Technical Papers
Biopharmaceutical Firm Demolishes Then Rebuilds Its Fill and Freeze-Dry Facility with Minimum Downtime by Following a Challenging 20-Hour, Seven-Day-a-Week Schedule
John Boneso, DPR Construction, Inc., Redwood City, CA, USA
TABLE OF CONTENTS
- ABSTRACT
- INTRODUCTION
- PROJECT DEVELOPMENT
- PROJECT APPROACH
- PRECONSTRUCTION PLANNING
- CONSTRUCTION BEGINS
- LYOPHILIZERS MOVED
- CLEAN-BUILD PROTOCOLS
This case study provides an in-depth look at the solutions employed during the engineering, procurement, and validation of a cleanroom demolition and reconstruction project under extreme fast-track conditions. The key to its success lay in elaborate preconstruction planning, a dedicated owner-designer-builder team, and everyone's ability to deal with a challenging schedule.
All production of a San Francisco Bay Area biopharmaceutical company's production was funneled through the site's one fill and freeze-dry facility, which operated nearly 24-hours a day, seven days a week. More than a million bottles a year were processed each year, not a large number by some standards, but high in value.
Over the years, this 2,500 sq. ft. facility underwent several upgrades and modifications, most recently in 1993. Although the company, which asked not to be identified, recognized that the fill area was due for renovation, particularly the HVAC system, it faced a quandary common to many businesses: how to finish the project in the shortest time feasible to minimize downtime losses while still maintaining high quality work throughout. The solution lay in a combination of precise preconstruction planning and close partnering among the company, the design firm of Jacobs Engineering, and DPR Construction.
The company's fill and freeze-dry facility utilized a relatively standard design. Bottles delivered at one end of the line passed from a washer into a tunnel sterilizer to be sterilized by dry heat. From there, a conveyor belt transferred them into the Class 100 environment where they were first filled with the product and then stoppered for lyophilization. The bottles were then automatically racked and placed into lyophilizers where they remained until the freeze-dry vacuum cycle reduced the contents to a 'cake.' Finally, the medicinal entry sites on the bottles were given a protective aluminum flip-top cap and placed in a holding area for quality checks prior to packaging.
Once the company made the decision to launch the upgrade, it made a significant departure from its standard policy of first hiring a design firm and then putting the project out to bid. Instead, the company implemented a design-assist approach where owner, designer and builder all contributed to the design effort.
For its general contractor, the company selected one it had successfully worked with on other aggressive schedule projects. More importantly, it made the general contractor an integral part of the project planning team. This decision recognized that the accelerated pace would require constant coordination between designer and builder. The builder, as part of the preconstruction planning, developed a schedule using the Critical Path Method to identify key milestones, implemented cost control measures with a system that incorporated accounting and project management, began value analyses of the project, determined long-lead procurement needs and established document control guidelines to assist validation.
To help guide the project, the company established a team that included members from engineering, production, quality assurance, regulatory affairs, manufacturing documentation, maintenance, purchasing, and accounting. Initially, the company considered a 14-week project schedule, but as the magnitude of the production impact became apparent, it reduced that timetable. The company team, together with the contractor, developed a timeline to determine that the construction phase could be reduced to exactly three weeks-if everything proceeded flawlessly. With three days for final air balancing included in that time period, this left 18 days for construction. Three additional weeks were allowed for validation.
"This was a very fast-track project," the company's project manager said. "Normally such implementation requires three months and we scheduled just six weeks."
One of the first tasks the project team resolved was to agree on the primary phases of the project:
- Demolish and reconstruct walls and ceilings
- Replace the old HVAC system serving the sterile filling core
- Upgrade the HVAC system serving the filling support areas
- Replace two of the lyophilizer chambers
- Install 11 laminar air flow modules
- Build a walkable ceiling to improve access in the interstitial spaces
That was the big picture; the infinitesimal number of details that had to be identified and organized presented the true challenge.
