Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
|10903 New Hampshire Avenue|
Silver Spring, MD 20993
August 26, 2013
VIA UNITED PARCEL SERVICE
Jeong Ku Seo
Bio Focus Co. Ltd
1202 Deahyun Technoworld
Korea, Republic of (South)
Dear Mr. Seo:
During an inspection of your firm located in Uiwang-si Republic of South Korea on April 15, 2013 through April 17, 2013, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures Sure-Aid brand pregnancy 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 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 Jeong Ku Seo, President/CEO dated May 3, 2013 concerning our investigator’s observations noted on the Form FDA 483 (FDA 483), List of Inspectional Observations, that 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 implementing corrective and preventive action as required by 21 CFR 820.100(a). For example:
a. Section 8.2.A.1 of your firms Corrective and Preventive Action Procedure (CAPA), BFQ-80.50 Revision 1 (effective 2006.10.16), states, “(b)(4),” but nonconformances found in process for the manufacturing and assembly of hCG test strips and Sure-Aid Pregnancy Tests did not trigger any Corrective Action Requests. For example, page 6 of 8 of the Sure-Aid Pregnancy Test Device History Record (DHR) for lot #(b)(4) indicates that there were (b)(4) in-process non-conformances found after cutting the test strips. In addition, page 6 of 8 of the Sure-Aid Pregnancy Test DHR for lot #(b)(4) indicates that there were (b)(4) in-process non-conformances found after cutting the test strips. Correction Action Requests were not initiated for these nonconformances as required.
b. Your procedure, Corrective and Preventive Action Procedure, BFQ-80.50 Revision 1 (effective 2006.10.16), indicates that quality data sources will be analyzed using appropriate statistical methods but not tracked. You did not include nonconformances found in-process in the analysis of the data. During the inspection, it could not be determined how many in-process nonconformances had occurred in the past (b)(4). For example, (b)(4). In addition, (b)(4).
We reviewed your firm’s response and conclude that it is not adequate. The response states that the corrective and preventive action procedure was revised. However, it is unclear what revisions were incorporated into the procedure and your firm has not provided a corrective action to ensure that the CAPA procedure will be followed or how the deficiencies identified in this observation will be addressed. Additionally, your firm has not indicated if a Corrective Action Request will be created to address the deficiency identified for the hCG test and the Sure-Aid pregnancy tests. Your firm has not indicated that a retrospective analysis of all other nonconformances within the (b)(4) was conducted to ensure corrective action requests were opened as outlined in the Corrective and Preventive Action Procedure, BFQ-80.50 Revision 1 procedure. Although your firm states that non-conforming products will be (b)(4), your firm did not provide evidence that these nonconformances would be included in the analysis of data as required by your firm’s CAPA procedure. In addition, your firm did not provide evidence that a retrospective review of all nonconformances would be conducted to ensure they were analyzed using appropriate statistical methods as required.
2. Failure to ensure that 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 procedures, as required by 21 CFR 820.75(a). For example, your firm’s validation of the Reel-to-Reel Dispenser, Model DAI-300 is not adequate/not complete. Specifically:
a. Your firm’s acceptance criteria for the validation of the Reel-to-Reel Dispenser, Model DAI-300 were not adequately defined for the Installation Qualification (IQ), Operational Qualification (OQ), or Performance Qualification (PQ). Specifically, the validation procedure BFQI-6031 Rev 0 (effective 2009.10.20), Section 5.3 on page 4 of 9, states that IQ should include contents such as checking that the machine or equipment system is installed correctly by following guidelines and the purpose, however, no acceptance criteria are specified.
b. A protocol that defines the test performed and acceptance criteria needed for the IQ to be successful was not established. Specifically, document BFF-6020-03 shows the installation report for the Reel-to-Reel dispenser dated 2005.10.10. The report states, “(b)(4),” but it does not have an established protocol for how all of these items are to be checked. Additionally, page 2 of 2 of this test report has a data table of values that were tested, but it could not be determined how these values were obtained.
c. OQ was not performed, as required by Section 5.4 of the Validation Procedure, BFQI-6031 Revision 0 (effective 2009.10.20). Specifically, section 5.4 shows the procedural requirements for performing an OQ. The procedure states that OQ should involve, “(b)(4).” However, your firm did not have any documentation to show that OQ was performed.
