山东 FDA 工厂审查警告信实例分享，让你体会FDA工厂审查的难度 及怎样应对FDA 工厂审查

FDA 工厂审查警告信实例分享

Warning Letter

Jiangsu JDC Medical Devices Co., Ltd.MARCS-CMS 598340 — DECEMBER 19, 2019

DeliveryMethod:

VIA UNITED PARCEL SERVICE

Product:

Medical Devices

Recipient:

Heng Yang Shi

General Manager

Jiangsu JDC Medical Devices Co., Ltd.

No. 8, Jing 8 Road, Lianyun Development ZoneLianyungang Shi Jiangsu Sheng, 222047China

Issuing Office:

OHT3: Office of Gastrorenal, ObGyn, General Hospital, and Urology Devices, Office of Product Evaluation and Quality

United States

December 19, 2019

WARNING LETTER

Dear Heng Yang Shi:

During an inspection of your firm located in Lianyungang, Jiangsu, China on September 16, 2019 through September 19, 2019, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures the Bulb Tip Yankauer and the Chemiluminated Vaginal Speculum. 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 your firm dated October 10, 2019 concerning our investigator’s observations noted on the Form FDA 483 (FDA 483), List of Inspectional Observations, which was issued to your firm. We addressed 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 the design of the device in order to ensure that specified design requirements have been met, as required by 21 CFR 820.30(a).

For example, your firm has established the document titled “Design and Development Control Procedure, Document No. (b)(4), Dated March 15, 2017.” This procedure does not ensure that all of the required elements of design controls are met, such as design and development planning, design input, design output, design review, design verification, design validation, design transfer, design changes and the design history file. Specifically, the Design Development Input Record for the Bulb Tip Yankauer states that it is intended to be used in conjunction with a medical vacuum aspirator for surgical body waste liquid. However, the record does not include Design Verification to ensure that the product meets its dimensional and functional specifications (e.g. ensure that the device works with a medical vacuum aspirator), and Design Validation to ensure that it performs according to its indications for use.

Your firm’s response dated October 10, 2019, is not adequate. In the response, your firm provided a copy of the following documents:

• “Design and Development Control Procedure” (Document number: (b)(4), Dated September 27, 2019) – Updated procedure
• Training Record (Document number: (b)(4), Dated September 28, 2019)
• “Inspection Report: Bulb Tip Yankauer” (Document number: (b)(4), Dated September 29, 2019)
• “Bulb Tip Yankauer Physical Property Test Original Record” (Document Number: (b)(4), Dated September 29, 2019)
• “Bulb Tip Yankauer Customer Trial Report for Lot (b)(4) and (b)(4)” Record Number: (b)(4), Dated September 29, 2019)
• “Bulb Tip Yankauer Customer Trial Report for Lot (b)(4) and (b)(4)” Record Number: (b)(4), Dated September 30, 2019)
• “Product Validation Record – Bulb Tip Yankauer” Document Number: (b)(4), Dated September 30, 2019) to address observation 1 of the FDA 483.

Your firm’s update to the procedure “Design and Development Control Procedure,” states that the “relevant responsible person of the project” determines the inputs related to the product requirements, and prepares the “Design and Development Input Record.” The
Procedure is not adequate because it still does not have the specific mechanism to support design and development planning, design input, design output, design review, design verification, design validation, design transfer, design changes and the design history file.

Also, your firm provided documents titled “Inspection Report: Bulb Tip Yankauer,” and the “Bulb Tip Yankauer Physical Property Test Original Record” as evidence to support that you have established the design inputs for the product. These documents were an analysis of Production Batch number (b)(4), where you performed visual observations, and confirmed dimensional size of the device for (b)(4) units out of a (b)(4) unit lot. It is unclear how this batch testing relates to the design verification / validation of your Bulb Tip Yankauer product. Your firm needs to perform testing in accordance with an established protocol with pre-defined acceptance criteria based on design inputs developed through the design control process, that clearly shows that the design outputs meet the design inputs, in order to perform adequate design verification activities.

Please provide documentation that demonstrates all of the required elements of design controls are met, such as design and development planning, design input, design output, design review, design verification, design validation, design transfer, design changes and the design history file. In addition, your firm has not performed an assessment of production records for product that was previously distributed to determine if the lack of adequate design controls could have led to distribution of nonconforming product, and evaluated whether action is necessary to mitigate any associated risks.