Central to the project's success, and the most time consuming, was installing a new HVAC system and replacing the laminar air flow modules. The project was further complicated by the need to schedule certain construction activities around critical preventive maintenance activities on some of the major pieces of equipment. Planning and scheduling became intensely focused.
With construction set to begin July 15, 1996, a little more than two months after the six-week timeline was established, all recognized that this schedule could only be accomplished by near-perfect teamwork from everyone involved, from the owner to the last tradesperson. However, a persistent optimism that the goal could be attained stemmed from the fact that all the subcontractors had a vested interest in making the project succeed. All those involved had worked on other company projects, all understood the company's project specifications and, most significantly, all wanted to be invited back.
The contractor determined that a challenging schedule-two 10-hour shifts, seven days a week-would be required to finish the job on time. The remaining four hours in each day would be used to cover the inevitable unexpected tasks. The work-force included 40 to 50 tradespeople on the day shift, and 20 to 30 on the night shift. Despite the demanding schedule, everyone in retrospect considered the harmonious teamwork that prevailed to be one of the most remarkable aspects of the job.
"To do that amount of work in that time frame, and still maintain quality, was remarkable," one engineer said afterwards. "When you have 60 to 80 tradespeople working 20 hours a day in just 2,500 square feet of space, you can expect friction, even under less extreme circumstances. All that tension and all that speed, and still no friction. A lot of that was because we were clear with everyone up front. Everyone knew exactly what was required and how tough the job would be."
Fundamental to the project's success was exhaustive preconstruction planning. Every move had to be plotted, every problem anticipated, and alternatives solutions prepared in advance. Once the project began, there would be no time to practice new techniques, no time to hesitate.
To accomplish this, the project was into five different but interlocking blocks, each with its own subset of tasks to be accomplished: Schedule, Computer Assisted Design, Prefabrication, As-builts and Facility Mock-up.
Schedule
Every morning for two months in advance of the start date, the company, project team, representatives of the 18 subcontractors involved, and the builder's team gathered not only to develop the schedule but to obtain everybody's buy-in. All knew in advance how arduous it would be, or at least thought they did. The order of construction was planned so precisely that in some instances each worker's shift was plotted by the hour. At the same time, each tradesperson's work was choreographed to avoid people interfering with each other. Keeping the schedule was critical; one element falling behind could trigger a devastating domino effect down the entire construction line.
As-Builts
Over the years, walls, wiring, piping and ducts had been changed and some systems needed additional documentation. Because the filling facility complex housed other production and support areas in addition to the aseptic fill area, the existing ducts and piping could not be arbitrarily removed. A number of mechanical systems that went through the fill facility also supplied other areas.
The most congested area was the low-ceilinged interstitial space fitted above the fill area that housed a maze of ducts, plenums, conduits, and process piping. Here, movement in some areas was restricted to catwalks which were often partially obstructed by ducts and piping.
Much of the piping and ducting in this area was unmarked and would have to be carefully identified prior to removal. All validated systems would require special handling and, if disrupted, recertification. A mistake here could kill the schedule.
The engineer responsible for designing the new HVAC system said "The biggest problem was working in such a tight space."
Efforts by the mechanical, electrical and process (MEP) subcontractors and the builder to identify everything in this interstitial space were further complicated by limited access. Not wishing to lose any production time, The company ran the facility much of each day, and no one was permitted to work in the interstitial area during production hours. As a result, workers had only four to six hours a day to map the routes of all ducting, piping and conduit in the interstitial area. The identification process had to be exact. As one HVAC engineer said, "Once this job started, there was no time to resolve ordinary problems, only extraordinary problems."
Computer-Aided Design
For such a schedule, architectural plans needed to be particularly detailed to avoid misunderstandings. Consulting with the owner and designer, the general contractor used CAD to draw portions of the plans in even more minute detail, laying out every joist, stud, header, door, and fixture in the facility. The object was to minimize delays and avoid errors once construction began. Specifications on everything from the fit and finish of walls, the location and design of architecturally complex low-wall returns, and plenum locations were detailed in advance. Hours were spent meticulously cross-checking the plans, fully aware that a seemingly insignificant mistake on paper could cost hours on the job.
