- Delivery Method:
- VIA UNITED PARCEL SERVICE
- Medical Devices
Recipient NamePingle Janardhan Reddy
Recipient TitleManaging Director
- Indus Medicare Limited
Sy No. 129, NH-44, Ramaipally Village, Manoharabad
Medak District 502336
- Issuing Office:
- Center for Devices and Radiological Health
May 4, 2020
Dear Mr. Reddy:
During an inspection of your firm located in Telangana, India on January 20, 2020 through January 23, 2020, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures the Invigra, a male natural latex condom. 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 Keshav Bhupal, Managing Director, dated February 3, 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 adequately 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 established Compounding Procedure (D 041.01.15) and Retrospective Validation of Compounding Procedure (D004.07.0). At the time of inspection, the compounding and mixing process for latex used in manufacturing all latex condoms at your firm’s site had not been validated.
We have reviewed your response dated February 3, 2020, and conclude it is not adequate. Your firm states it will update the existing procedures by June 30, 2020 but did not address the issue of not following your own procedures. Your firm did not commit to a retrospective review of whether the inadequate procedures and implementation extend to other areas of device manufacturing. Your firm did not provide plans to evaluate whether the lack of validation of the compounding process could have led to the release of nonconforming product, or whether action is necessary to mitigate risks posed by nonconforming product. Finally, your firm did not provide the updated procedures for review, nor documentation showing employees were trained in the new procedures.
2. Failure to establish and maintain adequate acceptance procedures, where appropriate, to ensure that specified requirements for in-process product are met, as required by 21 CFR 820.80(c).
For example, the procedure Quality Inspection and Test Plan for E.T., Foiling, Coding, and Packing Stage Procedure (D 015.04.22) does not require documentation of the results of the number of condoms tested and recorded as pass/fail at the water leak test after the condoms have been 100% electronically tested. Additionally, the procedure allows electronic retesting of condoms up to (b)(4) times, after they have failed the water leak test. As reported to the FDA investigator during inspection, repeating the electronic test is what your firm uses to rework product that failed the water leak test.
We have reviewed your response dated February 3, 2020, and conclude it is not adequate. Your firm states you will review and revise their procedures to clarify the definition of “rework” in the details of retesting and reevaluation after rework by February 22, 2020. Your firm does not include plans to address how and/or why it failed to adequately establish procedures for acceptance of in-process product. Your firm did not commit to a retrospective review of whether its inadequate procedures and implementation extend to other procedures or areas of device manufacturing. Your firm did not address training staff on the revised procedures or using repeat electronic testing to rework a failed product. Additionally, your firm did not provide plans to evaluate whether there was release of nonconforming product, and what action your firm will take to mitigate risks if non-conforming product was released. Finally, your firm provided no documentation supporting the proposed activities for review.
3. Failure to establish and maintain adequate procedures to control the design of the device in order to ensure that specified design requirements are met, as required by 820.30(a).
For example, the stated scope of your firm’s design and controls procedure, Design and Development Procedure (D 002.11.7), covers design changes and new designs of products. At the time of inspection, your firm failed to apply design controls for the Invigra Latex condoms (Lubricated and Black Colored - K022614), as confirmed with the FDA investigator during inspection. This product had been shipped since 2003.
We have reviewed your response dated February 3, 2020, and conclude it is not adequate. Your firm states that it is in the process of updating all Design History Files for all FDA cleared devices to be completed by June 30, 2020 but did not address the reason design controls had not been applied for this product. Your firm did not establish causes for this discrepancy, investigate whether this issue was systemic across other product types, or identify whether this discrepancy impacted other product related processes, compliance or quality (for example, any difficulties in establishing production specifications without proper design transfer). Furthermore, your firm’s plans did not include training staff on the procedures currently in place. Finally, your firm provided no documentation supporting the corrective actions for review.
4. Failure to establish and maintain adequate procedures for implementing corrective and preventive action, as required by 21 CFR 820.100(a).
For example, your firm’s Preventive Action Procedure (D 002.26.6) sets in-process control limits for various manufacturing stages and requires action for non-conformities. The review of your firm’s data analysis for 2018 and 2019, identified at least 14 instances where control limits were exceeded. At the time of the inspection, your firm had not initiated any corrective action for non-conformities for years 2018 through 2019, as required by this procedure.
We have reviewed your response dated February 3, 2020, and conclude it is not adequate. Your firm states it will start discussing preventive actions for deviations in quarterly management meetings, by June 30, 2020. Your firm’s response does not address how and/or why it failed to implement the CAPA for two years or train staff to their existing CAPA procedures. Additionally, your firm does not plan to perform a retrospective review of existing quality data to identify problems requiring corrective and preventive action. Finally, your firm did not submit any documentation for review in support of their proposed actions.
5. Failure to establish and maintain procedures for rework of non-confirming product, as required by 21 CFR 820.90(b)(2).
For example, the Quality Inspection and Test Plan for In-Process Stage Procedure (D 015.03.21), and Quality Inspection and Test Plan for E.T. Foiling, Coding and Packing Stage Procedure (D 015.04.22) allow for rework of the product. Your firm does not have written procedures in place for reworking.
