Archives: Case Studies

Manufacturing Automation for Medical Devices

Background

A medical device manufacturer developed custom automation equipment to assemble and weld medical-grade check valves, incorporating a PLC, HMI, vision system, and ultrasonic welder. During an ISO audit, it was discovered that the software controlling the automated assembly equipment had not been validated. Compounding the issue, newly built equipment—critical to meeting urgent production demands—also required validation, but the client lacked the necessary in-house software validation expertise.

Regulatory Compliance Associates® Inc. (RCA) was engaged to develop comprehensive validation documentation and deliver expert validation services. RCA ensured the software met regulatory requirements and that the valve assembly system was fully validated and ready for production—all within an aggressive timeline.

RCA Approach

RCA integrated software validation as a core component of the overall equipment validation process. Following GAMP 5 guidelines, a risk assessment was conducted to identify user and functional requirements that posed the highest risk to product quality and patient safety. These high-risk functions were subjected to the most rigorous testing to ensure the automation equipment consistently assembled components in compliance with critical product specifications. This risk-based approach not only ensured a robust and compliant validation but also significantly reduced the overall project timeline.

Result

The validation was successfully completed within the aggressive timeline, with efforts strategically focused on equipment functions that posed the highest risk to product quality and patient safety. As a result, the client received a dependable, risk-based validation, and the new equipment was ready for production by the project’s target date.

Creating Operational Discipline to Support Quality Initiatives

Background

A global health care company received an FDA Warning Letter for quality issues with its manufacturing facility. As the organization began working through the issues identified in the Warning Letter, it became clear, even with good quality systems, improved operational execution was needed to sustain successful results. The operational improvements were focused in areas such as shop floor discipline / execution, facility housekeeping and maintenance, managerial focus on all levels and, most of all, assessing and attacking specific operational shortfalls within all the operational groups.

RCA helped the organization recognize data quality gaps, develop action plans, and create tracking mechanisms to monitor operational progress of the Quality initiatives. RCA raised the bar on operational discipline and feedback.

RCA Approach

The manufacturing facility engaged Regulatory Compliance Associates® Inc. (RCA) to develop and implement a plan for operational improvements to support the evolving quality management system. This assessment and subsequent improvements involved needed support from the somewhat skeptical operations management group. RCA and the local operations management team worked jointly to assess the plant and identify gap areas needing improvement to support the quality initiatives.

RCA assisted the facility to develop and implement a tracking system to monitor operational tasks, ongoing process improvements and ways to enforce accountability of key personnel. This tracking included key performance metrics for the following areas: training compliance, floor audit performance, batch record error improvement, document timeliness and line clearance performance. Recognizing that the operations management team was inexperienced, RCA engaged and mentored the key operations floor managers as they began implementing improvements and tracking progress.

Result

Besides crafting and implementing the operations improvement plan, RCA assisted the company to instill a culture of operational excellence and individual accountability with an inexperienced team. RCA helped the organization recognize gaps, develop action plans and create a tracking mechanism to monitor operational progress. Not only did these actions clearly improve quality and compliance, but they provided financial returns such as a deviation and inspection cost reductions as well as increased available line time which more than covered the cost of RCA’s third party support. Most importantly, the management team learned the importance of communication across all departments and at all levels to achieve success. Ultimately, the facility’s commitment will contribute to an environment of sustainability long after the RCA consultants have left.

 

 

Process Validation Remediation

Client Challenge

A large global medical device manufacturer received a Warning Letter from the FDA due to recurring 483 observations related to process validation deficiencies. The company was required to remediate validations for over 500 products and establish a sustainable, risk-based validation program in advance of upcoming FDA inspections.

The remediation effort needed to take place without interrupting ongoing manufacturing operations. Additionally, extensive training was necessary to build internal capabilities and ensure long-term compliance. Foundational gaps—including missing or incomplete design and process risk analyses, as well as inadequate test method validations (TMVs)—had to be resolved before initiating process validations. Further complicating the effort, software validation studies were needed for automated manufacturing systems and electronic data collection platforms.

RCA Approach

Regulatory Compliance Associates® Inc. (RCA) designed and implemented a risk-prioritized remediation plan that aligned with both regulatory expectations and business continuity needs. The approach began with a comprehensive assessment of existing design and validation documentation across the product portfolio. RCA then developed robust risk analysis documents for each major product line, forming the foundation for a sustainable validation strategy.

In collaboration with stakeholders from 14 global manufacturing sites, RCA established a validation program that balanced compliance requirements with ongoing production demands. Customized training programs were developed and deployed to ensure internal teams could sustain the improvements long term. To expedite execution and maintain consistency, RCA deployed experienced validation teams to each site, working alongside local staff to perform the necessary validations efficiently and in full regulatory alignment.

Result

Over the course of the 18-month engagement, RCA delivered 24 updated risk management files and completed more than 1,800 unique Installation Qualification (IQ), Operational Qualification (OQ), Performance Qualification (PQ), and test method validation studies. RCA’s comprehensive training approach—combining classroom instruction with hands-on guidance—ensured that teams across all global sites were equipped to maintain compliance independently. Subsequent FDA inspections at client facilities resulted in no additional 483 observations related to validation, affirming the effectiveness and sustainability of the remediation effort.