Prefabrication
From the beginning, the construction team knew that separating the workers into two levels, one group in the fill area and the other in the overhead interstitial area, was crucial to meeting the schedule. To do this, once demolition was complete, new walls and ceiling joists had to go up immediately to provide the interstitial area floor.
Working from a detailed layout, the builder divided the facility into a dozen different sections, then pre-cut and labeled each wall framing member for each section. When construction began, the numbered bundles were erected with no time lost in measuring and cutting on the job.
Heavier gauge ceiling joists were selected so they could be covered with 1 1/8-inch plywood flooring throughout the interstitial area, making the entire area accessible for the group working there.
With the interstitial space plans formulated, the team then concentrated on the ceiling layout. In the aseptic core, eleven laminar flow units were to be installed above the conveyor line and in front of the lyophilizers. Precisely fixing their locations was essential; once construction began there would be no time for measuring and fitting.
Plans also called for a large amount of soffited areas to be fitted next to the laminar flow modules to form a flat ceiling that would be more efficient to clean. Three soffits, each four feet wide, 11 feet long and three feet deep, were built in advance. Each soffit, containing HEPA filters, lights and an intercom speaker, was built with just ¼-inch tolerances to form a smooth, air-tight ceiling. Once the ceiling was up, they were raised and bolted into place in a matter of hours. The builder estimated that this prefabrication saved four working days.
Mock-up
One of the most important parts of the preconstruction effort was building a mock-up that incorporated the more exacting construction elements. These included the large and complex low-wall air returns, window opening through double-wall plenums, laminar air flow modules, and the sheet vinyl flooring that had to be coved seamlessly into the wall covering.
The mock-up served several purposes:
- The company managers could see exactly how the finished product would appear. Rather than trying to visualize the aseptic area's function, appearance and cleanability, they could observe it first hand. Anything unacceptable could be corrected in advance.
- The mock-up was a dress rehearsal for the real show. Complicated construction techniques were refined while building it. By this process, details on how to construct a low-wall return plenum inside a double wall, how to seal it, and how to cove the flooring flush with the drywall were all worked out in advance.
- The mock-up allowed the builder to evaluate the quality of each tradeperson's work in advance and iron out inconsistencies. This then set the standards for subcontractors to follow. If a question later arose on how a segment should be done, they could refer to the mock-up.
- Finally, neither management nor subcontractors could claim in the middle of the project that they didn't realize it would be done this way. They need only study the mock-up.
With soffits, walls, ceilings and ductwork precut and waiting, and all workers fully briefed on their duties, the construction date arrived. Officially it was to begin Monday morning, July 15, but when the builder learned the facility would be empty Sunday night, all crews set to work. Every minute counted.
By Tuesday, two full days into the operation, the facility was almost completely gutted. Conveyors and fill line equipment were disassembled, walls and ceilings were down and much of the ductwork and piping in the interstitial space was gone. By the morning of the third day, new walls were going up, including ceiling joists topped with plywood flooring for the interstitial space. Workers could now operate with greater efficiency and safety in two separate areas.
Since the new HVAC system would provide three times the previous air flow volume, larger ducts had to be fitted into the same limited space. Additionally, the new system used preheat coils to supply each room, which took up more room. To fit, everything had to be woven and layered in the interstitial space with the skill of an artisan. And because it was such a tight space, ductwork could not be preassembled. Everything had to be cut and fitted on the job, which placed one of the heaviest responsibilities on the HVAC team.
When finished, the interstitial space contained 2,500 lineal feet of ductwork weighing more than 12 tons. These figures may not appear significant, but taken in conjunction with the speed and limited space in which the job was done, they were impressive.
The HVAC contractor, a 20-year veteran, said it was the fastest job of this complexity he had ever done. "Ordinarily this would have taken three months. We did it in three weeks."
