Archives: Case Studies

Strategy for Pharmaceutical Submission

Background

A major manufacturer of intravenous (IV) pharmaceuticals was experiencing product leakage issues with its IV bags. The company’s quality and engineering teams identified a solution involving a change to the resin ratio used in the bags to improve strength and eliminate leaks. However, due to unclear FDA guidance documents, the regulatory team was uncertain about the appropriate submission pathway and was preparing a time-consuming Prior Approval Supplement (PAS).

RCA Approach

Regulatory Compliance Associates® Inc. (RCA) was brought in to assess the proposed corrective action and determine the optimal regulatory strategy. RCA’s consultant reviewed the changes and confirmed that the improvement came from adjusting the ratio of existing resins—without introducing any new materials. Based on this analysis, RCA recommended submitting a Changes Being Effected in 30 Days (CBE-30) supplement rather than a PAS, significantly reducing the regulatory timeline.

Result

After consulting with the FDA and confirming agreement with the strategy, the manufacturer submitted a CBE-30. This approach enabled the company to swiftly resolve product complaints, avoid disruptions in supply, and maintain product revenue—without the delays associated with a PAS submission.

21 CFR Part 11 Gap Analysis

Challenge

In preparation for an upcoming FDA audit, a pharmaceutical-grade bulk chemical manufacturer engaged RCA to conduct a comprehensive gap analysis assessing compliance with 21 CFR Part 11 requirements for Electronic Records. RCA was tasked with evaluating eight quality software systems and twenty-nine laboratory software systems to identify gaps and ensure regulatory readiness.

RCA Approach

RCA designed a structured assessment strategy that included targeted interviews with key stakeholders for each software system to evaluate compliance with specific 21 CFR Part 11 requirements. A risk assessment was then conducted to identify high-risk systems based on their level of compliance. Using the results of this analysis, RCA prioritized the software systems and developed a risk-based remediation plan to ensure full regulatory compliance across all platforms.

Result

RCA presented the results of the gap assessment, risk analysis, and system prioritization to the client’s leadership team. Within a month, the FDA conducted an inspection and reviewed the assessment findings along with the remediation plans. Based on the thoroughness and clarity of the approach, the FDA concluded that the client had sufficiently demonstrated progress toward compliance with 21 CFR Part 11—and issued no regulatory observations.

FDA Warning Letter Response and Remediation

Background

A mid-sized company received a 10-item FDA Form 483 and submitted an initial response. However, the response was followed by the issuance of a Warning Letter, leaving the company uncertain about how to effectively engage with the FDA moving forward. The agency had clearly outlined its expectations for the manufacturing of drug and device products at the site, and the management team—having already responded once—was unsure how to construct an appropriate and effective second response.

RCA Approach

Regulatory Compliance Associates® Inc. (RCA) developed a phased program to address both the FDA Warning Letter and broader quality system deficiencies. In Phase I, RCA delivered a detailed response to the Warning Letter, including aggressive timelines and objective evidence demonstrating completed corrective actions. Phase II focused on a comprehensive assessment and remediation of the overall quality system.

RCA created a detailed implementation plan featuring realistic yet ambitious milestones, clearly defined roles and responsibilities, and interdependent task structures to ensure accountability. To lead the initiative, RCA assigned a certified Project Management Professional (PMP), supported by engineers with deep expertise in quality systems and manufacturing engineering, who worked collaboratively with the client’s internal team to drive execution.

Result

The FDA received the Warning Letter responses, timelines, and supporting objective evidence favorably, leading to closure of the Warning Letter within just six months. The best-in-class project management practices applied during Phase II played a critical role in the successful, on-time, and on-budget achievement of key quality system compliance milestones.

Document Management System

Background

Qualitest, a leading manufacturer of high-quality, affordable generic pharmaceuticals, aimed to improve the efficiency of its document change process. At the time, document changes were averaging 50 to 60 days to complete. The company sought to implement a compliant, streamlined process with significantly faster turnaround times.

RCA Approach

Regulatory Compliance Associates® Inc. (RCA) was engaged to assess and enhance the existing document change process. RCA quickly conducted a comprehensive analysis to identify bottlenecks and areas for improvement. In collaboration with Qualitest, RCA revised the applicable standard operating procedures (SOPs) to support a more efficient workflow. Training was conducted for both end users and management, and the new SOPs were piloted to evaluate effectiveness in real-time operations.    

RCA’s wealth of knowledge about our document management system & document control helped us speed up our process, halving the turn-around time.

Result

The pilot was successful and provided valuable feedback for minor refinements. Following the pilot, the improved process was implemented company-wide. As a result, document changes at Qualitest are now completed in under 30 days on average—and often even faster—representing a significant gain in operational efficiency while maintaining full compliance.

Improved Product Release Cycle Times, Improved Bottom Line

Background

A generic pharmaceutical manufacturer was interested in applying lean principles to the operation of the Quality team, with the objective to reduce the product release time frame. However, they lacked internal experience to embark upon this initiative.

The client engaged RCA’s experts to enhance operational efficiency across manufacturing processes, streamline batch record review, and accelerate product release to the distribution network.

RCA Approach

RCA’s experts employed process mapping to uncover redundancies, inefficiencies, and key areas for improvement. Collaborating closely with company process owners, they systematically designed and implemented optimized workflows across both Quality and Manufacturing operations.

Result

RCA experts successfully streamlined the product release process from 30 days to just four. This significant reduction in cycle time minimized the need to hold costly unreleased inventory, enabling the company to decrease its inventory investment while enhancing the speed and reliability of product delivery. Implemented across multiple manufacturing sites, this improvement had a substantial impact on cash flow—estimated by internal experts to be $50 million.*

Accelerating the movement of work-in-progress inventory into finished goods allowed the company to reduce carrying costs and optimize floor space utilization. The shortened product release cycle also led to fewer back orders and minimized short-dating issues. Furthermore, for certain export markets, the improved timeline enabled the company to shift from costly air freight to more economical sea freight, further reducing distribution expenses.

*Cash Flow Improvement = product unit cost X # units produced/day X # days release cycle time improvement

 

Risk Management in Product Development and Manufacturing

Background

A global pharmaceutical and medical device manufacturer sought to enhance integration of risk management throughout the product lifecycle. The FDA had identified deficiencies related to risk management in several Form 483 observations. Additionally, the company required standardization of its product development process (PDP) across diverse business units and international sites.

RCA Approach

Regulatory Compliance Associates® Inc. (RCA) provided subject matter experts specializing in product development and quality system regulations. RCA authored a comprehensive portfolio comprising more than ten new PDP procedures and over thirty supporting templates, designed to be flexible enough to address drug and device development, design changes, line extensions, and OEM manufacturing. Training sessions were delivered at client locations across the United States and Europe to ensure consistent implementation.

Result

The new PDP process was successfully implemented, incorporating risk management at multiple key stages:

  • Risk Management Planning is a part of Design & Development Planning
  • Risk Analysis is an input to Verification and Validation test planning
  • Risk Analysis via Process FMEA is required for OEM business
  • Risk Reports and Risk Benefit Analysis are inputs to Final Design Review
  • Risk Analysis and Reports reviewed periodically based on internally generated data and data received from customers (i.e., complaints)