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U.S. Department of Health and Human Services

Inspections, Compliance, Enforcement, and Criminal Investigations

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W.H.P.M., Inc. 3-19-2009

   

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

Public Health Service
Food and Drug Administration
  Los Angeles District
Pacific Region
19701 Fairchild
Irvine, CA 92612-2506
Telephone: 949-608-2900
FAX: 949-608-4415

WARNING LETTER

CERTIFIED MAIL
RETURN RECEIPT REQUESTED

W/L 15-09

March 19, 2009

Dr. John Wan
W.H.P.M., Inc.
9662 Telstar Ave
El Monte, CA 91731-3004

 

Dear Dr. Wan:

 

During an inspection of your medical device film located in El Monte, California from December 1 through December 19, 2008, our investigator determined that your firm manufactures in-vitro diagnostic (IVD) screening tests for drugs of abuse (including the One Step Drugs of Abuse Test), fecal occult blood and pregnancy testing. Under section 201(h) of the Federal Food, Drug and Cosmetic Act (the § 321(h), these products are considered devices because they are intended for use in the Act), 21 U.S.C. diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or intended to affect the structure or function of the body.

 

This inspection revealed that your firm's devices are adulterated within the meaning of section 501(h) of the Federal Food, Drug and Cosmetic 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 applicable requirements of Section 520(f)(1)(A), [21 U.S.C. § 360j(f)(1)(A)] and the Good Manufacturing Practice (CGMP) requirements of the Quality System (QS) regulation found at Title 21, Code of Federal Regulations (CFR), Part 820.

 

Significant violations include, but are not limited to, the following (numbering system corresponds to the numbering of Observations in the Form FDA-483, List of Inspectional Observations, which was issued to you on December 19, 2008):

 

1. A design history file was not established1 or maintained by your firm, as required by 21 C.F.R. § 820.30(j), for the following 510(k)'s: K032575 (First Sign of Drug Abuse Screening Tests for amphetamine, methamphetamine, opiates, cocaine, cannabinoids, and phencyclidine), K052197 (Drugs of Abuse Screening Test for Tricyclic Antidepressants, Barbiturates, MDMA, Benzodiazepines, Methadone and Oxycodone), K041202 (Hemosure One Step Immunological Fecal Occult Blood Test), and K051841 (One Step Pregnancy Test).

 

The inspection revealed the absence of any of the following supporting data for the above-mentioned 510(k)s: raw data for sensitivity studies; accelerated and real time stability study data and protocols; reproducibility data; and cut-off testing data, interference, pH and specific gravity data. Likewise, gas chromatography/mass spectrophotometry data, and method comparison data for the Drugs of Abuse Screening Tests was missing. When asked about these records, you told the inspectors that the 510(k) applications themselves are the design history files, and that raw data supporting these 510(k) applications had been "thrown out."

 

Your firm also has no records identifying design inputs, design outputs, design review, design verification, design validation, risk analysis or design transfer for these 510(k)'s, as required by 21 C.F.R. §§ 820.30(c)-(h).

2. Your firm has not established and maintained plans that describe or reference the design and development activities and define responsibility for implementation, as required by 21 C.F.R.. § 820.30(b). Your firm has not established and maintained a design and development plan identifying and describing the interfaces with different groups or activities that provide, or result in, input to the design and development process of your devices. Your firm was unable to provide documentation that its currently marketed products were developed using design plans. There is no assurance that all activities necessary to control the design of the firm's devices were identified and carried out, and that the manufacturing processes are controlled.

 

Additionally, your firm has not established and maintained procedures to ensure that the device design is correctly translated into production specifications, as required by 21 C.F.R. § 820.30(h). For example, although W.H.P.M., Inc. is responsible for design transfer to WHPM Bioresearch and Technology Co., Ltd, of Beijing, People's Republic of China, and to firms with which W.H.P.M., Inc., has original equipment manufacturer (OEM) manufacturing contracts, there are no records documenting the establishment and maintenance of procedures to ensure that the device design was correctly translated into production specifications as required by 21 C.F.R. § 820.30(h).

