- Delivery Method:
- VIA UNITED PARCEL SERVICE
SIGNATURE CONFIRMED DELIVERY
- Reference #:
- OBPO 19-08
Recipient NameGene Elliot
Recipient TitleChief Operating Officer
- Stratus BioSystems, LLC
918 S Main St
Grapevine, TX 76051-7575
- Issuing Office:
- Office of Biological Products and Operations Division 2
550 W. Jackson Chicago
Chicago, IL 60661
Dear Mr. Elliot:
The United States Food and Drug Administration (FDA) conducted an inspection of your firm, Stratus Biosystems, LLC, located at 918 S Main Street, Ste 215, Grapevine, Texas, from February 6 through February 28, 2019. During the inspection. FDA Investigators documented significant deviations from the regulations for human cells, tissues, and cellular and tissue-based products (HCT/Ps) set forth in Title 21, Code of Federal Regulations, Part 1271 (21 CFR 1271), and issued under the authority of Section 361 of the Public Health Service Act (42 U.S.C. § 264).
The deviations documented on a Form FDA 483, List of lnspectional Observations, were presented to and discussed with you at the conclusion of the inspection. The items of concern include, but are not limited to the following:
1. Failure to validate and approve a process according to established procedures where the results of processing cannot be fully verified by subsequent inspection and tests. The validation activities and results must be documented, including the date and signature of the individual(s) approving the validation [21 CFR 1271.230(a)]. For example, you failed to adequately validate the Amniotic Membrane Patch Allograft manufacturing process, which cannot be fully verified, to ensure that your process removes contamination that is present, and to ensure that processing prevents the introduction, transmission, or spread of communicable disease through the use of the HCT/P. Since March 2018, your firm has processed HCT/Ps into Amniotic Membrane Patch Allografts and distributed those products without a validated process.
2. You must not make available for distribution an HCT/P that is in quarantine, is contaminated, is recovered from a donor who has been determined to be ineligible or for whom a donor eligibility determination has not been completed, or that otherwise does not meet release criteria designed to prevent communicable disease transmission [21 CFR 1271.265(c)(2)]. For example:
a. Donor (b)(4),(b)(6) had a positive pre-processing culture on the amniotic membrane for Staphylococcus aureus, a Class 3 organism on your Bacteria Acceptance Criteria chart. According to your procedures, HCT/Ps with positive pre-processing cultures for a Class 3 organism should be discarded, however you did not discard this tissue and processed and distributed Amniotic Membrane Patch Allografts manufactured from this donor.
b. You distributed Amniotic Membrane Patch Allografts manufactured from donor (b)(4), (b)(6) after receiving a positive post-processing culture result for Clostridium perfringens on a different product manufactured from the same donor. Clostridium perfringens is a Class 3 organism (on your Bacteria Acceptability Criteria list) that requires discard of culture positive tissue from the donor, i.e. in this case, the amnion. We also note that this organism is not generally a contaminant introduced during processing, the source was likely the donor.
3. Failure of a responsible person to determine and document the eligibility of a cell or tissue donor based upon the results of donor screening and donor testing [21 CFR 1271.50(a)]. For example, since operations began in March 2018, your firm has failed to document whether donors of amniotic membrane are eligible. Although you receive relevant medical records from your recovery agency, including a donor medical history interview and a physical examination, you do not use the results of donor screening in accordance with Sec. 1271.75 and donor testing in accordance with Secs. 1271.80 and 1271.85 to document that a donor has been determined to be eligible.
4. Failure to retain the accompanying records with the HCT/Ps at all times following a donor eligibility determination including a statement whether, based on the results of screening and testing, the donor has been determined to be eligible or ineligible; and a summary of records used to make the donor eligibility determination [21 CFR 1271.55(a)]. Specifically, all Amniotic Membrane Patch Allograft products distributed since your firm's manufacturing operation began in February 2018, were distributed without a statement of donor eligibility and without a summary of records used to make the donor eligibility determination.
