Inspections, Compliance, Enforcement, and Criminal Investigations
B. Braun Medical Inc 12-Oct-05
Department of Health and Human Services
Public Health Service
New Jersey District
October 12, 2005
RETURN RECEIPT REOUESTED
Caroll H. Neubauer
Chief Executive Officer
B. Braun Medical, Inc.
824 Twelfth Avenue
Bethlehem, PA 1810806
Dear Mr. Neubauer:
During an inspection of your firm, B. Braun Medical Inc., located at 1940 Olney Avenue, Suite 200, Cherry Hill, NJ, from May 9 until May 23, 2005, an investigator from the Food and Drug Administration (FDA) determined that you manufacture PVC Right Heart Catheters (right heart cardiac balloon or non-balloon catheters), Temporary Pacing Catheters, Thermodilution Catheters, 12 Fr.-16 Fr. Introducer Sheaths, Tear Away Sheaths, 9 Fr Locking Dilator, 9 Fr. Standard Dilator MVV, 9 Fr. Locking Dilator MVV, 12 Fr. Standard Dilator, 12 Fr. Standard Dilator MVV, 14 Fr Standard Dilator, 15 Fr. Obturator MVV, and 14 Fr. Standard Dilator MVV. These products are medical devices within the meaning of section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act) (21 U.S.C. 321(h)), 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 any function of the body.
The 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 manufacturing, packaging, storage, or installation are not in conformance with the Quality System Regulation (QSR) for medical devices as set forth in Title 21, Code of Federal Regulations (CFR) Part 820. The deviations from QSR include, but are not limited to, the following:
1 . Failure to identify the action(s) needed to correct and prevent recurrence of nonconforming product and other quality problems as required by 21 CFR 820.100 (a)(3). For Example:
A) Corrective action #444 (dated May 28, 2003) failed to correct and prevent the recurrence of cracked/broken tips on Right Heart PVC catheters. Your firm continued to receive complaints regarding cracked tips of Right Heart Catheters, which led to your decision to place a hold on your Right Heart PVC Catheters at the warehouse level on May 8, 2005. However, at the time of this inspection, your firm failed to take action (failure to control devices that were distributed, which were suspected of having potential nonconformities) by not notifying your customers of the tip failures for your Right Heart PVC Catheters, which your firm's design control (risk analysis) identified as being a critical defect that could lead to serious harm to the patient.
B) Corrective action notification N4N1 (dated October 27, 2004) failed to identify all the risks associated with a cracked extension hub for the Right Heart Catheters, which your design control document (risk analysis) identifies as a major defect that could cause moderate harm to the patient. In addition, although your firm authorized re-works on November 17, 2004 of non-conforming product lots 0060714530, 0060715260, 0060716585, 0060720757, and 0060716589 (failed post sterilization compression testing), your firm failed to show that the re-works were completed prior to release.
C) Corrective action Request 2004-08-015 (dated August 3, 2004) failed to prevent the recurrence of leakage at the manifold (Hub leakage) on hand assembled Catheters (Thermodilution catheters containing a hand- assembled manifold). Your firm continued to receive complaints of leakage around the manifold, which resulted in corrective action notification # N5D3 (dated May 6, 2005). Your firm placed a warehouse inventory hold with plans to destroy all affected product; however, your firm failed to take action (failure to control devices that were distributed, which were suspected of having potential nonconformities) by not notifying your customers of the manifold leakage at the time of this inspection.
D) Corrective action Request 2004-08-017 (dated August 19, 2004) and 2004-09-08 (dated September 1, 2004) failed to prevent recurrence of Tearaway Sheaths breaking at the handle and not breaking cleanly/evenly. Your firm continued to receive complaints from September 22, 2003 through March 21, 2005 regarding sheaths splitting at the handle and peelability problems. In addition, your firm determined on September 24, 2004 (Corrective Action Notification Investigation Report # N4L2) that the Tearaway Sheath incidents would not impact patient safety. However, one of your customers filed MDR's for adverse events related to sheaths that resulted in surgical intervention to remove a broken portion of the Sheath assembly.