 

3. Your firm has not developed, conducted, controlled, and monitored production processes to ensure that a device conforms to its specifications, as required by 21 C.F.R. § 820.70(a). For example, your firm's process controls do not provide for documented instructions, standard operating procedures (SOPs), and methods that define and control the manner of production; monitoring and control of process parameters and component and device characteristics during production; and criteria for workmanship expressed in documented standards or by means of identified and approved representative samples; as required by 21 C.F.R. § 820.70(a).

 

3A: In preparing dilutions of an antigen, your firm performs "mini-pilot production runs" of the finished device. Your firm does not have written procedures for performing these mini-production runs.

 

Additionally, your firm lacks specified written workmanship criteria and specifications. For example, component lots from prior production runs that had functioned as intended are used as "constants" in the mini production runs; however, you have no specified acceptance criteria for the component lots. Likewise, signal strength is a final product acceptance specification but no specification has been established. You stated that employees were knowledgeable about the specifications but that the specifications were not written or approved.

 

3B: Your firm tests a sample of devices for minimal signal strength, and you told the inspection team that acceptance criteria for signal strength and color standards have been in effect since 2007. However, when the inspectors asked to see the written test methods and acceptance specifications, it was determined that the these specifications were in draft form only, and your firm's current written Quality Control (QC) Standards include neither test instructions nor formal acceptance specifications for minimal signal strength. Additionally, your firm's consultant (JT) stated that the color standard, which consists of a color chart printed at a local drugstore photography laboratory, is not controlled to ensure that the color standard does not change due to deterioration caused by time or exposure to elements such as heat and light.

 

3C: Your firm uses a notebook to document test line manufacturing for Drug of Abuse Screening tests. For any product lot documented in this notebook, the notebook constitutes part of the Device History Record that product lot. Therefore, the notebook must comport with the requirements of document control in 21 C.F.R. § 820.40.

 

Although the notebook has handwritten column headers specifying the information to be recorded for each test performed (such as lot number, date tested, quantity tested, results of testing, and employee conducting testing), these headers had not been reviewed and approved by the Quality Unit for suitability and completeness of information to be captured when each test is performed. Therefore, there is no assurance the column headers capture all pertinent information needed. The notebook also lacks documentation of the notebook's approval date, issuance date, effective date, name of approving official or any type of control number for traceability and revision control. Thus, the notebook is not a controlled document, as required by 21 C.F.R. § 820.40.

3D: Employee (JN) stated that the conjugate used in the Drugs of Abuse Screening Tests is concentrated by centrifugation, and that the actual settings for the rate of centrifugation was 9000 RPM at 30 minutes. However, this parameter differs from the established SOP, "Prepare Au Reagent (10000 RPM at 15 minutes)." Your consultant advised the inspectors that the operating parameters actually employed are the appropriate parameters.

 

These differences needed to be addressed in the design phase as to the effect of such differing parameters on the finished device. Manufacturers are required to identify, document, validate, verify, review and approve design changes before their implementation, as required by 21 C.F.R. § 820.130(i).

 

3E: Sheets used for the Drug of Abuse Screening Tests are placed in a drying room for stabilization. Your firm's log documented an acceptable temperature range of 32-40C, which differs from the narrower range established by the SOP, "Stabilization of 33-38C."

These differences needed to be addressed in the design phase as to the effect of such differing parameters on the finished device. Manufacturers are required to identify, document, validate, verify, review and approve design changes before their implementation, as required by 21 C.F.R. § 820.130(i).

 

3F: The Work Instruction titled "Preparation of Reagent Solution for Au Line," in effect since 8/15/2003, contains an incorrect formula for determining the volume of stock solution to be used in preparation of reagent solution for the Au line. Specifically, when examining the Device History Record for part number 20089, lot number L1126080598, date of manufacture 11/26/08, batch size 49 mL, Inspector Karsik pointed out to you that an employee had erroneously switched the actual values for optical density desired and optical density of solution when inputting those values into the pre-scripted formula in the instruction. You advised Inspector Karsik that the pre-scripted formula itself has erroneously switched the values for optical density desired and optical density of stock solution, and the employee filling out the form had merely switched the values to "correct" the formula.