By the fourth day, most walls were up, along with the ceiling joists and the plywood interstitial floor. One of the more challenging construction problem was the wall which divided the aseptic core from the mechanical control room, was 23-foot-long double-wall that housed a 17-inch wide return air plenum. The return air opening on the sterile fill side was 20 inches off the floor and ran the length of the wall. Moreover, the wall contained three windows to permit viewing from the mechanical control room into the aseptic core.
The constructor first built the wall on the control room side, and framed the window openings in it. To form one side of the plenum, the inside of this wall was lined with galvanized metal except for the area within four feet of the floor, which was covered with stainless steel. A matching wall for the fill side was constructed, lined in advance with metal for the plenum, then fitted against the first wall. A horizontal steel beam 20 inches off the floor in this wall supported the drywall and provided the return air opening. Once joined, the slimmest person on the construction crew was elected to slip up into the opening and seal the plenum joints from within.
The stainless steel windows were then fitted in place on both sides of the wall along with an epoxy-coated aluminum grill around the window openings inside the wall that could be removed for cleaning.
While ductwork, piping and conduit continued to be installed overhead, crews in the fill and freeze-dry area were ready to install the new lyophilizer chamber. To fit it into the core area, two removable walls had been designed in advance to permit passage of the seven-foot high chamber.
At this point, the company requested that the second lyophilizer be moved to where the first one had been, and the new one put in its place. Even though this required a significant number of additional labor hours to detach, move and re-pipe the second chamber, no additional time was allocated. Instead, the builder increased the pace.
As work progressed, 20 hours a day, seven days a week, the company added another request: it wanted the general contractor to design and procure all new equipment for the gowning room, including bins, benches, and lockers, plus stainless steel filter racks and accessories for the sterile equipment room. In the heat of the battle, the builder reorganized all priorities, met with the company team to determine what was needed, found a vendor to fabricate it, and then installed it. The extra hours to accomplish these tasks were again absorbed, even as time grew short.
As the sterile fill area was about to be buttoned up, a company engineer determined that a concrete block wall containing low wall return ducts required additional structural support. The change called for two ½" steel plates, each three feet wide and nearly 12 feet tall, to be bolted together on each side of the block wall, sandwiching and strengthening it. With just 10 hours remaining on the schedule, the steel had to be located, cut, drilled, delivered, installed and covered.
With vital support from the company's maintenance department, the steel plates were located and installed. The builder's challenge was then to ensure that the steel plate and the protruding ends of the ¾-inch bolts holding it in place did not break the room's sterile bioseal. Because drywall could not be applied directly over the plates, hat-channels were first screwed to the plate to space drywall away from it and support the drywall. Once the drywall was installed and coated with the company-approved paint, the steel reinforcement was effectively sealed.
The company's project manager later noted the builder's ability to cope with unforeseen circumstances or schedule alterations: "They reacted to changes very fast," he said, "and always found a means to get things done."
Throughout the project, clean-build protocols were rigorously observed. Even before construction started, equipment and work areas were covered, taped and barricaded as necessary to prevent contamination. Once the sheet vinyl floor was down, the clean-build mentality was reinforced by requiring everyone to don booties before entering the project area. All cutting, sawing or drilling required two workers: one to do the job and the other to simultaneously vacuum up debris. In some cases a plastic tent was rigged around work to further limit possible contamination. Such strict measures reinforced the continuous need for clean-build policies in everyone's mind.
As the 21-day deadline drew closer, the hectic pace held firm. Both the company's and the builder's team members routinely committed 16 hours a day or more to keep progress on schedule and maintain the quality work.
In the end, construction work ran long by one day, taking 19 days instead of the planned 18. The final step, balancing the air, required a minimum of three days. To meet this deadline, several air balancers worked 24 hours straight on the last day.
Still, the company considered the demolition and rebuilding of a new facility in 22 days to be a significant achievement in the limited time available. The final, and most crucial, compliment to all team members lay in the successful validation of all systems that was forwarded to the FDA. The company resumed production with no complications.
