Inspections, Compliance, Enforcement, and Criminal Investigations
Branan Medical Corp. Inc. 12/28/09
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
RETURN RECEIPT REQUESTED
December 28, 2009
Raphael C. Wong
President and CEO
Branan Medical Corp., Inc.
140 Technology Drive, Bldg. 400
Irvine, CA 92618
Dear Mr. Wong:
During an inspection of your firm, located in Irvine, California from July 15 to October 9, 2009 investigators from the United States Food and Drug Administration (FDA) determined that your firm manufactures the Fastect II®, Monitect® , Quicktox® , Toxcup®, and Intect® 7, Oratect III® and OratectPlus®, and Monitect in-vitro (IVD) drug of abuse kits. 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.
Our inspection revealed that the Oratect III, OratectPlus, Oratect XP and Monitect® X04-SC10 are adulterated under section 501(f)(1)(B) of the Act, 21 U.S.C. § 351(f)(1)(B), because you do not have approved application for pre-market approval (PMA) in effect pursuant to section 515(a) of the Act, 21 U.S.C. § 360e(a), or approved applications for an investigational device exemption (IDE) under section 520(g) of the Act, 21 U.S.C. § 360j(g). The Oratect III, OratectPlus, Oratect XP, and Monitect® X04-SC10 devices are also misbranded under section 502(0) of the Act, 21 U.S.C. § 252(o), because you did not notify the agency of your intent to introduce the devices into commercial distribution, as required by section 510(k) of the Act, 21 U.S.C. § 360(k) in that a notice or other information respecting the modification to the device was not provided to the FDA as required by section 510(k), 21 U.S.C. § 360(k). As was stated in the July 30, 2009 letter you received from the Center for Devices and Radiological Health, the marketing and distribution of these devices for use in the workplace requires FDA clearance. The kind of information you need to submit in order to obtain approval or clearance for your device is described on the Internet at http://www.fda.gov/cdrh/devadvice/3122.html. The FDA will evaluate the information you submit and decide whether your product may be legally marketed.
Our inspection also 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 Good Manufacturing Practice (GMP) requirements for the Quality System Regulation, specified in Title 21, Code of Federal Regulations (CFR), Part 820.
The following deficiencies were noted during the inspection:
1. Failure to adequately establish and maintain procedures for validating the device design, as required by 21 CFR 820.30(g). For example:
a. Protocol (b)(4), Stability Testing - Drugs of Abuse Products," issued 11/20/2000 states that during a (b)(4) Stress Stability Study testing should continue at (b)(4) However, Form (b)(4)"Stability Study Testing Schedule," dated 02/07/2003 shows that the (b)(4) testing for the Fastect II device (cat # (b)(4) was only performed at start, week (b)(4) and week (b)(4). The study was finished and approved at week (b)(4) without observing (b)(4).
b. Protocol (b)(4) "Stability Testing - Drugs of Abuse Products," issued 11/20/2000 states that (b)(4) lots of a device must pass (b)(4) and (b)(4) storage stability studies to validate and/or change the shelf life claim. The oven stress testing (b)(4) should continue (b)(4). However, Form (b)(4), rev C, "Stability Study Testing Schedule," completed on 08/18/2003 shows that the (b)(4) testing for the Fastect II device (cat#(b)(4))was performed using only one lot and only performed at start, weeks (b)(4) and (b)(4). The study was finished and approved at week (b)(4) without observing (b)(4).
c. When requested, no accelerated or real time stability studies were provided to support the QuickTox Multi Drug Dipcard's expiration date.
d. Protocol (b)(4), rev. C, "Stability Testing - Urine Drugs of Abuse Products," issued 01/16/2004 states that during a (b)(4) Temperature Stability Study testing should continue at monthly intervals until the (b)(4) for (b)(4) consecutive months or until product (b)(4) months storage. The procedure only requires that the test be read at (b)(4) minutes. However, the device's instructions for use indicate that the test can be read up to 60 minutes.
