Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
|New York District|
Food & Drug Administration
158-15 Liberty Avenue
Jamaica, NY 11433
February 26, 2016
WARNING LETTER NYK-2016-26
VIA UNITED PARCEL SERVICE
DELIVERY SIGNATURE REQUESTED
Mr. Andrew I. Sealfon, CEO
Repro-Med Systems, Inc. dba RMS Medical Products
24 Carpenter Rd.
Chester, New York 10918-1057
Dear Mr. Sealfon:
During an inspection of your firm located in Chester, NY, on June 3, 2015 through June 23, 2015, an investigator from the United States Food and Drug Administration (FDA) determined that your firm is a specification developer and manufacturer of Infusion Pumps (i.e., Freedom 60 Syringe Infusion Pump and the Freedom Edge Syringe Infusion Pump) and Intravascular Administration Sets. 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 any function of the body.
We received the responses from Mr. Marc L. Somelofski, Regulatory Affairs Director, dated July 15, 2015, and from Dr. Fred Ma, Chief Medical Officer, dated February 2, 2016, to the observations noted on Form FDA 483, List of Inspectional Observations that was issued to you at the close of our inspection. We address your responses below, in relation to each of the noted violations. These violations include, but are not limited to, the following:
- Our inspection revealed that the Freedom 60 Syringe and Freedom Edge Infusion Pumps are adulterated under section 501(f)(1)(B) of the Act, 21 U.S.C. § 351(f)(1)(B), because these devices are class III devices under section 513(f) of the Act, 21 U.S.C. § 360c(f), and you do not have an approved application for premarket approval (PMA) in effect as required by section 515(a) of the Act, 21 U.S.C. § 360e(a), or an approved application for an investigational device exemption (IDE) under section 520(g) of the Act, 21 U.S.C. § 360j(g). The Freedom 60 Syringe and Freedom Edge Infusion Pumps are also misbranded under section 502(o) of the Act, 21 U.S.C. § 352(o), because you did not notify the agency of your intent to introduce these devices into commercial distribution in that a notice or other information respecting the significant modifications to these devices and their new intended use was not provided to the FDA as required by section 510(k) of the Act, 21 U.S.C. § 360(k), and 21 C.F.R. 807.81(a)(3)(i) and (ii).
Specifically, you modified the Freedom 60 Syringe Infusion Pump, cleared under K933652, in a manner that could significantly affect safety and effectiveness when your firm:
a) Changed the pressure specification range from 13 psi maximum to 15 psi maximum;
b) Changed the flow rate specification range from 1 – 500 ml/hr. to 0.5 - 2400 ml/hr.; and
c) Developed and marketed a different version of the Freedom 60 Syringe Infusion Pump (i.e., Freedom Edge Infusion pump) that uses a different syringe volume, pumping mechanism and mode of operation.
In addition, the Freedom 60 Syringe Infusion Pump was cleared under K933652 with the following indications: “The Freedom 60 Syringe Infusion Pump is intended for use in the home setting or hospital environment using any intravenous fluids recommended for use with such syringes as the Becton Dickinson 309663 or Sherwood Medical 8881-560125. The Freedom 60 Syringe Infusion Pump is not indicated for the delivery of blood or blood products.” However, your firm is promoting the device for indications that would constitute a major change or modification to the device’s intended use, for which your firm lacks clearance or approval. Specifically, you are promoting this device for the infusion of prescribed liquid medicines including Immunoglobulin G (IgG,) antibiotics, Desferal, pain medications, chemotherapeutics and cardiac medications. These indications fall outside the cleared intended use because the Freedom 60 Syringe Infusion Pump is only cleared for IV infusion and not infusion of specific medications or blood or blood products, like IgG. Indicating the device for a different route of administration or for specific medications or classes of medications raises new scientific review questions, as such changes introduce new risks that are not normally associated with the cleared indication.
These changes in the design and intended use may affect the performance of the device and could significantly affect the safety and effectiveness of this device.
Your firm has not submitted any correspondence to the FDA regarding this violation to date.