2. Failure to have complete 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 (d). Specifically, product incident report A200503175 (dated March 23, 2005) failed to document any outcomes (injuries to patient) attributed to the adverse event (a ruptured balloon).
3. Failure to adequately validate a process according to established procedures, and failure to control process parameters for validated processes in order to ensure that the specified requirements continue to be met as required by 21 CFR 820.75 (a) and (b). Specifically, the PVC Right-Heart Catheter process is not capable of producing PVC ([redacted]) catheters that meet the threshold limit of [redacted] by weight needed to produce [redacted] which resulted in non-conforming product being distributed by your firm until May 8, 2005.
4. Failure to have complete procedures for acceptance or rejection of incoming product as required by 21 CFR 820.80(b). Speoifically, your firm's incoming inspection procedure for catheter tubing does not include the monitoring ,of the level of [redacted] in your PVC tubing, which was used to manufacture your Right Heart PVC Catheters. Your firm determined that degradation[redacted] of the [redacted] occurs at [redacted] and your vendor [redacted]. Your firm failed to check the level of [redacted] during incoming inspection, which led to non-conforming product being distributed until May 8, 2005.
5. Failure to establish the acceptance criteria prior to the performance of verification activities as required by 21 CFR 820.30(f). For example,
A) Your firm did not establish pull testing acceptance criteria for the 9 Fr. Locking Dilator, 9 Fr. Standard Dilator MVV, 9 Fr. Locking Dilator MVV, 12 Fr. Standard Dilator, 12 Fr. Standard Dilator MVV, 14 Fr. Standard Dilator, and 14 Fr. Standard Dilator MVV prior to performing the tests. Your firm initiated design changes without establishing acceptance criteria for anything above [redacted]
B) Your firm did not establish pull testing acceptance criteria for the 15 Fr.S Obturator and 15 Fr. Obturator MVV prior to performing the tests.
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 to submit information to the Food and Drug Administration as required by 21 U.S.C. 360i and the Medical Device Reporting (MDR) Regulation, as specified in 21 CFR Part 803. Specifically, you failed to adequately investigate and evaluate the cause of the complaint or to obtain adequate follow up information within 30 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(b)(3). 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 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) Product incident report A200504096 (dated April 13, 2005) for temporary pacing catheter lot # 60721451 regarding impossible pacing and sensing that led the doctor to remove the catheter at which time an electrode part came off and remained in the patient's hypodermal tissue (The product incident report documents "no" next to "any patient injury" but the complaint documents that the electrode part came off and remained in the hypodermal tissue). Although your firm sent a follow up letter on April 14, 2005, there is no evidence that additional attempts were made to investigate and follow up on the patient's condition, or to determine whether the electrode fragment was ever removed.
B) Product Incident report A200408110 (dated August 16, 2004) for WP 1107 Wedge Press Catheter lot # 060551093 and 060577421 regarding one balloon burst, longitudinal (unknown if there were any fragment's). Your design control risk analysis identifies balloon bursts or tears as critical defects whose failure could lead to serious harm to the patient. The bursting of the balloon would represent a malfunction, which could cause or contribute to a serious injury or death if it was to recur.
C) Product Incident report A200504122 (dated April 15, 2005) for lot # 60471081 regarding one balloon burst during introduction (Complaint # 73-05). The bursting of the balloon would represent a malfunction, which could cause or contribute to a serious injury or death if it was to recur.
D) Product Incident report A200503175 (dated March 23, 2005) for complaint # 05-0018 (Balloon Catheter) regarding one ruptured balloon. Your firm failed to evaluate any outcomes (injuries to patient) attributed to this adverse event.
Furthermore, the inspection revealed that your Right Heart Catheters and Tearaway Introducer Sheaths are misbranded within the meaning of Section 502(t)(2) of the Act (21 U.S.C. 352(t)(2)), in that a report of correction or removal was not submitted to FDA as required by Section 519(f)(1) of the Act (21 U.S.C. 360i(f)(1)). The Correction and Removal Regulation (21 CFR 806), promulgated under Section 519(f)(1), requires manufacturers and importers to promptly report to FDA, within 10 working days, any correction or removal of a device to reduce a risk to health .
