• Decrease font size
  • Return font size to normal
  • Increase font size
U.S. Department of Health and Human Services

Inspections, Compliance, Enforcement, and Criminal Investigations

  • Print
  • Share
  • E-mail

PhotoMedex, Inc. 1/26/12

  

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

Public Health Service
Food and Drug Administration
 PHILADELPHIA DISTRICT
900 U.S. Customhouse
2nd and Chestnut Streets
Philadelphia, PA 19106
Telephone: 215-597-4390 

 

WARNING LETTER
12-PHI-07


VIA UNITED PARCEL SERVICE

January 26, 2012
 


Mr. Dennis M. McGrath
President and Chief Executive Officer
ProCyte Corporation
147 Keystone Dr.
Montgomeryville, Pennsylvania 18936-9638


Dear Mr. McGrath:


During an inspection of your firm located in Montgomeryville, PA, on August 1 through 22, 2011, investigators from the United States Food and Drug Administration (FDA) determined that your firm manufactures wound and burn dressings, including the lamin Wet Dressing (marketed by your firm as GraftCyte Moist Dressing), lamin-2 Hydrating Gel (marketed by your firm as Complex Cu3 Intensive Hydrating Gel), and lamin Gel Wound Dressing (marketed by your firm as lamin Hydrating Gel) 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.


Quality System Violations


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 (Dennis M. McGrath, President and Chief Executive Officer) dated September 12, 2011, concerning our investigators' observations noted on the Form FDA 483 (FDA 483), List of lnspectional Observations, that was issued to your firm. We address this response below, in relation to each of the noted violations. Violations of Part 820 include, but are not limited to, the following:


1. Failure to adequately ensure that, when the results of a process cannot be fully verified by subsequent inspection and test, the process is validated with a high degree of assurance and approved according to established procedure, as required by 21 CFR 820.75(a).


For example, your firm did not ensure that the packaging and sterilization processes for the sterile GraftCyte Moist Dressings were adequately validated, in that packaging validation operations did not include (b)(4) of the GraftCyte moist dressing packaging to ensure that the (b)(4) process does not impact the finished-device pouches, which are (b)(4) that contain (b)(4)

We reviewed your firm's response and cannot determine its adequacy at this time. You confirmed that the contract manufacturer, (b)(4) has documented controlled process standard operating procedures (SOPs) and specific manufacturing process instructions for the device products covered during the inspection. These documents include (b)(4) and (b)(4) both before and after the product-(b)(4) operation. However, there was no documentation provided to show that a validation study was actually conducted. Your firm acknowledged that the processes above require validation and stated an intent to have the protocols and the validation studies completed by December 23, 2011.


Additionally, your firm stated that it would review validation documentation for the other products and carry out any additional validations as needed by October 07, 2011. Your firm also stated that it would conduct training to assure that relevant employees understand when and how to conduct process and product validations by October 14, 2011.


2. Failure to establish and maintain adequate procedures to control products that do not conform to specified requirements, as required by 21 CFR 820.90(a).

 

For example, the final acceptance activities documented with the device history records for GraftCyte moist dressings (lot #'s (b)(4) showed that product (b)(4) had been identified during inspection of finished products received from (b)(4). The defects included (b)(4), a (b)(4) gauze pad, and some pads that were (b)(4) instead of (b)(4). After conducting heightened inspection activities, which included either 100% visual inspections or additional destructive testing based on a predetermined sample plan, your firm (b)(4) the remaining products. However, your firm failed to document the (b)(4) on its (b)(4) form, as required by your firm’s procedure.
 
We reviewed your firm's response and cannot determine its adequacy at this time. Your firm said that it would document the (b)(4) of the referenced (b)(4) product and the associated approval on the correct form per SOP (b)(4). Your firm stated that the root cause of the failure to (b)(4) was (b)(4) per the procedure. Your firm also stated that it would retrospectively review the (b)(4) lots and fill out the correct form as part of the training process and review and revise (b)(4) to address potential problems, including a better definition of (b)(4) and the implementation of any necessary corrective actions.” Your firm stated that it will also retrain relevant employees on (b)(4) with appropriate documentation of this training. This corrective action was targeted for completion by October 14, 2011.
 
