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									FOCUS ON...                              FACILITIES

Integrating Modular
Design–Build Execution
Strategies into Biotech Projects
Meeting Schedule, Cost, and Compliance Goals

by Kevin L. Koffke and R. Grant Merrill

            ne of the earliest and most
            important decisions in a
            biopharmaceutical facility
            construction project is
choosing a project execution strategy.
This choice affects cost, schedule, and
quality of the immediate project as well
as further operations throughout the
facility life-cycle.
    As technology and best practices
evolve in the early 21st century, many
biopharmaceutical facility projects are
integrating some form of modularization
execution strategy to maximize
predictable costs, schedules, and quality          Cell culture room in the Cook Pharmica facility. AES CLEAN TECHNOLOGY , INC. (WWW.AESCLEAN.COM)
benefits. The modularization concept            BACKGROUND                                          scale up from process development
can manifest as prefabricated buildings,        Back in 1963, a legacy of innovation and            through clinical trials and into
modular process skid systems and                quality began in Bill Cook’s spare                  commercial manufacturing. The
HVAC systems, and preengineered                 bedroom in Bloomington, IN. This is                 company will use mammalian cell
modular construction techniques.                where Cook Group, Inc.’s first “factory”            culture to produce biopharmaceuticals
    Here we focus on a preengineered            was located — where Bill Cook                       for clients. Building on the grounds of
modular construction project execution          manufactured, stocked, and marketed                 a former Thompson Consumer
strategy adopted by Cook Pharmica for           custom-crafted medical devices. Today,              Electronics (RCA) television assembly
its new biotechnology active                    Cook Group is a leader in developing                plant, the project was taken from
pharmaceutical ingredient (API) contract        health-care devices used by physicians              conceptual design to a fully
manufacturing facility in Bloomington,          and hospitals all over the world. With              functional, tested, and validated
IN. This project won the 2007 Facility of       offices worldwide, the company is at the            facility in 26 months. It consists of
the Year award for facility integration         forefront of medical research and                   two independent buildings, each
from the International Society for              product development in minimally                    encompassing about 450,000 ft 2.
Pharmaceutical Engineering (www.ispe.           invasive medical-device technology for              Other locations were evaluated, but
org). That award confirmed the success          diagnostic and therapeutic procedures.              this site’s bilevel layout was ideal for
of integrating a modularization concept            Cook Pharmica has built a                        the placement of the bioreactors,
for meeting the goals of this                   technologically advanced facility with              which are suspended through the
biopharmaceutical facility project.             the capacity to expand as its clients               floors between levels.
24   BioProcess International    JANUARY 2008
PROJECT DELIVERY APPROACH                             ( for preengineered         2007 ISPE FACILITY OF THE YEAR
Once a business plan and functional                   modular cleanroom systems, CRB               AWARD: FACILITY INTEGRATION
strategy for this facility were developed,            Consulting Engineers, Inc. (www.crbusa.
                                                                                                   Project: “Project Phoenix”
an in-house team began to examine                     com) for modular process expertise, and a    Location: Bloomington, Indiana
which project delivery method would                   local construction firm, R.L. Turner, Inc.   Size: 124,000 ft2 Cost: US$70 million
best suit the company’s needs. This team              ( The team would
                                                                                                   Key Project Participants: CRB
established criteria for a delivery                   combine preengineered, modular               Consulting Engineers, Inc.; Mussett
approach that prioritized CGMP                        construction with a coordinated              Nichols and Associates; G.S. Ridgway &
compliance on a fast-track schedule and               facility design and construction             Associates; R.L. Turner Corporation; AES
emphasized single-source responsibility               approach for flexibility.                    Clean Technology, Inc.; Harry J. Kloeppel
as the best way to manage the                                                                      and Associates; Commissioning Agents,
complexity of the project.                            APPLYING THE CONCEPT                         Inc.; Harrell-fish, Inc.; Cassady Electrical
    “Time-to-market” was an especially                High-level coordination among team           Contractors, Inc.; Project Planning and
important consideration in selection of a             members was critical to identifying          Delivery; Trane; Spriax/UltraPure;
project execution strategy. The business              roles and responsibilities during the        Cummins, Inc.; the Rovisys Company,
                                                                                                   Inc. (Emerson Delta V); ESC; Cleaver-
case for this new facility included                   early stages of this project. The result
                                                                                                   Brooks, Inc.; YORK; Baltimore Air Coil
biopharmaceutical industry and patient                was a documented matrix of
                                                                                                   (BAC); ABEC; Wave Biotech; Westfalia
needs to move products from laboratory                responsibility that helped to minimize       Separator; IPEC; Millipore; Pall