 

These differences needed to be addressed in the design phase as to the effect of such differing parameters on the finished device. Manufacturers are required to identify, document, validate, verify, review and approve design changes before their implementation, as required by 21 C.F.R. § 820.130(i).

 

3G: The Work Instruction "Preparing the Reagent Solution for Control Line" has a formula for Final Concentration with units in milliliters. You stated that the units should have been in microliters.

 

These differences needed to be addressed in the design phase as to the effect of such differing parameters on the finished device. Manufacturers are required to identify, document, validate, verify, review and approve design changes before their implementation, as required by 21 C.F.R. § 820.130(i).

4. Your firm has not validated and approved the results of a process of your firm which cannot be fully verified by subsequent inspection and test, as required by 21 C.F.R. § 820.75(a).

 

4A: Your firm has not validated the control and test line dispensing process for your Drugs of Abuse Screening tests. Your firm does not even have a written procedure of the "validation of the control and test line" in-process test . Also, your firm only has installation qualification documentation for one of the three BioDot Sprayer XYZ3000 dispensing systems, and has failed to document the operation and performance qualification of any of the three dispensing systems.

 

4B: Your firm has not validated the pouch heat sealing process to ensure temperature, dwell time and pressure will consistently achieve a proper seal . You explained that moisture causes IVD products to degrade, which can negatively affect conjugate and cause a lowering of signal.

 

Additionally, your SOP for the heat-sealing process and the Work Instruction "Sealing Process for Pouches" have different operating temperature parameters. This is another example of deficient production and process controls (21 C.F.R. § 820.70(a)).

 

These differences needed to be addressed in the design phase as to the effect of such differing parameters on the finished device. Manufacturers are required to identify, document, validate, verify, review and approve design changes before their implementation, as required by 21 C.F.R. § 820.130(i).

5. Your firm has not established and maintained procedures for acceptance activities, as required by 21 C.F.R. § 820.80(a).

5A: Your firm has no written procedures for receipt and acceptance of incoming raw materials as required by 21 C.F.R. § 820.80(b). Employees receiving materials do not record the supplier's lot number or part number, the condition of goods upon receipt, or the internal part number. The results of examination of incoming product, where performed, is documented on a generic "Incoming QC Report." There are no written, approved, pre-established acceptance criteria on this Incoming QC Report; instead, acceptance criteria are handwritten on the form by the firm's employees only as the activity is performed. Material suitability is determined by performing a "mini-production run" conducted without written procedures.

 

Your firm has no written procedures for determining whether the calibrators (negative and positive urine standards) are acceptable for use. You stated that the suppliers of the calibrators are well-known but that you do not believe that the suppliers are operating in accordance with good manufacturing practices. Although incoming acceptance activities may be based, in part, on the degree to which each supplier has demonstrated a capability to provide quality products, your firm has not formally assessed any of its suppliers.

 

Additionally, your firm has no written procedures or acceptance criteria for acceptability of labels/labeling.

 

5B: Your firm has not established and maintained 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). For example, your firm has no written instructions for the in-process test performed on each In Vitro Diagnostic product after dispensing of control and test lines (known as "validation of the control and test line") onto sheets of product. This is especially significant, as your firm has received customer complaints alleging that the control line did not appear on some of your products.

 

5C: With the exception of a written procedure for testing finished human chorionic gonadotropin (HCG) pregnancy test strips, your firm has no written procedures defining test methods to ensure each lot of any of your finished devices meet acceptance criteria, as required by 21 C.F.R. § 820.80(d).

