Medical Device Daily Washington Editor
A July 2 FDA warning letter to Anika Therapeutics (Bedford, Massachusetts) ran to eight citations for the firm's manufacture of several products for orthopedic applications, including the knee joint therapeutic Orthovisc, and the news has probably hit some of the firm's investors, which according to the web site for Mutual Fund Facts About Individual Stocks (Long Beach, California) includes Ashford Capital Management (Greenville, Delaware) and Crown Capital Management (Greenbrae, California).
Crown purchased 37,000 shares of the company's stock on July 22. Whether the warning letter will give investors the jitters remains to be seen, but some of the citations suggest a lack of familiarity with the quality systems (QS) regulations or a substantially different view of the demands of those regulations compared to FDA.
The first citation states that the quality department "does not observe critical steps in the manufacturing process" such as environmental monitoring of aseptic operations. The warning letter states that there was no "basic hand-washing sink outside your sterile gowning room, even though your own standard operating procedure requires hand-washing to be complete."
This was determined by the company's quality assurance staff to be acceptable, but FDA writes that the decision leaves the agency "concerned that an effective quality system has not been implemented and maintained." The warning letter implies that Anika installed a hand-washing sink outside the gowning room with the response that "we ask that you describe the changes being made to your quality system that will prevent such QS violations from recurring."
FDA deemed the firm's media fill validations to be less than adequate because the validation tests "do not incorporate the numerous manual aseptic steps performed, nor do they incorporate the same equipment and times that are routinely used during the actual manufacturing process." Along with this citation was one that noted a failure of qualification of "critical areas" - presumably a reference to the media fill room - "that did not include evaluation of unidirectional air flow patterns under dynamic conditions with equipment in place."
Again, the firm's response evidently included an immediate correction that FDA found adequate, but the agency requested "that you address how you plan on preventing these validation lapses in the future."
FDA also hit the firm's complaint handling procedures in connection with a complaint received in August 2006. The warning states that Anika did not attempt to obtain a specific diagnosis from the complainant, who was said to have experienced inflammation. Despite the lack of a specific diagnosis, "the complaint was closed on March 5, 2007."
Anika CFO Kevin Quinlan told Medical Device Daily that the citations in the warning letter "are not about safety and efficacy, but refer to specific issues with regard to compliance." He said "moving forward, we continue to work closely with FDA" and that the company "look[s] forward to [its] next inspection when our corrective actions have been completed." However, no inspection has been scheduled.
Quinlan declined to respond to a question about whether any new quality control staff had been hired subsequent to the inspection.
Carematix reverses field on indications
A July 3 FDA warning to cardiac monitor systems maker Carematix (Chicago) hints at a change of heart on the part of the firm about the intended use of the Carematix wellness system, as well as some miscommunication within the company or with the agency.
On the other hand, the agency hammered the company's systems for corrective and preventive action (CAPA) with four citations, along with one citation for design control procedures.
According to the warning letter, the agency granted a 510(k) for the device this past January after the company notified FDA the previous month that it wanted to withdraw the indications of spirometry and peak flow measurements "since the spirometer used with your predicate device had been discontinued." The reference to a spirometer was to the Piko-1 Ferraris electronic peak flow meter with a wireless adapter. However, the firm apparently has promoted the Carematix with those indications, thus landing it a citation for promotion of unapproved uses.
The inspection also found that the company's device design documents "did not include dates as to when design activities were performed, thereby precluding any effective design review." The company's response came up short "because you have not completed the process of reviewing and updating" the design history file or an update to controls for those files. FDA also cited a lack of design verification/validation procedures.
The firm's files for CAPA caught the FDA investigator's attention. The warning letter states that 50 CAPA reports filed between August 2007 and this past February "remain open even though the action plan due date has passed for some of these. The agency states that Carematix "failed to identify or implement the actions needed to correct the quality system problems identified" that would allow systemic corrections that would prevent recurrence.
The warning letter addressed the company's response to the inspectional findings, including that Carematix has "made some personnel changes" and is "conducting internal audits to verify the effectiveness of your corrective actions," but FDA lamented the fact that the company has "not yet completed these actions or provided documentation of their completion."
The warning letter also notes a series of 24 complaints received in 2007 for "failure of the Carematix Wellness System to meet specifications." According to FDA, the company "failed to investigate or close any of them by the time of the inspection in March 2008." The company apparently proposed to rewrite its CAPA procedures and retrain employees, and claimed to have closed the 24 complaints, but again, the lack of documentation left the response without FDA's approval.
Among the balance of the total of nine citations were those for medical device reports, lack of finished device acceptance activities and lack of documentation of vendor qualification. At press time, the company had not responded to a call for comment.
Volk nets eight hits in warning
Contact lens makers are in the news of late, but not because of the July 7 FDA warning letter to Volk Optical (Mentor, Ohio). All the same, the maker of diagnostic contact lenses and lenses for vitrectomy (removal of the fluid between the lens and the retina of the eyeball) netted eight citations as a result of the April-May FDA inspection. One of those was a lack of documentation of a "correction and removal action for the slit lamp lens to FDA." The warning letter offered no further detail on this finding other than to note that the agency found Volk's June 30 response to this finding adequate.
The balance of the warning letter exhibits little in the way of a trend. The first citation is for failure to trend the quality data sources such as complaints, non-conforming devices and service data. However, FDA found the firm's proposed corrections adequate.
Complaint handling cropped up in that "19 of the 19 complaints reviewed had incomplete failure investigations." The warning letter offered no detail other than to state that the 19 complaints were pulled from a total of "1,070 complaints received in the last year," and that the agency found the company's proposed corrections satisfactory.
The warning letter also stated that Volk failed to validate "ultrasonic cleaning, polishing, sealing, gluing/curing and bonding processes used in the production of your class II lenses." FDA asked for a summary of the company's proposed validation program "to assure all applicable processes are validated."
The company's design controls for an unnamed wide-field contact lens were also cited as lacking. FDA states, "Your only documented review for the wide field lens project was conducted prior to the approval of design inputs." Among the other three findings under this heading was that "the design verification tests for outside diameter of glass, field of view and spatial resolution were out of specification and performed prior to the design inputs being approved." FDA requested further documentation for the proposed correction, scheduled for completion by Dec. 5.
Volk's president, Pete Mastores, told MDD that the firm is focused on "properly resolving the issues" and that "we see it as an opportunity to improve our business."
He said he could not be sure how much time has passed since the previous inspection, but acknowledged, "It has been an extended period of time." Mastores also said that among the other personnel additions the company is considering, "we're in the process of looking at hiring more quality control/regulatory affairs staff."