Archives: Case Studies

Biosimilar Drug Development

Client Challenge

A European based company engaged in biosimilar drug development requested RCA to develop a regulatory strategy for seeking approval for their drug in the US and EU. The challenge was that the client wanted to utilize the data from a recently completed Phase III clinical trial conducted entirely outside the US and not under an IND. RCAs regulatory affairs team confirmed that CDERs Office of Biotechnology would have jurisdiction and proposed that the client request an initial advisory meeting as their first contact with FDA.

RCA Approach

Originally, the client did not intend to seek FDA approval making the first step verification that the clients clinical data met cGCP and cGMP, as well as the regulations and guidance documents for the Use of Foreign Clinical Data. RCA supported the client as they retrieved the proper records and documents which were sorted to conform to EMAs similar but different requirements. When reconstructed, this documentation essentially met FDAs requirements for cGCP.

Step two was to document a briefing package on behalf of the client to support an Initial Advisory Meeting request with the FDA. As the client was in the process of preparing a Biological License Application in Europe at the time, substantial Safety, Efficacy, Pharmacology and Bioanalytical data was available. The client had substantial bioanalytical data comparing their biosimilar to the European marketed reference listed drug “RLD”. Generation of comparative bioanalytical data that could be used to build a bridge, to the US RLD drug, was still on-going.

RCA submitted the briefing package to the FDA on behalf of the client and the FDA rejected the meeting request based on insufficient bioanalytical comparison data between the clients biosimilar and the US RLD. Over a four- month time period the client was able to generate additional bioanalytical comparison data to the US RLD.

RCA updated the original briefing package to include the additional data and resubmitted another meeting request. This time the meeting request was granted. However, due to the extensiveness of the supporting data presented in the briefing package, FDA offered the option to the client to convert the advisory meeting into a BPD type II meeting request. As a result, the client saved a significant amount of time towards their goal of filing a BLA in the US.

Results

The outcome of the meeting request with FDA is being withheld at this time to maintain confidentiality for our client.

 

 

EU MDR Compliance and Regulatory Submission

Background

A global medical device manufacture needed to meet the May 26, 2021 EU MDR compliance deadline. Collecting the reference documentation from suppliers was a challenge due to their geographic location. Based on the new CE mark requirements, the client moved from a self-submission filing status, to a Class 1 medical device.

RCA Approach

RCA collaborated with the client’s leadership team to create a cohesive strategy based on the new EU MDR regulatory environment. Training sessions were conducted to educate their team on the changes from MDD to MDR.

RCA performed an assessment to understand the current state and identified all gaps that existed in relation to the new EU MDR. This included a review and assessment of the existing Design History Files (DHF) and the Quality Management Systems (QMS). It was identified that the documentation was in several locations and lacked the efficiency of a culture of quality.

A Project Plan was developed that outlined the creation or revision of 12 Standard Operating Procedures (SOP), along with the development of complete design history files for 3 current/legacy product families. Clinical Evaluation Reports were created for 3 product families to help the client determine their new MDR classification.

RCA increased the efficiency of the documentation process so a single hub of information was available for future assessments or audits. Change control processes were implemented to improve how revisions of SOP’s and quality records were documented.

Results

RCA successfully delivered submission files for the 3 product families on time. This enabled the client to continue their business under normal operating conditions in each global market.

Packaging validation was also optimized based on improved procedures that met the new MDR regulatory guidelines. Supply chain partners and suppliers were educated on the client’s new requirements for optimized validation protocols.

Finally, RCA helped the client identify additional opportunities to optimize their QMS and product portfolio based on the new regulatory environment. This led to the potential for expansion opportunities based on the current certification approval.

Client Takeaways

  • Technical files for EU MDR submission were optimized including generation or updates for every element of the file.
  • The Client successfully transitioned to ISO certification.
  • One of the client’s suppliers was impressed which led to additional assessment projects with vendors in the client’s model.

Outsourced QA Leadership Benefits Emerging Device Maker

Client Challenge

The client’s team had developed a strong business plan, secured a solid intellectual property (IP) platform, and established a clear manufacturing strategy. However, they lacked a defined regulatory affairs (RA) and quality pathway. Operating in a bootstrapped environment, they initially implemented off-the-shelf quality management system (QMS) software, only to later discover that this approach was insufficient to meet their regulatory and quality compliance needs.