to commercialization as rapidly as                    the duplication of efforts and eliminate     Corporation; Mueller and DCI;
possible. Return-on-investment (ROI)                  gaps in the scope of work.                   Cornerstone Flooring and Linings; and
was another driver for recouping the                     Design Process: The first part of this    Siemens Building Technologies, Inc.
expense of capital for facilities and                 project involved transferring a vision and   Timeline: Start December 2005, target
equipment, operations, engineering,                   technology developed by scientists in        completion date Q4 2006, contract
construction, start-up, commissioning,                research and development to the facility     signed December 2006
and validation.                                       project team. Initially, Cook Pharmica
    Modular systems with preengineered                retained engineers, architects, and              Early information in this project
performance criteria served as the                    specialist consultants to establish space    consisted of the specific space type, the
foundation for this project. Inherent                 programming and develop a project            plan of departments that would occupy
benefits of modular methodology include               concept and performance specifications.      that space, and the requirements of
concurrent engineering and procurement                That delivery approach allowed the in-       scientists and others who would work
tasks. Combined with the compressed                   house team to maintain active                there. Discussions with key scientists
field activities of modular construction              involvement with ongoing review of the       and process experts led to early user
and integrated commissioning–validation               conceptual design through facility           requirements in the form of basic system
approach, this effectively reduced the                construction. The cleanroom design           descriptions, simple flow diagrams, and
overall schedule while ensuring                       team thus began with a conceptual            utilities requirements.
regulatory compliance at every phase of               design, the first of the three phases of         Once preliminary process flows had
the project lifecycle (Figure 1). The                 construction documents, followed by          been sketched out, the architects used
company maximized modular                             schematic and detailed designs, the          block diagrams to create conceptual
construction benefits by integrating a                second and third phases.                     floor plans. Working with minimal
preengineered, modular CGMP                              Conceptual Design Phase: The              input, the engineers provided essential
architectural cleanroom core, mechanical              conceptual design phase is one of the        preliminary utility information. Using
systems, building automation, and                     most challenging aspects of facility         some general rule-of-thumb values (e.g.,
modular process equipment.                            design. On one hand, cleanroom               airflow per square foot and square foot
    After a rigorous due-diligence                    designers need to understand the quality     per cooling ton), they identified heating
process, Cook established a cross-                    and production process implications of       and cooling loads for the building,
functional project team of modular                    their work. On the other hand, the           thereby establishing utility requirements
system design-and-build experts.                      production team must understand how          for the master plan.
This team included members                            regulations guide these designs and              Those HVAC building loads were
from AES Clean Technology, Inc.                       impose certain limitations on engineers.     used to estimate potential electrical use
                                                                                                   and peak demand loads that the facility
 Figure 1: Accelerated project delivery chart
                                                                                                   would have to provide in support of its
                                ����������������������������                                       process requirements. Table 1
                                                                                                   illustrates utility requirements
                                                                                                   determined from the HVAC and
                    �����������������������������������������������                                process equipment loads. From that
                                                                ��������������������               early information, AES created an
                                                 �������������                                     order of magnitude (OOM) budget
                                                                                                   based on previous experience and
26   BioProcess International          JANUARY 2008
Table 1: Preliminary master utility summary (* included within above values)                                    conditions and accept the flush-coved,
 Space                              Area (ft2)    Natural Gas (ft3/hr)     Electrical (kW) Air (tons)           resinous flooring surface.
 Office                              60,000              4,200                   360          300                   A walkable ceiling was constructed of
 Laboratories                        25,000              2,200                   200          500               load-bearing, homogeneously
 Cleanrooms                         100,000             18,000                   800         3,200              constructed sections to withstand an
 Future fill and finish              30,000              5,670                   180         1,000              imposed load with a deflection limit of
