- Oscor, Inc.
- Issuing Office:
- Florida District Office
| || |
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
| ||Florida District |
555 Winderley Place, Suite 200
Maitland, Florida 32751
VIA UPS NEXT DAY AIR
w/ DELIVERY CONFIRMATION
June 13, 2016
Thomas P. Osypka
President and CEO
3816 Desoto Boulevard
Palm Harbor, FL 34683-1618 U.S.A.
Dear Mr. Osypka:
During an inspection of your firm located in Palm Harbor, Florida on February 29, 2016 through March 17, 2016, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures introducer catheters, i.e., Adelante® Magnum, and a neuromodulator for obesity, i.e.,Maestro® Rechargeable System. 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 written response dated April 6, 2016 from Dorit Segal, Director of Quality Assurance concerning the investigator’s observations noted on the Form FDA 483 (FDA 483), Inspectional Observations, which was issued to you. We address this response below, in relation to the noted violations. We also acknowledge receipt of your response to the Form FDA 483, Inspectional Observations, dated May 27, 2016. We will evaluate the May 27, 2016 response along with any other written material provided as the direct response to this letter.
The violations include, but are not limited to, the following:
1) Failure to develop, conduct, control, and monitor production processes to ensure that a device conforms to its specifications, as required by 21 CFR 820.70(a). For example:
a) Your firm’s use of Single Lot Release for the EO sterilization processing of the Maestro® Rechargeable System does not provide assurance that sterility requirements for the device are met. While Single Lot Release may provide for release of product from a sterilization process where there is only sufficient product to make up a single sterilization load and without going through a full validation, the sterility assurance level (SAL) must be supported through specified test data. This is not evident from your firm’s process control records. The records do not identify and record the required quantity of samples are selected at the appropriate stage of manufacturing or sterilization processing, for the testing of bioburden, product sterility, EO residuals, and bacterial endotoxin, to ensure requirements of your firm’s “EnteroMedics Single Sterilization Lot Release” procedure (EM-49-003X-E-01, approved 05/21/2015 – referenced to ISO 11135:2014, Annex E “Single Lot Release”) are satisfied. Specifically,
i) Your procedure requires samples selected for single lot release testing be identified and recorded on your Manufacturing Work Order (MO). Records for Sterilization Lot (b)(4), including the Sterilization Load Map and the Serial Number Verification Record and associated MO’s CR-01988, CR-01989, CR-01990, CR-01991, and CR-01992, do not distinguish which serialized samples underwent the (b)(4) or the (b)(4) cycle exposure for selection for testing. Your firm’s representative acknowledged to our investigator that your firm does not maintain any controlled record documenting which device serial numbers are sterilized in each cycle for single batch release.
ii) The document provided to our investigator records product bioburden samples for EO processing Sterilization Lot (b)(4) were selected from MO’s CR-01992 (3 anterior leads) and CR-01994 (3 posterior leads) as part of single lot release testing, in accordance with your procedure. However, process control records for Sterilization Lot (b)(4) do not list products from MO CR-01994 as being EO processed under the sterilization lot. Further, process control records for the sterilization lot do not demonstrate and/or provide for justification that product samples manufactured under MO CR-01994 are representative of the bioburden for single lot release purposes of Sterilization Lot (b)(4).
iii) Your process control records document multiple lots, i.e., MO’s CR-01988, CR-01989, CR-01990, CR-01991, and CR-01992 where EO processed under Sterilization Lot (b)(4). The document provided to our investigator records product samples selected for single lot release testing did not include product samples from MO’s CR-01990 and CR-1991. Not all products representing the sterilization lot have been sampled for single lot release, even though your process control records for the sterilization lot documents product samples were allocated for single lot release testing.
We reviewed your firm’s response and conclude that it is not adequate. FDA considers EO sterilization processing of medical devices a significant risk process. Your firm’s response indicates the OEM is directly involved in the conduct and documentation of EO sterilization processing of the Maestro® Rechargeable System and that procedures and production records will be revised. However, the response did not include documentation to this effect. In addition, your firm’s response does not address your firm’s use of the document provided to our investigator that has no signature of an approving individual(s) or the approval date.
b) Process control records for the fractional cycle (b)(4) for Sterilization Lots (b)(4) and (b)(4) of the Maestro® Rechargeable System do not demonstrate the operating temperature specification is met during the Vacuum Test phase for the sterilization run. The operating temperature specification under Oscor Validation #RST-001-09-00 is established at (b)(4), Set point (b)(4). Your sterilization reports list an operating temperature during the Vacuum Test phase ranging from (b)(4) for Sterilization Lot #(b)(4) and (b)(4) for Sterilization Lot #(b)(4) which are out-of-specification.
We reviewed your firm’s response and conclude that it is not adequate. Your firm’s response indicates revising the parameter for the operating temperature to ambient. Table 1 – Sterilization Specification (Oscor Validation #RST-001-09-00) states that an operating temperature of (b)(4) during the chamber tests, i.e., Vacuum, High Pressure, Low Pressure, is required to ensure proper chamber function during the exposure cycle. It is unclear whether revising the parameter for the operating temperature to ambient will be adequate to address the out-of-specification event. For example, your firm’s response does not define ambient temperature. A generous range for ambient temperature may generally be considered between (b)(4). Even at the upper range of (b)(4), the operating temperature for the sterilization lots would be out of specification.
c) Process control records do not accurately describe the (b)(4) process for the Adelante® Magnum devices. For instance, your firm’s “MANUFACTURING ORDER”, “Manufacturing Order Picklist”, and (b)(4) ” , Lots C8-05441 and C8-05444 were manufactured, in accordance with your procedure, (b)(4) ” (4D-48-043X-E-01, approved 10/20/2015). Section 6 of your procedure specifies that the (b)(4) process for the Adelante® Magnum device is conducted as a (b)(4) process using (b)(4) for hand application, but your manufacturing records document that the coating process is conducted by an (b)(4) process. Moreover, there are no process control records to describe the (b)(4) process for the Adelante® Magnum devices, Lots EN-14304, EN-14305, and EN-14306, used in the Particulate Matter Test submitted for testing under Protocol #C13747-1.
