- Medical Devices
Recipient NameMr. James R. Glidewell
Recipient TitlePresident and Chief Executive Officer
- Laboratorios Dentales De Zona Franca, S.A.
2212 Dupont Drive, Suite P
Irvine, CA 92612
- Issuing Office:
- Center for Devices and Radiological Health
May 15, 2020
Dear Mr. Glidewell:
During an inspection of your firm (Laboratorios Dentales De Zona Franca, S.A.) located in Cartago, Costa Rica, on January 27, 2020 through January 30, 2020, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures nightguards. 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 Herbert Schoenhoefer, Director of Regulatory Affairs and Quality Assurance, dated February 14, 2020, 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 procedures to control product that does not conform to specified requirements, as required by 21 CFR 820.90(a). For example:
a. Your firm released nightguards that do not meet specifications. Nonconformances found during final inspection are documented on an nonconformance report (NCR) form. NCR 2020-20, associated with case number 1105894204, was initiated due to a nightguard not meeting specifications described in the prescription order. Once reworked, the device was returned for final inspection which determined that it remained nonconforming due to material discoloration. Your firm released the device based on the justification that because the model and impressions were damaged, it could not be redone without contacting the dentist for a new model.
b. Nonconformances found during the manufacturing process are not evaluated to determine if an investigation is needed. These nonconformances are handled differently than those found during final inspection. The only information provided on the NC log is the “reason” to send it back to a previous step with no documented investigations of these in-process nonconformances.
The adequacy of your firm’s response cannot be determined at this time. SOP-0008 NCR along with SOP-0021 In-Process Inspection and SOP-0009 Final Inspection will be updated to include requirements for releasing products according to specification and what should be done if products are out of specification and to ensure all cases rejected during in-process inspection are investigated and the root cause documented along with disposition. Training will be conducted on all updated procedural requirements. Your firm will document reviews of the NCR process on a quarterly basis. The response indicated all corrective actions will be completed by April 20, 2020. However, documentation of these activities has not been provided for review.
2. Failure to ensure that where the results of a process cannot be fully verified by subsequent inspection and test, 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 has not validated the following processes used in the manufacturing of the nightguard: (b)(4); and the software used in modeling the nightguard such as (b)(4). Additionally, the disinfectant step used on the nightguard (b)(4) prior to packaging for shipment has not been fully validated to ensure that the process does not adversely affect the device.
The adequacy of your firm’s response cannot be determined at this time. Your firm will establish a process validation procedure and conduct training on all procedural requirements. A list of all equipment will be created to establish validation protocols for the Installation, Operational, and Performance Qualification of the equipment. The disinfectant validation for (b)(4) and (b)(4) will be conducted. The response indicated all corrective actions will be completed by May 31, 2020. However, documentation of these activities has not been provided for review.
3. Failure to establish and maintain procedures for implementing corrective and preventive action (CAPA), as required by 21 CFR 820.100(a). For example:
a. Your firm failed to initiate and document CAPAs prior to the establishment of CAPA procedures on October 15, 2019, even though quality system deficiencies were identified from internal audits conducted in 2017 and 2018.
b. The CAPA procedure, SOP-0007, “(b)(4) (CAPA)”, Rev. 1, dated October 15, 2019, does not ensure that CAPAs are verified for effectiveness prior to closure. Two CAPAs initiated for internal audit and traceability system deficiencies (CAPA 2019-001 and 2019-002) were closed prior to verification of effectiveness.
c. Your firm does not analyze all sources of quality data to identify existing and potential causes of nonconforming product or other quality problems, such as returned products.
The adequacy of your firm’s response cannot be determined at this time. SOP-0007 and Form TPL-0004 will be updated to ensure CAPA closure after the effectiveness check, and training will be conducted on all updated procedural requirements. An internal audit will be performed with all findings documented via the new CAPA process. The response indicated all corrective actions will be completed by March 31, 2020. However, documentation of these activities has not been provided for review.
4. Failure to establish and maintain procedures for finished device acceptance to ensure that each production run, lot, or batch of finished devices meets acceptance criteria, as required by 21 CFR 820.80(d). For example, SOP-0009 (b)(4) does not ensure that devices are meeting all specifications prior to shipping. A minimum of (b)(4) cases is required to be inspected out of approximately (b)(4) cases released every day (approximately (b)(4)). According to your firm’s analysis of final inspection data collected between October 28, 2019 and December 24, 2019, (b)(4) of devices failed final testing requiring an NCR. Additionally, (b)(4) different cases of nightguards are seen comingled on the workstation during the manufacturing process. There are no identifying marks on the devices or any way to tell which device belongs to which case number.
