Opinion ID: 223134
Heading Depth: 3
Heading Rank: 1

Heading: Express2 Phase One: Reducing Process Variability

Text: BSC began selling the Express2 system outside the United States in June 2001, and received FDA approval for U.S. sales in September 2002. The system was manufactured at company facilities in Maple Grove, Minnesota, and Galway, Ireland. In early 2003, BSC received 11 reports of complaints that the balloon on Express2 devices had not deflated, including 3 from the same manufacturing lot. While BSC had received occasional complaints of this problem since the product's launch, the increased rate and the existence of multiple no-deflates from the same batch caused BSC to conduct an inquiry. Multiple-complaint lots meant that the problem was not dispersed throughout all devices, and consequently that the normal method of calculating frequency did not apply. BSC initiated a Site Level Correction Action (SLCA) at Maple Grove led by Paul Weiss, and a corresponding Corrective and Preventative Action (CAPA) at Galway led by Niamh O'Byrne. SLCA and CAPA investigations are commenced to investigate issues that are systemic or could disrupt business operations. As part of their investigations, Paul Weiss and Niamh O'Byrne opened a Product Inquiry Report (PIR). A PIR is used to investigate and make recommendations for in-house actions or field actions to BSC's Field Action Committee (FAC), which has ultimate responsibility for instituting field actions such as recalls. Although the multiple-batch no-deflate complaints were about Express2, Taxus (which was only being sold outside the United States at the time) was included in the PIR because both systems were built using the same Express2 catheter. On May 15, 2003, the PIR team issued a report on the primary cause of the no-deflate problem. The team found that the problem was due to a condition known as focal necking or focal neckdown, where the distal outer (the portion of the catheter that is welded to the balloon) becomes elongated or stretched, preventing the withdrawal of the fluid used to inflate the balloon. The team further found that this focal necking had two primary causes: (1) excessive heat at the laser bond of the balloon and the distal outer, which could be caused by a laser that was too hot or misaligned, and (2) a subsequent excessive tensile force exerted in the area of the bond, which could occur either during or after manufacturing. While the team could not identify the specific cause of the tensile force, it was able to identify several in-house actions to prevent or lessen the incidence of focal necking. To address issues with the laser weld, it recommended reducing the laser energy settings, increasing the magnification of the alignment camera, and retraining operators. For the same reason, the team also recommended using only distal outers manufactured in Maple Grove, which were found to be more robust than those manufactured in Galway, and launching an investigation to understand why the Galway distal outers appeared more prone to focal necking. The PIR team also reported on the frequency of the no-deflate issue. For Express2 devices manufactured in Galway, it found twenty no-deflates out of over 260,000 revenue shipments, with two lots producing three complaints each; for those manufactured in Maple Grove, it found only one no-deflate. [2] For Taxus devices, which were only manufactured in Galway at the time, it found zero no-deflates out of over 31,000 revenue shipments. Given this low rate of occurrence combined with the limited severity in all but one case, the PIR team concluded that [n]o field action is recommended at this time. The team was asked at a May 22 meeting to determine the scope of the no-deflate issue in case a recall was needed, and it found no factors that could be used to identify some devices as being higher-risk. It considered data on numerous parameters of the focally necked devicesincluding laser weld, elongation, type of resin used, and extrusionsbut found no correlations from which to scope the problem. On May 23, the team issued a PIR with the same conclusions and recommendations that it had reached in the May 15 report. On May 27, the FAC accepted the PIR team's recommendations and conclusions. It agreed that a recall was not warranted at the time, finding that the product in the field was within all of its established specifications, the frequency of issues reported [from] the field were extremely low, and the consequences, while potentially severe in some cases are not outside those expected with this type of procedure. The Chairman of the FAC, Paul Sandman, later testified that the FAC did not institute a recall because there weren't any factors that indicated that these failures were caused by a manufacturing problem. The FAC also directed that the PIR be clarified to state that the issue involves units within specification, and indistinguishable from a visual standpoint, being subjected in the field to a level of tensile force exceeding that for which the product was designed. It is unclear whether this was meant to supplement, or replace, the PIR's statement that the tensile event may have also occurred during manufacturing. [3] In implementing the PIR team's suggestions, BSC sought to harmonize the robustness of the stent systems produced at Galway with those produced at Maple Grove. The changes focused on the properties of the distal outers and the proximal welding process. As to the proximal welding process, BSC increased the magnification used to line up the stent system components, making it identical with that in Maple Grove, and retrained the Galway operators on the proper alignment of the laser weld and the proper handling of the catheters to avoid tensile forces on the product. These changes were implemented in May. As to the quality of the distal outers, Galway immediately switched to using Maple Grove distal outers in its production, [4] and over the following three months, BSC implemented various changes to harmonize the manufacturing of distal outers at the facilities, including aligning their elongation testing equipment, extrusion parameters, and distal outer measurement methods. BSC also introduced changes to ensure that the area of the proximal weld was not exposed to excessive heat during laser welding, including implementing an in-process manufacturing acceptance criterion for the length of the weld (the Matte Finish Length). [5] Because none of these changes affected device design or performance specification, BSC determined that prior FDA approval was not required, and implemented them in accordance with its standard BSC Quality System procedures.