 Future stability suite                5,000              270                     50          150               1:360 on a 10-ft clear span and to
 Future packaging                     10,000             1,000                    50          200               support a load limit of 15 pounds per
 Warehouse                           170,000             1,300                   510          320               square foot. All openings for lights,
 Mechanical/computer rooms           20,000               100                     80          115               fixtures, and fittings were factory
 Process                                -0-              3,300                     *          500               formed in each panel prior to delivery.
 Totals                             420,000             36,040                  2,230        6,285              The ceiling panel sections were 4 ft × 10
 Estimated Range                                    27,000–37,000          11,000–12,000 6,300–                 ft wherever possible to minimize the
                                                                               (amps)        6,500              number of joints necessary.
                                                                                                                    The walkable ceiling panels were
benchmark costs from similar projects.                 laboratories, warehouse, and process
                                                                                                                supported from a suspended steel
Included with that budget was a basis                  utilities designed to support up to two
                                                                                                                system. The primary suspension system
of design (BOD) narrative, which can                   manufacturing trains).
                                                                                                                used extruded aluminum alloy ceiling
be an invaluable document for project                      Renovation of an existing building
                                                                                                                beams supported by drop rods threaded
scoping. It helped the team discover                   lent itself well to a modular approach for
                                                                                                                to a turnbuckle, which allowed accurate
gaps so that funds could be allocated to               construction of the manufacturing area.                  laser leveling of the flush ceiling system.
cover those areas.                                     The first cleanrooms were strategically                  The drop rods were installed at a
   Schematic Design (Program) Phase:                   placed adjacent to the office space, which               maximum of four feet on center along
Conditions of a manufacturing and                      left us with the most efficient layout of                the length of the ceiling beams, which
storage environment must be controlled                 unoccupied space for future                              were spaced on 10-ft centers providing
closely for compliance with current                    manufacturing expansion.                                 for 10-ft open bays. All wall-to-wall and
good manufacturing practice (CGMP)                         Preengineered, modular PVC-coated                    wall-to-ceiling junctions were trimmed
regulatory requirements. In addition,                  wall and ceiling systems met GMP                         with a white PVC coving system that
the latest ISO standard (14644)                        requirements for classified spaces by                    had vacuum-formed corner pieces to
provides guidelines for cleanroom                      providing nonshedding, nonporous                         allow efficient cleaning and
classifications (3).                                   surfaces that resist microbial and fungal                decontamination of the facility.
    With over 450,000 ft2 of usable                    growth and can withstand repeated                            Modular door systems with PVC
manufacturing space in the first                       cleaning and sanitization using various                  finishes were used to provide an
building, our initial efforts concentrated             chemical solutions (1). These wall and                   aesthetic, high-tech cleanroom. The
on space planning to allow for future                  ceiling panels were constructed and                      door fames were designed to produce a
expansions with little impact on the                   finished in the AES factory. Panels were                 flush-frame detail with the adjacent wall
initial manufacturing train. Therefore,                designed to allow future reconfiguration                 panel system. The doors were operated
phase one of the project concentrated on               with a single-joint detail that created a                with automatic door openers. Door
renovation and construction of 124,000                 flush, continuous wall and ceiling                       position switches were installed at all
ft2 of that first building. Within this                installation using welded joints and fully               gowning and airlock door locations, with
area, design and construction efforts                  swept cove details at the floors and                     connections to a localized GO/NO-GO
were dedicated to manufacturing and                    ceilings. Standard wall panels were                      (red/green) light alarm system.
support areas (office areas, one                       mounted on a 4-in.–high floor track,                         Modular glazed windows provided a
manufacturing train, support                           which was adjusted to suit the site                      flush, ledge-free finish throughout the
Table 2: Facility design criteria
                                                                                  Floor         Ceiling                                Humidity       Pressure
 Room                         AHU       Classification              ACPH        Area (ft2)     Height (ft)      Temperature (˚F)         (RH)           (WC)

