Based on a 17 acre site, the Pfizer Dublin Manufacturing facility has been in operation since 1970. In 2004, an overview of the freeze drying network within Pfizer concluded that there was a need for additional freeze drying capacity within PGM (Pfizer Global Manufacturing). A significant expansion of the Pfizer Dublin site was approved to provide this additional capacity. The project involved the construction of one new production module (PM2) containing four freeze dryers and support facilities including labs, warehousing, central utilities building, dispensary and personnel and administrative support areas.

The design, construction and integration of the facility into the existing site while adhering to strict "good neighbor" policies has earned the company a coveted category award for Integration in the annual Facility of the Year Award (FOYA) program and has put it in the running to win the overall award.

The Site Master Plan – The Key To Success

The Pfizer Fill Finish Facility represented a unique proposition for modern pharmaceutical companies. That is - how to act sustainably to support new products on a long standing established site in a residential suburban area.

Pfizer site management was determined to stay loyal to its suburban site, supporting staff and their family commitments, the local economic community and the inherent sustainability of remaining linked to public and transport infrastructure, laid down up to a hundred years ago.

However, this much-considered decision carried many risks. How would the new facility relate to its residential neighbors? Did the aging infrastructure have the carrying capacity? Could Pfizer operate the plant within tough environmental constraints? Would Pfizer disrupt existing production on such a very tight site? How best to optimize facility integration and leverage the embedded value of all the facilities and services on site? These kinds of issues demanded a rigorous and inclusive design process.

Design Process for Success

Pfizer approached each decision for this facility using a structured and rigorous assessment process.

Thus site selection, site due diligence and site master planning tackled the macro issues and likewise the internal facility scoping and planning tested the optimization of the operations and logistics.

The project team went through several design phases until they arrived at an acceptable site plan. Mairead Kennedy, Engineering Team Lead for the project, explains this process; how long it took, and how this process was factored into the overall construction schedule, "We went through a conceptual/preliminary design phase at which point the cost, schedule and business case was fully understood. This was the formal kick off point for the project where the company approved funding and the project team committed to delivery on cost and schedule, and kicked off detailed design. Generally the conceptual/preliminary phase involves a very small team of 3 or 4 people and takes anywhere from 3 months to even a year. The longer timeframe would generally relate to time for the business case to become certain, rather than technical design issues."

The Chosen Option

The chosen option was selected to maximize the advantages of site integration. Having selected this arrangement, the design was developed to minimize its impact on its neighbors with the following characteristics:

1. The overall manufacturing program is divided in 5 distinct buildings, each with smaller massing and impacts but each linked to a coherent site manufacturing pattern.

2. Each building was given a distinct shape to further break down the visual scale and optimize its function.

3. The buildings and structures are consistently colored gray to prevent them forming a monolithic mass with the existing brown structures and to neutralize its color in the landscape.

4. The buildings have large glazed areas and attractive design features. Curved roof and plan elements add variety and liveliness, enhancing the visual impact.

5. The main buildings are cut into the existing site to lower visual impact.

6. The earth released by the deep basement was used to generate a large-scale attractive bermed structure to fully enclose the site and, in particular, to build a local attractive planted hillock beside the nearest residences so that their views are predominantly of landscape structures rather than buildings.

7. The bermed and landscaped enclosure of the site also significantly reduced and removed any residual noise or night lights from the site.

8. A new safer car and truck entrance was integrated into the site plan including improved fire truck access.

Kennedy described how important it was to Pfizer to work with the local residents. "This site is part of a residential community with many neighbors living in very close proximity to the site. It was essential that the design of the facility and its landscaping integrated well into the community. We had an extensive consultation process during the planning phase, and many enhancements were made to the landscaping design to accommodate the concerns of the local community. Obscuring the plant while maintaining views of the Dublin mountains became the key challenge."

The Focus Is The Freeze Dryer

During the design stage of the facility, PM2 was intended to be a high volume manufacturing facility with a low level of product changeovers.

However, during the commissioning stage of the project the Site Strategy changed and Dublin became the site of choice in the Pfizer Network for Biologics Drug Product clinical trails and New Product Introductions.