The FDA has classified your actions regarding the Right Heart Catheters and Tearaway Introducer Sheaths as Class II recalls A class II designation indicates that exposure to the violative product may cause temporary adverse health consequences . See 21 CFR 7.3(m). FDA regulations require manufactures and importers to promptly report to FDA any correction or removal of a device if the correction or removal was initiated to reduce 9 risk to health. See 21 CFR 806.10(a)(1). Because your firm's action described above meets the definition of a "removal" in 21 CFR 806.2(i), and because FDA has found that the removal was initiated to reduce a risk to health, your failure to report the product removal until the issue was raised by our Investigator violated 21 CFR 806.10(a)(1). In addition, your firm failed to report the corrections made to. the PVC catheters [redacted] as required by 21 CFR 806.10(a)(1).
Furthermore, the inspection revealed that your PVC Right Heart Catheters are misbranded within the meaning of section 502(o) of the Act (21 U.S.C. 352(o)), in that a notice or other information respecting the device was not provided to FDA as required by 21 CFR 807.81(a)(3)(i), when the device was significantly changed or modified by converting from a [redacted] Material to a [redacted] material.
The PVC Right Heart Catheter is also adulterated within the meaning of section 501(f)(1)(B) of the Act (21 U.S.C. 351(f)(1)(B)), in that it is a Class III device under section 513(f) and does not have an approved application in effect pursuant to Section 515(a) of an approved application for an investigational device exemption under section 520(g). For a device requiring premarket approval before marketing, the notification required by section 510(k) of the Act is deemed satisfied when a premarket approval application (PMA) is pending before the agency [21 C.F.R. 807.81(b)].
This letter is not intended to be an all-inclusive list of deficiencies at your facility. It is your responsibility to assure adherence to each requirement of the Act and regulations. The specific violations noted in this letter and on the Form FDA-483 issued at the conclusion of the inspection may be symptomatic of serious underlying problems within your establishment's quality system. You are responsible for investigating and determining the causes of the violations identified by the FDA. If the causes are determined to be system problems, you must promptly initiate permanent corrective and preventive actions.
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. Also, no requests for Certificates to Foreign Governments will be approved until the violations related to the subject devices have been corrected.
You should take prompt action to correct these deviations. Failure to promptly correct these deviations may result in regulatory action being initiated by the FDA without further notice to you. These actions include, but are not limited to, seizure, injunction and/or civil monetary penalties.
We have received your written responses dated June 6, 2005, July 11, 2005, August 10, 2005, and September 14, 2005 to the list of FDA 483 observations. Your response to observations one and three does not explain why your firm continued to distribute nonconforming product (unable to prevent recurrence of non-conforming product and other quality problems) when you continued to receive complaints and MDR's filed by your customer (MDR's were provided by your customer during a meeting) concerning adverse events that resulted in surgical interventions. In addition, your response to observation one does not explain why none of the paperwork or certification was available to show completion of any of the re-works performed on the cracked extension hub for the Right Heart Catheters prior to release.
Your response to observation five states that you have reviewed FDA's MAUDE database and recognize that other balloon catheter manufacturers are filing MDR's for balloon ruptures regardless of the circumstances of the incident. However, it is clear that you should report events where the complaints report a balloon burst during the surgical procedures. Again, the bursting of the balloon would represent a malfunction, which could cause or contribute to a serious injury or death if it was to recur (See examples B through C on page 4 of this letter).
In your response to observation four, you have not evaluated whether any other adverse events were not reported to the FDA within 30 days.
As stated above, firms are required to investigate every device-related death, serious injury, and malfunction by the Quality System/GMP regulation, 21 CFR 820.198 and the MDR regulation, 21 CFR Part 803.
Please notify this office in writing, within fifteen working days of receipt of this letter, of the specific steps you have taken to correct the noted violations, including an explanation of each step being taken to identify and make corrections to any underlying systems problems necessary to assure that similar violations will not recur.
Your response should be directed to the New Jersey District, FDA, 10 Waterview Blvd., 3rd Floor, Parsippany, New Jersey 07054, Attn: Robert J. Maffei, Compliance Officer.
Douglas I. Ellsworth
New Jersey District