We reviewed your firm’s response and conclude that it is not adequate. Your response includes an updated (b)(4). The current revision of the procedure covering the specified model/product was not provided with your response; therefore, we are unable to access the adequacy of your response. In addition, your response does not include amended work orders used to produce the Adelante® Magnum test samples, to document the (b)(4) coating process that was utilized.
2) Failure to validate a process whose results cannot be fully verified by subsequent inspection and test according to established procedures, as required by 21 CFR 820.75(a). For example:
a) Your firm’s process verification documentation for the manufacture of the anterior and posterior leads of the Maestro® Rechargeable System does not identify equipment operating parameters, to ensure that the process can consistently produce products meeting their specification. Specifically, your firm failed to validate or establish sufficient inspections or tests for the silicone injection over-molding process used for the electrodes of the anterior and posterior leads. Your firm implemented instructions to conduct 100% inspection of the finished leads and released the devices for distribution to your customer. Your 100% inspection is not sufficient as evident by your customer complaint indicating silicone flash/residue was found on the electrodes of the anterior and posterior leads and is associated with non-conformances of high impedance and loss of therapy from use of the Maestro® Rechargeable System.
We reviewed your firm’s response and conclude that it is not adequate. Your firm has not provided supporting documentation identifying equipment operating parameters for the silicone injection over-molding process, the de-flashing process, and the inspection process. In addition, it is unclear how your firm will validate the de-flashing and inspection processes. Your response suggests these processes are (b)(4) processes. As such, these processes would require the qualification of personnel in the conduct of these operations. Your firm has not provided evidence to support personnel has been qualified to conduct this inspection and de-flashing processes. The FDA considers injection molding a process that must be validated and process parameters to support the validation activities can be verified. Please provide documentation describing how your firm determines when a process must be verified or validated, i.e. over-molding, de-flashing, and inspection.
b) Your firm has not validated the UV curing process used in the (b)(4) process of your Adelante® Magnum device. Your firm's procedure for this process (4D-48-043X-E-01, approved 10/20/2015) currently specifies a (b)(4) cure time for the device, but does not specify the appropriate UV intensity for the cure time to achieve a full cure. This (b)(4) cure time is specified outside the conduct of a complete UV curing process validation, including establishing the minimum and maximum exposure times and associated UV intensities. In addition, your firm's procedure (4D-51-036X-01, approved 04/19/2015) for in-process and final inspection activities consists of visual inspection for foreign matter, discoloration or flaky surface and specifies the applied coating surface should be smooth and shiny and the coating should be applied evenly. The procedure lacks adequate physical properties specifications and testing, i.e. adhesion, hardness, thickness, coefficient of friction, to support the quality of the cure for the (b)(4) devices.
We reviewed your firm’s response and conclude that it is not adequate. The response states your firm elected to use the bulb manufacturer specification of (b)(4) of use prior to replacement rather than UV intensity, for the Adelante® Magnum UV cure process. The response also states the UV bulb used for the Adelante® Magnum coating process was within the manufacturer’s specifications for bulb life and the bulb life specification is linked to intensity, and shows stable intensity within the bulb life on the specification. While this may be appropriate to address the UV intensity for the established cure time of (b)(4), you failed to include in the response this correlation between bulb life and UV intensity through the life of the bulb. In addition, the response does not include established physical properties specifications of the cure, i.e. adhesion, hardness, thickness, coefficient of friction, as verification of the quality of the full cure.
3) Failure to establish and maintain procedures to adequately control environmental conditions, where environmental conditions could reasonably be expected to have an adverse effect on product quality, as required by 21 CFR 820.70(c). For example, your firm does not monitor the environmental conditions, i.e. temperature and humidity conditions, in cleanroom (b)(4) where the (b)(4) process is conducted for the Adelante® Magnum devices.
We reviewed your firm’s response and conclude that it is not adequate. While your firm’s response indicates that procedures will be revised and the use of production environmental monitoring records will be implemented, the response did not include documentation to this effect.
Your firm 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 civil money penalties. Also, federal agencies may be advised of the issuance of Warning Letters about devices so that they may take this information into account when considering the award of contracts. Additionally, premarket approval applications for Class III devices to which the Quality System regulation violations are reasonably related 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 business days from the date you receive this letter of the specific steps your firm has taken to correct the noted violations, as well as an explanation of how your firm plans to prevent these violations, or similar violations, from occurring again. Include documentation of the corrections and/or corrective actions (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 actions 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 all violations included in this Warning Letter.
Your response should be sent to:
Salvatore N. Randazzo
555 Winderley Place, Suite 200
Maitland, Florida, 32751
Refer to the Unique CMS Identification Number 496385, when replying. If you have any questions about the content of this letter please contact: Salvatore N. Randazzo at (407) 475-4712.
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 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 the violations, and take prompt actions to correct the violations and bring the products into compliance.
Susan M. Turcovski
Director, Florida District