• Decrease font size
  • Return font size to normal
  • Increase font size
U.S. Department of Health and Human Services

Inspections, Compliance, Enforcement, and Criminal Investigations

  • Print
  • Share
  • E-mail

Section Contents Menu

Enforcement Actions

I.V. Flush, LLC 04-Aug-05

Department of Health and Human Services' logoDepartment of Health and Human Services

Public Health Service
Food and Drug Administration

 

Dallas District
4040 North Central Expressway
Dallas, TX 75204-3145


August 4, 2005

Ref: 2005-DAL-WL-22

WARNING LETTER

CERTIFIED MAIL
RETURNED RECEIPT REQUESTED

Mr. Patrick M. Scanlan, President
I.V. Flush, LLC
3905 Melcer, Suite 601
Rowlett, TX 75088

Dear Mr. Scanlan:

During an inspection of your establishment located in Rowlett, Texas, on January 28 through March 17, 2005, our investigator determined that your firm manufactures Heparin Syringes and I.V. Normal Saline Syringes. These syringes, as well as IV lines and shunts are medical devices as defined in 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 above-stated inspection revealed that these devices are adulterated under 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 conformance with the Current Good Manufacturing Practice (C(GMP) requirements for medical devices which are set forth in the Quality System regulation, as specified in Title 2'1, Code of Federal Regulations (CFR), Part 820. Significant deviations include, but are not limited to, the following:

Quality Svstem Regulation

1. Failure of the management with executive responsibility to ensure that an adequate and effective quality system has been fully implemented and maintained at all levels of the organization, as required by 21 CFR 820.20 [FDA-483 Items 1 through 301. Specifically, your firm has not (a) conducted sterility testing of your finished devices to ensure that they are sterile or aid in detecting bacterial contamination, or stability testing of your diluted Heparin solutions to validate their expiration dates; (b) established specified purchasing requirements, including drug quality requirements that must be met by the compounding pharmacy; or (c) audited the compounding pharmacy to ensure that sterility and other drug quality requirements for their Heparin concentrate solutions were met.

2. Failure to allocate necessary resources, including the assignment of trained personnel for management, performance of work, and assessment activities, as required by 21 CFR 820.20(b)(2) [FDA-483 Items 3 through 30]. Your firm does not allocate necessary resources to ensure that you and your manufacturing staff (a) obtain the necessary training in order to understand and implement the Quality System Regulation requirements; and (b) maintain your facility and adequate manufacturing controls to prevent manufacturing problems.

3. Failure to establish and maintain adequate complaint handling procedures for receiving, reviewing, and evaluating complaints by a formally designated unit and to ensure that all the requirements of 21 CFR 820.198(a) through (e) are met [FDA-483 Items 4 and 5]. For example, prior to our current inspection, FDA and CDC notified your firm of a report of patient infections associated with your devices contaminated with fluorescens. Since the initial FDA and CDC notifications to your firm, additional cases of patient infections were reported. This information was communicated to your firm by our office and during the inspection and was communicated to the public in three FDA press releases, dated January 31, February 4, and February 8, 2005. At the conclusion of our inspection, your firm had not (a) opened a complaint record and investigated all complaints of infections and documented the results of your investigations; (b) conducted microbiotogical testing of the quarantined devices, including recalled devices, all device components and raw materials, and manufacturing environments to determine the extent of bacterial contamination in your devices and where and why the contamination occurred in your device manufacturing process or the compounding pharmacy's drug manufacturing process; (c) established complaint handling procedures and maintained a complaint file documenting all complaints received by your firm since 2001; or (d) established proper device identification numbers or lot numbers for your finished devices in order to perform trace back investigations.

4. Failure to establish and maintain procedures for implementing corrective and preventive actions, as required by 21 CFR 820.100(a)(1) through (a)(7), and to include documentation of the results of corrective and preventive action activities, as required by 21 CFR 820.100(b) [FDA 483 Items 8 and 19]. For example, your firm indicated to our investigator that your firm does not have a corrective and preventive action procedure. Furthermore, your firm has not conducted an investigation into the root cause of the contaminated Heparin. Syringes and has not formulated a corrective and preventive action plan.

