PhM: How is your facility set up so as to maintain separation between highly active and other compounds in production?
J.C.: We conduct our safety assessment at the inception of each project. If the compound is deemed highly potent, that is to say that the operator exposure limit (OEL) is determined to be less than one micron per cubic meter of breathing zone air, all processing operations are conducted in a discrete GMP facility, designed to contain the compound down to 30 nanograms per cubic meter of room air in the breathing zone. This facility features totally independent access and egress, a dedicated one-pass air handler, multiple air pressure cascades, and is fitted with a unique system of isolators to ensure containment.
PhM: What’s your organizational strategy for separation? In other words, what aspects of the organization are devoted solely to potent compounds, and what aspects overlap between potent and non-potent?
J.C.: When Metrics made the commitment to fully segregate and contain highly potent compounds and to dedicate equipment to the new facility it was decided that the safest and most efficient way to utilize this capacity was to organize a dedicated team to work within the new area. The group of scientists and specialists that handle these compounds are specially trained in addition to the curriculum normally required to work in a GMP environment. We have specialized conveyance equipment and specialized procedures that govern the movement of these compounds to, from, and within the facility. When these operations are more focused we are able to attain better work-practice as a result of their routine experience.
Another benefit is that we are able to keep access to the area at a bare minimum. It makes for a tighter operation. However, we are integrated cross-departmentally with supporting groups such as QA, EHS, and Analytical. We haven’t seen the need to fully dedicate groups within these departments, although that remains a possibility as our services expand.
PhM: What are your main responsibilities in your role as director of potent pharmaceutical development, and how do you fit into the company’s overall organizational structure?
J.C.: I report to the Vice President of Pharmaceutical Development, Dr. Mike Ruff. My team focuses on the development and phase 1-3 clinical supplies’ manufacture of dosage forms containing highly potent compounds. We operate similarly to the two lateral groups within the department except we occupy the dedicated facility and employ the hard wall containment technologies. In addition to my project management, technical, and general managerial roles, I am responsible for the conceptualization and procurement of the technologies that allow us to contain highly potent compounds across a broad spectrum of process-types while remaining highly responsive to our customers. I also serve on the safety assessment team for new compounds.
PhM: Are your job responsibilities different from what you’ve seen at other companies?
J.C.: Yes. Launching and operating this new capacity at Metrics has been very rewarding. Years ago those of us in formulation development saw a clear trend in the rising ratio of projects involving highly potent compounds. Simultaneously we saw a strong evolution of the Industrial Hygiene discipline. The vernacular with regard to control banding, etc. seemed to become a bit more standardized across the industry. So as a company we recognized that we had to understand this landscape and then offer a best-practice service in our field.
The senior management team also appreciated that those ultimately working with isolation technology would need to be intimately involved with the design of the entire operation for it to be adopted successfully. Rolling out the capacity was framed as a challenge and an opportunity for the development scientists rather than a burdensome necessity imposed by EH&S or Industrial Hygiene groups. So they chose me, a formulation development scientist, to manage the addition of the capacity rather than a project engineer.
In my previous experiences, engineering groups generally led construction projects and the end-users supported by communicating their needs. But with this project I was able identify the footprint within the building to be renovated, sketched the layout, and conceptualized and designed a unique system of interlocking isolators. It involved daily meetings with the engineering disciplines, safety, the general contractor, and the equipment vendors. Fortunately we had very talented collaborators who got comfortable with this arrangement as I learned their language. And even though I manage day-to-day operations of the now-operational facility, I am still responsible for identifying and designing technologies and capacities to support our growth. It’s a larger role than that of a manager of pharmaceutical scientists but it has been a wonderful experience.
PhM: Did you develop staff expertise in-house for handling highly active ingredients, or did you hire external expertise? A little of both?
J.C.: It was a lot of both. From our involvement with ISPE’s community of practice we understood right away that there are about as many ways to tackle this issue as there are companies in the business. We looked at everything. Local ventilation and laminar/down-flow technologies have many benefits and really offer a lot of comfort and versatility but are very dependent on work-practice. Similarly, flexible containment solutions are very practical and achieve very good containment performance but concerned us from a cleaning standpoint, or if disposable, a cost of goods standpoint.
After we made the policy decision to adopt hard wall isolation and buy brand new equipment we designed the unique interlocking isolation system. So by looking outside we got a sense of best practice and then applied it at Metrics. We felt it was important for a third-party industrial hygiene consultancy firm to work with our EH&S group to conduct all of the containment challenges. It imparted more objectivity when we assessed the performance of the equipment. The whole process forced us to become experts. As you might imagine, we are still in the process of refining our procedures.