Inspections, Compliance, Enforcement, and Criminal Investigations
First Medical Source LLC 9/26/12
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
Los Angeles District
Irvine, California 92612-2506
Telephone (949) 608-2900
Fax (949) 608-4415
VIA UNITED PARCEL SERVICE
September 26, 2012 WL 46-12
Mr. Mark M. Shal
First Medical Source, LLC.
28581 Springfield Drive
Laguna Beach, California 92677
During an inspection of your firm located in Laguna Niguel, California, on April 26, 2012, through May 22, 2012, investigators from the United States Food and Drug Administration (FDA) determined that your firm manufactures First Medical Source (FMS) Pain Management Kits. 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 to affect the structure or any 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 response from you dated June 4, 2012, concerning our investigator’s observations noted on the Form FDA 483 (FDA 483), List of Inspectional Observations, which was issued to your firm. We address this response below, in relation to each of the noted violations. These violations include, but are not limited to, the following:
1. Failure to establish and maintain adequate procedures to control the design of the device in order to ensure that specified design requirements are met, as required by 21 CFR 820.30(a). For example, your firm’s FMS Pain Management Kit Development Plan (PMK-1002) and the Design Control Procedure (FMS-2012) required your firm to document design input, output, and verification, and to conduct design validation. Your firm was not able to provide records or results of design input, output, and validation.
We reviewed your firm’s response and conclude that it is not adequate. Your firm indicated that design validation is documented in the Design History File (DHF); however, the complete design validation documentation was not provided for our review and the design validation summary provided was not in sufficient detail to assess if it had addressed applicable elements required under 21 CFR 820.30(g). Also, your firm did not provide evidence of consideration of systemic corrective actions that addressed deficiencies within your firm’s design control system, to include documentation of completion of design input, output, design verification, and design validation activities.
2. Failure to establish and maintain adequate procedures for implementing corrective and preventive action and failure to document all activities under 21 CFR 820.100 and their results, as required by 21 CFR 820.100(a). For example:
a) CAPA #(b)(4) documented that “the new design leaves no leakage opportunity at the (b)(4)” of the infusion pump and that “(b)(4) changed the set configuration and the (b)(4) is now placed at (b)(4).” Your firm failed to provide records showing that this corrective action is effective and that it corrected the non-conformity of the leakage and does not adversely affect the function of the infusion pump. Furthermore, CAPA # (b)(4) indicated that the effectiveness was stated as, “the new design leaves no leakage opportunity at the (b)(4).” There were no records of how this effectiveness was verified. Additionally, the CAPA log mentioned that the (b)(4) were defective and that the new revision of the pump will replace the (b)(4) with a (b)(4). Your firm did not have validation/verification records or evidence of the validation performed of the new (b)(4) design and implementation of the (b)(4) change.
b) CAPA #(b)(4) was documented as a connector leakage. Your firm’s investigation of the cause of the nonconformity determined that it was due to the (b)(4). Your firm’s corrective actions included a cautionary notice in the Directions For Use to allow evaporation time if alcohol was used to swab connectors. The CAPA did not contain records of verification/validation of the effectiveness of this corrective action.
c) CAPA #(b)(4) stated that (b)(4) units sold of pump “lot #(b)(4) manufactured (b)(4), leaked in the hands of the customers ((b)(4)).” An investigation of the cause of the non‑conformity was not performed. The CAPA log mentioned that the samples got lost by the supplier. You stated that you sent the complaint sample to the supplier, (b)(4), but that (b)(4) lost the sample and so the investigation was not completed.