Product Cleaning Endotoxin Control

Background

A medical device manufacturer was encountering recurring instances of unacceptable endotoxin levels on finished, cleaned surgical needles. The issue led to an FDA 483 observation citing non conformances with established procedures related to needle cleaning and endotoxin control. Regulatory Compliance Associates® Inc. (RCA) was engaged to conduct a comprehensive analysis of the needle cleaning process, develop a protocol to evaluate cleaning efficacy, and recommend improvements to both the process and the associated specifications.

RCA Approach

RCA designed and executed controlled testing using a “worst-case” product scenario, inoculating surgical needles with approximately 300 EU/device. The objective was to achieve post-cleaning endotoxin levels below 2.15 EU/device. Testing revealed a gradual accumulation of bio-burden in the cleaning water across sequential batches, highlighting the need for process improvements. RCA supported the client in designing and building a new, automated cleaning system, which included clean compressed air and vacuum drying capabilities. The new equipment and cleaning process were fully validated. To further strengthen contamination control, RCA developed a clean-room behavior SOP and conducted comprehensive staff training. Additionally, a robust sampling plan was implemented, incorporating defined action and alert levels for endotoxin monitoring on finished product.

Result

As a result of the improvements, product endotoxin levels were substantially reduced, and the risk of nonconforming product reaching customers was effectively mitigated. These outcomes were supported and documented through rigorous process validation and enhanced process controls, ensuring compliance with regulatory expectations and strengthening overall product quality.

Regulatory Due Diligence

Background

A private equity firm pursuing the acquisition of a global medical enterprise engaged Regulatory Compliance Associates® Inc. (RCA) to perform a comprehensive technical due diligence analysis under a highly compressed timeline. The target company operated across North America, Europe, and East Asia, introducing significant complexity and potential risk.

Given the regulated nature of the enterprise, the risks spanned multiple dimensions—including technical, operational, legal, and compliance—with the potential to impact both valuation and deal structure. In addition to identifying critical risks, the private equity firm requested that RCA evaluate the company’s scalability and flag any infrastructure or regulatory barriers that could influence the transaction or provide leverage during negotiations.

Approach

RCA immediately mobilized a cross-functional team of regulatory, technical, and quality subject matter experts. Within 24 hours, appropriate resources were assigned to assess the target company’s regulatory compliance, operational readiness, and quality systems.

Using data room materials and client input, RCA rapidly identified key risk areas and developed a prioritized assessment plan. A detailed due diligence checklist was created to guide the evaluation process during on-site visits.

Over an intensive eight-day period, RCA conducted nineteen facility assessments and a corporate headquarters review. Throughout the engagement, the client received daily updates that were incorporated into active deal negotiations.

Result

RCA delivered a comprehensive due diligence report covering regulatory, technical, and quality-related findings, along with quantified assessments of health and safety liabilities, infrastructure gaps, and remediation costs. Expansion capabilities and potential structural limitations were also mapped, allowing the client to make fully informed decisions.

The findings provided the private equity firm with powerful insights that supported a successful negotiation and enabled them to adjust the purchase price to account for uncovered risks. RCA’s real-time guidance and expert recommendations ensured the client had a strategic advantage throughout the transaction process.

Pharmaceutical Development and Regulatory Submission

Client Challenge

A global pharmaceutical manufacturer encountered a critical supply chain disruption when their API supplier unexpectedly terminated the partnership. As a result, a substantial quantity of active pharmaceutical ingredient (API), though properly stored and controlled, was at risk of expiration due to a lack of FDA approval. The situation was further complicated by uncertainties regarding the completeness of the supplier’s Drug Master File (DMF), the availability of essential development and stability data, and the absence of a qualified replacement supplier.

RCA Approach

Regulatory Compliance Associates® Inc. (RCA) was engaged to resolve the issue and safeguard the client’s valuable API inventory. RCA initiated a comprehensive retesting protocol, confirming that the API had remained stable and within specification under controlled storage conditions. To reestablish supply continuity, RCA identified and qualified a new supplier, while deploying analytical chemists and development scientists to address critical manufacturing challenges—including issues with particle size and crystal drying in the new production process.

Concurrently, RCA’s regulatory experts located and thoroughly evaluated the previous supplier’s Drug Master File (DMF), uncovering essential development and stability data. Leveraging this information, RCA assisted the client in compiling and submitting a CBE-30 supplement to the FDA. This strategic submission enabled the client to gain FDA approval for continued use of the existing API, despite the supplier transition.

Result

The FDA found no deficiencies in the submission, allowing the pharmaceutical company to proceed with the use of the original API—realizing cost savings estimated in the eight-figure range. In parallel, RCA updated and streamlined the company’s Common Technical Document (CTD) framework, delivering structured templates to support ongoing lifecycle management of the product. This comprehensive effort not only averted a costly API replacement but also safeguarded a critical revenue stream and reinforced the long-term stability and compliance of the manufacturing process.