Case Study: Rules and regulations within the radiopharmaceutical industry
Project Overview and Objectives
To address these challenges, Alwin was brought on as an experienced EPCM (Engineering, Procurement, and Construction Management) project manager. His responsibilities included overseeing the commissioning and qualification (C&Q) of the general equipment in a Class C cleanroom, supporting procurement and construction queries, and assisting in the implementation of a quality management system (QMS). He requested additional help on C&Q hiring Thilo as a C&Q Engineer for general equipment and Johannes for HVAC & critical utilities. Following Alwin’s retirement, Thilo assumed responsibility as the role of project manager for the equipment group to see the project to delivery.
Challenges
From the outset, establishing a GMP-compliant facility within a traditionally nuclear-focused organization proved challenging. The organization, well-versed in nuclear engineering and primarily a supplier of raw materials for radiopharmaceuticals, was not accustomed to GMP requirements. This transition to GMP compliance was further complicated by high turnover among the project team and a reliance on smaller, less-experienced subcontractors instead of a seasoned GMP construction company.
Other key challenges included integrating the organization’s established nuclear safety workflows with the new GMP-compliant QMS and managing the construction of a GMP facility in a brownfield site. Located in a Natura 2000 protected area and in a region prone to seismic activity, this site presented additional environmental and regulatory hurdles that required careful planning and adaptation of the exiting building.
Progress Approach
To achieve project objectives, we adopted a structured validation process guided by industry standards to ensure full compliance. Our approach centered on key guidelines.
- ISPE Baseline Guide Volume 4 (Commissioning and Qualification, 2nd Edition): This guide provided a comprehensive framework for commissioning and qualification (C&Q), detailing a clear progression from user requirements specification (URS) to final performance qualifications (PQs). It was essential in aligning the facility’s systems and Class C cleanroom equipment with GMP standards, allowing us to achieve robust compliance at every stage.
- ISPE GAMP® 5 (A Risk-Based Approach to Compliant GxP Computerized Systems, 2nd Edition): We employed this standard to assess and mitigate risks linked to computerized systems, ensuring they met GxP compliance.
- EudraLex Annex 1 and Annex 3: Cross-Compliance with GMP and Radiation Safety Standards: Annex 3 compliance necessitates a unique blend of GMP standards for drug production and radiation safety protocols. Coordinating between GMP and nuclear safety requirements can be complex, as certain procedures may conflict, requiring additional controls and documentation to meet both standards. We leveraged our in-depth expertise and industry knowledge to implement EudraLex Annex 1 in a structured manner, ensuring robust compliance with GMP standards for sterile manufacturing. In parallel, we adhered to the specific requirements of Annex 3 to meet the stringent guidelines for radiopharmaceutical products. By integrating both Annexes into our approach, we established a dual-compliance framework that upheld regulatory standards for sterility and radiopharmaceutical safety. This approach ensured that each stage of production met the highest quality and safety benchmarks required in both areas.
- Given the sensitive nature of data at a nuclear facility, IT security was a critical priority for this project. To protect this data and ensure compliance, we adhered to internationally recognized standards, including ISO/IEC 27001, the NIST Cybersecurity Framework, and the IAEA Nuclear Security Series. These standards provided a comprehensive framework for cybersecurity, including conducting IT penetration tests to identify vulnerabilities and applying Failure Modes and Effects Analysis (FMEA) for thorough risk assessment and mitigation.
- In line with the ALCOA++ principles—Attributable, Legible, Contemporaneous, Original, Accurate, Complete, Consistent, Enduring, and Available—our approach emphasized data integrity at every level of the IT infrastructure. ALCOA++ is essential in GMP-compliant environments as it ensures data is trustworthy, traceable, and secure, which is especially critical in a facility handling both radioactive materials and sensitive clinical trial data. By upholding these principles, we maintained a high standard of data security and integrity, vital for regulatory compliance and the reliability of sensitive research outputs.
Teamwork
The project’s success depended on effective coordination across departments, including IT, engineering, quality assurance, nuclear engineering, and external vendors. At Progress, we emphasize a culture of open communication and cross-functional teamwork to support seamless collaboration. Regular meetings with all stakeholders ensured alignment on project goals, proactive problem-solving, and comprehensive decision-making by integrating diverse perspectives. This collaborative approach, fundamental to Progress culture, allowed us to achieve project milestones on schedule while maintaining the highest standards of quality and compliance.
To facilitate a smooth project handover, we actively involved client personnel in commissioning, installation qualification, and operational qualification activities. This hands-on approach equipped them with the skills and confidence to independently manage all commissioning and qualification activities once the project was delivered. Working as a unified team, we were able to navigate complex requirements and drive the project forward efficiently.
Results
The official opening of the facility marked a major milestone in achieving GMP readiness for our client, positioning them as a CDMO in the radiopharmaceutical field. Progress was able to deliver on the targets, with effective systems and protocols in place to support ongoing GMP operations. The client expressed strong appreciation for Progress’s ability to drive the project forward at a rapid pace while maintaining coordinated, high-quality execution across all phases.
