WARNING LETTER
Ocular Therapeutix Inc.
MARCS-CMS 564663 —
October 17, 2018
Delivery Method:
VIA UNITED PARCEL SERVICE
Reference #:
P130004/S002
Product:
Medical Devices
Recipient:
Recipient Name
Antony Mattessich
Recipient Title
President and Chief Executive Officer
Ocular Therapeutix Inc.
15 Crosby Drive
Bedford
,
MA
01730-1402
United States
Issuing Office:
Center for Devices and Radiological Health
10903 New Hampshire Avenue
Silver Spring
,
MD
20993-0002
United States
Dear Mr. Mattessich:
The Food and Drug Administration (FDA) approved your device, ReSure Sealant, under Premarket Approval (PMA) Application, P130004 on January 8, 2014. In addition to the periodic reporting requirements, FDA ordered your firm to conduct a post-approval study (PAS) in accordance with 21 CFR 814.82(a), to provide information on the long-term safety, effectiveness, and/or reliability of your device for its intended use. For your reference, the approval order is attached which details the PAS requirements that were imposed as a condition of approval for your device.
Under sections 515 and 519 of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. § 360e and 360i, and 21 CFR 814.82(a)(2), FDA may impose post-approval study requirements as a condition of device approval when necessary to provide reasonable assurance, or the continued reasonable assurance, of the safety and effectiveness of the device under the conditions of use prescribed, recommended, or suggested in the labeling of the device. A firm that fails to comply with such a post-approval study requirement violates section 519 of the Act.
By not reporting information to FDA required as a condition of PMA approval, your firm is in violation of section 519(a) of the Act. Noncompliance with section 519 of the Act constitutes a prohibited act under section 301(q)(1)(B) of the Act, 21 U.S.C. § 331(q)(1)(B), and causes the device to be misbranded under section 502(t)(2) of the Act, 21 U.S.C. § 352(t)(2). In addition, a firm that repeatedly or deliberately fails to make reports required under 21 CFR 814.84(a) may be subject to PMA withdrawal. See section 515(e)(1)(D)(i) of the Act; 21 CFR 814.46(a)(2) and 814.82(c).
As discussed in detail below, your firm has failed to comply with the postapproval study requirements imposed under 21 CFR 814.82(a)(2) for your device.
The Condition of Approval Order detailing the PAS requirements dated January 8, 2014 required your firm to do the following:
1. Evaluate the incidence of endophthalmitis for cataract surgery patients treated with ReSure Sealant when used by a broad group of physicians under what is identified in your protocol as the Device Exposure Registry (DER) Study, and
2. Evaluate the incidences of the major ocular adverse events in the postmarket setting for cataract surgery patients treated with ReSure Sealant under a clinical post approval study.
In response to the Approval Order, Condition of Approval no. 1, DER Study, your firm submitted a DER study protocol under PMA P130004/S002, which FDA received on February 7, 2014. In P130004/S002, you indicated that your firm was pursuing a Medicare code for tracking purposes, but did not identify the type of code. Among several deficiencies, you also did not provide the protocol related forms such as the Case Report Forms (CRFs) and Informed Consent Form (ICF). In addition, your protocol indicated that a patient is considered enrolled when the ReSure Sealant is applied and that their data will be linked to the Medicare database, but you did not describe in detail the enrollment visit and data to be collected. As a result, FDA issued your firm a Major deficiency (MAJR) letter dated April 8, 2014. In subsequent communications, FDA recommended that your firm work with the Centers for Medicare & Medicaid Services (CMS) subject matter experts on claims data to develop a methodology to link protocol subjects with the CMS database. After receipt of the MAJR letter, your firm submitted seven amendments (P130004/S002/A001; P130004/S002/A002; P130004/S002/A003; P130004/S002/A004; P130004/S002/A005; P130004/S002/A006; and P130004/S002/A007) to P130004/S002, in response to deficiencies that FDA had identified in the MAJR deficiency letter. On July 21, 2016, your firm’s protocol was approved by FDA under P130004/S002/A007.
Based on the approved protocol, your firm was expected to conduct a retrospective, multicenter, observational, single-arm post-approval registry study that included up to 100 US centers and at least 4,857 subjects treated with ReSure Sealant. Your protocol indicated that subject enrollment would begin November, 2016 and be completed by March, 2017. However, your firm submitted three interim reports: P130004/R012 (received January 31, 2017); P130004/R013 (received November 7, 2017); and P130004/R015 (received May 2, 2018) that reflected no progress in both site and subject enrollments. FDA reviewed P130004/R015, and issued your firm a Progress Inadequate (RDEF) letter dated July 3, 2018, stating your firm’s study status will be marked as “Progress Inadequate” on the FDA PAS webpage because “zero site/subject have been enrolled in the study since the protocol was approved on July 21, 2016.” During the reviews of the above interim reports, FDA on several occasions provided your firm advice regarding enrollment strategies for your study and recommended alternative approaches as possible solutions to the enrollment issues relating to the study. Your firm did not implement FDA’s suggestions or provide alternate approaches showing how your firm would comply with its PAS obligations. Instead, your firm
(b)(4)
(b)(4)
Your firm’s Report submitted under P130004/R013, stated zero sites or subjects were enrolled as of November 6, 2017. Prior to initiating FDA’s review of Report P130004/R013/A001, received February 1, 2018,
(b)(4)
.