2. Failure to develop, conduct, control, and monitor production processes to ensure that a device conforms to its specifications, as required by 21 CFR 820.70(a).

For example, your firm’s established procedures for the manufacturing of the “Single-Use Vaginal Speculum with Illumination Insert” product do not include any explanation of the following processes:

(b)(4)

Your firm’s response dated October 10, 2019, is not adequate. In the response, your firm provided translated versions of the following procedures to address observation 2 of the FDA 483.

• “Working Instructions for Vaginal Speculum” (Document number: (b)(4), Dated September 25, 2019)
• “Working Instructions for Bulb Tip Yankauer” (Document Number: (b)(4), Dated September 27, 2019)
• “Production Process Control Procedure (Document: (b)(4), Dated March 15, 2018)
• Training record titled “Production Process Control Procedure & Working instruction for Bulb Tip Yankauer and Vaginal Speculum (Document Number: (b)(4), Dated September 30, 2019)

Although these procedures identified the overall strategy for manufacturing the Vaginal Speculum and the Bulb Tip Yankauer, they do not identify the specifications for the finished device. For example, “Working Instructions for Vaginal Speculum” (Document number: (b)(4), Dated September 25, 2019) states that finished product is visually inspected to ensure that the product is smooth, round, and “free from any obvious impurities.” The procedure references a “Vaginal Speculum Product Inspection Card,” which was not included in your firm’s response to the FDA-483. The procedure identifies that this card is utilized by the Quality Inspections Department to verify that the finished product meets its design specifications. The work instruction did not establish clearly defined specifications for what constitutes a product that is smooth, round, and free form any obvious impurities.

The document titled “Working Instructions for Bulb Tip Yankauer”, (Document Number: (b)(4), Dated September 27, 2019) describes how to put the finished Bulb Tip Yankauer into its primary and secondary packaging. However, the procedure does not explain how the product is assembled, and how to perform the appropriate verification to ensure that it is assembled correctly. The procedure also does not clearly define the inputs to the process, in-process specifications, and process outputs to ensure that the process is under control.

In addition, your firm has not performed an assessment of production records for product that was previously distributed to determine if the lack of adequate production / process controls could have led to distribution of nonconforming product, and evaluated whether action is necessary to mitigate any associated risks.

3. Failure to establish and maintain procedures to adequately control environmental conditions, as required by 21 CFR 820.70(c).

For example, your firm uses (b)(4) to manufacture the medical products, (b)(4). However, you do not have procedures to monitor the following requirements for your (b)(4) manufacturing areas:

(b)(4)

Your firm’s response dated October 10, 2019, is not adequate. You provided a copy of your environmental procedure titled: “Environmental Sanitation and Monitoring Management Procedure”, Document number: (b)(4), Dated September 24, 2019. Specifically, you provided a protocol and specifications for the environmental monitoring of your clean rooms. The protocol provided criteria for “(b)(4)” designated areas, and specified pass/fail criteria and action limits for ambient temperature, relative humidity, wind speed (b)(4), air exchanges, room pressure, dust particulate counts, viable and non-viable particulate counts, and surface and hand sampling for viable and nonviable particulates. You also provided a training record to demonstrate that employees had been trained on the procedure.

The procedure claims conformance to a Chinese Standard titled “(b)(4) Good Manufacture Practice for Sterile Devices”. However, you did not provide a copy of the Standard, thus we could not assess the appropriateness of the environmental monitoring specifications for your designated “(b)(4)” manufacturing areas. You also provided an environmental monitoring test report. However, the report was not translated to English, thus we were unable to determine which area of the facility was tested, and whether the test satisfies the criteria established in your procedures.

To address the concerns identified above, please either:

1. Provide an English translation of the Chinese Standard titled “(b)(4) Good Manufacture Practice for Sterile Devices,” along with supporting documentation to explain how the standard was developed and an English translation of the environmental monitoring test report; or

2. Provide an English translation of the environmental monitoring test report and objective evidence that demonstrates the scientific validity of the acceptance criteria that you’ve established for environmental monitoring of your manufacturing areas; or

3. Demonstrate how your environmental monitoring procedures conform to the FDA recognized ISO 14644 family of Standards regarding “Cleanrooms and Associated Controlled Environments.”

