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U.S. Department of Health and Human Services

Inspections, Compliance, Enforcement, and Criminal Investigations

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EPS Biotechnology Corp. 9/11/12

  

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

Public Health Service
Food and Drug Administration
 

10903 New Hampshire Avenue
Silver Spring, MD 20993 


WARNING LETTER 

OCT 19, 2012

VIA UNITED PARCEL SERVICE
 
Mr. YC Lei
General Manager
EPS Biotechnology Corp.
No. 8 R&D RD.III
Hsinchu Science Park
Hsinchu, Taiwan 30077 

Dear Mr. YC Lei:

During an inspection of your firm located in Hsinchi City, Taiwan, on June 18, 2012, through June 21, 2012, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures glucose dehydrogenase glucose meters.  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 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 requirements of the Quality System regulation found at Title 21, Code of Federal Regulations (CFR), Part 820.  We received a response from you, dated July 10, 2012, concerning our investigator’s observations noted on the Form FDA 483 (FDA 483), List of Inspectional Observations, which was issued to your firm.  We address this response below, in relation to each of the noted violations.  These violations include, but are not limited to, the following:

1. Failure to establish and maintain adequate procedures for receiving, reviewing, and evaluating complaints by a formally designated unit, as required by 21 CFR 820.198(a).

For example, Complaint Handling Procedure/P-7203 did not include instructions on how to obtain and evaluate complaints.  Specifically, complaints for the EasyMax models V, N, and L from the United States were not found in the EPS complaint system.  EPS contacted its initial distributor, Oak Tree Holdings, during the inspection and it was determined that complaints were not being forwarded to EPS.  Approximately (b)(4) complaints from May 2012 were provided from by Oak Tree Holdings to EPS during the inspection.

We reviewed your firm’s response and conclude that it is not adequate.  Your firm provided a copy of the revised SOP that lists the requirements to plan, control, and maintain customer complaint handling.  However, your firm did not provide documentation that employees were trained on these procedures, that a corrective action was implemented, and that a systemic corrective action was considered, which should include a retrospective review of all complaints – including those submitted by Oak Tree Holdings during the inspection – to ensure that they were received and evaluated as required by the firm’s procedure. 

2. Failure to adequately ensure, when the results of a process cannot be fully verified by subsequent inspection and test, that the process shall be validated with a high degree of assurance and approved according to established procedure, as required by 21 CFR 820.75(a).

For example, the process validation for the (b)(4) for Easy Plus Mini/Glucose test strips did not demonstrate that the process could consistently manufacture product meeting specification over the full process condition range.  Worst-case criteria of process conditions were not included in the process validation.  The process sheet shows that the (b)(4) ((b)(4)) ranged from (b)(4) to (b)(4).  Mr. Jain, the firm’s Director of Quality Management, indicated the range should be measured in (b)(4). The actual process sheet shows that the (b)(4) range varies from (b)(4) to (b)(4). In addition, Mr. Jain indicated that the (b)(4) varies between (b)(4) to (b)(4); however, all validation challenges were made at (b)(4) only.

We reviewed your firm’s response and conclude that it is not adequate.  Your firm provided a copy of the revised SOP that lists the requirements to plan, control, and maintain process validation.  However, your firm did not provide documentation that employees were trained on these procedures, that a corrective action was implemented, and that a systemic corrective action was considered to include a retrospective review of other process validation activities to ensure that they were performed as required.  Your firm did not provide a description and evidence that the (b)(4) process was validated as required under the process conditions.

3. Failure to establish and maintain adequate procedures for validating the device design, as required by 21 CFR 820.30(g).

For example, the clinical accuracy and user acceptance testing for the DO44 EME Self Monitoring Glucose Meter design was not determined using initial production batches or equivalents.  The design validation was completed using “Sample Run” material stock sample units.  The investigator was informed that there was no documentation that sample units are equivalent to the production units.

We reviewed your firm’s response and conclude that it is not adequate.  Your firm provided a copy of the revised SOP that lists the requirements to plan, control and maintain device design validation.  However, your firm did not provide documentation that employees were trained on these procedures, that a correction and corrective action were implemented, and that a systemic corrective action was considered to include a retrospective review of design validation activities for other devices to ensure they were performed on initial production units or their equivalents.  Your firm did not provide evidence that the design validation for the DO44 EME Self Monitoring Glucose Meter was completed as required as a correction to this deficiency.