The project team combined with resources from the existing New Product Introduction team quickly adapted to the new requirements and added a Freeze Thaw unit (for cryo vessels), a disposable mixing system for making up small quantities of buffer, and adapted compounding and product transfer paths to minimize product losses. The Lev Mix disposable bag system in particular was a first of its kind qualification in Ireland.

This system consists of a single-use impeller inside sterile disposable fluid handling bags and a magnetic drive unit. When aligned with the specially designed impeller, the drive unit causes the impeller to levitate and lock in position. A variable speed controller allows the impeller to be run at the desired speed.

The IMA Edwards equipment consists of freeze dryers with automated, flexible loading and unloading systems

Asked specifically about the freeze dryer installation Kennedy adds, "We are particularly proud of our freeze drying technology. We have four pass-through freeze dryers each with a 42 square meter shelf area with fully automated loading and unloading system. They are arranged so that while loading is taking place on one side, another freeze dryer can be unloaded from the opposite side giving maximum flexibility for optimum plant throughput."

In compliance with Annex 1 the open product containers are handled under a grade A environment with grade B background. This means that the areas close to the freeze dryer slot-doors have received special attention having controlled airflow. Laminar air flow units were placed over the freeze dryer loading slot doors due to the risk of particulate generation when the doors were being opened. Doors are closed between cart loading to minimize moisture build-up during cold shelf loading.

The performance of the stoppering part of the freeze drying cycle has also been optimized. Historically, within the industry sticking stoppers have resulted in many problems with fallen vials and disordered vial packs. It has been almost impossible to avoid operator interference during unloading of a freeze dryer.

Jointly IMA Edwards and Pfizer initiated a collaborative action to solve this problem. A thorough, fundamental analysis of the cause and effect led to the development of an ideal solution. This solution is a combination of a specific surface structure of the metal surface and covered with a Teflon containing layer. The low surface-energy of this layer prevents the sticking of any material and therefore after CIP there is no remaining material.

A Bosch FLM filling and stoppering machine was chosen as the best technology to employ for this facility. The narrow balcony design allowed the filler to be installed against one wall of the filling suite, with only single-sided access required for the operator in the sterile area. All maintenance can be carried out from the Grade C area at the back of the machine. This has the significant advantage of eliminating the requirement for maintenance technicians and their tools to enter the sterile area and reduces downtime for cleaning and sanitizing of the room.

Based on the advanced technology used in the facility the selection of equipment vendors was obviously a critical part of the plants overall success, as Kennedy explains,

"Selecting the right equipment vendors was key to the overall success of the project. This plant would be on the high end of the equipment complexity scale, and integration of different vendor’s equipment was particularly important. The user requirements were very rigorous and detailed. On vendor selection we prequalified vendors and then competitively bid the equipment. The prequalification was rigorous so that once a vendor was on the bid list commercial performance in bidding was the only decision criteria."

Final Thoughts

Squeezing such a high-tech installation into an existing framework of buildings, while pleasing the neighbors was certainly an enormous task – and one well-deserving of an award. When asked about the facility and what she is most proud of Kennedy offered these thoughts, "While the project came in under budget, and construction was achieved with Zero LWD accidents, it was the schedule achievement which the project team was most proud of. There were many complexities to the build, and many challenges overcome in construction which made this achievement special. For example, planning permission came in 5 months late, and the team made up for this delay and still delivered ahead of schedule."

In addition, the facility has been getting a lot of notice, in particular the advanced freeze drying technology, as Kennedy mentions, "Our facility has received a very positive reaction within the pharmaceutical community, particularly in Ireland. We hosted a tour of our new facility for the Irish chapter of the ISPE in 2009 and have shared a lot of information regarding our freeze drying technology, and in particularly our automated load/unload systems with Genzyme, Allergan, Amgen and Octapharma."

Finally, when asked why the facility was chosen to receive the award, Kennedy opined, "I think our superior conceptual planning won the Facility Integration award for us. To take a narrow, steeply sloping site in a residential area and build a new Production Module, Central Utilities Building (CUB), Personnel Support Facility (PSF) and Warehouse while maintaining output from the existing Production Module was a fantastic achievement."