- Our inspection also revealed that the RMS HigH-Flo Subcutaneous Safety Needle Set is adulterated under section 501(f)(1)(B) of the Act, 21 U.S.C. § 351(f)(1)(B), because this device is a class III device under section 513(f) of the Act, 21 U.S.C. § 360c(f), and you do not have an approved application for premarket approval (PMA) in effect pursuant to section 515(a) of the Act, 21 U.S.C. § 360e(a), or an approved application for an investigational device exemption (IDE) under section 520(g) of the Act, 21 U.S.C. § 360j(g). This device is also misbranded under section 502(o) of the Act, 21 U.S.C. § 352(o), because you did not notify the agency of your intent to introduce this device into commercial distribution in that a notice or other information respecting the new intended use of the device was not provided to the FDA as required by section 510(k) of the Act, 21 U.S.C. § 360(k), and 21 C.F.R. 807.81(a)(3)(ii). Specifically:
The RMS HigH-Flo Subcutaneous Safety Needle Sets were cleared under K122404 with the following indication: “RMS HigH-Flo Subcutaneous Safety Needle Sets are intended for the delivery of medication to the subcutaneous tissue.” However, your firm is marketing the device for subcutaneous Immunoglobin (SCIg) infusion. Specifically, your consumer brochure explains how to use the Freedom Edge Syringe Infusion Systems, including the RMS HigH-Flo Subcutaneous Safety Needle Sets, for SCIg infusion. During the review of K122404, the intended use for SCIg infusion was specifically not covered by the cleared intended use because you were unable to supply the requested performance data. Accordingly, promoting the RMS HigH-Flo Subcutaneous Safety Needle Sets for this indication falls outside the cleared intended use. Indicating the device for a different route of administration raises new questions of safety and effectiveness.
Your firm has not submitted any correspondence to the FDA regarding this violation to date.
For a device requiring premarket approval, the notification required by section 510(k) of the Act, 21 U.S.C. § 360(k), is deemed satisfied when a PMA is pending before the agency. 21 C.F.R. 807.81(b). The kind of information you need to submit in order to obtain approval or clearance for your device is described on the Internet at http://www.fda.gov/cdrh/devadvice/3122.html. The FDA will evaluate the information you submit and decide whether your product may be legally marketed.
The FDA requests that your firm immediately cease activities that result in the misbranding or adulteration of the aforementioned Freedom 60 and Freedom Edge Syringe Infusion Pumps and RMS HigH-Flo Subcutaneous Safety Needle Sets, such as the commercial distribution of the devices for the uses discussed above.
Quality System Violations
This inspection revealed that your Freedom 60 and Freedom Edge Syringe Infusion Pumps and RMS HigH-Flo Subcutaneous Safety Needle Set 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, its 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. These violations include, but are not limited to, the following:
1. Failure to complete design verification activities to confirm that the design output meets the design input requirements, as required by 21 CFR § 820.30(f). Specifically, as it relates to design verification activities for the Freedom Edge Syringe Infusion Pump and accessories (flow rate tubing and needle sets):
A. Your firm failed to conduct a flow profile study or similar study to test different flow rates using various types of Precision Flow Tubing connected to your Freedom Edge Syringe Infusion Pump to verify that device outputs, flow rates, would meet design input requirements listed in your pump’s Instructions For Use (IFU) when using a 20 ml or 30 ml BD Luer Lok syringe. Additionally, you did not conduct a flow profile study or similar study to confirm that design inputs for flow rate requirements could be met with the use of various tubing to administer immunoglobulin drugs or other liquid medications, drugs or substances with variable viscosity.
B. Your firm failed to conduct adequate design verification activities associated with ensuring average pressure design outputs were achieved to meet input requirements of 13.5 psi (nominal) to 15 psi (peak). Review of your verification test plan allowed for only two infusion pumps to be tested for average pressure output. Your rationale for testing only two pumps, rather than a greater number of pumps from multiple production lots, is not conveyed and does not appear to be based on a sound statistical sampling plan. The two pumps selected do not adequately verify the product’s ability to reproduce similar, acceptable pressure outputs.
C. Your verification protocol outlined a need to establish a coefficient friction value for the 20 ml syringe used in conjunction with the Freedom Edge Syringe Infusion Pump. However, a coefficient friction value was not established for the 30 ml syringe which is also used with this pump.
D. Your Design Input Checklist for the Freedom Edge Syringe Infusion Pump showed essential input for the pump’s lifecycle was set for 4,000 cycles, however, this design input was later changed to 1,000 cycles as the understanding was that 1,000 cycles closely resembles two years of simulated use to support the product’s warranty. Verification test results did not fully support 1,000 cycles, therefore you reclassified the two year input to 730 cycles. The checklist currently still shows design input for two year life cycling as 4,000 cycles. You either failed to conduct additional design verification testing for life cycling to verify this design input (4,000 cycles) can be met; or, you failed to update design inputs and outputs to reflect 730 cycles and then failed to verify or validate to ensure 730 cycles is adequate to support device design.