e. Document (b)(4), Rev. A, "MET-500 Shelf-Life Stability Study," dated 4/01/2000 and Document (b)(4),Rev. A, "MTD: Shelf-Life Stability Study," dated 4/01/2000 indicate that the product should be tested at monthly intervals (b)(4) However, test results show that the studies were stopped at (b)(4) and (b)(4) weeks respectively (b)(4).
f. The firm's Fastect II, Fastect II CLIA Waived, and QuickTox device package inserts include claims for accuracy and precision, and read-time. When requested, no raw data, protocols, or final reports were provided to support these claims.
g. The real time stability study to extend the shelf-life of the Fastect II device from (b)(4) months to (b)(4) months is dated 5/9/2008. However, the raw data is dated 6/24/2008 and 2/12/2009.
2. Failure to adequately 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 CFR 820.30(i). For example:
a. The firm submitted a Special 510(k) submission on July 15, 2009, to (b)(4) the Monitect Single Drug Screen Dipstick Test into the QuickTox Multiple Drug Dipcard and to (b)(4) the test strips.
When requested, the firm did not provide any verification or validation protocols or data to support these changes.
b. The firm notified FDA on February 25, 2005, of a modification to the QuickTox Multi Drug Dipcard. The new device, the Fastect II Drug Screen Dipstick Test, was a change from a dipcard to a (b)(4). When requested, the firm did not provide any verification or validation protocols or data to support this change.
c. "Project 004 (Fastect II - CLIA. Waive)" includes a change in the (b)(4) of the Fastect II strips and holder from (b)(4) to (b)(4). When requested, the firm did not provide any verification or validation protocols or data to support this change.
d. The firm notified FDA on October 16, 2002, of (b)(4) to the QuickTox Multi Drug Dipcard. Changes to the device included (b)(4) for (b)(4) and (b)(4) from (b)(4) to (b)(4) and (b)(4) to (b)(4) respectively. When requested, the firm did not provide any verification or validation protocols or data to support this change.
3. Failure to adequately establish and maintain procedures for defining and documented design output including documenting, reviewing, and approving design outputs before release, as required by 21 CFR 820.30(d). For example, Form (b)(4),Rev. A, "Product Technical Specifications (PTS)," dated 4/09/2004 for the CLIA Waive Fastect II device does not document any design outputs. When questioned, the firm stated that they did not establish any final design outputs.
4. Failure to adequately establish and maintain procedures to ensure that formal documented reviews for the design results are planned and conducted at appropriate stages of the device's design development, as required by 21 CFR 820.30(e). For example, the design history file for "Project 004 (Fastect II - CLIA Waive)" does not contain documented design reviews for Phase IV Pre-Production, Phase V Design Verification, or Phase VI Design Validation.
5. Failure to establish and maintain a design history file for each type of device, as required by 21 CFR 820.30(j). For example, when requested, the firm indicated that they did not establish a design history file for the QuickTox Multi Drug Dipcard.
6. Failure to adequately establish and maintain procedures for receiving, reviewing, and evaluating complaints by a formally designated unit, as required by 21 CPR 820.198. For example, Procedure (b)(4),version E, Customer Complaint Procedure," effective January 7, 2008, states that complaints are to be resolved within 30 days and that a documented reason is needed when a complaint is not closed within 30 days or when a CAPA is not opened. Customer Complaint Number: (b)(4) was received on May 18, 2009 because of a complaint that the MF 19 Barbiturate 300 IVD, lot number (b)(4), failed to meet its 60 minute read time specification.. The firm determined that an investigation was required on May 29, 2009. However, as of September 10, 2009, the Complaint Investigation Results, Root Cause, Corrective and Preventive Action, and Resolution sections of Form (b)(4) were not complete. The complaint is still open and the reasons for the delay in closing or initiating a CAPA are not documented. When questioned, the firm stated that they had not started a root cause investigation or a CAPA.