3. Failure to establish and maintain adequate procedures to ensure that all purchased or otherwise received product and services conform to specified requirements, as required by 21 CFR 820.50. For example:
 
(a) A review of the signed supplier agreement, dated December 03, 2007, between your firm and (b)(4) did not define specific responsibilities for sterilization of the GraftCyte moist dressings, including: (b)(4) requirements for (b)(4) of the product, (b)(4) and documentation of (b)(4).
 
(b) The (b)(4) procedure (DOC. NO.: (b)(4)) states that it is the responsibility of Quality Assurance to schedule, perform, or contract the performance of internal and external audits. Your firm has not conducted an on-site supplier audit of its contract manufacturer for three currently-marketed medical device products (GraftCyte Moist Dressings, Complex CU3 Intensive Hydrating Gel, and lamin Hydrating Gel) as part of confirming that product specifications are being consistently met and that adequate quality system procedures are in place that address the requirements of the Quality System regulation.
 
(c) The requirements to be met by suppliers are not clearly defined. The specifications for (b)(4) in (b)(4) and (b)(4) have not been established. Testing for (b)(4) is not conducted as part of your firm’s acceptance activities. This material is a component in the manufacture of your firm’s products including GraftCyte Moist Dressing, Lamin Hydrating Gel, Complex Cu3 Intensive Hydrating Gel, for which intended uses include dressing of open wounds and first and second degree burns and application after dermatologic skin procedures.
 
We reviewed your firm’s response and cannot determine its adequacy at this time. Your firm requested that (b)(4) enter into a revised agreement that includes validation requirements for (b)(4) of the product and (b)(4) on a (b)(4) basis in those (b)(4) in which the product is manufactured. (b)(4) also stated that it would supply copies of the (b)(4) reports to your firm and document the (b)(4) and (b)(4) on the Certificate of Analysis. The revised agreement was scheduled to be completed by October 28, 2011.
 
Additionally, your firm was scheduled to visit (b)(4) in October of 2011.  The purpose of this visit was to conduct an audit to assure that your firm’s product specifications are consistently being met and that there is adequate quality system compliance, and to verify progress and completion of other required tasks. Your firm also stated the following:


• It would review all other supplier agreements and external audit plans for adequacy. Any deficiencies found would be corrected and documented by October 14, 2011.


• It would review and revise all specifications relevant to the device products to include the requirement and methodology for adequate testing for (b)(4) The review would include determination and documentation of acceptable limits of (b)(4) and characterization of the (b)(4) Additionally, relevant employees would be retrained on these activities.


• It contacted the supplier, (b)(4) to determine if it was in possession of any data relevant to (b)(4) or (b)(4) responded that it routinely tests for (b)(4) and provided data from a recent lot of product. (b)(4) sent Certificates of Analysis showing the (b)(4) component of the (b)(4) and the (b)(4) tests at (b)(4) pure with no (b)(4) greater than (b)(4) (b)(4) also indicated that it tests for possible (b)(4) The preliminary review of the data by your firm's resident expert shows that the levels of (b)(4) are very low and adequate for their intended use.


(b)(4) does a (b)(4) and (b)(4) count and (b)(4) types of bacterial tests (b)(4) for (b)(4). Your firm stated that it would characterize the (b)(4) activity, including confirming the suitability of (b)(4) purity of the (b)(4)


• It would take samples of each type of bulk (b)(4) develop a protocol, and send the samples to an independent lab to perform the (b)(4) testing and characterization. In addition, your firm would assist the independent lab in confirming the kind of concentrations of (b)(4) are acceptable to be applied to "broken skin." Your firm stated that its independent microbiology testing lab has confirmed the microbiology specification on its current parameters and determined that it has the capability to identify any microorganisms detected. These tasks were targeted for completion by December 23, 2011.

 

• Your firm is also looking into independent testing under USP (b)(4) of the USP (b)(4) and the (b)(4) and the products containing them.


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 failed to complete its complaint notification form as part of the documentation and investigation requirements for a complaint event (b)(4) received on July 15, 2009, for Complex Cu3 Intensive Hydrating Gel. The complaint was not evaluated to determine whether it represented an event that is required to be reported to FDA under 21 CFR Part 803, Medical Device Reporting.


