I-Flow Corporation Versus the FDA: Touche!
Posted by
Armand RossettiFebruary 13, 2009 3:15 PM
On December 22, 2008 the FDA sent a Warning Letter to I-Flow Corporation, manufacturer of the ON-Q pain pump. The Warning Letter stated numerous manufacturing and related violations, and the FDA informed the public of I-Flow's failure to respond sufficiently to a majority of the alleged violations.
The FDA uses a Warning Letter as a tool to ensure that manufacturers are aware of, and are complying with good manufacturing procedures (GMP) that will result in safe and effective medical device design and manufacture. The usual practice begins with an FDA establishment inspection, which results in an establishment inspection report (EIR). After the FDA reviews the EIR, if it finds evidence of substandard manufacturing practices or reporting procedures, it will issue a Warning Letter, containing details of the inspection and statements concerning insufficient GMP.
Thereafter, the FDA gives the manufacturer a period in which to respond, and if the manufacturer’s response is also insufficient, the FDA may allow a follow up response. However, if the FDA is not satisfied that the manufacturer has responded sufficiently, the next step would be termination of any and all manufacturing of violative medical devices destined for the US-American market.
The FDA’s December 2008 Warning Letter alleged that I-Flow had committed the following violations:
1) Failure to establish and maintain procedures for verifying the device design, as required by 21 C.F.R. 820.30(f).
2) Failure to establish and maintain procedures for the identification, documentation, validation or where appropriate verification, review, and approval of design changes before their implementation, as required by 21 C.F.R. 820.30(i).
3) Failure to ensure that when results of a process cannot be fully verified by subsequent inspection and test, the process shall be validated with a high degree of assurance and approved according to established procedure, as required by 21 C.F.R. 820.75(a).
4) Failure to ensure that for validated processes, the monitoring and control methods and data, the date performed, and, where appropriate, the individual(s) performing the process or the major equipment used shall be documented, as required by 21 C.F.R. 820.75(b)(2).
5) Failure to ensure that when changes or process deviations occur, the manufacturer shall review and evaluate the process and perform revalidation where appropriate, as required by 21 C.F.R. 820.75(c).
6) Failure to identify the actions needed to correct and prevent recurrence of nonconforming product and other quality problems, as required by 21 C.F.R. 820.100(a)(3).
7) Failure to verify or validate the corrective and preventive action to ensure that such action is effective and does not adversely affect the finished device, as required by 21 C.F.R. 820.100(a)(4).
8) 8) Failure to establish and maintain procedures for receiving, reviewing, and evaluating complaints by a formally designated unit, as required by 21 C.F.R. 820.198 (1)(a) & (3)(d).
9) Failure to ensure that complaints involving the possible failure of a device, labeling, or packaging to meet any of its specifications were reviewed, evaluated, and investigated, as required by 21 C.F.R. 820.198(c), and failure to ensure that the record of the investigation included the dates and results of the investigation and any corrective action taken, as required by 21 C.F.R. 820.198(e)(6)-(7).
10) Failure to record and investigate the nature of the complaint, as required by 21 C.F.R. 820.198(e)(5).
11) Failure to establish and maintain procedures for the identification, documentation, validation or where appropriate verification, review, and approval of design changes before their implementation, as required by 21 C.F.R. 820.30(i).
12) Failure to establish and maintain procedures for identifying valid statistical techniques required for establishing, controlling, and verifying the acceptability of process capability and product characteristics, as required by 21 C.F.R. 820.250(a).
13) Failure to establish and maintain procedures for rework, to include retesting and reevaluation of the nonconforming product after rework, to ensure that the product meets its current approved specifications, as required by 21 C.F.R. 820.90(b)(2).
14) Failure to establish and maintain acceptance procedures, where appropriate, to ensure that specified requirements for in-process product are met, as required by 21 C.F.R. 820.80(c).
15) Failure to establish and maintain procedures for finished device acceptance to ensure that each production run, lot, or batch of finished devices meets acceptance criteria, as required by 21 C.F.R. 820.80(d).
16) Failure to evaluate and select suppliers, contractors, and consultants on the basis of their ability to meet specified requirements, including quality requirements, as required by 21 C.F.R. 820.50(a)(1).
17) Failure to establish and maintain records of acceptable suppliers, contractors, and consultants, as required by 21 C.F.R. 820.50(a)(3).
18) Failure to maintain device history records, as required by 21 C.F.R. 820.184(d).
The Warning letter also listed numerous failures, concerning the sufficiency of I-Flow’s responses, and the FDA provided a host of examples of such failures.
In addition to issuing Warning Letters to medical device manufacturers, the FDA makes weekly Enforcement Reports available to the public. Those FDA Enforcement Reports contain information on actions taken in connection with Agency regulatory activities. In addition to providing the weekly Enforcement Reports, the FDA maintains a searchable website where it archives more than 20 years of those reports.
Here are some of I-Flow’s product recalls:
April 16, 2003:
PRODUCT
Homepump Eclipse Infusion Pump, Disposable Elastomeric Infusion System (100 ml x 50 ml/hr) Model E100500,
Part No. 5001065. Recall # Z-0687-03.
CODE
Lot 262074.
RECALLING FIRM/MANUFACTURER
I-Flow Corporation, Lake Forest, CA., by fax on March 4, 2003, and telephone on March 5, 2003. Firm initiated recall is ongoing.
REASON
Product infuses too fast at rate of 30 minutes instead of 2 hours. Component mix-up.
VOLUME OF PRODUCT IN COMMERCE
2,832 units.
DISTRIBUTION
CA, OH, WA,TX,UT, SC, MI, IL.
April 30, 2003:
PRODUCT
Paragon Administration Set (100 ml x 0.5 ml/hr) Part Number 5000936. Recall # Z-0709-03.