 1: Airlock                     1       ISO 8, ISO 9                  25            80             10                 70 ± 5           30–60%          0.05 in.
 2: Men’s Locker                1       ISO 8, unclassified           25            75             10                 72 ± 5              NA           0.03 in.
 3: Women’s Locker              1       ISO 8, unclassified           25            70             10                 72 ± 5              NA           0.03 in.
 4: Gowning Airlock             1       ISO 7, ISO 8                  40            87             10                 68 ± 5           30–60%          0.07 in.
 5: Degowning Airlock           1       ISO 7, ISO 8                  40            97             10                 68 ± 5           30–60%          0.07 in.
 6: Cell Banking                1       ISO 7                         40           450             10                 68 ± 5           30–60%          0.12 in.
 AHU = air-handler unit              ACPH = air change per hour                    WC = column of water pressure measurement
 Ambient Conditions: summer 95 °F high, 76 °F low; winter –5 °F low. Space Pressure shall be maintained positive or negative to a building common reference point
 at the pressure indicated in water-column inches under static conditions.

                                                                                                             JANUARY 2008       BioProcess International          27
Figure 2: Typical air handling unit serving production suites                Figure 3: Typical air handling unit serving corridor areas

cleanrooms. Maximized visual areas                    environmental control for products.              balanced air systems, active pressure
were created to support the company’s                 The cleanrooms are designed to                   control ensures that when doors are
goals for a facility with full exposure and           maintain 68 °F ± 5 °F and 30–60%                 opened, airflow continues to move in
optimized operator comfort.                           relative humidity to control electrostatic       the specified direction. Automatic
    The flooring for this project was                 charge, microorganism growth, and                control dampers were implemented into
crucial to maintaining cleanliness.                   personnel perspiration. Make-up air              this design to guarantee control of
Product and personnel traffic throughout              was used as ventilation for personnel            room pressure differential and
the new facility would be significant, so             and to provide pressurization for                directional airflow.
a clean, durable surface with good                    environmental control. Directional air               We used airlocks to help maintain air
traction was needed. Critical core                    flow was used to control pressurization,         pressurization differentials and directional
manufacturing areas received an epoxy                 preventing the migration of particles            airflow between adjacent areas. Each
flooring system with a polyurethane                   carried by the air stream from less-             airlock’s cleanliness classification and
mortar base designed to address                       clean to cleaner areas, and to ensure            airflow rate also matched the classification
variations in the floor slab.                         cleanliness in the most sensitive areas.         of the room that it entered into (Table 3).
    The cleanroom core was                                With this type of building, overall          The main reason to maintain high airflow
architecturally designed in accordance                pressure comes from leakage cascading            rates in airlocks is to reduce time for
with IEST lighting standards (from the                from cleaner to less-clean zones,                pressure build-up between door openings
Institute of Environmental Sciences and               ultimately flowing out of the cleanroom          while preventing cross contamination
Technology, and federal/                area (pressure cascade). An FDA                  between adjacent rooms.
ISO critical environment standards to                 guideline defines room pressure                      Heating and cooling load calculations
create an environment for contract                    relationships for two important areas of         began after a preliminary floor plan was
manufacturing (2). Each process suite                 exposure to drug product quality:                established. More substance is added to
was separated from the other suites by                critical areas and controlled areas (4).         such calculations — taking into account
entrance and exit airlocks off the main               Critical areas (where sterile dosage             fenestration, lights, people, and
