Inspections, Compliance, Enforcement, and Criminal Investigations
Baxa Corporation 14-Jan-08
Department of Health and Human Services
Public Health Service
Denver District Office
January 14, 2008
CERTIFIED MAIL -
RETURN RECEIPT REQUESTED
Mr. Gregory J, Baldwin
Chairman and CEO
14445 Grasslands Drive
Englewood, Colorado 80112-7062
Ref #: DEN-08-09
Dear Mr. Baldwin:
During an inspection of your firm located in Englewood, Colorado on July 12 through July 30, 2007, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures electro-mechanical infusion pumps and related sterile tubing sets, electro-mechanical pharmacy compounders, mixers and mixing/filling equipment, and other sterile and non-sterile pharmacy accessories. 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. These violations include, but are not limited to, the following:
1. Failure to follow your design control procedures to assure that design changes are identified, documented, reviewed, and approved before implementation.
21 CFR 820.30 (i).
For example: your Firm did not follow your design change procedures prior to implementing the Exacta-Mix 2400 (EM2400) Operating Software [redacted] Subsequently, the EM2400 was the subject of a recall initiated on June 27, 2007, due to defects that could cause a discrepancy in the total volume being added to a solution.
2. Failure to adequately validate design changes in that acceptance criteria were not established prior to performing validation activities. 21 CFR 820.30 (g).
For example: acceptance criteria were not established in the validation protocols prior to initiating design changes to the [redacted] and the [redacted]
3. Failure to establish and maintain corrective and preventive action (CAPA) procedures that identify the actions needed to correct the recurrence of nonconforming product and other quality problems have been identified. 21 CFR 820.100 (a)(3).
For example: complaints of intermittent shutdown, unable to close port due to the valve moving, and broken USB port from the connector PCA involving the EM2400 device were investigated and preventive action initiated through the initiation of various engineering change orders (ECOs). However, your files have no record of any corrective action being taken to address the units that were already distributed in the marketplace.
4. Failure to assure all complaints involving the possible failure of a device to meet its specifications were investigated. 21 CFR 820.198 (c).
For example: review of complaint files related to the EM2400 disclosed the following problems: failure to boot, the bubble detector was not working properly, bubble alarms and intermittent lockup on the touch screen display. The results of your investigation into these failures state that the root cause was attributed to customer error and/or normal wear and tear. There is no documentation as to how the determination of user error was made or what constitutes normal wear and tear.
5. Failure to establish and maintain procedures to ensure that complaints are evaluated to determine whether the complaint represents an event which is required to be reported to FDA under part 803, the Medical Device Reporting (MDR) requirements. 21 CFR 820.198 (a)(3).
For example: two complaints received in 2006 indicated serious injury resulted from the incorrect concentrations of solutions administered. Although you indicated to our investigator that these were not reported because you concluded the incidents were caused by user error, the MDR requirements specifically includes these types of events as required to be reported. Additionally, our investigator reviewed nineteen complaints involving inaccurate or incorrect delivery. The complaint records failed to contain sufficient patient information to effectively evaluate the events for MDR reportability, nor did they contain reasons for absence of the patient information and subsequent MDR evaluation.
6. Failure to establish and maintain procedures that assure that management with executive responsibility shall review suitability and effectiveness of the Quality System at defined intervals. 21 CFR 820.20(c).
For example: there is no evidence that the following were covered during Quarterly Management Reviews as required by your procedures: [redacted]
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:
Failure to submit an MDR report within 30 days of receiving or otherwise becoming aware of information that reasonably suggests that a marketed device may have caused or contributed to a death or serious injury. 21 CFR 803.50 (a)(1).
Failure to submit an MDR report within 30 days of receiving or otherwise becoming aware of information that reasonably suggests that a marketed device has malfunctioned or a similar device that you market would be likely to cause or contribute to a death or serious injury, if the malfunction were to recur. 21 CFR 803.50 (a)(2).
Failure to investigate each event and evaluate the cause(s) of the event.
21 CFR 803.50(b)(3).
We are in receipt of your firm's response from Mr. Pat Hynes dated August 29, 2007, concerning our investigator's observations noted on the Form FDA 483, List of Inspectional Observations that was issued to you, as well as status update reports dated October 2, November 1, December 4, 2007, and January 7, 2008. Your responses to our observations appear to be adequate, however a follow-up inspection will be required to assure that corrections are adequate.
Failure to promptly correct these violation(s) 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 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.
We are requesting that you submit to this office on the schedule below, certification by your outside expert consultant that he/she has conducted an audit of your establishment's manufacturing and quality assurance systems relative to the requirements of the device QS regulation (21 CFR, Part 820). You should also submit a copy of the consultant's report, and certification by you that you have reviewed the consultant's report and that your establishment has initiated or completed all corrections called for in the report. The initial certifications of audit and corrections and subsequent certifications of updated audits and corrections (if required) should be submitted to this office by the following dates:
• Initial certifications by consultant and establishment - May 5, 2008.
• Subsequent certifications - bi-monthly thereafter until all corrections have been made.
Your response should be sent to: Regina A. Barrell, Compliance Officer, Food and Drug Administration, Denver District, P.O. Box 25087, Denver, CO 80225-0087,
Finally, you should know that this letter is not intended to be an all-inclusive list of the violation(s) at your facility. It is your responsibility to ensure compliance with applicable laws and regulations administered by FDA. The specific violation(s) 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 violation(s), and take prompt actions to correct the violation(s) and to bring your products into compliance.
Susan J. Miller
Acting District Director