Mr. Nasrat Hakim
- Elite Laboratories Inc.
165 Ludlow Avenue
Northvale, NJ 07647
- Issuing Office:
- New Jersey District Office
Department of Health and Human Services
|Public Health Service
Food and Drug Administration
New Jersey District Office
Waterview Corporate Center
10 Waterview Blvd. 3rd Floor
Parsippany, New Jersey 07054
Telephone: (973) 331-4900
FAX: (973) 331-4969
August 25, 2016
VIA UNITED PARCEL SERVICE
Mr. Nasrat Hakim
President and Chief Executive Officer
Elite Laboratories, Inc.
165 Ludlow Avenue
Northvale, New Jersey 07647
Dear Mr. Hakim:
The United States Food and Drug Administration (FDA) conducted an inspection of your firm, Elite Laboratories, Inc., located at 165 Ludlow Avenue, Northvale, New Jersey between January 5, 2016 and February 2, 2016. The inspection revealed serious violations of Postmarketing Adverse Drug Experience (PADE) reporting requirements under section 505(k) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C.§355(k)] and Title 21, Code of Federal Regulations (21 CFR) 314.80 and 314.98. Failure to comply with Section 505(k) is a prohibited act under section 301(e) of the Act [21 U.S.C.§ 331(e)].
At the conclusion of the inspection on February 2, 2016, Investigators Krueger, Roy, Scheraga, and Cayuela, representing FDA, presented and discussed with you Form FDA 483, Inspectional Observations. We acknowledge receipt of your written responses dated February 17, 2016, March 31, 2016, and August 16, 2016 to the Form FDA 483, Inspectional Observations.
From our review of the FDA Establishment Inspection Report, the evidence submitted with that report, and your firm's written response dated February 17, 2016, we conclude that your firm did not adhere to the applicable statutory requirements and FDA regulations for PADE reporting. Specific violations include, but are not limited to, the following:
Failure to develop adequate written procedures for the surveillance, receipt, evaluation, and reporting of postmarketing adverse drug experiences (ADEs) as requiredby 21 CFR § 314.80(b) and 21 CFR 314.98(a).
As an application holder, your firm is required to develop written procedures for the surveillance, receipt, evaluation, and reporting of postmarketing adverse drug experiences (ADEs) to the FDA. Your firm does not have written procedures that describe how you, and your contractor acting on your behalf, comply with PADE regulations. Specifically:
a. Your firm's Standard Operating Procedures (SOP) fail to address how you monitor and receive ADEs from any source, foreign and domestic. Specifically, your firm's SOP 2810 entitled, "Adverse Event Reporting," (version 1, effective November 12, 2014) and SOP 2805 entitled, "Complaint Management System," (version 4, effective July 31, 2013) fail to describe how you handle the receipt of safety information, including how you (1) receive ADEs (e.g., via mail, internet, phone, literature, employees, etc.), (2) identify the existence of ADEs, (3) document the initial receiptdate, (4) identify who is responsible for triaging ADEs to your contractor, and (5) describe timeframes you follow to ensure compliance with PADE regulations. Additionally, your written procedures fail to describe how you handle ADE information received from entities that you have business agreements with, including how information is transferred to you, documented (including the initial receipt date), and reconciled. As the application holder and as a firm listed on products, you may receive ADE information directly, despite any agreements that you may have with a contractor.
As a result, our inspection determined that you failed to investigate at least half of the 15-day Alert Reports (b)(4) your firm received. Your firm's agreement with your contractor states that they (b)(4). However, as the application holder, you are responsible for ensuring that ADEs are appropriately investigated, follow-up information is submitted to FDA within 15 calendar days of receipt of new information (or as requested by FDA), and records of investigation attempts are maintained if additional information is not obtainable.
b. Your firm's SOPs fail to address how you evaluate all ADEs for seriousness, expectedness, and Reportability to FDA. According to your agreement with your contractor (b)(4), your firm is responsible for (b)(4)15-day Alert Reports and periodic Individual Case Safety Reports (ICSRs). Your firm's SOPs fail to describe how you fulfill your responsibilities, including how you (1) evaluate ADEs, (2) define serious and expected, (3) determine Reportability, (4) ensure that ADEs reported to FDA are complete and accurate based on source documents, and (5) define timeframes for completing evaluations and providing approval to your contractor to ensure timely reporting to FDA. Additionally, your firm's SOPs fail to describe how you ensure that all ADEs subject to 15-day Alert Reports are promptly investigated and that all attempts to obtain additional information are recorded as required by 21 CFR § 314.80(c)(1)(ii).
