Company: Biosafe Laboratories
Subject: CGMP/QSR/Medical Devices/Adulterated
Issuer: Chicago District Office
Issued: Sept. 5, 2008 Closed:
Not applicable.
Source ucm1048140 Archive Code:

Biosafe Laboratories 05-Sep-08

Department of Health and Human Services

Public Health Service
Food and Drug Administration

Chicago District
550 West Jackson Blvd., 15th Floor
Chicago, Illinois 60661
Telephone: 312-353-5863

September 5, 2008




Mr. Henry A. Warner, Chairman
Biosafe Laboratories
8600 W. Catalpa
Chicago, IL 60656

Dear Mr. Warner:

During an inspection of your firm located in Chicago, IL, on May 15 through June 2, 2008, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures an Anemia meter and blood specimen collection system for the testing of C-Reactive Protein, Age-Mediated Asthma Panel, and Prostate Test (PSA) as well as other in-vitro diagnostic tests. 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 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. For example, the firm lacks a quality plan. Design history records are not being kept or do not provide assurance that devices or design changes were designed according to regulation. The firm does not have documentation of corrective and preventive action activities and sources of non conformity are not being analyzed and followed up. Your complaint handling procedures lack instruction and detail to ensure that complaints are being documented, reviewed, and evaluated. Complaints are not being fully documented and are not being investigated when indicative of a failure of the device or labeling.

2. Failure to have a quality organizational structure established to ensure compliance with quality system requirements, as required by 21 CFR 820.20(b). For example, the Director of QA/RA has been vacant since July 2007.

3. Failure to establish a quality plan, as required by 21 CFR 820.20(d). For example, your SOPs were limited to laboratory operations and failed to cover/include, among other things, SOPs for management controls, corrective and preventive action, and handling nonconformance.

4. Failure to establish procedures for management review and to conduct management reviews at defined intervals and with sufficient frequency, as required by 21 CFR 820.20(c). For example, your firm does not have a procedure for performing management reviews of the quality system.

5. Failure to maintain procedures for conducting quality audits as well as failure to conduct quality audits, as required by 21 CFR 820.22. For example, your firm does not have a procedure for performing internal audits of the quality system.

6. Failure to establish and maintain procedures to control the design of the device in order to ensure that specified design requirements are met, as required by 21 CFR 820.30(a)(1). For example, your limited design procedures lack detail and specificity to Biosafe's operations and do not include a procedure for design planning. Your current design procedure is merely a reproduction of 21 CFR 820.30.

7. Failure to establish and maintain a design history file that contains or references the records necessary to demonstrate that the design was developed in accordance with the approved design plan and the design control requirements, as required by 21 CFR 820.30(j). For example:

• There is no design history file for the Hemoglobin Alc kit.
• The design history file for the Anemia Pro/Anemia Meter lacked a clearly identified design plan, design inputs, design outputs and documentation of design verification. There was no documentation of completed design reviews.

8. Failure to document all activities required under 21 CFR 820.100, including, but not limited to, analysis of sources of quality data, the actions needed to correct or prevent recurrence of nonconforming product and other quality problems, the verification or validation of corrective actions, implementation of corrective and preventive actions, and dissemination of information about quality problems or nonconforming product to responsible parties as required by 21 CFR 820.100(b). For example, there is incomplete documentation of corrective and preventive action activities pertaining to cracking of BTS IgE/Allergy devices.

9. Failure to establish and maintain procedures for implementing corrective and preventive actions that include requirements for analyzing appropriate sources of quality data to identify existing and potential causes of nonconforming product and other quality problems, as required by 21 CFR 820.100(a)(1). For example:

• QC test records of BTS IgE/Allergy products document quality failures that were not investigated or followed up with the contract manufacturer
• There is no procedure for 100% inspections that are made and the results of the inspections are not documented
• Confirmed nonconformance are not reviewed and analyzed to identify potential and existing causes of non conforming product.

10. Failure to verify or validate changes to a process, as required by 21 CFR 820.70(b).

For example, the contract manufacturer for the Anemia Meter was changed and the new molds that were prepared failed to produce product that met specified tolerances. Despite these failures, you approved the product, and you did not define or demonstrate equivalence acceptance criteria.