4. Failure to establish and maintain adequate 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 CFR 820.90(b)(2). 

For example, the sampling/inspection of (b)(4) pieces from the total of (b)(4) records for the Meter Assay MG D025/5110-20120326006 resulted in a reject of the product due to a (b)(4). The material was returned to manufacturing for 100% inspection and rework.  The rework/inspection document does not show that all (b)(4) pieces were inspected as required and determined to be acceptable.  The record shows that (b)(4) of the (b)(4) were found to be nonconforming.  (b)(4) of the (b)(4) were repaired and found to be acceptable.  (b)(4) of the (b)(4) pieces were reworked, but there was no documentation that the pieces were re-tested.  (b)(4) of the pieces were reworked and were found not to be acceptable.  All of the (b)(4) pieces, including the reworked pieces, were mixed with (b)(4) other pieces, and (b)(4) pieces were tested and found to be acceptable although the testing record indicates that the sampling quantity for the Meter Assay MG D025/5110-20120326006 was (b)(4).

We reviewed your firm’s response and conclude that it is not adequate. Your firm provided a copy of the revised SOP that lists the requirements to plan, control, and maintain non-conforming product.  However, your firm did not provide documentation that employees were trained on these procedures, that a corrective action was implemented, and that a systemic corrective action was considered to include a retrospective review of reworked product to ensure that rework and retesting were conducted as required by your firm’s procedure.  In addition, your firm did not provide a description or evidence of implementation of a correction for this deficiency to include retrieving product that was determined to be unacceptable or implement action that will ensure product released meets specification.

5. Failure to establish and maintain adequate procedures to control product that does not conform to specified requirements, as required by 21 CFR 820.90(a). 

For example, nonconformance is not adequately documented to identify possible corrective actions.  (b)(4) defects are not adequately described to allow for evaluation of process deficiency that may require corrective actions.  (b)(4) defects do not describe the type of observed defect or the location of the defect on the strip sheet.

We reviewed your firm’s response and conclude that it is not adequate.  Your firm provided a copy of the revised SOP that lists the requirements to plan, control, and maintain corrective and preventive action of nonconformance. However, your firm did not provide documentation that employees were trained on these procedures, that a corrective action was implemented, and that a systemic corrective action was considered to include a retrospective review of nonconformances to ensure that they were conducted and documented as required by your firm’s procedure. 

6. Failure to establish and maintain adequate process control procedures that describe any process controls necessary to ensure conformance to specifications where deviations from device specifications could occur as a result of the manufacturing process, as required by 21 CFR 820.70(a). 

For example, the setting for the speed of the (b)(4) used for the (b)(4) has not been verified.  There are no controls to ensure that (b)(4) speed is accurate. The process speed is defined as (b)(4) mm/min, but this rate has not been verified.

We reviewed your firm’s response and conclude that it is not adequate.  Your firm provided a copy of the calibration report for the (b)(4) speed. However, your firm did not provide the SOP that lists the requirements to plan, control, and maintain corrective and preventive action of (b)(4) speed.  Nor did your firm provide documentation that employees were trained on these procedures, that a corrective action was implemented, and that a systemic corrective action was considered to include a retrospective review of process controls for other processes to ensure that device specifications continue to be met. 

U.S. federal agencies may be advised of the issuance of 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.  

Please notify this office in writing within fifteen business days from the date you receive this letter of the specific steps your firm has taken to correct the noted violations, including an explanation of how your firm plans to prevent these violations, or similar violations, from occurring again.  Include documentation of the corrections and/or corrective action (including any systemic corrective actions) that your firm has taken.  If your firm’s planned corrections and/or corrective actions will occur over time, please include a timetable for implementation of those activities.  If corrections and/or corrective actions cannot be completed within fifteen business days, state the reason for the delay and the time within which these activities will be completed.  Please provide a translation of documentation not in English to facilitate our review. 

Your firm’s response should be sent to: Food and Drug Administration, Center for Devices and Radiological Health, Office of Compliance, Field Operations Branch, White Oak Building 66, Rm 2609, 10903 New Hampshire Ave., Silver Spring, MD 20993.  Refer to CMS case #333178 when replying.  If you have any questions about the contents of this letter, please contact: James L. Woods at 301-796-6225 or via fax at 301-847-8514. 

Finally, you should know that this letter is not intended to be an all-inclusive list of the violations at your firm’s facility.  It is your firm’s responsibility to ensure compliance with applicable laws and regulations administered by FDA.  The specific violations noted in this letter and in the Inspectional Observations, FDA 483, issued at the close of the inspection may be symptomatic of serious problems in your firm’s manufacturing and quality management systems.  Your firm should investigate and determine the causes of the violations, and take prompt actions to correct the violations and bring the products into compliance.  

Sincerely yours,  

/S/

Alberto Gutierrez 
Director
Office of In Vitro Diagnostic Device
Evaluation and Safety
Center for Devices and 
Radiological Health