Inspections, Compliance, Enforcement, and Criminal Investigations
EP Medsystems 27-Sep-06
Department of Health and Human Services
Public Health Service
Telephone (973) 526-6006
September 27, 2006
RETURN RECEIPT REQUESTED
Mr. David Jenkins
Chief Executive Officer
575 Route 73 North, Bldg. D
Cooper Run Executive Park
West Berlin, NJ 08091
Dear Mr. Jenkins:
During an inspection of your firm located at 575 Route 73 North, Building D, Cooper Run Executive Park, West Berlin, NJ, on April 13, 2006, through May 3, 2006, investigators from the United States Food and Drug Administration (FDA) determined that your firm manufactures External Programmable Pacemaker Pulse Generators (EP-4 Clinical Stimulators). 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 any function of the body.
This inspection revealed that your 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, the manufacture, packaging, 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 (C.F.R.) Part 820. The deviations included, but are not limited to, the following:
1. Failure to establish and maintain complaint handling procedures to ensure that all complaints are evaluated to determine whether the complaint should be filed as a Medical Device Report, as required by 21 CFR § 820.198(a), and failure to review, evaluate, and investigate all complaints that represent an event that must be reported under 21 CFR part 803, as required by 21 CFR § 820.198(d). For example, your firm .failed to report EP-4 Clinical Stimulator malfunction complaints (complaint # 17407 on September 7, 2005, and complaint # 18210 on November 29, 2005), where the patients experienced ventricular fibrillation and atrial fibrillation while using your devices. Your firm did not conduct a field investigation into the incident reported in complaint #17407 until after you made the decision that the complaint did not require filing of a MDR.
2. Failure to implement design validation procedures that ensure that devices conform to defined user needs and intended uses and that include testing of production units under actual or simulated use conditions, as required by 21 C.F.R. § 820.30(g). Specifically, your firm did not have design validation data for your EP-4 two channel and four channel stimulators.
3. Failure to implement procedures for ensuring that participants at each design review include an individual who does not have direct responsibility for the design stage being reviewed, as required by 21 C.F.R. § 820.30(e). Specifically, your firm failed to implement procedure 1066A.DOC (procedure for conducting and documenting design reviews, dated July 26, 2001) for the design review of the EP-4 Stimulator, which should have included a [redacted] review from [redacted]. Your design review summary report for the EP-4 Stimulator (dated January 16, 2004) only included a review from the [redacted] and not an individual who does not have direct responsibility for the design.
4. Failure to follow procedures for the identification, documentation, validation or verification, review, and approval of design -changes before their implementation; as required by 21 C.F.R. § 820.30(i). Specifically, your firm did not have any documentation at the time of this inspection to demonstrate that the use of an [redacted] on the EP-4 Stimulator [redacted] had been validated or verified, reviewed, and approved prior to use.
5. Failure to conduct and control production processes in accordance with documented instructions and standard operating procedures as required by 21 C.F.R. § 820.70(a)(1). Specifically, your firm failed to follow procedure 24-0020-000 (Software release procedure) which requires quality assurance to review and sign off on any engineering change request form (ECR), which is used for the approval of software release. For example:
A) Software [redacted] was installed in an [redacted] used with EP-4 Stimulator in March of 2005, at [redacted] prior to receiving quality assurance approval on August 17, 2005.
B) Software [redacted] was installed in at least [redacted] (earliest installment date to be October 25, 2005, at the [redacted]), prior to receiving quality assurance approval on February 8, 2006.
