Warning Letter Analysis: Device Companies, Tissue Bank Hit Hard for Deficiencies

The US Food and Drug Administration's (FDA) newest batch of warning letters was released on 29 May 2012, and some familiar faces have come under further scrutiny.

Medical device manufacturer McNeil PPC, a subsidiary of Johnson & Johnson, was hit with a lengthy list of claims by FDA, which said the firm is manufacturing no fewer than ten adulterated products. Three of the company's Pennsylvania facilities are currently the subject of an FDA consent decree after the facilities repeatedly experienced manufacturing deficiencies and "several extensive recalls." The company's recent warning letter is extensive enough to draw parallels to the deficiencies which lead to the consent decree.

Medical device manufacturers Advanced OrthoPro Incorporated and Lebanon Corporation Incorporated also received citations for Quality System Regulation (QSR) deficiencies, while tissue bank company Gramercy Fertility Services was found to have violated human cells, tissues and cellular and tissue-based product (HCT/P) regulations.

McNeil PPC (Medical Device)

Johnson & Johnson subsidiary McNeil is back in FDA's warning letter spotlight after an inspection found its Skillman, New Jersey facility to be manufacturing adulterated products and an unapproved product.

No fewer than ten products manufactured by McNeil were found by FDA to have been manufactured without being in accordance with current good manufacturing practices (CGMP). These products include a wide range of "K-Y" personal lubrication products, Visine eye drops, O.B. Tampons, Reach Floss and Stayfree and Carefree Menstrual Napkins.

FDA investigators claim McNeil failed to establish or maintain procedures for receiving and processing dozens of complaints related to its products and failed to investigate a number of complaints related to products consistency and quality.

McNeil was additionally cited by FDA for lacking a premarket approval for its K.Y. Liquibeads Vaginal Moisturizer product, and failing to notify the agency of intent to distribute the product after making "significant changes" to both the product's physical characteristics and labeling.

FDA further contends McNeil failed to establish a designated process for handling complaints requiring FDA notification-an offense FDA referred to as "repeated."

The company also failed to document design review results, failed to establish procedures for implanting corrective and preventive action (CAPA), failed to report potential serious adverse event cases to FDA, and failed to a supplemental report to FDA as required after information not initially known to McNeil became available.

The Lebanon Corp., Inc. (Medical Device)

In a 17 May warning letter to Lebanon Corp sent by Glenn Bass, District Director of FDA's Detroit District Office, FDA cited the company for manufacturing adulterated devices as the result of manufacturing deficiencies.

Among the deficiencies cited:

• The company is making "major modifications" to the device's FDA-approved claims on its website.
• The company is selling its Honan Intraocular Pressure Reducer device without a pressure relief valve-a state or sale not cleared by FDA.
• The company has instructions contained with its device describing how to sterilize the device despite it being FDA-approved as a single-use sterilized device.
• The company manufactured nearly 1,700 devices which failed inspection in one form or another, but the company did not implement CAPA procedures to determine how to stop future device failures.
• The company did not establish a procedure for handling complaints or adverse events despite receiving nearly three dozen reports between 2007 and 2012.
• Failure to establish procedures to control non-conforming products, failure to establish design change control procedures, failure to establish or maintain adequate data referencing specific quality requirements and failure to exercise proper document controls.
• Lebanon maintained a device master record without any dimensional specification and tolerances for assembly components.
• Lebanon's management was found to be deficient in its executive responsibility to review the suitability and effectiveness of the devices' respective quality systems.
• The company failed to establish the training needs and training requirements for site personnel.

Gramercy Fertility Services (Blood and Tissue Products)

In an 18 May letter to Gramercy Fertility Services, FDA's District Director for New York, Ronald Pace, alleges the company is guilty of "significant deviations" from HCT/P regulations for biological products.

Gramercy's New York-based facility purportedly failed to screen donors for communicable disease such as transmissible spongiform encephalopathy (TSE) or Creutzfeld-Jakob disease. At least seven instances were noted by FDA to have occurred since August 2011. Other donors who disclosed activities which could have resulted in certain risks did not receive proper follow-up, including three donors who had received body piercings and tattoos. The facility should have questioned all three regarding if sterile procedures were used while obtaining the body modifications, noted FDA.

Gramercy was further cited for deficiencies including failure to document donor eligibility, failure to maintain fully legible or accurate records and failure to establish and maintain consistent testing procedures.

Advanced OrthoPro, Inc. (Medical Device)

Indianapolis-based medical device manufacturer Advanced OrthoPro received an 18 May warning letter from FDA in which it is cited for a litany of CGMP deficiencies related to its AOI Cranial Remolding Helmets.

FDA alleges OrthoPro was deficient in its failure to establish quality assurance and control procedures to ensure its products conform to specifications, failure to maintain raw materials standards or supplier controls, failure to test or verify incoming raw materials, failure to establish methods to evaluate device complaints, failure to adequately maintain a device master file (DMF), failure to maintain Device History Records (DMRs) and failure to identify staff training needs and requirements.