communicating corridors. This design                  forms and container–closures are                 equipment heat gains — as end-users
lent itself well to close-coupled process             exposed to the environment) should               finalize their process equipment
steps while reducing the risk of                      have a positive pressure differential            selections. Preliminary heating and
contamination. The manufacturing                      relative to adjacent less-clean areas (0.05      cooling equipment selections determined
areas were constructed to be compliant                in. H2O is acceptable). In controlled            the required utility infrastructure:
with FDA and ICH requirements for                     areas (where unsterilized product and            chillers, pumps, cooling towers, steam
personnel, equipment, materials, and                  in-process product and container–                boilers, and heat exchangers.
bulk product flows.                                   closures are prepared), a positive                   The process rooms were grouped
    At this point, temperature, humidity,             pressure differential of at least 0.05 in.       based on process similarities and room
pressure, and air-change requirements                 H2O is acceptable (with all doors                classifications, which resulted in 12
were established for the cleanrooms. A                closed) relative to adjacent uncontrolled        separate air-handling systems with
“room data sheet” was created for each                areas. When doors are open, outward              similar temperature, humidity, and
cleanroom, providing data AES would                   airflow should be sufficient to minimize         filtration requirements. Grouping similar
use to develop the BOD. Those would                   ingress of contamination.                        process rooms this way allows
become facility design criteria in                        For this project, room pressure              recirculation of the return airflow, which
construction documents to be used by a                differential was designed as follows:            helped reduce operational costs. The
construction qualification team. Table 2              Across same-room classification,                 main advantage of having multiple
displays examples of design criteria for              differential pressure was maintained at          systems rather than a few “once-through”
the project.                                          0.02 in. H2O and across different room           airflow systems was a 33% capacity
    Heating and cooling requirements                  classification, differential pressure was        reduction of the required cooling tonnage
of this project were driven by a need to              maintained at 0.05 in. H2O. Although             and associated energy use. The 12 air-
balance operator comfort and                          it is acceptable to design for static            handling systems each use two levels of
28   BioProcess International          JANUARY 2008
mixed-air filtration (95% prefilters with      Table 3: Cleanroom air changes per hour for       Table 4: HVAC cleanroom check figures for
                                               different classifications of cleanroom            different classes of cleanroom — and the total
terminal HEPA filters), a steam preheat                                                          for all of them
coil (as required) and a chilled water          Classification       Air Change Per Hour
                                                                                                  Classification     cfm/SF      ACPH       SF/ton
cooling coil, a hot water reheat coil, and a    ISO 7                 40 (process rooms
                                                                          and airlocks)           ISO 7                6.8        41          9
variable frequency drive (VFD)
controlled centrifugal supply fan. Air          ISO 8                 25 (process rooms           ISO 8                 4.6        28           27
                                                                          and airlocks
handlers serving the production suites                                                            Unclassified          2.3        14           351
                                                Controlled/             25 (airlocks and
dehumidify 100% of the airflow through          Nonclassified           support rooms)
                                                                                                  Total                 2.6        NA           69
the cooling coil (Figure 2).                    Unclassified          15 (support rooms)
                                                                                                  SF = sulfurhexafluoride (an insulating gas)

    The air-handling systems will operate                                                         ACPH = air change per hour