Additionally, the inspection revealed that your devices are misbranded within the meaning of Section 502(t)(2) of the Act (21 U.S.C. § 352(t)(2)), in that your establishment 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. Specifically:
1. You failed to report to us no later than 30 calendar days after receiving information which reasonably suggested that one of your commercially distributed devices may have caused or contributed to a death or serious injury, as required by 21 CFR § 803.50(a)(1), You also did not conduct an investigation of each event and evaluation of the cause of the event, as required by 21 CFR § 803.50(b)(3). For example:
A) Complaint 17407 (dated September 7, 2005) for your EP-4 Stimulator reports an incident involving an incorrect stimulation at 40 msec when the value was set at 320 msec. This resulted in the patient's rhythm degenerating into ventricular fibrillation since the induced ventricular tachycardia could not be terminated using burst (overdrive) pacing. The patient needed to be externally cardioverted with 200 joules of bi-phasic energy. Your firm determined that this incident was not reportable prior to conducting a field investigation into the incident.
B) Complaint 18879 (dated February 13, 2006) reports intermittent problems with your EP-4 Stimulator where the system was off or not connected. According to your investigation, the customer induced ventricular fibrillation during the electrophysiology (EP) study but could not pace the patient out of ventricular fibrillation with the EP-4 Stimulator. The customer needed to cardiovert the patient, which your investigation indicated was not uncommon, but could not do so with the EP-4 Stimulator because it was not providing stimulation, which your investigation indicated was uncommon. Your firm determined that this event was not reportable where your investigation into the incident was still open.
(2) In addition, you failed to submit an MDR report to FDA within 30 days after receiving information .which reasonably suggested that your marketed devices malfunctioned, and that the device or a similar device would likely cause or contribute to a death or serious injury if the malfunction were to recur, as required by 21 CFR § 803.50(a)(2). For example:
A) Complaint 18210 was reported on November 29, 2005, regarding your EP-4 Stimulator where the customer indicated that this system delivered a high rate stim in the atrium prior to hitting the stim button, which put the patient into atrial fibrillation. Your firm installed a new EP-4 Stimulator on November 30, 2005, to replace the malfunctioning unit. Nonetheless, your firm decided on December 7, 2005, not to report this incident.
B) Complaint 16849 was reported on July 15, 2005, regarding your EP-4 Stimulator where the customer stated that this device gave an output when they selected a pacing site, which induced the patient into atrial fibrillation. Your firm's investigation initially concluded that the problem was not found on the EP-4 because you could not recreate the event [redacted],however, you later concluded that the [redacted] According to the complaint form, your firm did not consider this an MDR reportable event.
C) Complaint 16070 was reported on May 3, 2005, regarding your EP-4 Stimulator malfunctioning where there was noise on channel 1; channel 4 was difficult to capture even when using high current, and the channel 2 pacing LED is always lit. The patient went into atrial fibrillation prior to channel 2 activation. Your firm did not consider this incident lo be an MDR reportable event.
Furthermore, our inspection revealed that your External Programmable Pacemaker Pulse Generators (EP-4 Clinical Stimulator) are misbranded within the meaning of Section 502(t)(2) of the Act (21 U.S.C. § 352(t)(2)), in that your firm failed or refused to furnish information or material respecting the device that is required by or under Section 519(f)(1) of the Act (21 U.S.C. § 360i(f)(1)), and 21 CFR, Part 806-- Reports of Corrections and Removals. The Correction and Removal Regulation requires manufacturers and importers to submit a written report to FDA of any correction or removal of a device to reduce a risk to health. See 21 C.F.R. § 806.10(a). This written report must be submitted to FDA within ten (10) working days of initiating such correction or removal. See 21 C.F.R. § 806.10(b).
Your firm initiated corrections due to complaints of intermittent or no channel output (loss of stimulation output from one of the channels) for your EP-4 Stimulators, which, as explained below, your own hazard evaluations indicated could pose significant health risks. Accordingly, your failure to report the following product correction or removal actions to FDA within 10 days of initiating the correction or removal is a violation of 21 C.F.R. § 806.10(b):
A) Your firm had initiated a field correction on January 11, 2005, in order to replace [redacted] with [redacted] on EP-4 stimulator [redacted]. As of March 13, 2006, your firm had replaced the [redacted] EP-4 Stimulators due to [redacted] which caused [redacted] (the production line failure rate for this nonconformity was [redacted]). Your May 8 and May 24, 2006, responses indicated that this has the potential to result in a loss of stimulation output from one of the channels of the device. Accordingly, your health hazard evaluation (dated September 30, 2005) documents that a loss of channel output during an EP study would present a significant risk if it occurred when an asystolic patient was being assessed.