5. Failure to establish and maintain procedures to control the design of the device in order to ensure that specified design requirements are met and all design control steps are followed, as required by 21 CFR 820.30(a) to {j) [FDA-483 Item 91. For example:

a) Your firm has been manufacturing and distributing Heparin Syringes and I.V. Normal Saline Syringes since 2001 without establishing any design control procedures and maintaining a design history file for each of these products.

b) Your firm indicated to our investigator that it had changed the types of syringes and their associated sterilization processes (e .g., changes of OEM brands of syringes, change from use of non-sterile syringes and a contract sterilizer to the use of pre-sterilized syringes) several times since 2001 but had no design change procedure for the identification, documentation, validation or verification, review, and approval of design changes before their implementation.

c) Your firm has not conducted any stability testing or documented the testing results to support the [redacted] expiration dating of the incoming Heparin concentrate solutions processed by the compounding pharmacy and the dilution of Heparin concentrate solutions processed by your facility.

6. Failure to establish and maintain procedures for acceptance or rejection of incoming product, including documentation of the results of acceptance or rejection, as required by 21 CFR 820.80(b) [FDA-483 Item 15j. Your firm has not (a) established acceptance procedures for the inspection, testing, or verification of incoming products to ensure that they meet your firm's specified requirements, and (b) documented the results of acceptance or rejection of your firm's receipt of bulk Heparin powder, Heparin concentrate solutions, non-sterile or pre-sterilized syringes and caps, Sodium Chloride (saline) IV bags, and other manufacturing components.

7. Failure to establish and implement procedures for finished device acceptance to ensure that each production run, lot, or batch of finished devices meet acceptance criteria, as required by 21 CFR 820.80(d), and to include maintaining acceptance records, as required by 21 CFR 820.80(e) [FDA-483 Items 16 and 17]. For example, your firm failed to follow your procedure" P 012 End Product Testing," dated March, 28, 2004, which requires a [redacted] inspection for particulates and the correct volume, sterility, and pyrogen testing of your diluted Heparin solutions. Your firm acknowledged to our investigator that it had not conducted finished product testing nor kept any testing results since 2001.

8. Failure to establish and maintain procedures for identifying valid statistical techniques, including sampling plans, required for establishing, controlling, and verifying the acceptability of process capability and product characteristics, as required 21 CFR 820.250(a) [FDA-483 Item 18]. Your firm acknowledged to our investigator that it did not have a sampling rationale or did not follow any sampling standard. For each of the following sampling plans, no sampling rationale or valid statistical rationale is referenced:

a) [Redacted] Heparin Syringes and I.V. Normal Saline Syringes are selected from [redacted] units manufactured and visually inspected for particulates and correct volume.

b)[Redacted] Heparin Syringes and I.V. Normal Saline Syringes are selected from each [redacted] units manufactured and tested for sterility.

c) [Redacted] Heparin Syringe and I.V. Normal Saline Syringe are selected from each [redacted] units manufactured and tested for pyrogens.

d) [Redacted] Heparin Syringe and I.V. Normal Saline Syringe are selected from each [redacted] units manufactured and tested for concentration accuracy.

9. Failure to establish and maintain procedures to adequately control environmental conditions, as required by 21 CFR 820.70(c) [FDA-483 Item 26]. For example:

a) Procedures outlining environmental monitoring of the clean room where the Heparin concentrate solutions were diluted and filled and Sodium Chloride solutions are filled into syringes have not been established.

b) Your firm has not monitored the temperature, humidity, and pressure of the clean room, and has not conducted routine bioburden testing to monitor and identify viable and non-viable particulates in the clean room.

10. Failure to establish and maintain procedures for the control of storage areas and stock room to prevent mixups, damage, deterioration, contamination, or other adverse effects, as required by 21 CFR 820.150 [FDA-483 Item 29]. For example, your firm has not established complete procedures to control the receipt and storage of non-sterile and sterile products in order to prevent mixups. At the time of our inspection, your procedure "SOP 015 Materials Flow," dated March 28, 2004, was not complete and implemented, and some products were observed stored in wrong locations.

11. Failure to establish and maintain procedures to ensure that device history records for each batch, lot, or unit are maintained to demonstrate that the device is manufactured in accordance with the device master record, as required by 21 CFR 820.184 [FDA-483 Item 14]. For example:

a) Your firm has not established procedures defining the specific types of information and acceptance records needed to be included in the device history records.

b) Lot numbers of the incoming Heparin concentrate solutions and syringes and the diluted Heparin solutions were not documented. Your firm was not able to link the dilutions of the Heparin concentrate solutions to a particular batch of syringes because the dilutions and filling of syringes were not done on the same date and because no lot numbers or control numbers were used.

c) Copies of product labels affixed to the product packaging and boxes were not attached or referenced in the device history records.

d) The original number of syringes filled with diluted Heparin solutions, the number of filled syringes later rejected or scrapped, and the final number of filled syringes accepted for shipping were not always documented.

e) There is no quality assurance review of the device history records prior to release of the finished Heparin Syringes and I .V. Normal Saline Syringes.

