Early Approval of Key Biologic Product Ensured Through Professional Project Leadership


A large medical company had salvaged a medical device system from a failing company and planned to commercialize this product for new medical indications. The company was in the process of changing the European manufacturing location for a key biologic product component, which involved three countries on two continents, and production in the new facility needed to be approved by the FDA (CBER). In addition to the manufacturing transfer, process improvements were being added and remedial validations were being completed. Although validation and testing studies had been set up, no overall plan had been developed for how this vital new information was to be documented, stored, summarized, interconnected, and approved. As a result, the project of transferring and validating the manufacturing process in the new facility was at risk of significant delays.

This was the first extensive manufacturing change that this management team had undertaken, and procedures had not been developed to handle the design control process from a quality and regulatory perspective. A new quality management team had not yet set a strategy for handling international product changes of this magnitude. To augment the skeletal team working on the project, product testing and quality issue resolution had been outsourced to a number of international consultants, with varying results.

The technical leader for the product had developed a simple schedule of activities to manufacture conformance lots and validate test methods. However, the overall design validation had not been fully detailed, yet the project was in its second year and there was pressure to complete it. Since the original plant had been closed, timely approval of the new facility was necessary to keep the product available worldwide and continue clinical trials.


The company engaged Integrated Project Management Company, Inc. (IPM) to drive project completion. IPM completed a gap analysis to assess and identify missing critical project elements. A series of meetings were held with the international technical, operations, quality, and regulatory teams to develop a detailed breakdown of the work required and a realistic, albeit aggressive, project schedule. The schedule analysis highlighted new critical path activities that were previously not understood by the team. These activities were prioritized and the appropriate resources sought from senior management.

Although this was a highly visible project in the company, inadequate internal staff was available to handle a project of this complexity. In addition, conflicting procedures between European and U.S. operations had left the team with uncertainty about the appropriate path to follow. Partnering with the technical leader, the IPM project manager led senior level discussions to determine how to meet the product design control requirements for documentation, test method validation, process qualification, and design validation.

The FDA regulatory submission had to effectively communicate the quality system and supporting validation studies that proved equivalency of the new manufacturing location with the original plant. IPM led the process of collecting design control records, interpreting and summarizing the information, and ensuring clear, accurate creation of the submission document. When initial attempts by the company to use a regulatory consulting firm did not result in an acceptable submission package, IPM set up a “war room” to bring the required focus to the submission package. Coordinating all the activities and ensuring effective prioritization aided the team to write and assemble the entire submission package in an organized and effective manner.

The quality records for the process validation manufacturing lots from the European plant needed to be translated and prepared for inclusion in the FDA submission. The IPM project manager took over the full process control when the internal regulatory group was unable to complete the process. IPM ensured that all records were transferred, translated, audited, and controlled for submission.


The on-time filing of the FDA submission was a major success. The completeness of the filing was confirmed when the FDA only asked some clarification questions and approved it without an inspection of the new facility. The manufacturing facility change was approved in six months, which was more than six months early. This major achievement resulted in significant savings of management staff time and avoidance of other consulting costs. Activities necessary for an FDA audit (preparation, audit, and follow-up) were avoided, allowing the client company to focus resources on other critical activities. Reaching this critical milestone early ensured the uninterrupted continuation of important clinical trials and patient access to needed therapy.