all day, every day, year-round for                Detailed (Construction) Design Phase:             For air balancing, designers assume
contamination control. So each air             After the floor plan was finalized and           leakage values to size air-handling
handler serving a corridor area was            heat gain information from process               equipment. The actual make-up airflow
designed with a bypass section that            equipment confirmed, our engineers               for a particular system will depend on
allows a portion of return air to bypass       finalized the facility’s cooling load            how tightly the room and ductwork are
the cooling coil because the airflow           calculations. Table 4 lists the final            constructed and installed. Once supply
required for room classification is greater    HVAC cleanroom check figures. Final              airflows are met, the TAB contractor
than the room cooling load. This               airflow diagrams were created and                concentrates on room differential
configuration allows return air to mix         equipment selections then completed.             pressures. Most balancers want to meet
with precooled supply air to maintain          Engineers began detailed design layouts          the return airflow values shown on
temperature, thereby reducing both             of air handlers and ductwork. Process            design drawings, although in reality the
cooling and reheat requirements. It            and utility piping systems were                  room pressures are what is validated.
reduced cooling from 50 to 30 tons, a          coordinated into the design to allow for         Accuracy of the return airflow compared
40% reduction (Figure 3).                      proper pitch in the piping systems               with design values is directly
    The speed of air supply fans is            (process and utility steam), all                 proportional to the quality of a system.
regulated through VFDs and                     coordinated with the support structure.              While the balancing was performed,
controlled by velocity pressure sensors            A construction cost estimate was             engineers worked very closely with the
in the supply duct that will save              further refined into a guaranteed                owner’s automatic temperature controls
energy cost around 11% of each fan’s           maximum price with shared savings on             (ATC) contractor to create a document
power consumption (~$1,460/year).              the final project cost. Table 5 shows the        that tested the readiness of the systems
That figure is based on filter loading         various activities for each discipline.          to be turned over to the commissioning–
of about a 1-in. water-column per                                                               qualification teams. For a functional test
year, running constantly ~340 days,            QUALITY AND COMMISSIONING                        of the active pressure control system, a
with an electricity unit price of $0.08/       Through a comprehensive quality                  series of computer screen shots were
kwhr. Payback on those VFDs should             plan (created and approved with                  taken from the building automation
be seen within two years.                      Cook Pharmica’s quality assurance                system. The first was a static display
    Preliminary equipment layouts              department), spreadsheets were used              showing all doors closed to prove that
began at this stage because it was             to record the receipt, installation, and         the rooms were within spec and under
important to establish the locations of        start-up of equipment and products.              control. Then one room’s door was
prime HVAC equipment such as air               This process verified construction               opened, and a second screen shot was
handlers, chillers, and boilers. Structural    and installation as demanded by good             taken to display the control dampers
engineers worked to design the most            engineering practices (GEPs) as well             reacting in the proper direction as
efficient steel support system that would      as installation qualification (IQ ) for          required to maintain the directional
work within building constraints. Most         systems identified as directly                   airflow. That test challenged several
cleanroom ceilings were 10 ft high, so         affecting products manufactured in               systems working together to verify that
9.5 ft of clear interstitial space remained    the facility (direct impact).                    the performance of the systems met the
to house a new structural support                 Operational support included a                operational qualification of direct-impact
system for air handlers, ceilings,             testing, adjusting, and balancing                systems. The validation team leveraged
ductwork, and piping.                          (TAB) contractor along with a third-             this commissioning and qualification
    Airflow diagrams were created after        party certification contractor.                  report to eliminate additional testing
the room airflow requirements had been         Engineers worked closely with the                during IQ and OQ.
established and were a vital design tool       TAB contractor to verify that each                   Results of such tests were included in
for scope review. From the information         system was within specified airf lows            the engineering turn-over package
developed during the schematic phase.          and room pressures. QA documents                 (ETOP) and used to prove that all
The cost estimate was further developed        verified GEP operation and                       systems and equipment met established
from the OOM budget as firm quotes             operational qualification (OQ )                  user requirements specifications (URS)
were received from equipment vendors           for the systems that were identified             as well as end-user expectations. The
and subcontractors.                            as direct impact.                                commissioning process verified that

