Speakers interviewed:

• Michael Parks, Manager, Site Technical Services, Pfizer
• Michael Thomas, Director, Manufacturing, Amgen
• Marcelo Anderson, MBA, Associate Director, Manufacturing Sciences, Biogen Idec
• Gene Schaefer, Sc.D., Senior Director, Large Scale API Development, Janssen Pharmaceutical Companies of Johnson & Johnson
• Jean Bender, Ph.D., Director, Purification Engineering, MedImmune, Inc.

1. How does facility design and flexibility aid in the success of technology transfer?

(Michael Parks, Pfizer) Network supply strategies are increasingly reliant on flexible multi-product facilities to maximize asset utilization and provide for rapid adjustment to changing supply requirements. Understanding and implementing flexible multiproduct facility use, standard operations, and validated platforms is essential to maximize assets and to create robust processes that allow technology transfer to become a routine business. Some examples include, sharing of suites between clinical and commercial manufacturing, and sharing of suites to manufacture different products concurrently in closed systems.

(Michael Thomas, Amgen) Facility flexibility is a critical component to the success of a tech transfer. Different molecules have different processing requirements. To successfully demonstrate product comparability between two facilities, the fewer process changes required, the better.

(Marcelo Anderson, Biogen Idec and Gene Schaefer, JNJ) A detailed knowledge of the facility and scaleup allows for targeted development activities, streamlined facility fit evaluations, reduced variability in process performance. For example, almost without exception our shared programs have performed as expected, which is a testament the quality of designing the process to fit into the facility and the deep understanding of how processes scale. Design flexibility and capability allow the alliance to more quickly respond to programmatic and process needs. For example, when a program showed promising clinical results, we were able to accelerates the program by 7 months and were able to start producing some non GMP material within 3 weeks.

2. De-risking technology transfer - what are some of the risk-mitigating strategies companies are using today?

(Michael Parks, Pfizer) Multiproduct facilities present technical and regulatory challenges that must be considered when establishing product supply strategies. Some risk mitigating strategies include applying a standard Quality Risk Management (QRM) methodology in support of multiproduct facility use; Setting standard network changeover and cleaning practices and procedures; Engaging and partnering within the industry in defining and adopting best practices; Engaging and partnering with Boards of Health in proactively seeking accepted practices.

(Michael Thomas, Amgen)

• Detailed FMEA's looking at each unit operation are critical to understanding risk and taking steps to mitigate it.
• Harmonizing raw materials to the furthest extent possible eliminates many of the critical variables during a complex tech transfer, ultimately decreasing risk.
• Minimizing process changes between facilities helps mitigate the risk of failure from one facility to the next.

(Marcelo Anderson, Biogen Idec and Gene Schaefer, JNJ) First it is important to recognize that the process risk stratification is critical to ensure the time is spent in the most productive areas. Layering, knowledge, analogy, real time monitoring, standardization and decision making are the core strategies deployed to reduce programmatic and process risk. Layering is evaluation of processes and programs by a broad range of experts with different perspectives and backgrounds and feeding that information into a central location for consumption. Knowledge is establishing a deep understanding of the underlying science and equipment capabilities to anticipate performance risk points and to most effectively respond to changes. Analogy is comparison of process risk to existing platforms and focusing limited time on non-platform or novel activities. Real time monitoring allows the early obviation to prevent trends from becoming deviations or lost batches, through advanced monitoring the leading companies can simultaneously monitor hundreds of critical parameters and quickly isolate trends. Standard practice reduces variability in process inputs and allows more time to focus on high priority risks. Finally, having a rapid and effective decision response plan to address the inevitable deviations from plan is as important as preventing the issue.

3. What are the steps you need to take to protect IP while preserving collaboration during technology transfer?

(Marcelo Anderson, Biogen Idec and Gene Schaefer, JNJ) In operations, we have few things which are truly proprietary, so the concern over IP is overblown. More IP is lost each time we lose a team member than through any other means such as collaborations. Further, we are fooling ourselves if we think we invented a completely novel unit operation, as it's likely been done a thousand times over already. The more you fret over miniscule IP matters, the more you destroy a relationship and creation of true IP. So limiting focus and concern to only those very few areas of important IP dramatically reduces concerns. This also fosters trust and openness. For those rare items that are proprietary, controlling access to that information, ensuring internal teams are aware of what is not to be shared, being clear with collaborators about what is off limits, remaining consistent with those limits and effective contracts that protect each parties IP.

(Jean Bender, MedImmune)

1. Discuss with all relevant groups the specific information that is considered to be intellectual property or trade secrets. Document in a "do not disclose" list and communicate this list to the entire team. Establish procedures to guard against accidental disclosure (e.g., use codes for raw materials, dispense into secondary containers, etc.). Contact vendors to discuss confidentiality agreements between the companies.
2. Develop separate documentation systems or redact common SOPs that the CMO would need access too. Establish a controlled document sharing policy and electronic exchange site.