pump (b)(4) problem, it introduced the potential for Curlin 6000 infusion pumps to experience (b)(4). This revision was not adequately validated. Curlin 6000 infusion pumps containing (b)(4).
• Servicing requirements were not identified, documented, validated (or where appropriate verified), reviewed and approved prior to the implementation of (b)(4) for Curlin 6000 infusion pumps.
• A change was made to the User Manual for the Curlin 6000 infusion pumps stating “Important Safety Note*** In a life sustaining situation, it is recommended that your Curlin Infusion pump use the AC adapter and have a back up pump available.***” This change was not incorporated into the User Manual available on your firm’s website.
We reviewed your response and concluded that it is not adequate for Observations 1 and 3 because your firm did not submit validation documentation for the various design changes for the Curlin 6000 software. Although your response provided a chronology of the revisions and the efforts to mitigate the failure, there was no documentation provided which ensures that the validation of the software was conducted at every change to include compatibility with previously released software and servicing requirements. Additionally, the version of the software called (b)(4) has been developed to address the (b)(4). However, there was no documentation submitted to FDA for the ongoing validation you have been conducting for (b)(4).
The adequacy of your response for Observation 2 cannot be determined at this time. The Curlin 6000 pump user’s manuals on your Website have been replaced with the current version instructing users to employ a second pump when administering life sustaining therapies. Your firm also stated that you have completed a review of all other product labeling posted on your website to assure that only the current versions are posted. However, the review documents related to product labeling on the website and your firm’s procedure which was implemented on February 18, 2011, addressing how the user’s manual will be updated on the website, were not submitted as part of your response.
3. Failure to adequately establish and maintain procedures for receiving, reviewing, and evaluating complaints by a formally designated unit, as required by 21 CFR 820.198(a).
• Neither (b)(4) Complaint Handling nor (b)(4) Failure Investigation contain provisions to ensure complaints are evaluated and, when necessary, investigated (or document the reason why complaints are not investigated) when no product is returned. (b)(4), were closed without any evaluation or investigation because the pumps were not returned.
• The term “early warning” which may elevate a complaint to the level of a CAPA is not adequately defined in (b)(4) Complaint Handling.
• Failure to implement (b)(4), Complaint Handling, (b)(4) which states that all complaints should contain an Adverse Event Determination Form(b)(4). Complaint records associated with (b)(4) did not contain an Adverse Event Determination Form.
Your response to Observations 6B-6E appears to be adequate. (b)(4) of your firm’s (b)(4) Complaint Handling procedure currently includes the information to be gathered related to the device, the return of the device, the responsible person evaluating the complaint and whether the device is available to be returned for the purpose of investigation. The procedure further makes the stipulation that if the device is not received back for investigation, the investigation form shall be completed and includes a review of the Device History Record (DHR) before the complaint can be closed. (b)(4) discussed how complaints related to death, serious injury attributed to device failures, malfunctions or improper or inadequate design will be investigated.
The adequacy of your response for Observations 6A and 6F cannot be determined at this time. Your firm’s (b)(4) procedure for Complaint Handling no longer mentions (b)(4) (Adverse Event Determination Form). Instead, (b)(4)]refer to the pertinent information necessary for a complaint to be forwarded to your firm’s responsible representatives for evaluation of reportability as an Adverse Event. It appears that the complaint form has taken the place of (b)(4). However, you did not submit a copy of the complaint form (b)(4) in your response. You also did not include a definition of what would constitute an “early warning” which may elevate a complaint to the level of a CAPA. (b)(4). The adequacy of your response cannot be determined until the assessment and development of the corrective action plan which was completed on (b)(4), is submitted to the FDA.
4. Failure to establish and maintain adequate procedures to ensure that the design requirements relating to a device are appropriate and address the intended use of the device, including the needs of the user and the patient, as required by 21 CFR 820.30(c). For example, the design of the Infinity Orange Enteral Feeding Pumps failed to include requirements for the servicing of the pumps.
The adequacy of your response for Observation 3 cannot be determined at this time. Your firm acknowledged the importance of including servicing provisions as a design input that must be considered, implemented as appropriate and verified and validated prior to release of a new product as part of the Design Control process. (b)(4). The adequacy of your response cannot be determined until the completion of the action plans for the Design Controls process, the DHR updated and submitted to FDA for review.
5. Failure to establish and maintain records of acceptable suppliers, contractors and consultants, as required by 21 CFR 820.50(a)(3).
For example, (b)(4), Purchasing Controls, Rev (b)(4), requires suppliers to be rated on a scale of (b)(4). A supplier (b)(4) received a rating of (b)(4), Acceptance Activities, (b)(4), requires the supplier status to be on the Approved Vendor List (AVL) which will determine whether the supplier-provided parts that were sampled by QA on a normal or tightened sampling schedule. The AVL list provided on December 14, 2010, did not reflect the current status of (b)(4) as “conditional” reflecting their vendor rating of (b)(4).
Your response to Observation 15 appears to be adequate. You explained in your response and evidenced by the submitted documentation that the supplier rating for (b)(4) was an isolated incident. Your review of the monthly reports from December 2009, to the present indicated that (b)(4) had an acceptable rating every month except for (b)(4). The problem with the low rating was resolved in (b)(4), but the records were not updated to reflect the supplier’s status. You have also indicated that the Quality Manager responsible for updating the suppliers on the Approved Supplier List has been re-trained to update the records.
6. Failure of management with executive responsibility to review the suitability and effectiveness of the quality system at defined intervals, as required by 21 CFR 820.20(c).