 

You stated that instead of written acceptance criteria procedures, your employees "just follow the package insert instructions" supplied with the finished product to customers. However, you also stated that your firm tests samples for -50%, +50% and sometimes +300% of cut-off value; the package inserts do not have instructions for testing at -50%, +50% and +300% of cut-off value.

 

While your firm does not have written procedures describing finished product test methods, some QC Standards are in place. However, not all acceptance criteria for the Drug of Abuse Screening Tests are defined in controlled and released documents. For example, the Quality Control Standards for Drugs of Abuse Screening Tests do not include the specifications for signal strength, specifications as to allowable differences between control and test line signal strength, or specifications for the +300% of cut-off value above.

 

Without clear, written test methods and acceptance criteria, there is no assurance that all lots produced are tested in the same manner, meet the same standards, and are capable of performing as intended.

6. Your firm has not established and maintained procedures for implementing corrective and preventive action, as required by 21 C.F.R. § 820.100(a). Your firm has three Corrective and Preventive Action Procedures, requiring that information related to quality problems or nonconforming product be disseminated to those directly responsible for assuring the quality of product or for the prevention of quality problems. These procedures also require investigation into the causes of quality problems, determining root cause where possible, and implementing prescribed corrective and/or preventive action to prevent recurrence. However, the procedures for implementing corrective and preventive actions were not implemented.

 

6A: Customer complaint C0709081 alleged that the control line did not appear and resulted in a Corrective and Preventive Action Report (CAPAR) on 7/9/08. However, there was no evidence that the manufacturer (WHPM, China) was informed or asked to assist in the investigation. The CAPAR remained open as of 12/11/08 and there was no final corrective action.

 

6B: Customer complaint C0317081 alleged that the THC dip card (lot numbers K284504, A106291) tested negative when tested against + 50% of the cut-off value. This resulted in a CAPAR with a due date of 3/21/08 but it had remained open as of 12/11/08 with no final corrective action.

For both complaints, products were not recalled and customers were not notified of the problems. The associated CAPARs were not provided for management review.

 

The purpose of the CAPAR subsystem is to collect and analyze information, identify product quality problems and take appropriate action to prevent reoccurrence. Verifying or validating corrective and preventive actions, communicating this to responsible persons, providing relevant information to management and documenting activities can prevent recurrence and minimize device failures.

 

7. Your firm has not established procedures for identifying training needs and ensuring that all personnel are trained to adequately perform their assigned responsibilities, and has not documented training, as required by 21 C.F.R. § 820.25(b).

7A: Until 11/28/08, your firm's SOPs titled "Corrective and Preventive Actions (effective 4-24-08) and "Corrective and Preventive Action" (effective 1-1-03) both assigned you, the firm's President, with the responsibility for oversight of the firm's Corrective and Preventive Action Reporting (CAPAR) program, including assigning CAPAR numbers, coordinating investigations, identifying corrective actions, determining corrective action effectiveness, assuring timely closure of CAPARs, trending data and presenting trend data to the management review board. However, there was no documentation that you had ever been trained on the Corrective and Preventive Action Procedure.

 

7B: There was no documentation that employee (ML), responsible for training employees on the use of the spectrophotometer, had been trained on the operation of the spectrophotometer. Additionally, you stated that your employees (including ML) have a limited understanding of English; however the spectrophotometer manual is written solely and entirely in English.

8: Your firm has not established and maintained procedures to ensure that all purchased or otherwise received product and services conform to specified requirements, as required by 21 C.F.R. § 820.50. Specifically, you have not established requirements that must be met by suppliers,contractors, and consultants (21 C.F.R. § 820.50(a)), nor have you evaluated and selected suppliers, contractors, and consultants on the basis of their ability to meet specified requirements (21 C.F.R. § 820.50(a)(1)).

 

Your firm has no written system for qualifying suppliers and no documentation that demonstrates that your suppliers and contractors, including vendors of urine standards, membrane, antigen, antibody, goat anti-mouse IgG, and Drug of Abuse Test Sheets, as well as consultants (AS) and (JT), were evaluated and selected based on their ability to meet specified requirements.