We reviewed your firm’s response and conclude that it is not adequate. You provided an outline of the IQ and OQ protocols and expect to conduct the IQ (b)(4), OQ (b)(4) and PQ (b)(4). You stated that the IQ/OQ procedures were written in consultation by the dispenser manufacturer and acceptable ranges were determined. However, you have not indicated that employees were trained on the revised procedures. Your firm did not provide evidence that a systematic review of all processes requiring validation was considered to determine whether process validations were conducted as required.
3. Failure to establish and maintain adequate procedures for validating the device design that include software validation and risk analysis where appropriate, as required by 21 CFR 820.30(g). For example, your firm’s Design and Development Process procedure, BFQP-7020 Rev. 4 indicates that risk management is performed by the (b)(4). The (b)(4) for the Sure-Aid Pregnancy Test (hCG test), (b)(4) 40A-R-01 dated 2006.06.12, has not been updated to include all possible (b)(4) that have been identified by your firm. Specifically, (b)(4) for the Sure-Aid Pregnancy Test, BFF-7021-02 (effective 2006.07.31), lists the potential (b)(4). Your firm did not have any other risk analysis or (b)(4) related to the hCG rapid test strips. Page 4 of 6, sections 6.5.6 and 6.5.7 of the Sure-Aid Pregnancy Test Manufacturing Process Control/Standard of Test document, BFQI-7020-302 Rev. 1 (effective 2012.03.15) state that personnel should (b)(4). The (b)(4) does not identify the risks associated with these identified non-conformances/defects in the hCG test strip and possible mitigations for these risks.
We reviewed your firm’s response and conclude that it is not adequate. Your firm stated that the Risk analysis and (b)(4) has been updated however it is unclear if all identified non-conformances or defects have been included in the updated risk analysis and (b)(4). Your firm has not identified the cause of this deficiency and did not provide a description of the correction or corrective action implemented to ensure that risk analysis are conducted as required. Additionally, your firm has not provided evidence that a systemic corrective action was considered to include a retrospective review of risk analysis of all products to ensure they were performed as required.
4. Failure to establish and maintain the requirements, including quality requirements, that must be met by suppliers, contractors, and consultants, as required by 21 CFR 820.50(a). For example, your firm did not perform supplier evaluations or have any other purchasing controls for non-domestic suppliers. Part 2.1 under the evaluation section of the Management of Purchasing for the Raw Materials Procedure, BFQP-7030 Revision 3, states, “(b)(4).” Your firm’s management stated that your firm does not have a supplier evaluation for (b)(4) because they are a foreign supplier.
We reviewed your firm’s response and conclude that it is not adequate. You state that the Management of Purchasing for the Raw Materials Procedure was revised to include “(b)(4).” However it is unclear what action your firm has taken to correct the deficiency and ensure that it does not recur. You have also not indicated if employees have been trained on the revised procedures or if all suppliers have been evaluated as required.
5. Failure to establish and maintain data that clearly describe or reference the specified requirements, including quality requirements, for purchased or otherwise received product and services as required by 21 CFR 820.50(b). For example, your firm’s initial importer and exclusive distributor of Sure-Aid over-the-counter (OTC) Pregnancy Tests serves as the only point of contact for consumer complaints/feedback in the United States, but there are no purchasing documents in place to define how this third party handles potential complaint information to ensure quality requirements are met. There are no provisions in your firms’ existing contract with the distributor that define what a complaint is, how complaint related information is collected, and how this information is disseminated to your firm. The distributor’s Complaint Receipt & Handling Procedures do not adequately address this process. Furthermore, your firm’s Customer Complaint Process Procedure, BFQP-7010 Revision 3, and Guidelines of Complaint Management (Overseas) Procedure, BFQI-7010-02 Revision 0, are internal procedures and were not provided to the importer/distributor to define their complaint handling process. Your firm’s management stated that there were no sections in the contract that define how complaint handling is to be handled.
We reviewed your firm’s response and conclude that it is not adequate. Your firm stated that it is updating the contract with Kareway, exclusive distributor of hCG in American market and include a complaint handling clause to address and maintain complaint handling procedure. In part, the contract between Bio Focus and Kareway states that, “(b)(4).” Your firm further stated that the new contract would be signed in (b)(4). The response is not adequate in that your firm has neither conducted nor indicated a timeframe for completing a systematic review of all suppliers to ensure compliance with the complaint handling regulation including defining complaints.
