Bausch & Lomb, Rochester, NY, Oct. 31 (Atlanta).

During a March 22 through May 15 inspection of Bausch & Lomb's Greenville, SC-facility, FDA investigators determined the manufacturer of contact lens solutions was not in conformity with the current Good Manufacturing Practice (GMP) requirements of the QS regulation.

According to the warning letter, although the March-May 2006 inspection focused primarily on the MoistureLoc contact lens solution, the inspection also identified and documented significant QS regulation violations that were systemic and were relevant to all products manufactured at the Greenville, SC-facility.

Violations noted during the inspection included, but were not limited to, failure to establish design plans that described or referenced the design and development activities, and identified and described the interfaces with other groups or activities.

Specifically, the agency noted that the initial design plan for MoistureLoc contact lens solution began in 2001 and the formulation contained a different preservative than was later used by the company.

However, when Bausch & Lomb produced an alternate product project--ReNu with MoistureLoc Multi-Purpose Solution--alexidine was added to the same original design and development plan in 2004, but initial feasibility and risk-assessment still showed the two products with two preservative agents alexidine and the original, unnamed preservative, under one design project.

Bausch & Lomb was further cited for failure to adequately ensure that raw material specifications were determined and firmly established prior to process validation, and for failure to keep complete validation data for ReNu with MoistureLoc Multi-Purpose Solution.

Moreover, the agency noted that initial scale-up activities at the Greenville plant were performed in 2003 on an unnamed similar product utilizing the updated product formulation but was replaced with the original product formulation after white particles were noted on soft contact lens while performing a lens compatibility study. However, the validation data available indicated that cleaning of the bulk mix tanks and filling lines, the filling process, the hold time study, and purging processes were not revalidated after the alternate product was added. Chemistry testing was limited to the compounding batches and no USP sterility testing was performed for the scaled-up batches of ReNu with MoistureLoc Multi-Purpose Solution. Additionally, no hold time studies or purge evaluations were done; and, no tank or filter sterilizations were done for ReNu with MoistureLoc, although its ingredients are sterile additions.

FDA also pointed out that Bacteriostasis/ Fungistasis (B/F) testing was not performed for all validation runs as specified in the established protocol, and that for some filled bottles in batch 3, the release specification was subsequently lowered to meet an OOS on the lower end for osmolality at the time of fill.

Thus, Bausch and Lomb was cited for failure to establish procedures to ensure that the device design was correctly translated into production specifications and failure to establish procedures to ensure that the design requirements relating to a device included a mechanism for addressing incomplete, ambiguous, or conflicting requirements. Moreover, FDA noted, the company was not ensuring that formal, documented reviews of the design results were being planned and conducted at appropriate stages of the device's design development.

Additionally, the company was hit with failure to establish procedures for quality audits and conduct such audits to assure that the quality system was in compliance with the established QS requirements; failure to establish procedures to prevent contamination of equipment or product by substances that could reasonably be expected to have an adverse effect on product quality; and, failure to establish procedures to adequately control environmental conditions.

Other citations listed in the warning letter included failure to ensure that all equipment used in the manufacturing process met specifications and was appropriately designed; failure to document maintenance activities; and, failure to review, evaluate and investigate any complaint involving the possible failure of a device labeling, or packaging to meet any of its specifications. For example, FDA noted that the Fusarium keratitis investigation did not include sterility or biocidal testing for ReNu with MoistureLoc Multi-Purpose Solution product lots implicated in complaints received from Hong Kong, and that the firm had not performed sterility testing on the returned/retained samples in conjunction with the Fusarium investigation for complaints received from Malaysia and Singapore.

Finally, Bausch & Lomb was hit with failure to establish procedures to ensure that mix-ups, damage, deterioration, contamination or other adverse effects to product did not occur during handling; failure to establish procedures for the control of storage areas and stock rooms for product to prevent mix-ups, damage, deterioration, contamination or other adverse effects; and failure to submit a Medical Device Reporting (MDR) within 30 calendar days after receiving or otherwise becoming aware of information that reasonably suggested that a marketed device may have caused or contributed to a death or serious injury.

For example, although Bausch & Lomb received reports of Fusarium keratitis from Singapore's Minister of Health in February 2006 relating to ReNu with MoistureLoc Multi-Purpose Solution, none of the complaints were reported to the agency as of April 7.

The agency acknowledged that a quarterly update had been received from Bausch & Lomb on Oct. 12 and that the company had recalled all MoistureLoc contact lens solution worldwide to eliminate the serious risk to health associated with an outbreak of Fusarium keratitis. FDA added that it found Bausch & Lomb's response inadequate as the update only indicated that the company planned to audit for inconsistencies but did show any indication that the firm had completed any revisions or submitted them to FDA for review. AE, C-H, Design, E-M, MDR, OOS, QC/QS, Stab, Ster, Val; Doc. 14013W

Bausch and Lomb

* Neglected to perform testing for all validation runs.

* Failed to ensure that all equipment used in the manufacturing process met specifications.

* Failed to establish procedures for quality audits.