 

Because your firm lacks these purchasing controls, there is no assurance that materials or services purchased or supplied are suitable for their intended use, and do not adversely affect the safety and effectiveness of the finished medical device. The failure to implement purchasing control may result in component failure requiring product recall.

 

9: Your firm has not established and maintained document control procedures, as required by 21 C.F.R. § 820.40. Your firm's document control procedure, titled "Document Control" (effective 11-1208) defines the system used to control all documents and data required by the quality system. However, you stated that your firm did not have an official document control system prior to 11/12/08, even though your firm has been manufacturing and distributing devices since 2003.

 

Section 6.6.3 of your firm's Document Control procedure states that obsolete originals are to be labeled as obsolete, control copies are to be destroyed, and new documents and forms must be approved before they are officially released for implementation. However, the inspection found multiple procedures addressing the same elements of the quality system simultaneously in effect without any of these procedures having been marked as obsolete, superseded, or otherwise controlled to prevent their use by personnel. The multiple procedures observed included two quality system manuals, three management review procedures, two employee training procedures, two design control procedures, three corrective and preventive action procedures, three medical device reporting procedures, two complaint handling procedures, three procedures for handling of non-conformances, and two lot numbering assignment procedures. In addition, procedures documents that were not approved were observed at locations where they were being used before they were officially released for use.

Procedures for control of documents must be implemented to ensure accuracy and usage of current versions, as well as to ensure that documentation developed is adequate to fulfill its intended use or meet requirements.

 

10: Your firm has not established and maintained procedures for identifying product throughout all stages of receipt, production, packaging, distribution, and installation to prevent mix-ups, as required by 21 C.F.R. § 820.60.

10A: Your firm has no written procedures for incoming receipt and acceptance of raw materials. Your firm lacks traceability as to specific shipments of raw material used in product and testing of each lot of finished devices. No internal lot number or other control number is assigned to clearly differentiate each shipment of material received from other shipments, and supplier lot numbers are not recorded.

 

10B: Part numbers recorded on the work instruction forms for the raw material goat anti-mouse antibody and the Reagent Solution produced from that raw material were noted to be the same.

 

The lot number of the manufacturer's raw material is used by the firm as its production lot number. Further, the firm uses the same manufacturer's lot number for the raw material goat anti-mouse antibody to produce different concentrations of the Reagent Solution for Control Line, and continues to assign the same lot number to each batch of finished Reagent Solution for Control Line produced. In sum, unique lot and part numbers are not assigned in order to prevent mix-ups.

 

10C: Laminated sheets were observed to lack any product identification whatsoever.

Among other things, without a system to uniquely identify and clearly distinguish in-process materials, the incorrect material could be used in manufacturing resulting in production of a finished device which does not meet specifications.

 

11: Your firm has not established and maintained procedures to ensure that device history records (DHRs) 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 System regulation, as required by 21 C.F.R. § 820.184. Four of your firm's 11 DHRs lacked initials of the relevant employee performing each processing step for that product; four of 11 DHRs lacked any documentation whatsoever that processing steps were performed; and four of 11 DHRs lacked documentation of the specified lot numbers of the calibrators used.

 

12: Your firm has not established, maintained and documented procedures to ensure that equipment is routinely calibrated, inspected, checked, and maintained, as required by 21 C.F.R. § 820.72(a).

12A: Your firm has no records to demonstrate that the pressure gauge for vacuum level, used in testing seal integrity of heat-sealed pouches containing bulk Drugs of Abuse Test sheets and finished product cassettes, has ever been calibrated, and you stated it had never been calibrated. Additionally, personnel were observed to utilize their cell phones to time the duration of the Seal Integrity test, rather than a designated timer associated with this equipment and procedure.

 

12B: The vacuum test system for assessing pouch seal integrity for the Drugs of Abuse Test sheets packaging has not been qualified, and the method has not been validated. The vacuum seal for these test sheets safeguards against moisture entering the finished product; as you noted, the presence of moisture may cause product degradation, as well as a negative affect on both conjugate (with an associated signal drop of 5 to 10%), and labeled shelf life.