We reviewed your firm’s response and conclude that it is not adequate. Your firm indicated that the document provided by (b)(4), in the “Design Changes” section of the DHF, shows the changes made. Your firm also stated that the pump manufacturer, (b)(4), not FMS, is responsible for validation and verification of any design changes of the pump, as well as maintenance of associated records. Also, your firm stated that the cautionary notice in the Directions For Use is a general industry solution to the connector leakage nonconformity and indicated that samples of the same lot of pumps ((b)(4)) were recaptured by FMS and sent to (b)(4). Your firm stated that tests were performed by (b)(4) and did not show any evidence of the problem. Your firm stated that one sample was tested by FMS, also without showing any evidence of any leak; this problem seems to have been associated with lot # (b)(4) only. However, your firm did not provide documentation or evidence of the verification/validation for both the design change made as a corrective action to the infusion pump leakage and the changes made to the Directions for Use as a corrective action for the connector leakage. Your firm failed to provide documentation that it completed an investigation of the cause of the nonconformity of pump, lot #(b)(4), as a correction to this deficiency. Lastly, your firm did not provide documentation or evidence of consideration of systemic corrective actions, to include retrospective review of verification/validation activities for corrective actions identified prior to implementation of those actions.
d) CAPA #s (b)(4) were identified in your firm’s CAPA log with brief annotations of disposition, follow-up action, root cause analysis, and status. However, your firm did not have corresponding records, including those that detail investigations, verification, implementation, and effectiveness check activities regarding these CAPAs. You indicated that you performed the investigation for these CAPAs but did not document the results on the CAPA form, as required.
We reviewed your firm’s response and conclude that it is not adequate. While your firm indicated that hard copies of CAPAs will be added to the CAPA file by August 31, 2012, your firm did not provide documentation or evidence that it completed the CAPA investigation, documented results of the investigation, and retrospectively reviewed all CAPAs to ensure that activities were completed and documented as required. Also, the response did not include documentation or evidence of consideration of systemic corrective actions that addressed the CAPA deficiencies described above.
3. Failure to establish and maintain procedures for acceptance activities that include inspections, tests, or other verification activities, as required by 21 CFR 820.80(a). For example, your firm’s Certificate of Conformance (COC), certifies that the FMS Pain Management Kit, FMS 8” introducers, (b)(4) 300ml Infusion Pumps, and FMS Dual 5” Catheter Kits are manufactured and tested per FMS’s procedures and passed. Your firm uses evaluation of these COCs as its acceptance activities for receiving (b)(4) 300ml Infusion Pumps and FMS Dual 5” Catheter Kits from suppliers (b)(4) and (b)(4). You indicated that your firm does not have procedures for accepting these products received from its suppliers. You also indicated that your firm does not have procedures for ensuring that each lot of these kits assembled by FMS meets final specifications.
We reviewed your firm’s response and conclude that it is not adequate. Your firm stated that certificates included in the pumps and catheters shipments from its suppliers are used by your firm to make the COC. Your firm did not provide an acceptance procedure for the FMS Pain Management Kit, FMS 8” introducers, (b)(4) 300ml Infusion Pumps, and FMS Dual 5” Catheter Kits. The response did not include documentation or evidence of consideration of systemic corrective actions, including documentation of completion of acceptance activities, as required; review of other products received to ensure that acceptance activities were performed; and a retrospective review of acceptance activities for all products to ensure that they were completed as required.
4. Failure to establish and maintain adequate procedures for receiving, reviewing, and evaluating complaints by a formally designated unit, as required by 21 CFR 820.198(a). For example, your firm’s FMS-2017, Incident and Complaint Handling procedure, section 7.6, requires complaint files to include, at a minimum, an Adverse Event Determination Form (QSF-1198). However, no such form accompanied the complaint file # (b)(4). There is no indication of your firm having conducted MDR evaluation related to over‑infusion of pain medication. The MDR evaluation section in the complaint file # (b)(4) is blank.
We reviewed your firm’s response and conclude that it is not adequate. Your firm provided a revised complaint form (FMS-4013, Rev B) with a modification in the MDR section to include the question “risk of death or serious injury?”. Your firm stated that all complaints on file will be reviewed by August 31, 2012, for completeness and consistency using FMS-4013, Rev. B. However, your firm’s response did not address consideration of systemic corrective actions regarding the evaluation of complaints for MDR reportability.
