Archives: Case Studies

FDA 483 Warning Letter Remediation

Background

A Fortune 500 company received a Warning Letter from the FDA citing findings of device adulteration and misbranding, along with potential regulatory actions including product seizure, injunction, and civil monetary penalties. The Warning Letter followed the FDA’s determination that the company’s responses to specific FDA 483 observations were inadequate.

Regulatory Compliance Associates® Inc. (RCA) was brought in to provide leadership, subject matter expertise, and project management support to address the cited issues. Given the severity of the situation, RCA operated with a heightened sense of urgency, ensuring that remediation efforts were both timely and rigorously executed without compromising quality or compliance.

RCA Approach

RCA provided a team of regulatory specialists who led remediation teams in the following areas:

  • Process Mapping
  • CAPA Leadership
  • Formal Problem Solving
  • Complaint Handling
  • Procedure Audits/Reviews
  • Data Trending Methods & Analysis
  • Independent Design Reviews
  • Medical Device Reporting (MDR)

Remediation included gap analyses, development, implementation and training of new or improved procedures, and comprehensive documentation in preparation for a follow-up audit from the FDA.

Result

Formal problem solving, corrective and preventive action (CAPA), and non conformance data trending methods were implemented, and comprehensive documentation providing objective evidence of effective remediation was prepared.

Extensive RCA leadership and coaching over several months were key in transitioning the clients Quality Culture to ensure that improvements would be sustainable.

The subsequent FDA audit following the Warning Letter resulted in zero 483 observations.

DHF Design History File Remediation

Background

A large medical device manufacturer received a critical warning from its Notified Body: unless significant deficiencies in its Medical Device Directive (MDD) technical files were corrected promptly, the company’s ISO certification would be withdrawn. Loss of certification would prevent the continued use of the CE Mark, effectively halting sales in all markets where CE Marking is required.

To address this urgent risk, Regulatory Compliance Associates® Inc. (RCA) was engaged to provide program oversight and deploy expert teams across multiple design centers and manufacturing sites. RCA was also tasked with supporting the transition from MDD to the EU Medical Device Regulation (MDR). Given the scope and complexity of the remediation effort, a phased, risk-based implementation strategy was developed to ensure steady progress within defined budget constraints.

Approach

RCA led and staffed cross-functional remediation teams to address gaps across a wide range of critical areas, including:regulatory compliance

  • Customer Requirements
  • Risk Management – Use, Design, and Process
  • Sterilization Validation
  • Design Validation Testing
  • Essential Requirements Checklist
  • Product Specifications
  • Design Verification Testing
  • Shelf Life Testing – Product and Package
  • Process Validation
  • Remediation included gap analyses, development and execution of test protocols, risk analyses, and updating of documentation as required to support the technical files for each product family.

Result

As remediation activities were completed, updated technical documentation was submitted for each product family. The Notified Body acknowledged the quality and thoroughness of the remediation program and the steady progress made. As a result, ISO certification was maintained, CE Marking privileges were preserved, and the company avoided costly market disruptions.

Medical Device Validation: Shelf Stability

Background

A large medical products manufacturer encountered a critical issue during the development of a new blood collection device. Accelerated shelf-age validation testing revealed that the protective sheath surrounding the needle did not maintain adequate reseal integrity after aging. Post-aging, the sheath failed to reliably prevent blood leakage following needle puncture—a problem not observed in unaged test samples. These unexpected reseal failures delayed the development timeline and posed a significant risk to the overall success of the product launch.

RCA Approach

Regulatory Compliance Associates® Inc. (RCA) was brought in to investigate the root cause and identify a viable material solution. The original sheath material was synthetic polyisoprene. RCA led a series of experiments evaluating alternative synthetic polyisoprene formulations. However, it was ultimately determined that meeting the required reseal performance would necessitate transitioning to natural polyisoprene (natural rubber latex), known for its superior elasticity and resealing capabilities.

Result

Following the material change, the device successfully passed design verification and validation testing. Subsequent design reviews and design transfer activities were completed, the design history file was updated, and the product was successfully launched using natural rubber latex sleeves.

 

Brand Name Re-Registration with New Logo

Background

A medical device manufacturer was consolidating its product portfolio, resulting in product and logo changes for 15 products distributed across 60 countries. Although the company name and manufacturing address remained the same, the manufacturer was uncertain about the regulatory registration requirements needed to support these changes globally.

RCA Approach

On a country-by country basis, Regulatory Compliance Associates® Regulatory Compliance Associates® Inc. (RCA) conducted a comprehensive, country-by-country assessment of registration and customs requirements. Where re-registration was necessary, RCA managed the submission process. In many countries, the primary challenge was ensuring the newly labeled products complied with customs regulations. RCA proactively communicated the updated labeling information to local Ministries of Health and the manufacturer’s distributors to facilitate smooth customs clearance.

Results

Thanks to RCA’s strategic approach and regulatory guidance, the manufacturer successfully implemented the product label changes without any interruption to product sales across all markets.

CE Mark: Clinical Evaluation

Background

Devicor, the leading breast biopsy device manufacturer, wanted CE markings to expand distribution with new products and provide continuity with legacy products obtained through a divestiture.
The Medical Device Directive requires a clinical evaluation to verify medical device clinical safety and performance.

RCA Approach

Devicor engaged RCA to build a clinical evaluation process. RCA identified clinical data by conducting literature searches based on key words and phrases, filtered through studies and data for relevant information and developed abstracts for incorporation with Devicor’s final submission.

Results

Besides crafting the plan, RCA was instrumental in data collection and analysis of clinical data, reviewing thousands of papers. This expertise helped Devicor complete the submission, leading to the CE Markings and enabling continuity of existing products and expanded distribution of new product. Based on this successful experience, Devicor will gladly look to RCA for future needs in clinical evaluations.

Production and Process Control

Background

A Fortune 500 biotechnology company faced ongoing challenges during campaign changeovers due to missing parts critical to equipment assembly. These deficiencies frequently led to costly, last-minute part fabrication and heightened the risk of production delays and revenue loss. Each near-miss placed increasing stress on operations management and threatened overall manufacturing continuity.

Further complicating the issue, equipment setup was based solely on Process and Instrumentation Diagrams (P&IDs) and relied heavily on employee memory, making the process inconsistent and prone to human error.

Regulatory Compliance Associates® Inc. (RCA) was engaged to identify and implement a comprehensive solution. During the initial assessment, RCA determined that the existing process lacked proper documentation and did not meet current Good Manufacturing Practice (cGMP) requirements. The solution not only needed to resolve the missing parts issue, but also establish robust GMP-compliant documentation to ensure the process was repeatable, controlled, and inspection-ready.

RCA Approach

Following a thorough investigation, RCA developed and implemented a standardized process to eliminate the recurring issues. This solution included the creation of detailed build lists, standard operating procedures (SOPs) featuring embedded color photographs, and 3D exploded diagrams for each equipment setup. To improve traceability and ease of identification, all equipment components were laser-etched with part numbers aligned with the supporting documentation. Campaign-specific sealed containers were introduced to organize and secure the necessary parts in advance of changeovers. RCA also conducted extensive employee training and established continuous improvement metrics to monitor performance and ensure long-term program sustainability.

Result

As a result of RCA’s solution, missing parts during equipment setup have been fully eliminated. The new documentation meets cGMP requirements and now serves as a key training resource, significantly reducing reliance on tribal knowledge. Campaign changeover times have been reduced by a minimum of two days—and up to six days in some cases—leading to a substantial annual cost savings of $4 million.