12. Failure to establish and maintain procedures for the identification, documentation, evaluation, segregation, and disposition of nonconforming product, as required by 21 CFR 820.90(a) [FDA-483 Item 20]. For example:

a) Your firm has not established procedures to control products that do not conform to specified requirements.

b) Some of the finished syringes, without any known defects, that did not complete a shipping box or a case were placed into the bin containing rejected syringes.

c) All rejected syringes, regardless of the type of nonconformance, were commingled into the same reject bin. Your firm has not sorted the types of nonconformances, determined their causes and significances, and implemented appropriate corrective actions.

13. Failure to establish and maintain procedures to ensure that all purchased or otherwise received product and services conform to specified requirements, as required by 21 CFR 820.50 [FDA-483 Items 21, 22, 23]. For example:

a) Your firm has not established specified requirements, including quality requirements that must be met by the compounding pharmacy that contract manufactured and provided Heparin concentrate solutions to your firm for further dilutions. All requirements for the compounding pharmacy were verbal in nature and were not documented.

b) Your firm failed to (1) evaluate or audit the compounding pharmacy to ensure that sterility and other drug quality requirements of their Heparin concentrate solutions were met; and (2) document the results of your firm's evaluation or audit. Your firm acknowledged to our investigator that it had not received any certificate of analysis or any other test results from the compounding pharmacy documenting that the Heparin concentrate solutions meet sterility requirements.

c) Your firm has not established and maintained purchasing data that clearly describe or reference specified requirements, including quality requirements, for purchased items, such as bulk Heparin powder, Heparin concentrate solutions, sterile and non-sterile syringes and caps, and other manufacturing components.

14. Failure to establish and maintain procedures to ensure the calibration of inspection, measuring, and test equipment, as required by 21 CFR 820.72(a) and (b), and to maintain calibration records, as required by 21 CFR 820.72(b)(2) [FDA-483 Item 24]. For example, your firm failed to (a) establish calibration procedures, and (b) maintain records of calibration of the [redacted] repeater pumps and adjustments made to these pumps during production.

The repeater pumps are used to pump the correct volume of Heparin and Sodium Chloride (saline) solutions into the syringes.

15. Failure to establish and maintain procedures to control labeling activities, labeling inspection, labeling storage, and labeling operations, and to ensure that printed labels remain legible, as required by 21 CFR 820.120 [FDA-483 Items 27 and 28]. For example:

a) Your firm has not established labeling procedures addressing the content of labels, how labels are generated, where labels are affixed to the syringes and/or their packaging, and how labels and labeling are inspected prior to manufacturing use.

b) Our investigator observed that the labels that were affixed to the Heparin Syringes and I .V. Normal Saline Syringes can smear off by rubbing fingers over the print.

c) Discarded syringes were observed to be present with other syringes from the previous production runs in the labeling area, and there were typographical errors on the syringe labels. For example, the letter "C" at the beginning of the lot number on the Sodium Chloride (saline) syringe's label was supposed to indicate Sodium Chloride (saline) concentrate. However, your firm responded to our investigator that Sodium Chloride (saline) was never concentrated. In another example, your syringe production report, dated November 15, 2004, for the production of [redacted] syringes documented that the fill material was [redacted]% Sodium Chloride (saline). However, the labels that were affixed to the individual syringes had a lot # HCJ4K595 which indicated "H" for Heparin as the fill material.

16. Failure to establish and maintain procedures for control and distribution of finished medical devices to ensure that only those devices approved for release are distributed, including maintaining adequate distribution records, as required by 21 CFR 820.160 [FDA-483 Item 25]. For example, your firm's distribution records do not contain lot numbers or any control numbers for the distributed devices. The recorded date(s) and quantities of shipped devices are not always accurate.

17. Failure to maintain device master records (DMR's) to include or refer to the location of device specifications, production process specifications, quality assurance procedures, and packaging and labeling specifications, and to ensure that each DMR is prepared and approved in accordance with 21 CFR 820.40, as required by 21 CFR 820.181 [FDA-483 Item 13]. For example, your firm has not established a device master record for each type of Heparin Syringe and LV. Normal Saline Syringe.