5. Failure to review, evaluate, and investigate any complaint involving the possible failure of a device, labeling, or package to meet any of its specification unless such investigation has already been performed for a similar complaint and another investigation is not necessary, as required by 21 CFR 820.198(c). For example:
a) Complaint # (b)(4): The complaint form stated, “tubing occlusion,” and the corrective action stated, “up to (b)(4) to see if there are any recurrences and patterns.” The complaint was closed without a failure investigation of the reported incident and the complaint form was not dated. Also, your firm did not document the reason for no investigation, which is required by FMS-4019, Complaints Handling Process Flow 820.198, dated June 03, 2010.
b) Complaint # (b)(4): The complaint form stated “TBD; Under investigation. There was no investigation data in the complaint that was closed on October 13, 2011. Also, your firm did not document the reason for no investigation, which is required by FMS-4019, Complaints Handling Process Flow 820.198, dated June 03, 2010.
We reviewed your firm’s response and conclude that it is not adequate. Your firm stated that the (b)(4) pumps from lot # (b)(4), with a known history of leakage, were returned to (b)(4). (b)(4), in turn, sent the pumps back to the manufacturer, (b)(4), which could not determine any problem. Your firm indicated that (b)(4) suggested possible (b)(4). Your firm stated that the sample tested from the same lot # (b)(4), by FMS, showed (b)(4). Your firm did not provide documentation or evidence that it completed investigations for Complaint # (b)(4) and Complaint # (b)(4). Your firm did not provide documentation or evidence of consideration of systemic corrective actions, such as retrospectively reviewing all complaints to ensure that investigations were completed as required, or that it documented why no investigation was needed.
6. Failure to adequately evaluate and select potential suppliers, contractors, and consultants on the basis of their ability to meet specified requirements, including quality requirements and failure to document this evaluation, as required by 21 CFR 820.50(a)(1). For example, your firm’s Purchasing Control Procedure, FMS-2015, requires your firm to document supplier evaluations. It also states that (b)(4) and (b)(4) suppliers are grandfathered, but all new and potentially new suppliers are subject to the evaluation of this procedure. However, your firm failed to document evaluation of suppliers that are not listed as grandfathered, such as (b)(4) and (b)(4), supplier of (b)(4) infusion pumps, as well (b)(4), which is a catheter kit assembler overseeing your firm’s products sterilization.
We reviewed your firm’s response and conclude that it is not adequate. Your firm provided a copy of the Suppliers List dated June 1, 2012, (FMS-4029) but did not provide supplier evaluations for those non-grandfathered suppliers. Your firm also did not provide any evidence of having implemented any correction and corrective action or having considered a systemic corrective action to include retrospective review of other purchasing control requirements to ensure that they were completed as required.
7. Failure to establish and maintain adequate data that clearly describe or reference the specified requirements, including quality requirements, for purchased or otherwise received product and services, as required by 21 CRF 820.50(b). For example, your firm does not have any agreement with the infusion pump distributor and supplier to notify your firm if any process or product is changed. During the “discussion with management” and issuance of the FDA-483, your firm disagreed, saying that your firm’s purchase order (FMS-4002) included a statement for the supplier to notify your firm of any changes to the product. During the close-out inspection, your firm printed a copy of your firm’s purchase order (FMS-4002) and no such statement appeared on the form.
We reviewed your firm’s response and conclude that it is not adequate. Your firm provided a copy of the revised purchase order (FMS-4002 Rev. B), which includes a statement requiring its suppliers to inform FMS of any planned changes in the product. However, your firm did not provide evidence of implementation of corrective actions or consideration of systemic corrective action, such as a retrospective review of all other purchase orders to ensure that FMS-4002 Rev. B was completed for each supplier. Your firm also did not provide evidence that form FMS-4002 Rev. B was completed for the infusion pump distributor.