The adequacy of your firm’s response cannot be determined at this time. The NCR procedure will be updated to reflect in-process and final inspection requirements respectively. A separate procedure will be developed for sampling plan evaluation and changes to ensure tightened and loosened sampling plans are adjusted to match nonconformance issues as well as a procedure for developing a more robust identification and traceability of products. Training will be conducted on releasing products according to specification and what should be done if products are out of specification and on ensuring all cases are segregated so that case identification is seen on all products during work flow. Your firm will conduct trending analyses based on the extent of the observations found and initiate CAPAs if necessary. The response indicated all corrective actions will be completed by April 10, 2020. However, documentation of these activities has not been provided for review.
5. Failure to establish and maintain procedures to ensure that all purchased or otherwise received product and services conform to specified requirements, as required by 21 CFR 820.50. For example, your firm’s supplier controls procedure does not ensure that all suppliers used in the manufacturing of nightguards are approved. The supplier of all raw materials used in the manufacturing and shipping of nightguards has neither been evaluated nor a supplier agreement developed to ensure requirements are met.
The adequacy of your firm’s response cannot be determined at this time. Critical suppliers will be reviewed per the Approved Supplier List (ASL) to determine if surveys have been sent out along with supplier quality agreements. The ASL will include all suppliers identified per procedure as significant and non-significant. Supplier quality audits will include all significant suppliers on the supplier audit log along with status and next required audit or follow-up. The response indicated all corrective actions will be completed by April 15, 2020. However, documentation of these activities has not been provided for review.
6. Failure to establish and maintain procedures for receiving, reviewing, and evaluating complaints by a formally designed unit, as required by 21 CFR 820.198(a). For example, four out of five returns reviewed from 2019 appear to be complaints but are not documented, evaluated, and investigated as complaints. Your firm’s complaint handling procedure became effective on January 21, 2020.
The adequacy of your firm’s response cannot be determined at this time. SOP-0022 (b)(4) will be updated to clearly state how product complaints are evaluated and how the corporate office receives the obtained information for regulatory reporting. A procedure will be developed for returns to ensure there is adequate control on the production floor and products are returned as needed to the appropriate party. Training will be conducted on all updated procedural requirements. A local formally designated unit will be created to evaluate and send complaints to the corporate office for initial and supplemental complaint reporting. A complaint log will be created along with investigation criteria for all remakes/returns from doctors and/or patients. All 2018 and 2019 complaints will be remediated. The response indicated all corrective actions will be completed by April 17, 2020. However, documentation of these activities has not been provided for review.
7. Failure to establish and maintain procedures to control all documents that are required by 21 CFR Part 820, as required by 21 CFR 820.40. For example, your firm’s document controls procedure does not ensure that documents used in the manufacturing process are adequately controlled. Eleven Device History Records (DHRs) do not include all documentation used throughout manufacturing such as the routing sheets, which document movement throughout the manufacturing floor including nonconformances. Additionally, signature stamps are not adequately controlled. Seven stamps at six different work stations are seen in manufacturing areas, and the documentation showing which employees have been issued stamps is incomplete.
The adequacy of your firm’s response cannot be determined at this time. All documentation will remain with each work order (hard copy and scanned copies for soft copy retention). The stamp log will be updated to include all stamps on the manufacturing floor and who they are assigned to including Quality Assurance. (b)(4) staff only. The DHR procedure will be updated with (b)(4) created for the manufacturing floor to (b)(4). A control stamp SOP will be developed (b)(4). Training will be conducted on all updated procedural requirements. The response indicated all corrective actions will be completed by May 10, 2020. However, documentation of these activities has not been provided for review.
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, should FDA determine that you have Quality System regulation violations that are reasonably related to premarket approval applications for Class III devices, such devices will not be approved until the violations have been corrected. Also, should FDA determine that your devices are adulterated or misbranded do not meet the requirements of the Act, requests for Certificates to Foreign Governments (CFG) may not be granted. More information on processes for persons denied a CFG can be found at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/process-request-review-fdas-decision-not-issue-certain-export-certificates-devices. If you believe that your products are not in violation of the Act, please respond to FDA with your reasoning and any supporting information for our consideration.
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 actions (which must address systemic problems) 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. We will notify you regarding the adequacy of your firm’s responses and the need to re-inspect your firm’s facility to verify that the appropriate corrections and/or corrective actions have been made.
Your firm’s response should be sent to: Food and Drug Administration, Center for Devices and Radiological Health, Office of Regulatory Programs, Division of Regulatory Programs 2, FDA Inspections and Regulatory Audits Team, White Oak Building 66, Room 3540, 10903 New Hampshire Ave., Silver Spring, MD 20993. Refer to CMS case #607719 when replying. If you have any questions about the contents of this letter, please contact: Srinivas Nandkumar, Ph.D., at +1(301)796-6480 (telephone).
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.
Malvina B. Eydelman, M.D.
OHT 1: Office of Ophthalmic, Anesthesia, Respiratory,
ENT and Dental Devices
Office of Product Evaluation and Quality
Center for Devices and Radiological Health
Prismatik Dentalcraft Inc.
2212 Dupont Drive, Suite P
Irvine, CA 92612