As a result, our inspection determined that over half of your case files (b)(4) did not contain evidence that you performed any evaluation or provided approval for submission to FDA.
c. Your firm's SOPs fail to address how you report ADEs, both 15-day Alert Reports and non expeditedI CSRs, and Periodic Adverse Drug Experience Reports (PADERs) to FDA in the correct format and on time. As of September 8, 2015, FDA requires that all postmarketing drug safety reports be submitted in an electronic format that FDA can receive, process, and archive, in accordance with the final rule "Postmarketing Safety Reports for Human Drug and Biological Products; Electronic Submission Requirements" (79 FR 33072, 80 FR 30151).
During the inspection, we determined that you submitted approximately half of your 15-day Alert Reports late (b)(4). Additionally, for abbreviated new drug applications (ANDAs) 076723 and 202248, you incorrectly submitted PADERs late, without a descriptive section, on the wrong reporting schedules, or on paper after September 8, 2015.
In your February 17, 2016 written response, you stated that you plan to: (1) create and implement new SOPs for the receipt of ADEs, evaluation of ADEs, and submission of PADERs; (2) revise SOP 2810; (3) evaluate and modify your Quality Agreements as needed; (4) review the ADEs cited on the Form FDA 483 that were not investigated; and (5) discuss the follow-up of literature ADEs with your contractor. You also reported that you resubmitted the PADERs that were sent to the (b)(4) on paper in an approved electronic format, reorganized the unit responsible for reporting to FDA, and instituted Weekly Site Review Meetings in 2014 to address the timely reporting of safety information to FDA.
Your firm's written response is inadequate because you failed to assess the root causes and impact of the observations. You also failed to describe how you will monitor and review your actions to ensure effectiveness and prevent recurrence. For example, you did not assess the need for investigation and evaluation of all of your 15-day Alert Reports, describe how you will conduct and process follow-up information, or describe what the 2014 reorganization and institution of Weekly Site Review Meetings will accomplish. Your response dated 17-Feb-2016 also failed to provide evidence of your corrective and preventative actions such as adequate SOPs, updated Quality Agreements, or demonstrate that you investigated 15-day Alert Reports.
In addition, we are concerned about your firm's fundamental understanding and implementation of PADE regulations, including how they relate to your use of contractors. As the application holder of 11 ANDAs, you are ultimately responsible for ensuring compliance with the Act and PADE regulations. The lack of adequate written procedures observed during the inspection and examples of failure to report safety information to FDA in a complete, accurate, and timely manner raises concerns about your firm's ability to assess the safety of your drug products.
The violations cited in this letter are not intended to be an all-inclusive statement of violations that exist at your firm. It is your responsibility to ensure compliance with all requirementsof federal law and FDA regulations. You should take prompt action to correct the violations cited in this letter. Failure to promptly correct these violations may result in legal action, including injunction, without further notice. Federal agencies are advised of the issuanceof all Warning Letters about drugs and devices so that they may take this information into account when awarding contracts. FDA may re-inspect your firm to verify corrective actions have been completed.
If you are considering
an action that is likel
y to lead to
sruption in the supply of
drugs produced at your
facility, FDA requests that
you contact CDER
's Drug Shortages Staff immediately
, at firstname.lastname@example.org,
so that FDA can work with you
on the most
to bring your operations into compliance
with the law. Contacting the Drug Shortages
Staff also allows you
to meet any
may have to report discontinuances
or interruptions in your
drug manufacture under
21 U.S.C. § 356C(b) and allows FDA to consider, as soon as
, what action
s, if any, may be needed
to avoid shortages
the health of patients who depend on your products
Within fifteen (15) working days of receipt of this letter, please notify this office in writing of the specific steps that you have taken to correct the violations. Include an explanation of each step taken to prevent the recurrence of similar violations, as well as copies of any supporting documentation. If you cannot complete the corrective actions within fifteen (15) working days, state the reason for the delay and the time within which you will complete the correction. You may wish to include dates for when each corrective action will be fully implemented.
Your response should be sent to the following address: U.S. Food and Drug Administration,10 Waterview Blvd., Parsippany, New Jersey 07054, Attn. Stephanie Durso, Acting Director of Compliance. If you should have any questions regarding any issue in this letter, please contact Robert J. Maffei, Compliance Officer, by telephone at 973-331-4906.
Craig W. Swanson
Acting District Director
New Jersey District Office
Close Out Letter