                                                                                             JANUARY 2008        BioProcess International             29
“what was specified was installed, that it                      quality integrated design. In                    phase by eliminating a code inspection
functions properly, and that it was                             collaboration with one another, the              step in the field and speeding the
successfully turned over to the end user.”                      team members optimized modular                   installation of wires and cables.
                                                                systems design and construction to                  Also during the design phase,
MODULAR PROJECT BENEFITS                                        reduce costs. Customer and vendor                architectural and process system
Cook Pharmica had selected a modular                            quality teams were involved from the             components were integrated into the
execution strategy as an alternative to                         earliest stages to contribute their shared       design. These include remote-
stick-built or other options as the best                        and unique abilities in validation and           mounted electrical panels and piping-
approach to meet its project goals. The                         commissioning the facility for                   transfer panels within the prefinished
company established a cross-functional                          biomanufacturing. Preengineered                  walls. The apertures were coordinated
team of design–build experts as the best                        modular systems manufactured in                  and cut at the factory during
way to manage the complexity of this                            factory-controlled conditions and                fabrication. This integration was
project instead of using typical design–                        assembled in the field ensured                   closely coordinated during design to
bid–build methods.                                              predictable, repeatable quality form, fit,       improve the construction schedule by
    It was strongly committed to                                and finish results.                              allowing process equipment to be
collaboration for achieving a fast,                                Design–Construction Integration:              installed in the field without
effective, cost-controlled, and fully                           Concurrent cross-functional                      sacrificing factory designs.
integrated project. The congenial team,                         engineering and design activities                   Early Procurement: Once equipment
with the company’s confidence and                               allowed this project’s cleanroom                 selections were approved (before
respect in its critical capabilities,                           designers to create detailed panel               completion of the detailed engineering
infused the project with loyalty, pride,                        layout drawings for fabrication of the           drawings), all long–lead-time items
and a unified vision. Routine peer                              modular architectural systems while              were identified and released for
review of the whole project allowed the                         the engineering team was finalizing              procurement, including air handlers, a
team to address the kinds of issues that                        the design. Designers integrated the             packaged chiller plant and a boiler
arise hourly, daily, and weekly on a                            architectural features and mechanical            plant, utility pumping skids, process
typical construction project. A high                            systems using preengineered return-              equipment skids, and the modular
level of coordination and                                       air wall details that eliminated sheet-          architectural systems.
communication within the team                                   metal ductwork below the cleanroom                  Construction Benefits: The walk-on
benefited schedule, quality, and cost.                          ceiling level. Captured in the detailed          ceiling system reduced the project
    Compared with traditional modes,                            design phase of the project, the                 schedule because much wiring,
the modular construction sequence,                              innovation manifests in the                      ductwork, and control activities could
methods, and procurement strategy                               construction phase as cost savings and           be completed by workers on top of the
yielded better scheduling resulting in                          construction schedule improvement                ceiling while room finishes were being
faster construction of the GMP space.                           because no return air duct had to be             finalized. The end result was a CGMP
Conventional construction of the office                         installed in that space. Designers then          room-side ceiling finish and a topside
space and non-GMP areas was                                     integrated architectural and electrical          maintenance platform all within a
concurrent with the modular cleanroom                           systems with preengineered, UL-                  single system. This gave field
system to deliver the overall project                           approved electrical paths within the             construction benefits in cost, flexibility,
more rapidly. Early integration of                              prefinished walls. This integration              and adaptability.
modular process and cleanroom system                            was also captured in the detailed                   Preengineered modular systems
experts into the project team supported                         design phase of the project. It created          were combined in the field to create
proper allocation of resources and                              cost savings and schedule                        the cleanroom facility, minimizing the
accurate cost analysis to create a high-                        improvement in the construction                  amount of on-site labor and thereby
Table 5: Various phases of design development
                Process                    Architectural                    Mechanical                       Electrical               Cost
                Sketch of the basic        Develop floor plan from          From rough layouts, areas and    From mechanical data,    Snapshot of a master

                chemical process flow      block diagrams (tool to          heights can be established;      power requirements can   plan: utility
                diagram                    visualize concept).              ACPH assigned to determine       be established.          requirements based
                                                                            airflow.                                                  on ft2, rough ballpark
                                                                                                                                      cost estimate
                Personnel, material, and   Room data sheets define          Create room data sheets for      Room data sheets;        Based on the

                waste flow diagrams        layouts based on process         BOD. HVAC loads, equipment,      electrical loads,        schematic layout, a
                                           flows, equipment, and            and single line duct are         equipment, and single    magnitude cost
                                           future expansion (materials      developed.                       line power were          estimate was
                                           of construction).                                                 developed.               established.

