Audit of medical device manufacturer yields warning letter, 4-item 483.

IND Diagnostics, Delta, BC, Canada, Center for Devices

IND Diagnostics, Delta, BC, Canada, was hit by the Center for Devices with a four-item 483 and subsequent warning letter for "objectionable practices" in the firm's product and process controls and validation activities.

IND Diagnostics is a manufacturer of a variety of in-vitro diagnostic devices for clinical diagnostic testing, including the MiniStrip HCG One Step Urine Pregnancy Test Strip.

In addition, a Dec. 23, 2003, warning letter cited IND Diagnostics for "failure to validate processes and document the validation activities and results, including the date and signature of the individuals approving the validation and, where appropriate, the major equipment validated."

For example, an undisclosed product was "manufactured in various stages that begin with the cutting and measuring of the membrane material," the warning letter noted. "After the membrane dimensional attributes [were] obtained, the resultant membrane materials [were] washed and dried."

The purified membrane was then coated with antibody and incubated for a specific time. Next, the treated membrane was blocked to properly disperse the coating materials, and the blocked membrane was tested to ensure uniformity of the coating materials. "There is no documentation indicating that any of the processes described have been validated," the warning letter noted.

The firm's written response to the agency stated it intended to document all in-process quality inspections regularly and provide a library of specific, quality-testing data for the agency's review. FDA said the response was inadequate because the firm "did not provide documentation to FDA that this plan is completed."

Next, IND Diagnostics was cited in the 483 because "appropriate design and installation of manufacturing equipment have not been ensured." For ex-ample, there was no documentation that showed that an undisclosed water system used in the product re-agents, buffers, conjugate and controls used in the manufacture of the MiniStrip HCG Urine Pregnancy Test would consistently produce deionized water that met pre-determined quality attributes.

The warning letter cited the firm because it did not establish and maintain procedures that ensured that all inspection, measuring and test equipment was suitable for its intended purpose and could produce valid results.

For example, "the laboratory Mettler scale was observed bearing a calibration date indicating repeat calibration should have been performed four months prior to this inspection."

Additionally, "certain measuring equipment is not suitable for its intended purposes or capable of producing valid results," the 483 stated. For example, there was no calibration sticker on the pH meter used to conduct pH readings for reagents, conjugate, buffers and controls. There were also no documented re-cords for calibration available for review.

The company replied: "[We have] set up a monthly calibration procedure ... and label the device indicating the status of calibration. Training will be provided to employees to reinforce the practice."

Lastly, the report cited IND Diagnostics be-cause "acceptance procedures, tests or other verification activities are not complete." Specifically, there was no documentation that demonstrated the shelf- life for production reagents, controls or conjugates.

The firm responded: "Shelf-life for all solutions that are used for production purposes and their acceptance criteria will be documented in a procedure describing the method for routine testing. The preparation of solutions will be validated according to documented acceptance criteria."

The agency replied: "Your firm has not pro-vided to FDA documents to show that a system for stability testing has been put into place."

The investigators also reviewed the company's written procedures for all of their CAPAs [corrective and preventive actions]. They found that the firm's procedures defined all minimal data sources needed to conduct their evaluations and dispositions. "All corrective actions are thoroughly documented, including any justification not to take any corrective measures," the EIR noted.

IND Diagnostics, Delta, British Columbia, Canada, 6/2-5/03, Doc. 109644M, $7.00 plus retrieval.