Your firm's response to this observation appears to be adequate. Your firm stated that this product was officially discontinued as part of a planned removal of the product line on August 24, 2011, due to slow sales, and that no replacement has been planned.


Your firm's response stated that the product was not returned and that the complaint log lacked the customer's identity or phone number; therefore, your firm could not follow-up on the complaint. Additionally, your firm stated that there were not enough facts to determine whether this was a reportable event. It was determined that the reason for return, (b)(4) would not cause or contribute to a death or serious injury. Your firm stated that it would retrospectively create a complaint file for this event, including documentation of its medical device reportability determination. This corrective action was targeted for completion by September 23, 2011.


Further, your firm's systemic corrective action involved a complete (b)(4) of the complaint handling process and development of a corrective action plan to improve (b)(4) all complaint records. You stated this would include better instructions to record the complainant's name and phone number as part of the complaint log, and that there would be additional training and process analysis. These corrective actions were targeted for completion by October 28, 2011.


Medical Device Reporting Violations


Our inspection also revealed that your firm's wound dressings 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 as 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 adequately develop, maintain and implement written MDR Procedures, as required by 21 CFR 803.17. For example:


Your firm's MDR procedure fails to establish internal systems that provide for:


(1) Timely and effective identification, communication, and evaluation of events that may be subject to MDR requirements, as required by 21 CFR 803.17(a)(1). For example, there are no definitions of what your firm will consider to be a reportable event under 21 CFR Part 803. To facilitate the correct interpretation of reportable events and to assure the quality of MDR submissions, the procedure should include definitions based on Part 803.3 of the terms: become aware; caused or contributed; malfunction; MDR reportable event, and serious injury, and definitions of the terms reasonably known, found in Part 803.50(b), and reasonably suggests, found in Part 803.20(c)(1).


(2) A standardized review process or procedure for determining when an event meets the criteria for reporting under this part, as required by 21 CFR 803.17(a)(2). For example:


• There are no instructions for conducting a complete investigation of each event and evaluating the cause of the event.


• The procedure does not state who makes the decision for MDR reportability.


(3) Timely transmission of complete medical device reports, as required by 21 CFR 803.17(a)(3), including:


• The types of information to be included on the FDA Form 3500A;


• How your firm will submit all information reasonably known to it;


• The circumstances under which your firm must submit a supplemental or follow-up report and the requirements for such reports; and
 

• The address for submission of MDR reports: FDA, CDRH, Medical Device Reporting, P.O. Box 3002, Rockville, MD 20847-3002.


Your firm's procedure also fails to describe how it will address documentation and record-keeping requirements, as required by 21 CFR 803.17(b), including:


• Documentation of adverse-event-related information maintained as MDR event files;


• Information that was evaluated to determine if an event was reportable;


• 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


• Systems that ensure access to information that facilitates timely follow-up and inspection by FDA.


The adequacy of your firm's response cannot be determined at this time. Your firm stated that it will conduct a retrospective review to assess complaints for MDR reportability. It also stated that it will conduct training for MDR reportability. However, there is no evidence that your firm has completed its retrospective review of complaints and there is no evidence that training on MDR reporting has taken place.


If your firm wishes to submit MDR reports via electronic submission it can follow the directions stated at the following URL:


http://www.fda.gov/Forlndustry/FDAeSubmitter/ucm107903.htm


If your firm wishes to discuss MDR reportability criteria or to schedule further communications, it may contact the MDR Policy Branch at 301-796-6670 or by email at MDRPolicy@fda.hhs.gov.


Unapproved Device Violations


Our inspection also revealed that the lamin Wet Dressing (Copper Saline), lamin Gel Wound Dressing, and lamin-2 Hydrating Gel are 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 (IDE) under Section 520(g) of the Act, 21 U.S.C. § 360j(g) for the changes in intended use discussed below. The lamin Wet Dressing (Copper Saline), lamin Gel Wound Dressing, and lamin-2 Hydrating Gel are 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 devices into commercial distribution with the changes in intended use discussed below, as required by Section 510(k), 21 U.S.C. § 360(k), and 21 CFR 807.81 (a)(3)(ii).