6. 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, your firm’s Non-conformance Procedure, BFQP-8040 Revision 0 (effective 2005.05.01), is inadequate in that there are no requirements for the evaluation of nonconformance to determine the need for an investigation or the documentation of these activities. Non-conformances were identified and documented on the device history records for the Sure Aid Pregnancy Test for Lot #(b)(4) and Lot #(b)(4), but were not evaluated to determine if there was a need for an investigation.
We reviewed your firm’s response and conclude that it is not adequate. Your firm stated that the procedures for Non-conformance management process have been modified to include setting up standards of in-process non-conformance, provisions on corrective action of non-conformance and modification of the rights and responsibilities on non-conformance disposal and training has been implemented for the relevant departments. However, your firm did not provide a description and evidence of implementation of an additional correction to this deficiency to include an evaluation of the nonconformances identified in the device history records for the Sure Aid Pregnancy Test for Lot #(b)(4) and Lot #(b)(4) to determine if there is a need for an investigation. Additionally, your firm did not provide evidence that a retrospective review was performed of all nonconformances to ensure that they were evaluated as required.
7. Failure to establish and maintain adequate procedures to control the environmental conditions where environmental conditions could reasonably be expected to have an adverse effect on product quality, as required by 21 CFR 820.70(c). For example, the Assembly Room Temperature/Humidity Checklist indicated that the relative humidity was above specifications on (b)(4), (b)(4), and (b)(4), however, the factory manager and factory director that reviewed the record did not identify that the values were out of specifications. Additionally, there were no corrective actions documented to bring the relative humidity back into conformance. Specifically, your firm’s Guideline for Temperature and Humidity of Assembly Rooms Procedure, BFQI-8020-020 Rev 0 (effective 2009.10.05), page 3 or 3, states that the humidity should be maintained at (b)(4), however the humidity was observed on the above referenced dates to be (b)(4) respectively and signed off by your firm’s management.
We reviewed your firm’s response and conclude that it is not adequate. Your firm stated that the production environment management process has been revised and operators have been trained on the new process. Included in the revision is a modified temperature/humidity checklist. Specifically, one of the main modifications in the assembly room includes (b)(4). This response is inadequate in that your firm has not provided evidence that the environmental controls for the relative humidity for the assembly room was controlled as required as a correction to this deficiency. In addition, your firm did not provide evidence that a systemic review of all environmental conditions was completed to ensure that they were controlled as required or a timeframe for conducting this retrospective review.
8. Failure to identify by suitable means the acceptance status of product, to indicate the conformance or nonconformance of product with acceptance criteria, as required by 21 CFR 820.86. For example, in-process product stored in (b)(4), is not clearly identified or adequately segregated to indicate the products acceptance status during all stages of production. This practice could lead to mix-ups that result in releasing assay strips that have not been passed by quality control. On (b)(4), it was observed that (b)(4) chambers of the (b)(4) contained in-process product and production materials whose acceptance status could not be identified. The in-process product and production material included (b)(4).
We reviewed your firm’s response and conclude that it is not adequate. Your firm has provided a correction addressing the observation. Specifically, your firm states that the product within (b)(4) has been organized as QC and production product and labeling has been attached to the products indicating its acceptance status. Your firm states that the QC labeling indicates if the product is in-testing, finished testing or waiting for testing. Your firm provided (b)(4) in the response to support this correction. Your firm also states that training for in-process manager and task manager has been implemented to prevent recurrence of corrected issue. You also state that the identity/trace management process has been revised (BFQP-7041 Rev. 2 effective 2013.04.22) to include details on how products are classified (raw/sub material, product in process and finished product), how the products are identified and the party responsible for the process. Additionally, you have provided on page 198 of 375 example labeling to be attached to product as it moves from in-process to finished product. However, this response is inadequate because your firm has not indicated that it completed a retrospective review of all products to ensure only product which has passed the required acceptance activities is distributed, used or installed as required by the regulation.
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 #407508 when replying. If you have any questions about the contents of this letter, please contact: James Woods at 301-796-6225.
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.
Office of In Vitro Diagnostics and
Center for Devices and