Case Studies in Pharmaceutical Project Management - Pharmaceutical Technology

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Case Studies in Pharmaceutical Project Management
A technical forum featuring Catalent Pharma Solutions, SAFC, and Neuland Laboratories.


Pharmaceutical Technology
Volume 36, Issue 2, pp. s14-s22

Viral product manufacturing

Nick Johnson, marketing manager at SAFC

This case study in project management involved the partnership between SAFC and Oncolytics Biotech, a biotechnology company headquartered in Calgary, Canada, which has developed a novel cancer treatment, Reolysin, based on a modified wild-type reovirus expressed in suspension-adapted human embryonic kidney cells (HEK 293). In 2007, Oncolytics partnered with SAFC's Carlsbad, California, site as part of the commercialization process for Reolysin. After officially announcing SAFC as the contract manufacturer for the project in early 2011, Oncolytics announced in November 2011 that validation studies were underway. Now in Phase III clinical trials, SAFC and Oncolytics have worked as partners to manage this project from the initial phases of identifying how to make the technology work through to making the consistent batches required for licensure. The current goal is to obtain a successful regulatory approval for Reolysin.

Project challenges. The production of the modified reovirus presented a significant manufacturing challenge. Not only was it going to be the first time for this type of product to be made on such a large scale, it also involved transferring technology from a contract development organization (CDO) in Canada to the SAFC site in Carlsbad. At the beginning of the project, there were four partners in different locations, including Oncolytics, its CDO, SAFC, and SAFC Biosciences in St Louis, which developed the novel media used in the production process.

SAFC Carlsbad already was filling the bulk product for clinical trials out of a product that was being made at another CMO in the United Kingdom. As the product progressed into later-stage clinical trials, the production was ramped up and transferred to Carlsbad, at first on a 40-L scale, and up to the present 100-L batches. The technology transfer was a whole new ballgame in terms of scale and complexity and required a new project team to be formed. On the SAFC side, this included a director of operations plus senior managers in manufacturing, quality assurance, quality control, and project management. Business-development support was also brought in when new scopes of work and new contracts needed to be worked out and finalized.

Despite the disparate locations, the communication between the teams in the different sites worked well with routine weekly conference calls and many coordinating activities carried out electronically. Some face-to-face meetings were essential, including the manufacturing representative and project manager visiting the CDO to address process scale-up. A week also was spent with all partners, including the CDO, watching the process and filming it so that it could later be used for operator training in Carlsbad.

The whole process took quite some time with many technical challenges, leading to a stop–start of operations from late 2008 through to 2009. By the end of 2009, however, sufficient clinical material had been made to continue with the trials, so there was less urgency from that perspective. Once the 100-L scale was reached, one or two batches were made per year until the program was ready to initiate process validation batches. Now that the product has advanced to conformance batches, three to six batches will be made per year.

Tracking progress. From a production standpoint, Gantt charts (i.e. charts used to show the project's schedule) are used for all SAFC projects. They are mapped out further than just a single department and include everything that might affect the timeline from the vendor through to the customer. The anticipated timings were all shared with the customer as well as the troubleshooting of possible technology-transfer issues that the technical team mapped. The team was tasked to look through historical data from the previous partnership to identify where there were areas for improvement and to help resolve issues quickly with input from both the SAFC team and the CDO. Specifically, SAFC Biosciences also helped by developing a custom growth media that increased the viral productivity and eased the purification process.

When SAFC inherited the contract, it already contained the required specifications that were used as an ultimate metric for success. The new goal became making and purifying the product to the required level for a commercial launch. After a number of changes to the process on the CDO's side and a few creative manufacturing approaches from SAFC, these specifications were exceeded and brought the project to the current point. Oncolytics is now in a position where accessing materials for its clinical needs is no longer a constraint, and the project has advanced into process validation in anticipation of commercial launch.

Issue resolution. One issue the team faced was the presence of an impurity that prevented the product from meeting specifications. The teams were brought together, and all the possibilities that might have led to the impurity were considered. From there, action items were distributed to the teams for them to pursue, including the review of historical data. This approach was successful as by the time of the next team meeting, the problem had been pinpointed. By adapting the process for the next batch slightly, a solution was found allowing the product to met specifications and the issue was resolved.

A key factor in the overall project's success was the customer relationship. In addition to the customer having a very good project manager, the relationship was developed based on trust and a common goal. Another key factor was ensuring that we had the resources needed to move the project forward. When the program moved into the process-validation phase, a second project manager was added to increase bandwidth. The way all parties worked together allowed the manufacturing to enter into conformance batches within a relatively short period of time with only a limited number of clinical batches having been completed.


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