11. Failure to complete complaint handling procedures for receiving, reviewing, and evaluating complaints as required by 21 CFR 820.198(a). For example, the existing SOP for complaints lacks detail and instruction regarding, among other things, how complaints are recorded and followed up and when reports are required under 21 CFR Part 803.

12. Failure of a formally designated unit to maintain records of complaint investigations that include the nature and detail of the complaint, as required by 21 CFR 820.198(e). For example, complaint records for anemia meters and IgE/Allergy devices did not always include, among other things, a record of the lot number, the address of the complainant, and the nature and details of the complaint.

13. Failure to review, evaluate, and investigate, where necessary, complaints involving the possible failure of a device, labeling, or packaging to meet any of its specifications, as required by 21 CFR 820.198(c). For example:

• Numerous complaints were logged between December 2007 and May 2008 for faulty Anemia Meters, which were not further reviewed, evaluated or investigated.

• Over 20 complaints were logged between December 2007 and May 2008 for the cracked/damaged IgE kits, which were not further reviewed, evaluated or investigated.

• Additional complaints were logged between December 2007 and May 2008 for the PSA Test, which were not further reviewed, evaluated or investigated.

14. Failure to establish and maintain procedures for nonconforming product that address the identification, documentation, evaluation, segregation, disposition, and investigation of nonconforming product, as required by 21 CFR 820 .90(a), and failure to document disposition of nonconforming product, as required by 21 CFR 820.90(b)(1). For example, there is no adequate procedure for controlling nonconforming product and no record of disposing cracked/failed BTS IgE devices.

15. 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 and the Quality Systems regulation, as required by 21 CFR 820.184. For example, no device history records are prepared /kept for the assembly of the Biosafe kits.

16. Failure to establish and maintain procedures that evaluate potential suppliers on the basis of their ability to meet specified requirements, as required by 21 CFR 820.50(a)(1). For example, although your SOP for qualifying suppliers "prior to awarding contracts for medical device manufacturing" requires that the potential supplier complete a complete a comprehensive questionnaire, not all of your suppliers had completed the questionnaire.

Our inspection also revealed that the C-Reactive Protein, IgE-Mediated Asthma Panel, and Prostate Test are adulterated under Section 501(f)(1)(B) of the Act, 21 U.S.C. 351(f)(1)(B), because you do not have an approved application for premarket approval (PMA) in effect pursuant to Section 515(a) of the Act, 21 U.S.C. 360e(a), or an approved application for an investigational device exemption (IDE) under Section 520(g) of the Act, 21 U.S.C. 360j(g). The device is also misbranded under Section 502(o) the Act, 21 U.S.C. 352(o), because you did not notify the agency of your intent to introduce the device into commercial distribution, as required by Section 510(k) of the Act, 21 U.S.C.3 60(k). For a device requiring premarket approval, the notification required by Section 510(k) of the Act, 21 U.S.C. 360(k), is deemed satisfied when a PMA is pending before the agency [21 CFR 807.81(b)]. The kind of information you need to submit in order to obtain approval or clearance for your device is described on the Internet at . The FDA will evaluate the information you submit and decide whether your product may be legally marketed.

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 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 received a response from Jack A. Maggiore, MT, ASCP, President and Chief Scientific Officer dated June 10, 2008, concerning our investigator's observations noted on the Form FDA 483, List of Inspectional Observations that was issued to you. The response promises corrections, but it does not provide the details of those corrections or include copies of revised or created procedures.

Please notify this office in writing within 15 working days from the date you receive this letter of the specific steps you have taken to correct the noted violations, including an explanation of how you plan to prevent these violations, or similar violations, from occurring again. Include documentation of the corrective action you have taken. 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: Lorelei Jarrell, Compliance Officer, Food and Drug Administration, 550 W. Jackson Blvd., 15th Floor, Chicago, IL 60661. If you have any questions about the content of this letter please contact: Ms. Jarrell at 312-596-4216.

Finally, you should know that this letter is not intended to be an all-inclusive list of the violations at your facility. It is your responsibility to ensure 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.



Scott J. MacIntire
District Director