A Medical Device Daily
Warning letters are routinely posted at the FDA web site, which one assumes would serve as fair warning to makers of devices and diagnostics that there are some lapses you simply do not want to allow to persist. On the other hand, the steady stream of firms that receive warnings for garden-variety deficiencies seems to belie the notion that warning letters help to keep industry on its toes.
FDA’s July 17 warning letter to Nanogen (San Diego) addressed operations in the diagnostic maker’s Toronto location, and cited the firm for a dozen violations of good manufacturing practices (GMPs). However, the firm was apparently concerned about trade secrets if the heavy redacting of the warning letter’s content is any indication.
The first finding was that Nanogen failed to follow its own procedures for non-conforming products for monoclonal antibody production in that the company did not commence with a non-conformance report (NCR) for multiple lots. FDA acknowledged “the initiation of an NCR during and as a result of the inspection,” but said that “this correction alone is inadequate because there was no evaluation made for corrective and preventive actions” in systemic terms.
The warning letter said that Nanogen did not document a failure investigation into the lots of monoclonal antibody and did not document rework procedures or retests of the monoclonal antibody product.
FDA cited Nanogen for failure to perform installation qualification (IQ) studies and a validation for a bioreactor “which has been in the production area since” February 2006. A bioreactor was also the subject of a finding of failure to periodically inspect the reactor, although it is not clear whether this is the same bioreactor cited for the IQ finding.
One of the findings cited the company for failure of design control procedures to include “procedures for managing design changes” in the case of two design programs at the Toronto plant. Again, considerable detail was redacted from the warning letter.
SCM True Air Technologies (Louisville, Kentucky), snared a Sept. 24 warning letter for its production of air mattresses designed to help in the healing of decubitus ulcers, also known as pressure sores. The lead citation stated that SCM, “from 2005 to the start of this inspection ... manufactured approximately 400 low air-loss and alternating pressure mattresses” while having no procedures for corrective and preventive action or for control of non-conforming product.
The bullet-point warning letter also indicated that SCM had no procedures for in-process and finished product testing or for labeling activities. The company’s response was said to have indicated that it had put in place a quality system, but FDA requested a copy of those procedures and documentation to the effect that employees had been trained on those procedures.
In another finding, FDA said that a “review of delivery tickets from one rental customer between June of 2006 and June of 2007 by the FDA investigator revealed that there were 37 complaints by this customer” and that SCM did not review the complaints or establish a file for them. The agency indicated that the company’s response to this finding lacked sufficient information to determine the adequacy of the response. A similar conclusion was attached to a finding for lack of device history records for the mattresses, which also included a request for documentation of employee training on such matters.
The warning letter addressed to Zinnanti Surgical (Hershey, Pennsylvania), maker of the Bayonet electrosurgical pencil, presumably a device for cauterization of blood vessels, detailed three different FDA trips to the company’s plant in July and November 2006 and this past March, but despite the extensive interaction with the agency, the company ended up with eight unresolved deviations from GMPs.
In the first finding, FDA noted that Zinnanti did not validate a sterilization process for the Bayonet, which the company indicated in a December letter to the agency was “previously validated under a different company.” By the time of the March inspection, Zinnanti had not validated the sterilization despite having shipped two lots of the Bayonet. A May 5 letter to FDA was deemed inadequate “because the data for the sterilization process fails to include information specified in your protocol.”
Zinnanti was also said to have possessed no procedures for environmental monitoring in the manufacturing room for the Bayonet. According to the warning letter, Zinnanti responded in December to the effect that it had developed “written specifications for environmental controls and that bioburden testing will be done on samples from each production lot.” However, Zinnanti personnel evidently told the FDA investigator during the March follow-up that it had decided against the clean room “because the results of the bioburden testing came back low” and proposed that “wiping” the Bayonet would suffice. The investigator was said to have documented “organic material, hair and particles ... within several pouches of the units” during the March audit.
After listing the eight GMP problems, the warning letter detailed two problems with medical device reporting regulations (MDRs). According to FDA, Zinnanti had no procedures to establish whether a complaint was reportable as an MDR, and the firm’s December response included “no guidance on how to determine if a complaint is MDR-reportable.” Likewise, the firm’s May letter to the agency was deemed inadequate “because it does not reference MDR nor address how MDR events will be determined.”
FDA also cited Zinnanti for perhaps the most egregious violation of all, failure to file a PMA or a 510(k) for the device prior to distribution.