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U.S. Department of Health and Human Services

Inspections, Compliance, Enforcement, and Criminal Investigations

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Aptalis Pharma Us Inc 10/25/13

  

Department of Health and Human Services logoDepartment of Health and Human Services

Public Health Service
Food and Drug Administration
 
New Orleans District
404 BNA Drive
Building 200 – Suite 500
Nashville, TN 37217
Telephone: (615) 366-7801
FAX: (615) 366-7802

 

October 25, 2013
WARNING LETTER NO. 2014-NOL-02
  
UNITED PARCEL SERVICE
DELIVERY SIGNATURE REQUESTED
 
Frank Verwiel, M.D., President and CEO
Aptalis Pharma US, Inc.
22 Inverness Center Parkway, Suite 310
Birmingham, AL 35242
 
Dear Dr. Verwiel:
 
On August 21 - 22, 26, and 28 - 29, 2013, a United States Food and Drug Administration (FDA) investigator inspected your firm, located at 22 Inverness Center Parkway, Birmingham, Alabama. The inspection determined your firm is operating as a specification developer of a Class II medical device called Flutter. Under Section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 United States Code (USC) 321(h), this product is a device because it is 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 this device is adulterated within the meaning of Section 501(h) of the Act [21 USC 351(h)], because 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.  Our investigators’ observations were presented to Mr. Andrew M. Stribling, Quality Assurance Manager, on Form FDA 483, Inspectional Observations, at the conclusion of our inspection on August 29, 2013. You may find the Act through links on FDA’s Internet home page at www.fda.gov.
 
We received your firm’s response to the Form FDA 483 on September 17, 2013, and our evaluation of your response is discussed below.  Violations revealed during the inspection include, but are not limited to, the following:
 
1.    Failure for the written Medical Device Reporting (MDR) procedures to include documentation and recordkeeping requirements for all information evaluated to determine if an event was reportable, as required by 21 CFR 803.17(b)(1). For example, your written MDR procedure did not require all information evaluated to make the determination if an event is reportable, to be documented and maintained, as part of the event file. 
 
We reviewed your response to the FDA 483 received on September 17, 2013. The procedure appears adequate. We will verify the implementation of this procedure during our next inspection of your firm.
 
2.    Failure to provide justification for not reporting the correction or removal action of your device to FDA, which included conclusions, follow-ups, and reviews by a designated person, as required by 21 CFR 806.20(b)(4). Specifically, your contract manufacturer reworked (b)(4) devices in 2012 and (b)(4) devices in 2013 to correct issues for (b)(4) customers. There was no record of a written justification for not reporting the correction to FDA.
 
We reviewed your response to the FDA 483 received on September 17, 2013. You provided “CAPA-13-011” as your record of correction and removal not required to be reported to the FDA. This corrective and preventive action (CAPA) did not include a description of the event(s) giving rise to the information reported and the corrective or removal action that has been, and is expected to be taken, as required by 21 806.20(b)(3). Additionally, please provide your health risk assessment as indicated in “CAPA-13-011,” under the “Action Plan” for lot (b)(4) for review.
 
3.    Failure to establish adequate procedures for CAPA, as required by 21 CFR 820.100(a). For example, your firm failed to establish procedures for the following requirements:
 
a.   Analyzing processes, work operations, concessions, quality audit reports, quality records, service records, complaints, returned product, and other sources of quality data to identify existing and potential causes of nonconforming product, or other quality problems. Appropriate statistical methodology shall be used where necessary to detect quality problems;
b.   Investigating the cause of nonconformities relating to product, processes, and the quality system;
c.   Verifying or validating the CAPA to ensure such action is effective and does not adversely affect the finished device; and,
d.   Implementing and recording changes in methods and procedures needed to correct and prevent identified quality problems.
 
We reviewed your response to the FDA 483 received on September 17, 2013. The procedure appears adequate. We will verify the implementation of this procedure during our next inspection of your firm.
 
4.    Failure to adequately document CAPA activities and/or results, as required by 21 CFR 820.100(b). Specifically, your firm received complaints in 2012 alleging (b)(4) of your Flutter percussor device to perform (b)(4).  Your complaint records referenced (b)(4).  Your firm failed to initiate a CAPA and document all corrective and preventive action activities related to this issue.
 
We reviewed your response to the FDA 483 received on September 17, 2013. The procedure appears adequate. We will verify the implementation of this procedure during our next inspection of your firm. 
 
5.    Failure to establish and maintain procedures for receiving, reviewing, and evaluating complaints by a formally designated unit, as required by 21 CFR 820.198(a). Specifically, your written complaint handling procedure only applies to complaints alleging issues with (b)(4) It did not include all types of complaints. Per 21 CFR 820.198(a), the complaint procedures shall ensure:
 
  1. All complaints are processed in a uniform and timely manner;
  2. Oral complaints are documented upon receipt; and,
  3. Complaints are evaluated to determine whether the complaint represents an event which is required to be reported to FDA, pursuant to 21 CFR 803-MDR. 
 
We reviewed your response to the FDA 483 received on September 17, 2013. The procedure you provided, “Receiving Complaints from Clients,” does not state all complaints will be documented, including oral complaints, as required by 21 CFR 820.198(a)(2). Please provide the procedure for (b)(4) that (b)(4) will receive, as referenced in your procedure, for review. All complaints must be documented.
 