RCA Approach

Regulatory Compliance Associates® Inc. (RCA) was engaged to perform a gap analysis, identifying discrepancies between the company’s existing systems and the regulatory affairs (RA) and quality management system (QMS) requirements. RCA initiated a structured remediation effort, providing targeted support where needed—such as aligning standard operating procedures (SOPs) with the company’s unique business needs and refining the product development process to meet evolving QMS expectations. To support the development of a compliant and robust QMS, RCA deployed experts in quality systems and quality engineering, including specialists in electronics.

As the new product launch approached, RCA further supported the implementation of a Corrective and Preventive Action (CAPA) system, a complaint management process, and an internal audit plan—ensuring a sustainable and inspection-ready quality infrastructure.

Results

Through the combination of RCA’s outsourced quality and regulatory expertise and the client’s internal team, the company successfully launched its product, achieved full regulatory compliance, passed audits, and implemented a robust Quality Management System—all without the need to hire costly full-time executives. By addressing compliance gaps and optimizing the use of existing QMS software, RCA helped the company preserve its prior investment and avoid unnecessary system replacement costs.

Additionally, RCA structured a flexible payment plan with fixed monthly fees, enabling the client to manage cash flow effectively during a critical growth phase. Following RCA’s initial engagement, the product achieved commercial success. As the company scaled, RCA was retained for ongoing support as the outsourced QA/RA manager, providing strategic guidance while keeping operational expenses manageable.

This successful partnership and the company’s continued growth ultimately attracted investor interest, culminating in an acquisition by one of the top 100 global medical technology companies.

Pharmaceutical Shipping Validation Study

Background

A pharmaceutical start-up, located in the USA, approached RCA to design their shipping validation study given the complexity of their supply chain, manufacturing, and distribution process.

The challenge is to design a study that proves the SQuIPP of the drug product is maintained throughout the multi-national manufacturing and distribution process given the multiple modes of transportation and multiple hand offs between four different companies. The company has two API manufacturers, located in different parts of Europe, that they need qualified using both air and sea transportation between Europe and Canada. The finished drug product is to be manufactured in Canada and then shipped to the USA by air or ground transportation for distribution.

RCA Approach

Based on the request of the client, multiple shipping studies were required. Each API manufacturer needs to be qualified for each route using different modes of transportation, and each route needs to be challenged by “anticipated extremes”. There were a multitude of shipping configurations (# of drums, drum sizes, drum weights, # of pallets per container, types of containers, etc.) that differed by manufacturer, but in some cases also changed within the same manufacturer, that added complexity to this project. Additionally, any possible new challenges associated with international shipping practices had to be identified (languages, time zones, holidays, etc.).

RCA was able to generate multiple shipping study protocols. These protocols included representative transportation load configurations, defined packaging configurations, and calibrated temperature monitor positioning. Given the delicate nature of the API, lot samples were pulled and sent with each shipment to undergo chemical testing following shipment. The testing results were used to illustrate that the SQuIPP of the API material was not impacted by the shipment. Since the client couldn’t be present at each CSP site, the protocol included clear, multilingual instructions and diagrams to ensure correct temperature monitor placement and pallet configuration.

Multiple different companies were involved in manufacturing and distributing the finished product, therefore, the hand offs had to be effectively managed. Each company was required to provide documentation to RCA illustrating the protocol had been followed. Given that the product is temperature-sensitive, a delayed or missed hand off puts the product at risk. It was RCA’s job to analyze the shipment documentation and temperature data to determine whether the validation passes and generate the final reports.

Results

The company was able to provide sufficient data proving the drug product and it’s materials was maintained within the established temperature range throughout the cold chain distribution by all modes of transport during both winter and summer seasons. The data also illustrated the SQuIPP of the product was not impacted during the shipments. The thorough design of the study, combined with data tracking and analysis from RCA, enabled the company to prove this consistency over time.

Outsourcing Pharmacovigilence

Client Challenge

A global pharmaceutical and medical device company faced challenges in scaling its workforce to meet the demands of rapid business growth and increasing regulatory oversight. Specifically, the company struggled to secure incremental staffing resources with the specialized expertise required for critical functions such as pharmacovigilance (PV), device vigilance (DV), complaint management (CM), and medical information (MI). Local resource shortages made it difficult to maintain compliance and operational efficiency across these high-impact areas.