18. Failure to establish and maintain procedures for quality audits and to conduct such audits to assure that the quality system is in compliance with established quality system requirements and to determine the effectiveness of the quality system, as required by 21 CFR 820.22 {FDA-483 Item 10]. Your firm told our investigator that it had no quality audit procedure and had not conducted any internal quality audits.

Premarket Notification and Establishment Registration and Device Listing

Your Heparin Syringe and IN. Normal Saline Syringes are also adulterated under section 501(f)(1)(B) of the Act, 21 U.S.C. 351(f)(1)(B), in that they are class III devices under section 513(f), 21 U.S.C. 360c(f), and do not have approved applications for premarket approval in effect pursuant to section 515(a), 21 U.S.C. 360e(a), or approved applications for investigational device exemptions under section 520(g), 21 U.S.C. 360j(g). Your Heparin Syringe and I.V. Normal Saline Syringes are misbranded under section 502(o), 21 U.S.C. 352(o), in that the devices were manufactured, prepared, propagated, compounded, or processed in an establishment not duly registered under section 510, 21 U.S.C. 360, were not included in a list required by section 510{j) 21 U.S.C. 360{j), and a notice or other information respecting the devices was not provided to the FDA as required by section 510(k), 21 U.S.C. 360(k).

Medical Device Reporting Regulation

Additionally, the above-stated inspection 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 any material or information required by or under section 519, 21 U.S.C. 360i, and 21 CFR Part 803-Medical Device Reporting (MDR) regulation, respecting the device. Significant deviations include, but are not limited to, the following:

1. Failure to submit an MDR to the FDA 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, as required by 21 CFR 803.50(a) (1) [FDA 483 Item 6]. For example, your firm failed to file an MDR within 30 days of becoming aware that the Heparin syringes were contaminated with P. fluorescens, causing a number of patient infections.

On January 26, 2005, your firm became aware that the contaminated Heparin syringes were causing infections at the [redacted] Hospital. Since the affected patients required medical intervention, the event is reportable as an MDR serious injury. Your firm still has not filed an MDR serious injury report with the FDA.

2. Failure to develop, maintain, and implement written MDR procedures that address the review of complaint information to determine the need to report information as an MDR, as required by 21 CFR 803.17 [FDA 483 Item 7].

Responding to This Letter

This letter is not intended to be an all-inclusive list of deficiencies at your facility. It is your responsibility to ensure adherence to each requirement of the Act and regulations. The specific violations noted in this letter and in the Form FDA 483 issued at the close of the inspection may be symptomatic of serious underlying problems in your firm's manufacturing and quality assurance systems. You are responsible for investigating and determining the causes of the violations identified by the FDA. You also must promptly initiate permanent corrective and preventive action on your quality system.

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, no applications for premarket approval to which the Quality System regulation deficiencies are reasonably related will be approved until the violations have been corrected. 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 violations. 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.

We acknowledge receiving your firm's response, dated April 19, 2005, to the Form FDA 483, Inspectional Observations, issued to you at the conclusion of our inspection on March 17, 2005. You indicated that your firm will not distribute any devices until FDA clears the 510(k) submission, and will submit an MDR report for the contaminated incidents associated with the use of your firm's Heparin syringes with a copy of the MDR report to our office. You further indicated that your corrective action plan would include developing a complete quality system.

Your response is inadequate for the following reasons:

1. You have not responded to each of the FDA 483 items, particularly the results of your investigation into the root cause of bacterial contamination, and you have not specified the time frame for completion of these Issues.

2. During the inspection, you stated to our investigator that your firm would stop using the compounding pharmacy to obtain the concentrated Heparin solutions. You have not confirmed this commitment in your response. You also have not identified any other drug suppliers of Heparin and provided (a) the results of your evaluation of their ability to meet your specified requirements, and (b) evidence of their substantial compliance with drug CGMP requirements of 21 CFR Parts 210 and 211.

3. You still have not submitted the MDR report and followed with a copy to our office.

4. You still have not submitted a 510(k).

5. You still have not registered your firm's establishment and listed your devices with FDA

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, or will take to identify and correct the noted violations, including (1) the time frames within which the corrections will be completed, (2) any documentation indicating the corrections have been achieved, and (3) an explanation of each step being taken to identify and make corrections to any underlying systems problems necessary to ensure that similar violations will not recur. 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 Thao Ta, Compliance Officer, Food and Drug Administration, 4040 North Central Expressway, Suite 300, Dallas, Texas 75204.

Sincerely,

/S/

Michael A. Chappe
Dallas District Director