7. Failure to adequately establish and maintain procedures for implementing corrective and preventive action which shall include requirements for investigating the cause of nonconformities relating to product, processes, and the quality system; and indentifying the action(s) needed to correct and prevent recurrence of nonconforming product and other quality problems, as required by 21 CFR 820.100(a)(2) and 21 CFR 820.100(a)(3). For example, Customer Complaint Number: (b)(4) was received on May 18, 2009 because of a complaint that the MF 19 Barbiturate 300 IVD; lot number (b)(4) failed to meet its 60 minute read time specification. The initial investigation confirmed the complaint and also identified lots (b)(4), (b)(4), (b)(4), (b)(4) and (b)(4) as exhibiting the same failure. The CAPA to address these nonconformaces was requested on 8/03/2009, 8/25/2009, 8/31/2009, and 9/08/2009. Each time the firm responded that a CAPA had not yet been opened.
8. Failure to adequately establish and maintain procedures that define the responsibility for review and the authority for the disposition of nonconforming product, as required by 21 CFR 820.90(b). For example, Procedure (b)(4), Ver. E, "Control of Nonconforming Product," effective 12/09/04 states, "To Accept/Release a nonconforming product "As Is" is considered an Atypical Release and requires the approval of at least two (2) department managers, The justification (rationale) for use must be documented on Form (b)(4)." Form (b)(4) for product numbers (b)(4), (b)(4), (b)(4), and (b)(4) includes a final disposition of "Accept/Release As Is." However, the rationale for the atypical release is incomplete and not fully documented.
9. Failure to adequately 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 DMR and the requirements of this part and shall include, among other things, the primary identification label and labeling used for each production unit, as required by 21 CFR 820.184(e). For example, the firm stated that finished product labels and labeling are not included or referenced in the DHR.
10. Failure to adequately establish and maintain data that clearly describe or reference the specified requirements, including quality requirements, for purchased or otherwise received services, as required by 21 CFR 820.50(b). For example, the firm provided an "Assemble and Manufacturing Agreement" dated November 10, 2003 as their current agreement between themselves and (b)(4) the firm's contract assembler located in China. The agreement states, "Term, This Agreement shall be effective for a period of (b)(4) from the date hereof, unless sooner terminated in accordance with the provisions of (b)(4)."
11. Failure to adequately establish and maintain procedures for identifying training needs and ensure that all personnel are trained to adequately perform their assigned responsibilities, as required by 21 CFR 820.25(b). For example:
a. Quality System Procedure (b)(4), Ver. A, "Resource Management," approved 7/01/2009 indicates that professional staff such as the COO should be trained on "pertinent company policies, procedures and/or SOPs." The firm's procedures indicate that the management representative and COO may be consulted during the complaint handling process and is responsible for ensuring that potential MDR reportable events are investigated. However, the employees' training records do not document training on Procedure (b)(4), "Customer Complaints Procedure," or Procedure (b)(4) "Medical Device Reporting (MDR) Procedure."
b. Quality System Procedure (b)(4) Ver. A, "Measurement, Analysis and Improvement," effective 07/13/09 states, ''The Sales, Marketing and Operation Department who are in contact with customers are responsible for documenting Customer Complaints." However, the firm's Sales Department employees' training records do not document training on this procedure.
c. The Manufacturing Manager's responsibilities documented in Form (b)(4), Rev. B, "Job Description," dated 9/01/2008 includes reviewing and addressing quality control and quality assurance issues as a member of the Management Review Board. The Management Manager participated in a management review meeting on 4/14/2009. The employee's training records do not document training on how to review quality control and quality assurance issues.
Our inspection also revealed that your Fastect II Drug Screen Dipstick BAR300 MF19 is misbranded within the meaning of Section 502(t)(2) [21 U.S.C. § 352(t)(2)], in that you failed or refused to furnish any material or information respecting the device that is required by or under section 519, 21 U.S.C. § 360i, and 21 CFR Part 806 (Reports of Connections and Removals).
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 ill 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.
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 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.
Please notify this office in writing within fifteen (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:
Acting Director, Compliance Branch
Food and Drug Administration
Irvine, CA 92612-2506
If you have any questions about the content of this letter please contact Marco S. Esteves, Compliance Officer at 949-608-4439.
Alonza E. Cruse
Los Angeles District
Cc: Branch Chief
Food and Drug Branch
California Department of Public Health
1500 Capitol Avenue - MS 7602
P.O. Box 997413
Sacramento, CA 95899-7413