Our inspection also revealed that your devices are misbranded under section 502(t)(2) of the Act 21 USC § 352(t)(2), in that your firm failed or refused to furnish material or information respecting the devices that is required by or under section 519 of the Act, 21 USC § 360i, and 21 CFR Part 803 – Medical Device Reporting (MDR) Regulation. Significant deviations include, but are not limited to:
Failure to develop, maintain, and implement written MDR procedures as required by 21 CFR 803.17. After reviewing your firm’s Incident and Complaint Handling Document # FMS-2017, Revision B, effective date 06/21/2010, the following issues were noted:
1) FMS-2017 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) Your firm’s procedure includes definitions from 21 CFR 803.3, but omits the definition for the terms: “reasonably known” and “reasonably suggests,” found respectively in 21 CFR 803.50(b)and 21 CFR 803.20(c)(1). The exclusion of these terms 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).
b) The procedure does not reference a process for investigating events identified as MDRs, to ensure that MDRs are submitted to FDA within the required reporting timeframes, as required under 21 CFR 803.17(a)(1).
2) FMS-2017 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, your firm’s procedure states “Form FDA 3500A” in reference to the form for submission of MDR reportable events to FDA. However there are no instructions for how to obtain and how to complete the FDA Form 3500A.
3) FMS-2017 does not establish internal systems that provide for timely transmission of complete medical device reports. Specifically, the address referenced for submission of MDRs to FDA is incorrect. The correct address is: FDA, CDRH, Medical Device Reporting, P.O. Box 3002, Rockville, MD 20847-3002.
4) FMS-2017 does not describe how your firm 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; and
d) Systems that ensure access to information that facilitates timely follow‑up and inspection by FDA.
FMS-2017 includes references to baseline reports. Baseline reports are no longer required and we recommend that all references to Baseline Reports be removed from your firm’s MDR procedure (see: 73 Federal Register Notice 53686, dated September 17, 2008).
We reviewed your firm’s response and have determined that it is not adequate. Although your firm included a copy of its “Complaint Form FMS-4013,” your firm did not include a revised version of its procedure addressing the above-cited omissions.
If your firm wishes to submit MDR reports via electronic submission it can follow the directions stated at the following URL:
If your firm wishes to discuss MDR reportability criteria or to schedule further communications, it may contact the Reportability Review Team of the MDR Policy Branch by email at ReportabilityReviewTeam@fda.hhs.gov.
Our inspection also revealed that the FMS Pain Management Kit is adulterated under section 501(f)(1)(B) of the Act, 21 U.S.C. § 351(f)(1)(B), because your firm does 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 under section 520(g) of the Act, 21 U.S.C. § 360j(g). The device is also misbranded under section 502(o) the Act, 21 U.S.C. § 352(o), because your firm did not notify the agency of its intent to introduce the device into commercial distribution, as required by section 510(k) of the Act, 21 U.S.C. § 360(k). For a device requiring premarket approval, the notification required by section 510(k) is deemed satisfied when a PMA is pending before the agency. 21 CFR 807.81(b). The kind of information that your firm needs to submit in order to obtain approval or clearance for the device is described on the Internet at
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/default.htm. The FDA will evaluate the information that your firm submits and decide whether the product may be legally marketed.
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 (including any systemic corrective actions) 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 firm’s response should be sent to: Blake Bevill, Director, Compliance Branch, Los Angeles District Office, Food and Drug Administration, 19701 Fairchild, Irvine, California 92612. Refer to the Unique Identification Number (CMS case # 233718) when replying. If you have any questions about the contents of this letter, please contact: Jessica Mu, Compliance Officer at (949)-608-4477 or fax: (949)-608-4417.
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.
Alonza E. Cruse
Cc: Ingeborg Small, Branch Chief
California Department of Public Health
Food and Drug Branch
1500 Capitol Avenue, MS-7602
P.O. Box 997413
Sacramento, CA 95899-7413