On January 26, 2018, FDA sent an email to your firm’s Regulatory Affairs Specialist (initials JC), to follow up on the recommendations and your firm’s actions. However, FDA did not receive a response prior to March 8, 2018, when FDA issued your firm an Overdue Deficiency (OVDE) letter after its review of P130004/R013 and Amendment A001 to P130004/R013. This OVDE letter requested a detailed plan explaining how your firm planned to improve study initiation to ensure the agreed upon study milestones were met. Your firm was expected to provide responses to these deficiencies within 30 days, April 7, 2018, of receiving the aforementioned OVDE letter. FDA sent a follow-up email to your firm dated April 20, 2018 to request an update on the status of your response to the deficiencies identified in P130004/R013. Your firm indicated on May 10, 2018, that it did not receive the original deficiency letter due to a change in point of contact. On the same day, FDA forwarded the deficiency letter to the new contact. FDA did not receive a written response from your firm to the March 8, 2018 OVDE letter, until August 30, 2018.
FDA received an interim report, P130004/R015 on May 2, 2018; your firm indicated that the study status remained unchanged (zero sites or subjects enrolled). On May 23, 2018, during an interactive review, FDA communicated that it was willing to continue discussions on recruitment challenges and provide further advice to facilitate study enrollment. Your firm responded on May 24, 2018, stating that
(b)(4)
. On July 3, 2018, FDA issued your firm a deficiency letter, stating that your firm failed to provide a detailed study plan
(b)(4)
; and, stating that it was unclear if the
(b)(4)
was sufficient to address the PAS question. FDA again requested that your firm provide a detailed plan describing how to facilitate study initiation to ensure the study requirements are met per the approval order. In accordance with FDA’s suggestion to submit responses to deficiencies issued for P130004/R013 and P130004/R015 in one submission, FDA received such a response on August 30, 2018. Your firm reported that the PAS is no longer relevant because feasibility is not probable
(b)(4)
. In response, on October 9, 2018, FDA accepted the amendments to interim reports P130004/R013/A002 and P130004/R015/A001 and issued an advisory that study progress is inadequate, referring your firm to FDA’s October 3, 2018 decision letter in response to
(b)(4)
discussed further below.
(b)(4)
(b)(4)
In summary, your firm failed to collect any DER PAS data, in the 4.5 years since the issuance of the P130004, Condition of Approval Order.
Your firm’s failure to comply with the post-approval study requirements imposed under 21 CFR 814.82(a)(2) renders your device misbranded. Failure to promptly correct this failure may result in withdrawal of your PMA. In addition, the introduction or delivery for introduction into interstate commerce of your device that is not in compliance with its conditions of approval may be a violation of law. Section 501(f)(1)(B) of the FD&C Act (21 U.S.C. § 351(f)(1)(B)); 21 CFR 814.80.
FDA also advised that failure to conduct any post-approval studies in compliance with the institutional review board regulations in 21 CFR Part 56 and the informed consent regulations in 21 CFR Part 50 may be grounds for withdrawal of approval of the PMA.
You should take prompt action to correct the violations addressed in this letter. Failure to promptly correct this violation may result in regulatory action being initiated by the FDA without further notice. These actions include, but are not limited to, seizure, injunction, and/or civil money penalties.
Within 15 working days from the date of this letter, please provide a plan to address the deficiencies described in this letter, or provide documentation showing that you have complied with your firm’s post market surveillance study requirements that addresses the deficiencies identified in FDA’s multiple deficiency letters and notify this office in writing of the specific steps you have taken to correct the noted violation. Include documentation of the corrective actions you have taken. If the corrections and/or corrective actions cannot be completed within 15 days, state the reasons for the delay and the time within which the corrections will be completed.
Your response should reference CTS number P130004/S002 and CMS Case # 564663, and be sent to:
U.S. Food and Drug Administration
Center for Devices and Radiological Health
Office of Compliance,
Field Inspections Support Branch
Building 66, Room 3540
10903 New Hampshire Avenue,
Silver Spring, MD 20993
Finally, you should understand that there are many FDA requirements pertaining to the manufacture and marketing of devices. This letter pertains only to the issue of post-approval study requirements ordered as condition of this approval dated January 8, 2014, and does not necessarily address other obligations your firm has under the law.
If you have any questions about the contents of this letter, please contact Alan Gion, at 301-796- 5463 or by e-mail,
Alan.Gion@fda.hhs.gov
.
Sincerely yours,
/S/
CAPT Raquel Peat, PhD USPHS
Director
Division of Premarket Labeling Compliance
Office of Compliance
Center for Devices and
Radiological Health
Content current as of:
02/13/2019
Regulated Product(s)
Medical Devices