We have reviewed your response dated February 3, 2020, and conclude it is not adequate. Your firm states it will review and revise the procedures to clarify the definition of “rework” in the details of retesting and reevaluation after rework by February 22, 2020. This response does not address the failure to establish procedures for rework or describe a plan for training staff to the new procedures. Additionally, your firm does not provide plans to evaluate whether there was a release of nonconforming product, and if so, what action your firm will take to mitigate risks posed by that product. Finally, your firm did not provide any revised procedures, employee training records on the updated procedures or any other documentation supporting their proposed actions for review.
Our inspection also 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:
1. Failure to adequately develop, maintain and implement written MDR procedures, as required by 21 CFR 803.17. For example, after reviewing your firm’s MDR procedure titled “Medical Device Vigilance System & Medical Device Reporting Procedure”, SPEC. No: D 002.29.12, Dated 22.08.2019, the following deficiencies were noted:
a. The procedure does not establish internal systems that provide for timely and effective identification, communication, and evaluation of events that may be subject to MDR requirements, as required by 21 CFR 803.17(a)(1). For example:
i. The procedure includes definitions from 21 CFR 803.3 for the terms “malfunction” and “serious injury”. However, the procedure omits definitions of the terms “become aware,” “caused or contributed,” and “MDR reportable event” from 803.3, and the definition of the term “reasonably suggests” found in 803.20(c)(1). The exclusion of the definitions for these terms from the procedure may lead your firm to make an incorrect reportability decision when evaluating a complaint that may meet the criteria for reporting under 21 CFR 803.50(a).
ii. The procedure, as written, combines language from the requirements of other regulatory or competent authorities with the requirements in 21 CFR Part 803 in a manner that will result in incomplete, inadequate or even non-reporting of adverse events that meet the reportability requirements under 21 CFR Part 803.
b. The procedure 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, as required by 21 CFR 803.17(a)(2). For example:
i. There are no instructions for conducting an investigation of each MDR reportable event and evaluating the cause of the event.
ii. There are no instructions for how your firm will evaluate information about an event to make MDR reportability determinations in a timely manner.
iii. Although the procedure includes instructions for how your firm will evaluate information about an event to make a reportability decision, it fails to include instructions for making determinations in a timely manner.
iv. The flowchart in your firm’s procedure does not reference a process for investigating events identified as MDRs to ensure that MDRs are submitted to FDA within the required reporting timeframes, as required under 21 CFR 803.17(a)(1).
c. The procedure does not establish internal systems that provide for timely transmission of complete medical device reports, as required by 21 CFR 803.17(a)(3). Specifically, the following are not addressed:
i. Instructions for how to complete the FDA 3500A form.
ii. The circumstances under which your firm must submit initial 30 days, supplemental or follow-up, 5-day report and the requirements for such reports.
iii. The procedure does not include a process for submitting MDRs electronically in accordance with the Final Rule for electronic Medical Device Reporting (eMDR) published in the Federal Register on February 14, 2014. Information about the Final Rule for eMDR and the eMDR set-up process can be found on the FDA website at:
v. Although the procedure includes references to 30 days and 5-day reports, it does not specify calendar days and work days, respectively.
vi. How your firm will submit all information reasonably known to it for each event.
vii. Specifically, which sections of the 3500A will need to be completed to include all information found in your firm’s possession and any information that becomes available as a result of a reasonable follow up within your firm.
d. The procedure does not describe how your firm will address documentation and record-keeping requirements, as required by 21 CFR 803.17(b), including:
i. Information that was evaluated to determine if an event was reportable.
ii. Documentation of the deliberations and decision-making processes used to determine if a device-related death, serious injury, or malfunction was or was not reportable.
iii. Systems that ensure access to information that facilitates timely follow-up and inspection by FDA.
In addition, your firm’s procedure includes references to baseline reports. Baseline reports are no longer required, and we recommend that all references to a Baseline Report be removed from the firm’s MDR procedure (see: 73 Federal Register Notice 53686, dated September 17, 2008). Also, your firm’s procedure includes references to annual certifications. Annual certifications are no longer required, and we recommend that all references to an Annual Certification be removed from the firm’s MDR procedure (see: Fourth Notice, Federal Register, dated March 20, 1997: Medical Device Reporting; Annual Certification; Final rule). This cite is supported by Observation 6 of the FDA 483, page(s) 22-24 of the EIR, and Exhibit(s) No. 23.
We have reviewed your response dated February 3, 2020, and conclude it is not adequate. Your firm reports it will update this procedure as per 21 CFR 803 Medical Device Reporting but does not address the systemic issue of not following the procedures currently in place, implementation of a corrective action plan to prevent recurrence or training staff to the updated procedures. Finally, your firm did not provide updated procedures for review.
Given the serious nature of the violations of the Act, all products manufactured by your firm 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 violation(s) described in this letter. We will notify you regarding the adequacy of your firm’s response(s) and the need to reinspect 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# 606159 when replying. If you have any questions about the contents of this letter, please contact: Monica Garcia, DHT3B Acting Assistant Director at 420-402-2791 or firstname.lastname@example.org.
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.
Benjamin R. Fisher
OHT 3: Office of Gastrorenal, ObGyn, General
Hospital and Urology Device
Office of Product Evaluation and Quality
Center for Devices and Radiological Health
Eagle TWE Inc.,
4761 Hugh Howell Road, Unit M
Tucker, Georgia 30084