 

12C: Your firm has not performed installation, operation, and performance qualification studies for the spectrophotometer used to determine: 1) final protein concentration of control line solutions, 2) protein concentration in Au conjugate solutions, 3) confirmation of protein concentration in incoming raw material antigens to be used in test line manufacturing, and 4) for development of color standards to be used for quality control release testing. Therefore, there is no assurance that the test results obtained from this equipment are accurate, or that any dilutions based upon these results will result in production of finished devices that meet their specifications.

Device manufacturers must ensure that all inspection, measuring and test equipment is suitable for its intended purpose and is capable of producing valid results. Procedures are required to be established and maintained for calibration, inspection and maintenance and these activities are to be documented.

 

13: Your firm has not established and maintained procedures to control labeling activities, as required by 21 C.F.R. § 820.120.

13A: There are no written procedures for label preparation, inspection, issuance and storage. You stated that some package inserts are produced at the firm but there was no record of production.

 

13B: Other than pouch labels, labels and labeling are not documented in the DHRs.

 

Device manufacturers are required to establish and maintain procedures to control labeling activities. Labeling must be released by a designated individual and the activities are to be documented in the DHR. Labeling and packaging are to be controlled to prevent label mix-ups. Failure to control labeling activities may result in erroneous label content, inaccurate storage, incorrect expiration dates and inaccurate instructions for use.

 

14: Your firm has not established and maintained procedures for reviewing and evaluating complaints by a formally designated unit, as required by 21 C.F.R. § 820.198(a). Although your firm appears to have three separate complaint handling procedures, your firm failed to conduct adequate investigations into six of seven complaints alleging possible device failures. For four of seven complaints, the actual manufacturer of the device, WHPM Bioresearch and Technology Co., Ltd, of Beijing, People's Republic of China, was not notified or consulted. There is no documentation that written responses were provided, per your firm's procedures, to six of seven complainants.

 

Device manufacturers are required to establish and maintain procedures for receiving, reviewing and evaluating complaints by a formally designated unit. This is required in order to ensure that all complaints are processed in a uniform and timely manner. Without a complete investigation, the firm may fail to identify a root cause and take appropriate corrective and preventive action and fail to file a Medical Device Report, if appropriate.

 

15: Your firm failed to conduct Quality Audits at sufficient regular intervals, as prescribed by internal procedures, to verify that the quality system is effective in fulfilling your quality system objectives, as required by 21 C.F.R. § 820.22. Your firm's procedure, titled "Internal Quality Audits," version A 1.1, dated 2/1/08, states that internal audits are to be conducted quarterly, with a full audit by a Consultant annually. There was an annual audit in February 2008 but no evidence of quarterly audits in 2007-2008.

 

Your firm could not provide any documentation of having performed any internal auditing procedure before February 2008, and you stated to Investigator Karsik that to your knowledge, your firm had no internal auditing procedure prior to February 2008, despite having been manufacturing and distributing class II medical device products since 2003.

 

Device manufacturers are responsible for establishing and implementing procedures for quality audits to assure the quality system is in compliance with the established quality system requirements and to determine the effectiveness of the quality system. Reports are to be made and reviewed by management having responsibility for these matters.

 

16: Management reviews were not conducted by your firm at defined intervals, as required by 21 C.F.R. § 820.20(c). Your firm's procedures state that management reviews are to be held quarterly. No records of management reviews could be located during the inspection. Following a search by your staff, you told Inspector Karsik that the last meeting covering topics which might qualify as a management review was held on March 1, 2005. Although the firm's Management Review procedures require preparation of agenda, you advised Inspector Karsik that agendas were never prepared for these meetings, so no specific record of this March 1, 2005 meeting was collected.