E. Your verification protocol for the Freedom Edge Syringe Infusion Pump did not always identify an adequate test method. For example, the Force Gauge Test was briefly described but lacked information concerning type of force gauge test equipment to be used, amount of samples that would be tested, the acceptance criteria for final force output, and what correlation this measurement has on the pump’s average operating pressure.
We reviewed your firm’s response and concluded that it is not adequate. We acknowledge your firm is initiating CAPA 20150625-1 to improve the design control process and eliminate the root cause of the problem, however a copy of this CAPA and its contents were not made available for review. We acknowledge your response states you will take necessary steps to correct lacking verification activities noted in parts A-E above, however your response lacks inclusion of the necessary attachments, references and reports necessary to support the validity of your proposed corrections.
Also, your response does not include any information regarding a systemic corrective action that includes a retrospective review of other products to ensure that design controls were documented and completed as required.
2. Failure to establish and maintain plans that describe or reference the design and development activities and define responsibility for implementation, as required by 21 CFR § 820.30(b). Specifically, your firm does not have a plan that describes the design and development activities for the Freedom Edge Syringe Infusion Pump.
In addition, your Design Plan procedure #2015, Rev B is incomplete in that it does not describe all major design phases from market concept to design launch. This design plan, therefore, fails to outline a road map for implementing and handling design and development activities, in order to ensure all design steps are performed, reviewed and documented prior to design release.
We reviewed your firm’s response and concluded that it is not adequate. While you indicate a design plan will be created to outline activities for the Freedom Edge Syringe Infusion Pump, no such plan has been provided for review to date. You provided revised design procedures such as Design Plan procedure #2015, Rev C, however we will need to assess successful training and implementation of this procedure during our next inspection.
Also, your response does not include any information regarding a systemic corrective action to include a retrospective review of other products to ensure that design controls were documented and completed as required.
3. Failure to establish procedures to ensure that equipment is routinely calibrated, inspected, checked, and maintained, as required by 21 CFR 820.72(a). Specifically, your procedure, DAS Calibration Procedure #8057, Rev A, containing calibration instructions for the cell load tester Omega Dyne Pressure Transducer, (b)(4), that was used to test Freedom 60 Syringe Infusion Pumps, does not contain sufficient instructions to ensure routine calibration and maintenance, adequate instructions for completing calibration, adequate documentation of calibration results, and provisions for remedial action to correct the fixture if not operating within precision or accuracy limits.
Also, your firm does not have any preventative maintenance schedule or procedure, or similar procedure(s) to check and/or replace sensors and any additional parts or equipment at your firm that may need maintenance.
We reviewed your firm’s response and concluded that it is not adequate. We acknowledge your response indicates you will be developing a calibration manual and master validation plan. We also acknowledge you state you will develop a preventative maintenance procedure for your test fixture and have the load cell calibrated by a supplier of calibration services. However, these activities have not been completed to date and/or documents to support these proposed actions have not been provided. Also, your response does not include any information regarding a systemic corrective action to include a retrospective review of other products and their equipment to ensure all calibration and preventative maintenance activities are controlled as required.
4. Failure to establish and maintain procedures for rework, to include retesting and revaluation of nonconforming product after rework, to ensure that the product meets its current approved specifications, as required by 21 CFR 820.90(b)(2). Specifically, rework and revaluation activities, including a determination of any adverse effect from the rework upon the product, were not documented in the Device History Records (DHRs) for your Freedom 60 Syringe Infusion Pumps. For example, pump serial (b)(4) was tested on 3/13/2015 four times. Each time the pump was rejected. On the fifth test the pump was released without evidence documented that the pump had been reworked and/or how the pump had been reworked to meet specification(s).
We reviewed your firm’s response and concluded that it is not adequate. We acknowledge your procedure Freedom Pump Performance Test (DA) #5013, Rev H allows for replacing of parts and retesting, however the regulations require documentation of such actions in the DHR. We acknowledge you state you will be revising form 05-277 to include a field to specify when the Negator part on the pump is replaced and a field for when additional parts are replaced, however, objective evidence to observe and evaluate the stated correction is still in progress and/or was not provided.
Also, your response does not include any information regarding a systemic corrective action to include a retrospective review of other products and their DHRs to ensure all rework and revaluation activities are being documented as required.