• (b)(4) Management Review specified personnel that were required to attend (b)(4) Management Review meetings. The Management Review meeting held on (b)(4), was not attended by required Zevex/Moog personnel (e.g. President, General Manager of Operations, Group Director of Quality/Regulatory, Group Director of Operations, Group Director of Research and Development, General Manager of Sales and Marketing, Finance Manager, Human Resource Manager).
• (b)(4) Management Review specified that the Director of Marketing be present for Management Review meetings. The Director of Marketing did not attend the Management Review meeting held (b)(4).
The adequacy of your response for Observation 16 cannot be determined at this time. Your firm provided an explanation why the required attendees for Management Reviews were absent. You stated in your response that Zevex (b)(4). The procedure, (b)(4) Management Review has been updated to allow authorized designees to attend the management review meetings for the required attendees. (b)(4) limits the number of designees allowed to attend Management Review to (b)(4). Since the procedure states that Management Review Meetings occur (b)(4), and the last meeting occurred on (b)(4), the adequacy of the procedural change cannot be determined until the next management review meeting is held.
Our inspection also revealed that your Curlin 6000 Infusion pump 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 violations include, but are not limited to, the following:
a. Failure to have an adequate written MDR procedure establishing internal systems that provide for timely and effective identification, communication, and evaluation of events that may be subject to MDR requirements, a standardized review process or procedure for determining when an event meets the criteria for reporting, timely transmission of complete medical device reports, and documentation and recordkeeping requirements, as required by 21 CFR 803.17.
b. Failure to report to the FDA no later than 30 calendar days after the day that you receive or otherwise become 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 CFR803.50(a)(1).
For example, the MDR procedure does not provide a process for complying with the documentation and recordkeeping requirements of 21 CFR 803.17(b). Although your procedure indicates who is responsible for submitting a report to the FDA when needed, it does not indicate who is responsible for making a reportability determination. The procedure also does not indicate your responsibility to collect all information reasonably known for transmission of complete MDRs.
If your firm is not able to collect all information required, you should indicate this on the 3500A along with an explanation for why it is not included and what efforts you are making to collect the information, as required by 21 CFR 803.50(b)(3). In addition, your incident report for CAPA (b)(4) refers to an incident which you became aware of on (b)(4). This event should have been submitted as a serious injury MDR within 30 calendar days of receiving or becoming aware of the event, as required by 21 CFR 803.50(a)(1).
We reviewed your response dated January 20, 2011, and concluded that it is not adequate for Observations 9, and 10. Although you have outlined a plan to assess your complaint/MDR management process, you did not describe what specific actions you will take or when the corrective actions will be implemented. Your response to Observation 10 is not adequate because you have not yet submitted an MDR for the referenced event and have not yet provided the results of your retrospective review outlined in your response.
Our inspection also revealed that your Curlin 6000 Infusion pump 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 806 – Reports of Corrections and Removals regulation.
a. Failure to submit a written report to FDA of any correction or removal of a device initiated by such manufacturer or importer if the correction or removal was initiated to reduce a risk to health posed by the device, as required by 21 CFR 806.10(a)(1).
b. Failure to submit a written report to FDA of any correction or removal of a device initiated by such manufacturer or importer within 10 days of initiating that removal, as required by 21 CFR 806.10(b).
For example, the Curlin 6000 infusion pumps with V2.0 software were found to contain a defect resulting in an (b)(4) which could pose a serious risk to health when pumps are used in life sustaining therapies. As a result, customers were instructed not to use the pumps until a correction to the software could be made and the software on pumps containing V2.0 could be upgraded. Some pumps were received due to complaints, while others were returned for "service" and these pumps have been placed on hold pending an upgrade and correction to the V2.0 software. This correction was not reported to FDA.
We reviewed your response and concluded that it is not adequate for Observation 12. You provided an explanation why the changes in the software were not reported as field corrections. It appears that not reporting the field correction was a decision made by the previous Group Director in charge of Quality and Regulatory Affairs and he based his decision on what he thought was the perceived risk. Your firm decided to submit the field correction and is currently conducting a voluntary recall of the Curlin 6000 infusion pumps but only as a result of a recent inspection and after a telephone conference with FDA’s Center for Devices and Radiological Health.
A follow up inspection will be required to assure that corrections and/or corrective actions are adequate.
You should take prompt action to correct the violations addressed in this letter. Failure to promptly correct these violations may result in regulatory action being initiated by the Food and Drug Administration without further notice. These actions include, but are not limited to, seizure, injunction, and/or civil money penalties. Also, 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 violations 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) business days from the date you receive this letter of the specific steps you have taken to correct the noted violations, as well as an explanation of how you plan to prevent these violations, or similar violations, from occurring again. Include documentation of the corrections and/or corrective actions you have taken. If your planned corrections and/or corrective actions will occur over time, please include a timetable for implementation of these activities. If corrections and/or corrective actions cannot be completed within 15 business days, state the reason for the delay and the time within which these activities will be completed. Your response should be comprehensive and address all violations included in this Warning Letter.
Your response should be sent to: Food and Drug Administration, Denver District, P. O. Box 25087, (6th Ave. and Kipling Pkwy., DFC, Bldg 20), Denver, CO 80225-0087, Attention: William H. Sherer, Compliance Officer. If you have any questions about the content of this letter, please contact Mr. Sherer at telephone number (303) 236-3051 or fax (303) 236-3551.
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 Form FDA 483, issued at the closeout of the inspection may be symptomatic of serious problems in your firm’s manufacturing and quality management 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.
LaTonya M. Mitchell
Acting District Director