 

We have received two (2) responses from you concerning the observations noted on the Form FDA-483, List of Inspectional Observations, which was issued to you on December 19, 2008. In your initial response, dated December 23, 2008, you did not include full documentation of corrective actions planned, started or completed; the results of any actions taken/recommended by your consultants; or the results of equipment validation.

 

In your subsequent response, dated January 29, 2009, you provided evidence of the creation of certain procedures and forms. These corresponded to procedures and forms that were either not created and/or not current at the time of the inspection. However, the response lacked overall detail regarding whether the firm has implemented such procedures. The response did not address whether your firm will provide periodic updates, including pertinent data, of accomplished actions to FDA.

 

Your responses also failed to provide assurance that the upper level of management, including the President, provides adequate control of the Quality System.

 

Finally, your responses did not address the disposition of products on hand or already distributed that were produced during the period when the film had no functional Quality System.

 

We find your responses are inadequate and do not provide assurance that your firm's devices are not adulterated.

 

In addition, we note that on December 16, 2008 you submitted a written request to withdraw your pending 510(k), K081271, after FDA uncovered serious issues implicating the veracity and reliability of the data submitted in support of K081271. Those issues were reported to you in a letter from FDA dated November 25, 2008. As previously noted herein, the December 1 through December 19, 2008 inspection revealed that four-cleared 510(k)s (K032575, K052197, K041202, K051841) lacked any reliable source documentation. These deviations raise questions about the reliability of data in your cleared submissions. Moreover, it is unlikely that the data reliability problems identified in K081271 would be confined only to that submission; rather, those problems include methods of comparison and reproducibility testing that would be common to other devices your firm manufactures.

 

Consequently, we recommend that your firm undertake a validity assessment to determine the reliability of data submitted to FDA for the four cleared 510(k)s K032575 (First Sign of Drug Abuse Screening Tests for amphetamine, methamphetamine, opiates, cocaine, cannabinoids, and phencyclidine), K052197 (Drugs of Abuse Screening Test for Tricyclic Antidepressants, Barbiturates, MDMA, Benzodiazepines, Methadone and Oxycodone), K041202 (Hemosure One Step Immunological Fecal Occult Blood Test), and K051841 (One Step Pregnancy Test). Guidance for firms in conducting validity assessments may be found in a document entitled, "Points to Consider for Internal Reviews and Corrective Action Operating Plans" (enclosed). A copy of this document can also be accessed at the following Internet addresses:

 

www.fda.gov/ora/compliance_ref/frn/fraud_ill_grat.html 
www.fda.gov/ora/compliance_ref/aip_points.html

 

If you are unable to determine the reliability of data previously submitted as part of these cleared 510(k)s, or to verify the accuracy of your previous submissions, you may request withdrawal of any cleared application that contains unreliable or unverifiable data.

 

If you wish to replace any unreliable or unverified data with a new submission, the new submission should be in the form of a new 510(k) application. The new application should identify the parts of the original application that could not be established as reliable. The truthfulness and accuracy of the new application should be certified by the president, chief executive officer, or other official most responsible for the applicant's operations. FDA recommends that such certifications be based upon independent audit and corrective action operating plans, submitted to the agency for review and comment prior to implementation.

 

You should take prompt action to correct the violations addressed above 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 notification applications for Class II 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.

 

It is your responsibility to ensure compliance with applicable laws and regulations administred by FDA. The specific violations noted in this letter and in the Inspectional Observations, Form 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.

 

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. You should include documentation of the corrective action you have taken. If your planned corrections will occur over time, please include a timetable for implementation of these 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:

Mark Harris
Acting Director, Compliance Branch
Food and Drug Administration
19701 Fairchild
Irvine, CA 92612-2506

If you have any questions about the content of this letter please contact Dr. Raymond W. Brullo, Compliance Officer at 949.608.2918.

Sincerely yours,

/S/

Alonza E. Cruse
District Director

Bcc: internal

_________________________________________________________________________

1 The terms "establish" or "established," as used in this letter, follow the definition at 21 C.F.R. § 820.3(k), and mean "define, document (in writing or electronically), and implement."