In addition, your firm has not performed an assessment of production records for product that was previously distributed to determine if the lack of adequate environmental controls could have led to distribution of nonconforming product, and evaluated whether action is necessary to mitigate any associated risks.

4. Failure to establish and maintain procedures to control labeling activities as required by 21 CFR 820.120.

For example, at the time of the inspection, your firm had not established procedures to control labeling activities for the Bulb Tip Yankauers to include: label integrity; labeling inspection; labeling storage; and labeling operations.

The adequacy of your firm’s response dated October 10, 2019, cannot be determined at this time. In the response, your firm has submitted the procedure titled: “Labeling, Instruction and Language translation Control Procedure, Document number: (b)(4), Dated September 28, 2019,” to identify the key elements regarding the control of medical device labels as identified in 21 CFR 820.120. However, the response does not demonstrate that relevant staff have been trained on the process. The adequacy of this response will be
assessed at the next inspection.

Our inspection revealed that your firm’s devices are misbranded under section 502(t)(2) of the Act, 21 U.S.C. § 352(t)(2), in that your firm failed or refused to furnish material or information respecting the device that is required by or under section 519 of the Act, 21 U.S.C. § 360i, and 21 CFR Part 803 - Medical Device Reporting. Significant violations include, but are not limited to, the following:

Failure to develop, maintain, and implement written Medical Device Reporting (MDR) procedures, as required by 21 CFR 803.17.

For example, your firm’s Medical Device Report (MDR) Procedure for US Market is inadequate in that:

1. It does not establish internal systems that provide for timely and effective identification, communication, and evaluation of events that may be subject to MDR requirements.
2. It does not establish internal systems that provide for a standardized review process to determine when an event meets the criteria for reporting under this part.
3. It does not establish internal systems that provide for timely transmission of complete medical device reports.
4. It does not describe how your firm will address documentation and record-keeping requirements.

Your firm’s response dated October 10, 2019, is not adequate. In the response, your firm provided a copy of its revised MDR procedure titled: “Medical Device Reporting Procedure for US Market”, Document number: (b)(4), Dated September 30, 2019. However, the revision did not establish systems to:

·       Provide for timely and effective identification, communication, and evaluation of events

·       Provide for a standardized review process to determine when an event meets the criteria for reporting

·       Provide for timely transmission of complete medical device reports

·       Address documentation and record-keeping requirements

Given the serious nature of the violations of the Act, devices manufactured by your firm (Class II, non-sterile, products: Suction Catheter and Tip (Bulb Tip Yankauer), Nonmetal Vaginal Speculum, Connecting Flexible Aspirating Tube. Class I, non-sterile, products: Irrigating Syringe (Non-Dental), Endoscopic Bite Block, Endoscopy Cleaning Brush, Tracheobronchial Suction Catheter, Tracheobronchial Suction Catheter Kit) are subject to refusal of admission under section 801(a) of the Act, 21 U.S.C. § 381(a), in that they appear to be adulterated. As a result, FDA is taking steps to refuse entry of these devices into the United States, known as “detention without physical examination,” until these violations are corrected. In order to remove the devices from detention, your firm should provide a written response to this Warning Letter as described below and correct the violations described in this letter. 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.

Also, 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.

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.

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: Establishment Support, Regulatory Inspections and Audits Team, White Oak Building 66, Rm 3657, 10903 New Hampshire Ave., Silver Spring, MD 20993. Refer to CMS case # 598340 when replying. If you have any questions about the contents of this letter, please contact: Nikhil Thakur, Assistant Director at (301) 796-5536 or nikhil.thakur@fda.hhs.gov.

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/

Benjamin R. Fisher, PhD
Director
OHT 3: Office of GastroRenal, ObGyn, General
     Hospital, and Urology Devices
Office of Product Evaluation and Quality
Center for Devices and Radiological Health

CC:
Fiona Chan
SUNGO Technical Services Inc.
6050 W Eastwood Ave Apt 201
Chicago, IL 60630
855-957-7779
Sungo.group@yahoo.com

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