5. Failure to clean, sanitize, and maintain equipment according to established schedules [21 CFR 1271.200(a)]. For example, you do not maintain your (b)(4) (SN (b)(4), model #(b)(4) to ensure proper functioning. This (b)(4) is used to sterilize your processing equipment and supplies for the Amniotic Membrane Patch Allograft products. According to the owner's manual, the (b)(4) requires (b)(4) maintenance. You have not performed (b)(4) maintenance on this equipment since you began operations in March 2018.
6. Failure to establish and maintain procedures appropriate to meet core current good tissue practice (CGTP) requirements for all steps that you perform in the manufacture of HCT/Ps. You must design these procedures to prevent circumstances that increase the risk of the introduction, transmission, or spread of communicable diseases through the use of HCT/Ps [21 CPR 1271.180(a)]. For example, you do not have a procedure providing guidance on what to do if an unknown bacterium (not included on your Bacteria Acceptability Criteria list) is identified on a post-processing culture.
The deviations identified above are not intended to be an all-inclusive list of deficiencies at your facility. It is your responsibility to ensure that your establishment is in compliance with all applicable requirements of the federal regulations. You are responsible for reviewing your firm's operations as a whole to assure that you are in compliance with all of the FDA regulatory requirements.
This Warning Letter only addresses your Amniotic Membrane Patch Allograft product. At this time, FDA has not evaluated the compliance status of the Suspension Allografts or Purified Fluid Allografts manufactured by Stratus Biosystems. Accordingly, references to HCT/Ps in this letter do not include such products. Please be advised that it remains your responsibility to ensure that all your products, whether specifically mentioned in this letter or not, are manufactured in accordance with the law, including all applicable FDA regulations.
We acknowledge receipt of your written response, dated March 8, 2019, which provides a response and corrective actions to FDA's inspectional observations (FDA-483). We note that you have ceased processing of HCT/Ps and have committed to implementing new procedures and re-training your staff. The effectiveness of your corrective actions will be evaluated during the next inspection. We also have the following comments regarding your responses:
1. You stated that part of your corrective actions included the establishment of new procedures and forms for your operations. We remind you that you in accordance with 21 CFR 1271.180(a), you must ensure that you establish and maintain procedures for all steps you perform in the manufacture of HCT/Ps.
2. In response to Observations 3 and 7.a., you noted that you have written a validation protocol and completed process validation. We request that you submit your validation protocol and results of validation for the Amniotic Membrane Patch Allograft process to FDA for review. Additionally, we note that if you have not already written a new procedure for the Amniotic Membrane Patch Allograft process following validation, such a procedure will also need to be established and maintained.
3. In response to Observation 2, you stated that you are updating SOP F-SB-021 to include all bacteria that may affect your validation and that you will reject any tissue that is positive on preprocessing cultures for organisms not already on your Bacteria Acceptability Criteria list. However, we note that your Bacteria Acceptability Criteria list classifies organisms as Class 1, 2, or 3 based on their pathogenicity and (b)(4). According to your procedure Donor Eligibility Review, Class 3 organisms require discard of culture-positive tissues. However, for Class 1 and 2 organisms, your procedure states that tissues with positive cultures for either class of organism "shall be considered incidentally contaminated." Your procedure does not indicate if additional processing steps are required when Class 1 or 2 organisms are identified. Please explain how you manage tissues when pre-processing cultures identify such organisms.
You should take prompt action to correct the violations addressed in this letter and prevent their recurrence. Failure to promptly correct these violations may result in regulatory action being initiated by the FDA without further notice.
We request that you respond in writing within fifteen (15) working days from your receipt of this letter, outlining the specific steps you have taken or plan to take to correct the noted violations and prevent their recurrence. If you cannot complete all corrections within fifteen (15) working days, please explain the reason for your delay and the time frame within which the remaining corrections will be completed.
Your response should be sent to the following address: Sam Labinjo, U.S. Food and Drug Administration, 550 W. Jackson, Ste. 1500 Chicago IL 60661 or emailed to Samuel.firstname.lastname@example.org. If you should have any questions, please contact Sam Labinjo, Compliance Officer at 312-596-4254 or via e-mail.
Program Division Director
Office of Biological Products Operations - Division 2