6.    Failure to establish and maintain adequate procedures to control the design changes of the Flutter device in order to ensure specified design requirements are met, as required by 21 CFR 820.30(i). For example, your firm failed to establish and maintain procedures for the identification, documentation, validation, or where appropriate, verification, review, and approval of design changes before their implementation.
 
We reviewed your response to the FDA 483 received on September 17, 2013. Your “Change Control Procedure” does not include validation of changes to the device. Please revise the procedure to include this requirement, as stated in 21 CFR 820.30(i). Additionally, please provide validation documentation of the change.
 
7.    Failure to maintain Device Master Records (DMRs) for your class II Flutter device, as required by 21 CFR 820.181. For example, your firm has not documented, or referenced the location of, the following required information for the device you manufacture:
 
a.   Device specifications;
b.   Production process specifications;
c.   Quality assurance procedures and specifications; and,
d.   Packaging and labeling specifications.
 
We reviewed your response to the FDA 483 received on September 17, 2013. We understand your firm may need until (b)(4) to come into compliance with observation seven on the FDA 483. We will verify the implementation of this procedure during our next inspection of your firm.
 
8.    Failure to conduct quality audits at defined intervals to assure the quality system is in compliance with the established quality system requirements and to determine the effectiveness of the quality system, as required by 21 CFR 820.22. Specifically, your written internal audit procedures require self-audits be conducted annually. Your firm failed to conduct internal audits of your quality system for your Flutter device for 2011 and 2012.
 
We reviewed your response to the FDA 483 received on September 17, 2013. The procedure appears adequate. We will verify the implementation of this procedure during our next inspection of your firm.
 
9.    Failure of management with executive responsibility to review the suitability of the quality system at defined intervals and with sufficient frequency according to established procedures to ensure the quality system satisfies the requirements of this part, as required by 21 CFR 820.20(c). For example, your firm failed to establish management review procedures, conduct management review as a manufacturer of a medical device, and provide documentation that a management representative has been appointed.
 
We reviewed your response to the FDA 483 received on September 17, 2013. Your statement (b)(4) does not put your firm in compliance with 21 CFR 820.20(c). We appreciate your creation of the procedure titled “Management Review for Medical Devices” to assist you in coming into compliance with this regulation.  Unfortunately, you provided documentation of your intention for a management review meeting in the first quarter of 2014. At this time, we still have no evidence your firm has conducted a management review meeting to ensure your firm is in compliance with 21 CFR 820.20(c). 
 
10.    Failure to establish and maintain procedures for acceptance activities, as required by 21 CFR 820.80(a). Specifically, your firm failed to establish written procedures for the acceptance activities being conducted for the initial release of your product.
 
We reviewed your response to the FDA 483 received on September 17, 2013. Your response states “(b)(4)” Our inspection revealed (b)(4) was performing the initial release of bulk Flutter devices from (b)(4) and provided a (b)(4) to Aptalis as assurance the devices were being manufactured in accordance with the Quality System Regulations. However, there was no written procedure that described this process. Additionally, the Device History Record for lot (b)(4) of the Flutter device included sections where the devices did not appear to have been signed off as approved for release. We appreciate your revision of the procedure titled “Finished Products Release” to assist you in coming into compliance with this regulation. We will verify the implementation of this procedure during our next inspection of your firm.
 
You should take prompt action to correct the violations addressed in this letter. Failure to promptly correct these violations 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. Also, Federal agencies are advised of the issuance of all warning letters about devices so they may take this information into account when considering the award of contracts. Additionally, premarket approval applications for Class III devices will not be approved until the violations have been corrected. Requests for Certificates to Foreign Governments will not be granted until the violations related to the subject devices have been corrected.
 
Please notify this office in writing within fifteen (15) working days from the date you receive this letter of the specific steps you have taken to correct the noted violations, including an explanation of how you plan to prevent these violations, or similar violations, from occurring again.  Include documentation of the corrective action you have taken.  If your planned correction will occur over time, please include a timetable for implementation of those corrections.  If corrective action cannot be completed within 15 working days, state the reason for the delay and the time within which the corrections will be completed.
 
Finally, you should know this letter is not intended to be an all-inclusive list of the violations at your facility.  It is your responsibility to ensure compliance with applicable laws and regulations administered by FDA.  The specific violations noted in this letter and in the FDA 483, issued at the close out of the inspection, may be symptomatic of serious problems in your firm's manufacturing and quality assurance systems.  You should investigate and determine the causes of the violations, and take prompt actions to correct the violations and to bring your products into compliance.
 
Your response should be sent to: Ms. Kimberly Dutzek, Compliance Officer, at the address above. If you have any questions about the content of this letter please contact Ms. Dutzek at (615) 366-7826.
 
Sincerely,
/S/ 
Patricia Schafer
District Director
New Orleans District
 
 
cc: David W. Mims, President of Aptalis U.S. Specialty Pharmaceuticals
      Aptalis Pharma US, Inc.
      22 Inverness Center Parkway, Suite 310
      Birmingham, AL 35242-4887
 
      Andrew M. Stribling, Quality Assurance Manager
      22 Inverness Center Parkway, Suite 310
      Birmingham, AL 35242-4887