Edge Biologicals Inc.

During an inspection of your firm located in Memphis, TN on March 20, 2023 through April 4, 2023, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures class I and class II in vitro diagnostics (IVDs) for medical applications. 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 are intended 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 Walter C. Edge Jr, President, dated 04/05/2023, concerning our investigator’s observations noted on the Form FDA 483, List of Inspectional Observations, that was issued to your firm. We address the response below, in relation to each of the noted violations. The violations include, but are not limited to, the following:

1. Failure to validate a process whose results cannot be fully verified by subsequent inspection and test according to established procedures, as required by 820.75(a). For example:

A). You failed to validate the cleaning process for controlled environmental areas used for the aseptic processing of Mueller Hinton Agar antimicrobial susceptibility test culture media and other culture media devices.

B). You failed to validate the (b)(4) sterilization of tubing sets used in aseptic fill operations for culture media devices.

Your response does not ensure that processes whose results cannot be fully verified with subsequent inspection are validated.

2. Failure to adequately establish procedures for corrective and preventative actions, as required by 820.100(a). For example,

A). You failed to analyze sources of quality data to identify existing and potential causes of nonconforming product or other quality problems. Analysis of quality data from 2019-2022 does not include data from product quality investigations, incoming inspection rejects, or audits as required by your procedure, QMS-005/J, Corrective and Preventive Action. Furthermore, your firm does not conduct analysis of environmental monitoring data for aseptic processing operations.

B). Your firm failed to adequately investigate and identify actions needed to correct and prevent the recurrence of product sterility failures of (b)(4), Lot (b)(4), identified on 04/29/2021 and Lot (b)(4), identified on 05/07/2021, as required by your procedure QA-008/L, Product/Process Quality Incidents (PQI’s).

Your response does not address requirements needed to ensure the causes of nonconformities relating to product, processes, and the quality system will be investigated, and actions will be taken to correct and prevent the recurrence.

3. Failure to adequately establish procedures and maintain requirements that must be met by suppliers, contractors, and consultants, as required by 820.50(a). For example, your firm purchases components and services critical to product quality; however, you failed to evaluate suppliers on their abilities to meet specific requirements.

4. Failure to maintain a device master record, as required by 21 CFR 820.181. For example, your firm failed to demonstrate that the Mueller Hinton Agar was manufactured according to the Device Master Record (DMR). Your quality manager could not locate the DMR to ensure the device production record (DHR) for each batch or lot of the Mueller Hinton Agar met specifications, including specifications for manufacturing, label requirements, and testing. ***This is a repeat observation cited during the 2018 inspection***

5. Failure to adequately establish procedures to control environmental conditions, as required by 21 CFR 820.70(c). For example, your firm failed to implement the procedure 003-007, Environmental Monitoring, revised on 02/26/2021. Updates made to Attachment’s A, B, and H located within the procedure 003-007 were not implemented within the facility. (b)(4), Mueller Hinton Agar, and other culture media is manufactured each day in controlled area which are not monitored as specified in your Environmental Monitoring procedure.

6. Failure to establish procedures for acceptance activities, as required by 21 CFR 820.80(a). You did not ensure that product is controlled until required acceptance activities have been completed and final release is authorized. In-process, nonconforming, and released IVD products were observed throughout production and storage areas without any indication of acceptance status. For example, testing media ((b)(4)) was observed stored in the employee breakroom refrigerator with food items.

7. Failure to conduct quality audits to determine whether the quality system activities and results comply with quality system procedures, as required by 21 CFR 820.22. From 2013 to 2019 your firm failed to conduct quality audits as required per QMS-003/L, Quality System Internal Audit Program.

8. Failure to ensure that personnel have necessary training and experience to perform their jobs, as required by 21 CFR 820.25(a). You failed to document adequate training as required by your procedure MAN-005/I, EBI Employee Training. Five out of (b)(4) production employees have no documented training records and no annual training on the quality system regulations has been documented for any employee.

The adequacy of your firm’s response cannot be determined where no documents were provided for review. Your firm’s response promised to implement corrective actions however the response was not comprehensive to address the systemic deficiencies identified including a corrective action plan and corrective actions to address the concerns along with timeframes to correct them.

Your firm should take prompt action to address any violations identified in this letter. Failure to adequately address this matter may result in regulatory action being initiated by the FDA without further notice. These actions include, but are not limited to, seizure, injunction, and civil money penalties.

Other federal agencies may take your compliance with the FD&C Act and its implementing regulations into account when considering the award of federal 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 addressed. Should FDA determine that your devices or facilities do not meet the requirements of the Act, requests for Certificates to Foreign Governments (CFG) may not be granted.

We are requesting that you submit to this office on the schedule below, certification by an outside expert consultant that he/she has conducted an audit of your firm’s manufacturing and quality assurance systems relative to the requirements of the device Quality System regulation (21 CFR, Part 820). You should also submit a copy of the consultant's report, and certification by your establishment's Chief Executive Officer (if other than yourself) that he or she has reviewed the consultant's report and that your firm has initiated or completed all corrections called for in the report. The initial certifications of audit and corrections and subsequent certifications of updated audits and corrections (if required) should be submitted to this office by the following dates:

Initial certifications by consultant and establishment – 12/27/2023

Subsequent certifications – 12/27/2024 and 12/27/2025

Please notify this office in writing within fifteen business days from the date you receive this letter of the specific steps you have taken to address the noted violations, as well as an explanation of how you plan to prevent these violations, or similar violations, from occurring again. Include documentation of the corrections and/or corrective action (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 action cannot be completed within fifteen business days, state the reason for the delay and the time within which these activities will be completed. Your firm’s response should be comprehensive and address any violations included in this Warning Letter. If you believe that your products are not in violation of the FD&C Act, include your reasoning and any supporting information for our consideration as part of your response.

Your firm’s response should be sent to: Melissa I. Michurski, Director, Compliance Branch, via e-mail correspondence to ORADevices2FirmResponse@fda.hhs.gov. Refer to the Unique Identification Number (CMS Case # 660003) when replying. If you have any questions about the contents of this letter, please contact: Ashley Mutawakkil, Compliance Officer, via email at Ashley.mutawakkil@fda.hhs.gov or by phone at 305-816-1432.

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 any violations and take prompt actions to address any violations and to bring the products into compliance.