5. Failure to establish and maintain procedures for implementing corrective and preventive action, as required by 21 CFR 820.100(a). Supplier Corrective Action Report (SCAR) #2014-003, dated 9/22/2014, documented your supplier of PE bags (b)(4) was supplying packaging with wrinkles in the seal. The root cause was determined to be improper pressure for the rewind belt and the operator using excessive tension settings and the SCAR was closed based on employee retraining on 9/30/2014. However, review of your Material Disposition Log for your High-Flo 4-needle set, 26 gauge 9 mm length needles (b)(4), documented continued problems with seal quality, to include wrinkles in the seal, for additional seals provided by this supplier on 12/2/2014. Your SCAR did not adequately verify or validate the corrective action made by the supplier to ensure the action was effective and did not adversely affect the finished device. The SCAR was closed without requiring or ensuring the root cause of the seal wrinkles was corrected and effective. When continuing issues were identified with package seals from this supplier on 12/2/2014, you did not re-evaluate or re-investigate the SCAR.
We reviewed your firm’s response and concluded that it is not adequate. You indicate you revised the corrective action process, SOP 8034 Revision G. Revised written CAPA procedures, however, have not been provided to date. Your response does not indicate any further corrective action activities will take place with respect to the package issues with your supplier.
6. Failure to establish and maintain procedures for acceptance activities, as required by 21 CFR 820.80(a). Specifically, your Tubing and Needle Set Flow Test Procedure, #8001, Rev L, does not include test parameters or acceptance criteria for your F8, F20 and F500 Precision Flow Tubing to indicate the acceptable flow rate for these products.
We reviewed your firm’s response and concluded that it is not adequate. You indicate that omission of the F8 and F500 tubing from the procedure is an oversight and does not affect product quality and you state that F20 has never been manufactured or distributed by the organization. You state you will be revising your Tubing and Needle Set Flow Test Procedure, #8001 to include acceptance criteria for F8 and F500 tubing; however, because you have not yet completed this revision, we are not able to evaluate the stated correction.
Our inspection also revealed that the Freedom 60 Syringe Infusion Pump System with Syringe Set & Tubing devices (K935632 Infusion Pump) are misbranded under Section 502(t)(2) of the Act, 21 U.S.C. § 352(t)(2), in that your firm failed or refused to furnish material or information regarding the devices that is required by or under Section 519 of the Act, 21 U.S.C. § 360i, and 21 CFR Part 803 - Medical Device Reporting. Significant violations include, but are not limited to:
Failure to adequately develop, maintain and implement written MDR procedures, as required by 21 CFR 803.17. For example, after reviewing your firm’s MDR procedure titled “Adverse Event & Incident Reporting,”Procedure No. SOP 1050, Rev. A, dated 5/28/2015, the following issues were noted:
(1) SOP 1050, Rev. A does not establish internal systems that provide for timely and effective identification, communication, and evaluation of events that may be subject to MDR requirements. For example:
a. The procedure omits definitions for the terms “become aware”, “caused or contributed”, from 21 CFR Part 803.3, and definition for the term “reasonably suggests” from 21 CFR 803.20 (c)(1). The exclusion of the definitions for these terms from the procedure may lead your firm to make an incorrect reportability decision when evaluating a complaint that may meet the criteria for reporting under 21 CFR 803.50(a).
(2) SOP 1050, Rev. A does not establish internal systems that provide for a standardized review process to determine when an event meets the criteria for reporting under this part. For example:
a. The procedure does not specify who makes the decision for reporting events to FDA.
b. There are no instructions for how your firm will evaluate information about an event to make MDR reportability determinations in a timely manner.
(3) SOP 1050, Rev. A does not establish internal systems that provide for timely transmission of complete medical device reports. Specifically, the following are not addressed:
a. Although the procedure includes references to 30 day and 5 day reports, it does not specify calendar days and work days, respectively.
b. How your firm will submit all information reasonably known to it for each event.
(4) SOP 1050, Rev. A does not describe how it will address documentation and record-keeping requirements, including:
a. Documentation of adverse event related information maintained as MDR event files.
b. Information that was evaluated to determine if an event was reportable.
c. Documentation of the deliberations and decision-making processes used to determine if a device-related death, serious injury, or malfunction was or was not reportable.
d. Systems that ensure access to information that facilitates timely follow-up and inspection by FDA.
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 written response should be sent the Food and Drug Administration; Attention:
LCDR Catherine Beer
U. S. Food and Drug Administration
One Winners Circle, Suite 110
Albany, NY 12205
If you have any questions about the content of this letter please contact: LCDR Catherine Beer at (518) 453-2314 x1015.
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 in 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.
Ronald M. Pace
New York District