RCA Approach

To address its resource challenges, the company partnered with Regulatory Compliance Associates® Inc. (RCA) to design and implement a cost-effective, scalable outsourcing model. This strategic solution was developed to accommodate current operational needs while remaining flexible for future changes in staffing and regulatory requirements. The approach centered on the following key elements:

  • Strategic Resource Allocation: Lower-cost outsourced staff were engaged to manage repetitive, high-volume, low-complexity tasks, enabling internal high-value resources to concentrate on complex, high-risk activities with greater patient impact.
  • Call Center Outsourcing: RCA helped transition call center operations for pharmacovigilance (PV), device vigilance (DV), complaint management (CM), and medical information (MI) to external providers, ensuring effective stakeholder engagement—including medical professionals, sales representatives, and consumers.
  • Data Management Support: Internal information management systems were supplemented with outsourced data entry, quality monitoring, and case surveillance services to improve accuracy and throughput.
  • Global Partner Identification: A Business Process Outsourcing Partner (BPOP) with a large global footprint was selected to provide offshore and outsourced call center capabilities, improving efficiency and reducing operational costs.
  • End-to-End Process Support: Outsourced PV, DV, and CM functions included contact management, intake, triage, logistics, and categorization/prioritization of potential high-risk events (e.g., adverse events, product malfunctions) for escalation and regulatory reporting.
  • Medical Information (MI) Support: Frontline customer service functions—such as call handling, case logging, and the delivery of verbal and written medical information—were successfully transitioned to outsourced resources.
  • Retention of Critical Control: Throughout the process, the company maintained control over all critical decisions, including report ability assessments, product safety determinations, regulatory strategy, and risk management

Results

The business challenge was effectively resolved through the implementation of an outsourced and off-shored contact center model. This strategic shift yielded measurable improvements and long-term benefits across operational, financial, and regulatory areas. Key outcomes included:

  • Significant Cost Savings: The new model led to a reduction in annual operational expenses by $1.3 million, representing a 16%savings on a functional annual spend of $8.0 million.
  • Process Efficiency Gains: By leveraging the core competencies of the outsourcing partner, the company achieved key performance improvements that were unattainable with internal resources alone. Notably, the complaint registration cycle time was reduced from five days to same-day processing.
  • Strategic Resource Allocation: High-cost internal resources were redirected to focus on critical decision-making activities by offloading repetitive, high-volume tasks.
  • Established Strategic Growth Partner: The outsourcing partner became a reliable resource during business expansion, regulatory responses, recalls, and acquisitions—providing scalable support aligned with evolving business needs.
  • Centralized Operations: The shift from a decentralized structure to a centralized contact center enabled streamlined operations, improved process oversight, and resource optimization at the regional level.
  • Customer-Centric Flexibility: The model supported adaptation to evolving customer communication preferences (e.g., transitioning from phone to email-based intake).
  • Enhanced Data Quality Oversight: With added quality surveillance processes in place, the company improved data integrity and content accuracy—capabilities that were previously unsustainable with internal staffing.
  • Leadership Enablement: Functional leadership was freed to focus on process design, Voice of Customer initiatives, and critical regulatory strategy, rather than day-to-day transactional execution.
  • Strengthened Regulatory Standing: The functional organization emerged as a strong point in regulatory audits by maintaining a clear focus on compliance, managing variability, and demonstrating continuous process improvement.
  • Built-in Redundancy: The outsourced model provided built-in crisis resilience, including redundancy and backup operations during disruptions such as severe weather or system outages.

The outsourced and off-shored contact center model was recognized as a major success within the organization. It enabled access to high-caliber medical professionals, established a scalable and strategic partnership for future growth, and delivered substantial operational cost reductions. The implementation process was benchmarked as a best-in-class approach and now serves as a model for other functional areas within the company.

Compliance Assurance Leads to Passed FDA Inspection

Background

Qualitest, a leading developer and manufacturer of affordable, high-quality generic pharmaceuticals, wanted to be prepared for upcoming FDA inspections.

RCA Approach

Qualitest engaged Regulatory Compliance Associates® Inc. (RCA) to prepare the company in advance of an FDA Audit. RCA reviewed over 170 investigations relating to Qualitest operations to suggest improvements and identify areas of risk. By working efficiently and by tapping into scheduled downtime, RCA was able to complete the project in three months.

“RCA not only remediated our warning letter, but they also improved our workforce efficiency and preparedness for agency audits. We didn’t realize what it took to be prepared for an inspection. Prior to RCA, we had cursory reviews by auditors and inspectors, but we always suspected there were issues that weren’t identified. We experienced a thorough inspection when RCA came. Our systems were closely examined by RCA’s mock inspectors, to the point where we really felt like we had been through a real inspection. They identified many deficiencies and areas for process improvement. We now know we are in good shape and are getting better by practicing what we learned. RCA provided great value to us.”

Result

Qualitest implemented the recommended changes, including company-wide training, and received no observations during the next FDA inspection.