CODE
Lot numbers: 262111 (manufactured June 2002, expires May 2005); 282233 (manufactured August 2002, expires July 2005).
RECALLING FIRM/MANUFACTURER
I-Flow Corporation, Lake Forest, CA, by fax on March 5, 2003, and email on March 6, 2003. Firm initiated recall is ongoing.
REASON
Wrong component may result in over infusion of medications.
VOLUME OF PRODUCT IN COMMERCE
5,808 units.
DISTRIBUTION
NY, MA, and Internationally.
May 7, 2003:
PRODUCT
Easypump LT 6024 Easypump InfusionPump (60 ml x 22 ml/hr). Recall # Z-0741-03.
CODE
Lot numbers 04434366/2A2469 and 04434367/2A2470.
RECALLING FIRM/MANUFACTURER
I-Flow Corporation, Lake Forest, CA, by email on March 18, 2003. Firm initiated recall is ongoing.
REASON
Overinfusion due to misassembly.
VOLUME OF PRODUCT IN COMMERCE
2,638 units.
DISTRIBUTION
France.
January 21, 2004:
PRODUCT
Eclipse Infusion Pump, 250 ml X 250 ml per hour) Part
5001247. Recall Z-0312-04.
CODE
Lot 262073.
RECALLING FIRM/MANUFACTURER
I-Flow Corporation, Lake Forest, CA, by telephone on August 19, 2002 and by letter on August 27, 2002. Firm initiated recall is complete.
REASON
Slower than expected infusion of medications, such as antibiotics.
VOLUME OF PRODUCT IN COMMERCE
3,240.
DISTRIBUTION
Nationwide.
March 15, 2006:
PRODUCT
a) Easypump ST 100-1 infusion pump, Recall # Z-0584-06;
b) Easypump L T 60-24 infusion pump, Recall # Z-0585-06
CODE
a) Lot # 562791;
b) Lot # 562857
RECALLING FIRM/MANUFACTURER
I-Flow Corporation, Lake Forest , CA , by letter dated January 17, 2006 , firm initiated recall is ongoing.
REASON
The sterile pack may contain the wrong infusion pump inside.
VOLUME OF PRODUCT IN COMMERCE
1,179 units
DISTRIBUTION
France
January 24, 2007:
PRODUCT
I-Flow ON-Q PainBuster (100 ml, 2 mI/hr) Pump, PM012, Recall # Z-0358-2007
CODE
Lot numbers: 662449 & 662742
RECALLING FIRM/MANUFACTURER
I-Flow Corp., Lake Forest, CA, by faxed letter on November 29, 2006. Firm initiated recall is ongoing.
REASON
The pump flow rate labeling may not match the package labeling. The label on filter may not match the label on the top of the pump or the package labeling.
VOLUME OF PRODUCT IN COMMERCE
3,475 units
DISTRIBUTION
Nationwide
October 17, 2007:
PRODUCT
ON-Q PainBuster with OnDemand (270 ml, 2 ml/hr + 5 ml bolus /60 min refill), Model PMB01, anesthetic/ narcotic medication pump. Recall # Z-0057-2008
CODE
6A4171 (exp. MAR 2009), 694133 (exp. FEB 2009), 654920 (exp. OCT 2008), 5A4732 (exp. MAR 2008), 584699 (exp. JAN 2008)
RECALLING FIRM/MANUFACTURER
I-Flow Corporation, Lake Forest, CA, by letter on March 27, 2007. Firm initiated recall is complete.
REASON
Misassembly: The ON-Q PainBuster PMB01 package may contain a Soaker catheter instead of a Non-Soaker catheter. As a result, the bolus button may remain latched in the down position which may cause the device to deliver continuously at 7 ml/hr instead of 2 ml/hr.
VOLUME OF PRODUCT IN COMMERCE
2,582 units
DISTRIBUTION
Nationwide and Internationally
September 24, 2008:
PRODUCT
ON-Q PainBuster Infusion Pump (270 ml, 5 ml/hr), REF PS6504, Part No. 5001260. The pump is indicated for continuous and/or intermittent delivery of medication (such as local anesthetics or narcotics) to or around surgical wound sites and/or close proximity to nerves for preoperative, perioperative and postoperative regional anesthesia and pain management. Routes of administration may be intraoperative, perineural, percutaneous and epidural. The ON-Q Pump is also intended to significantly decrease narcotic use and pain when used to deliver local anesthetics to or around surgical wound sites or close proximity to nerves when compared with narcotic only pain management. Recall # Z-1869-2008
CODE
Lot Number: 772166
RECALLING FIRM/MANUFACTURER
I-Flow Corporation, Lake Forest, CA, by letters on February 12, 2008. Firm initiated recall is ongoing.
REASON
The ON-Q PainBuster, REF PS6504 (lot number 772166), box may contain the wrong product, ON-Q PainBuster, REF PS6502. If the wrong product is used, patients would receive a 2 ml/hr infusion rather than a 5 ml/hr infusion, which could result in inadequate pain relief.
VOLUME OF PRODUCT IN COMMERCE
345 units
DISTRIBUTION
Internationally
Perhaps the FDA has used some or all of the I-Flow recalls as examples in its December 22, 2008 Warning Letter. However, given the prodigious number of I-Flow violations and recalls, and the FDA’s heavy handed propensity to redact identifying information, I will leave it to the reader to plow through this mess and to identify any pertinent connections between the two.
All in all, I-Flow has failed to provide sufficient responses, concerning the FDA's alleged GMP and adverse event reporting violations found in the FDA's December 22nd Warning Letter. In addition, the FDA's Enforcement Reports show that I-Flow has had to make numerous medical device recalls. The documents discussed above speak volumes about I-flow's laissez faire attitude toward medical device quality control and safety.