B) Your firm upgraded the EP workmate software to [redacted] and the touchscreen software to [redacted] due to complaints about intermittent or no channel output for your EP-4 Stimulator. As of April 4, 2006, your firm had update [redacted] workmates with software version [redacted] and [redacted] touchscreens with software version [redacted]since your health hazard evaluation documents that a loss of channel output would present a significant risk if it occurred when an asystolic patient was being assessed.
FDA has received your written responses, dated May 8, 2006, and May 24, 2006, to the List of Inspectional Observations ("Form FDA-483") that was issued to you at the end of FDA's most recent inspection of your firm. These responses, however, do not establish that you have adequately corrected your violations of the Act.
Your May 8 and 24, 2006, responses to FDA-483 observations one and two, which are discussed above as violations of 21 CFR § 803.50(a)(1) & 21 CFR § 803.50(a)(2); are not adequate. For example, your medical device reporting work instructions procedure (created May 22, 2006) on page [redacted] does not address the reporting requirements for MDR Supplement Reports, 21 CFR 803.56. Your MDR Supplemental Reports are referred [redacted].
Furthermore, your MDR decision form thai was included in your revised May 22, 2006, procedure is not adequate since the first question in [redacted] [redacted] do not need to assess the likelihood that a malfunction will recur. The fact that the malfunction occurred once leads to the presumption that the, malfunction will occur. In addition, your second question [redacted].See for example, FDA's, guidance, "Medical Device Reporting for Manufacturers "(available at http://www.fda.gov/cdrh/manual/mdrman.html) and the preamble to the 1995 MDR Final Rule (FR Vol. 61, No. 148)) which describe other considerations for evaluating the reportablity of a malfunction. Please note, this letter does not constitute a comprehensive evaluation of your revised procedures. It is your responsibility to assure compliance with
all requirements of the act and regulations.
Your firm's responses (May 8 and 24, 2006) to observation three, which is discussed in this letter as violations of 21 CFR § 820.198(a)
and (d), were not adequate since your firm failed to identify the actions needed to correct or prevent the recurrence of nonconforming product and other quality problems. For example, your firm's corrective actions for the complaints received from December of 2004 through April of 2006 for your EP-4 Stimulator were not adequate since your firm failed to prevent the recurrence of the nonconformities.
Your firm's responses (May 8 and 24, 2006) to observation four, which was discussed in this letter as violation of 21 CFR § 806.10(b), were not adequate since your MDR decision form [redacted] included in your revised MDR procedure (May 22, 2006) does not address the requirements in 21 CFR § 806 to include a report of correction or removal (21 CFR § 806.10(a)), or maintain records of corrections and removal not required to be reported under 21 CFR § 806.20(a).
Your responses to FDA-483 observations five, six, and nine, discussed in this letter as violations of 21 C.F.R. § § 820.30(g), 820.30(e), and 820.70(a)(1), do not provide us with enough information to determine that adequate corrective actions were implemented by your firm. Your response to observation seven, discussed in this letter as a violation of 21 C.F.R. § 820.30(i), will need to be verified during a follow up inspection at your firm.
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 FDA without further notice. These actions include, but are not limited to, seizure, injunction and/or civil monetary 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 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 of receipt of this letter, of the specific steps you have taken to correct the noted violations, including an explanation of how you plan to correct these violations, or similar violations, from occurring again. 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.
Your response should be sent to Robert J. Maffei, Compliance Officer (HFR-CE300), New Jersey District Office, FDA, 10 Waterview Blvd., 3rd Floor, Parsippany, New Jersey 07054.
Finally, you should know that this letter is not intended to be an all-inclusive list of violations at your facility. It is your responsibility to assure 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.
Douglas I. Ellsworth
New Jersey District