Our client, a medical device manufacturer specializing in global solid dose, parenteral, and cellular therapy, received a lengthy Form 483 and subsequent Warning Letter addressing the site’s aseptic manufacturing controls and practices, validation methodology, and quality systems. Upon receipt of the 483, Treximo was engaged to support the review of open CAPAs addressed during the investigation through a risk-based assessment within two months, as required by the FDA. While progressing with the quality improvement expectations of the Warning Letter, Treximo was further engaged to lead and support all improvement work streams.

Key Challenges

  • 1200 Open CAPAs required risk assessment, prioritization and project plans
  • 2011 Guidance for Process Validation had not been incorporated into site standards
  • Product requiring aseptic production was not qualified to be manufactured under aseptic conditions
  • Efficient return to normal site production was crucial

Treximo Solution

CAPA Review

The initial project scope was to review the current CAPA backlog and establish interim risk evaluation. While the backlog was initially thought to include a few hundred CAPAs, 1200 CAPAs were ultimately identified. This change in scope increased the workload significantly, as the original review timeline was predicated on the two to three hundred CAPA reviews. Despite the unforeseen expansion, the Treximo team supported the additional scope and provided review within the original deadline provided to the agency.

Workstream Management

During the CAPA review, the site received a Warning Letter subsequent to the initial Form 483. This revealed a significantly deeper need for a work plan that would properly support the quality system improvements required. Treximo was selected to provide leadership and SME support to the quality work streams identified, focusing on the following areas:

  • Management Controls
  • Validation
  • Facilities Improvement
  • Equipment Improvement
  • Quality Systems Redesign
  • Supply Chain and Manufacturing Systems
  • Backlog Reductions (Investigations, CAPAs, Complaints)

In total, Treximo deployed more than twenty resources to support site improvement initiatives. Work stream management provided project management and subject matter expertise to inform and establish realistic program timelines and approaches to risk mitigation and process improvement.


Today, the site is continuing to support quality improvement initiatives and has a remediation work plan in place for 2018. Treximo has partnered with the site’s leadership and subject matter experts as internal support for their remediation project, rather than a purely oversight directive. This has allowed the team to provide tactical subject matter expertise and solutions, delivering realized value to the client in fixing encountered challenges rather than a critique of processes and practices.