                Process finalized (final   Final floor plan is signed off   Final process equipment loads Final process equipment     GMP pricing

                selection of process       after final selection of         are incorporated into cooling is confirmed for power
                equipment)                 process equipment.               load.                         requirements.

30            BioProcess International           JANUARY 2008
Figure 4: Productivity comparison of wall construction                                                 FACILITIES ENGINEERING GLOSSARY
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     ������������      ��������
                                          ��������          ���������      �����         �����         closely with commissioning and
                                          ���������          �������
                                                                                                       qualification teams will reduce overall
                                                                                                       construction schedules — and
                                                                                                       therefore, project cost.
reducing project cost. Preengineered                       commissioning and qualification. The
modular construction methodology                           quality assurance group maximized its       REFERENCES
excels in productivity over stick-built                    efforts by including the commissioning–         1 Biopharmaceutical Manufacturing
                                                                                                       Facilities Task Team. Table 4-1, Pharmaceutical
construction (Figure 4).                                   validation team as part of its structure.
                                                                                                       Engineering Guides for New and Renovated
    Another significant advantage to                       That integration ensured FDA and            Facilities, Volume 6: Biopharmaceuticals.
modular project execution is increased                     ICH compliance in terms of personnel,       International Society for Pharmaceutical
flexibility. The collaborative team                        equipment, materials, and bulk product      Engineering: Tampa, FL: June 2006.
planned for late-arriving process                          flows. After construction,                      2 American Society of Heating,
equipment during construction by                           commissioning and qualification efforts     Refrigerating, and Air Conditioning
                                                                                                       Engineers. Chapter 16: Clean Spaces. HVAC
including access paths. The flexibility                    were supported by the design team to
                                                                                                       Applications Handbook. ASHRAE: Atlanta,
of a field-assembled modular                               assist in completion of the IQ/OQ           GA, 2003.
cleanroom system meant that wall                           testing while reducing the schedule and         3 Institute of Environmental Sciences
sections could be left open to                             saving project costs.                       and Technology. ISO 14644-1: Part 1 —
accommodate late-arriving large pieces                         Design of the manufacturing areas       Classification of Air Cleanliness. Cleanrooms
of equipment into the rooms for                            began in July 2004. Construction            and Associated Controlled Environments. IEST:
                                                                                                       Arlington Heights, IL.
installation. Following clean-build                        started in February 2005 and was
                                                                                                           4 CBER/CDER/ORA. Guidance for
protocol (an inherent attribute of                         completed in December 2005.
                                                                                                       Industry: Sterile Drug Products Produced By Aseptic
modular systems), the installers closed                    Commissioning and qualification began       Processing. US Department of Health and Human
those spaces afterward with no concern                     in December 2005, and the facility was      Services, Food and Drug Administration:
for contamination of the equipment                         turned over to validation by April 2006.
                                                                                                       cber/gdlns/steraseptic.htm. 
                                                                                                       Rockville, MD, September 2004;
itself or the utilities that serve it.                         The company has reported that
                                                           based on its experience with other
INTEGRATION SAVES                                          building methods, this approach has         Corresponding author Kevin L. Koffke,
TIME AND MONEY                                             had significant impact on time-to-          PE, is director of engineering, and R. Grant
The most significant benefit to Cook                       market and cost. Speed in decision-         Merrill is director of project development
Pharmica was an accelerated                                making (especially for change orders)       at AES Clean Technology, 422 Stump Road,
construction schedule with its associated                  and aggressive engineering efforts led      Montgomeryville, PA; 1-215-393-6810;
cost benefits. The integrated approach                     to about a 9% savings on total    , kkoffke@
to engineering, procurement, and                           engineering costs — a big difference;
construction created time savings that                     when millions of dollars are being
were enhanced through well-planned                         spent. This project is testimony to the

32    BioProcess International              JANUARY 2008

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