Specifically:


(a) The lamin Wet Dressing was cleared under K964468 with the following indications: "a hydrogel for the dressing and management of both graft recipient and donor sites, postoperative incisions, pressure ulcers, diabetic ulcers, stasis ulcers, 1st and 2nd degree burns, arterial ulcers, pressure sores, and skin conditions associated with peristomal care. The dressing is intended to cover a wound or burn on a patient's skin, provide a moist wound environment, absorb wound exudate, and protect against abrasion, friction, desiccation, and contamination." However, your firm is marketing the device as part of the GraftCyte Men's Kit for therapeutic claims that represent major changes in intended use. For example, the GraftCyte Men's Kit product brochure includes the following claims:


"crusting, itching and redness are minimized, comfort is restored ... edema progressively diminishes ... "


"the clinically proven GraftCyte Sytem (sic) is enriched with patented GHK Copper Peptide Complex ... leading to faster healing of transplants, and earlier regrowth of the hair shafts."


"Intended for post-operative topical treatment of hair transplant surgery graft sites" (GraftCyte Moist Dressings Containing Copper Peptide)


FDA acknowledges your written response, dated September 12, 2011, in which you state that your firm has discontinued the GraftCyte product brochure and that it will limit claims on product labels and inserts to those claims that are 510(k)-cleared by the FDA. We cannot determine the adequacy of your firm's response at this time.


(b) The lamin Gel Wound Dressing was cleared under K953853 with the following indications: "a hydrogel for the dressing and management of pressure ulcers, diabetic ulcers, stasis ulcers, 1st and 2nd degree burns, arterial ulcers, pressure sores, donor sites, postoperative incisions, cuts, abrasions, irritations of the skin, and skin conditions associated with peristomal care. The hydrogel dressing is intended to cover a wound or burn on a patient's skin, provide a moist wound environment, absorb wound exudate, and protect against abrasion, friction, desiccation, and contamination." However, your firm is marketing the device as part of the GraftCyte Men's Kit for therapeutic claims that represent major changes in intended use. For example, the GraftCyte Men's Kit product brochure includes the following claims:


"crusting, itching and redness are minimized, comfort is restored ... edema progressively diminishes .... "


"the clinically proven GraftCyte Sytem (sic) is enriched with patented GHK Copper Peptide Complex ... leading to faster healing of transplants, and earlier regrowth of the hair shafts."


"Intended for post-operative topical treatment of hair transplant surgery graft sites" (GraftCyte Moist Dressings Containing Copper Peptide)


FDA acknowledges your written response, dated September 12, 2011, in which you state that your firm has discontinued the GraftCyte product brochure and that it will limit claims on product labels and inserts to those claims that are 510(k)-cleared by the FDA. We cannot determine the adequacy of your firm's response at this time.


(c) The lamin-2 Hydrating Gel was cleared under K970153 with the following indications: "lamin-2 Hydrating Gel is intended to be used for the dressing and management of pressure ulcers (stage I-IV), diabetic ulcers, stasis ulcers, 1st and 2nd degree burns, arterial ulcers, pressure sores, cuts, abrasions, irritations of the skin, and skin conditions associated with peristomal care. The dressing is intended to cover a wound or burn on a patient's skin, provide a moist wound environment and protect against abrasion, friction, desiccation, and external contamination." However, at the time of the inspection, your firm was making claims that represent major changes in intended use. For example, the Complex Cu3 product brochure includes the following claims:


"Helps eliminate crusting and scabbing, relieves itching and tightness ... stimulates collagen, improves the skin's elasticity, combats free radical and oxidative damage" and " ... helps restore the skin's ability to repair itself".


FDA acknowledges your written response, dated September 12, 2011, in which you state that your firm has discontinued marketing the Complex Cu3 Intensive Hydrating Gel (cleared via K970153 under the name lamin-2 Hydrating Gel), effective August 24, 2011.
 

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, as indicated in 21 CFR 807.81(b). The kind of information that 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.


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 (15) 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: U.S. Food and Drug Administration, U.S. Customhouse Room 900, 200 Chestnut Street, Philadelphia, PA 19106, Attention: Kristina Donohue, Compliance Officer. If you have any questions about the contents of this letter, please contact: Kristina Donohue at Kristina.Donohue@fda.hhs.gov or 215-717-3078.


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 lnspectional 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.


Sincerely yours,
/S/
Kirk Sooter
District Director
Philadelphia District Office