Confidential – CAR-T Cell Therapy Lab

Cyma Builders and Construction Managers were retained by a confidential client to construct a new pilot plant at their existing PA facility. This pilot plant was designed to support a new cell therapy suite that was being designed and constructed at another facility.  Due to the role of this new suite, it was imperative that it be completed and put into operation before the other facility was constructed.

The overall project consisted of the demolition of an existing suite that was renovated to accommodate the new program. The new suite included some new mechanical infrastructure while also re-purposing and modifying two existing packaged AHU’s that were used for the previous suite. The overall finishes installed in the suite included epoxy paint throughout, as well as a troweled epoxy floor. Cyma was also responsible for installing a number of bio safety cabinets and clean room pass thru’s as part of the project.

The original project schedule showed the suite being completed in early June of 2018, and was contingent on receiving funding for the project in November of 2017. Unfortunately, funding was not released for the project until late January of 2018. Due to the criticality of the suite to future operations, the client insisted that the early June completion date be maintained as much as possible. Once released, Cyma builders worked extensively with the design engineers and vendors to identify the long lead components on the critical path. Once identified, a methodical approach was taken to try to ensure that the long lead components were onsite when needed to achieve the project schedule. Using this strategy, Cyma was able to receive over 95% of the equipment on time, with the remaining 5% not arriving due to manufacturer related shortages.

Once the issue with the long lead equipment was resolved, Cyma began working on constructing the suite. The original construction schedule assumed 20 weeks of construction, but the work now had to be performed in 16 weeks due to constraints caused by the lead times of the materials and lack of funding. Cyma developed and implemented a construction plan to complete the work in the required time frame using a negotiated overtime allowance. The allowance was strictly managed to ensure that the money was being spent efficiently to allow the maximum amount of schedule to be recovered for each dollar spent.

During the project, Cyma was also able to use previous work experience in clean room environments to provide useful suggestions to the client. This included recommendations for clean room phones, various finish details, and materials of construction for the various signage that was installed as part of the project.

Confidential – Compounding & Filling Suite

Cyma Builders and Construction Managers were retained by a confidential client to construct a new manufacturing suite with a corresponding compounding suite at their New Jersey facility. The project was commissioned to fulfill the manufacturing needs of a new client that had recently been entered into a contract to manufacture certain products.

The 8,500 SF clean room was constructed to GMP EU classification and within the footprint of an active cGMP manufacturing facility. At the onset of the project, Cyma had to take extensive precautions to ensure the construction activities would not affect the active pharmaceutical manufacturing operations that were being conducted directly adjacent to the new suite. These precautions included clean room temporary partitions, strategic placement of negative air machines to ensure the control of dust and maintain pressure, as well as a diligent clean up effort to ensure that no dust or construction debris migrated into the plant. Cyma was also directly responsible for the flow of the contractors on site and ensuring they did not deviate from approved egress pathways. The FDA, EU, and the manufacturer’s clients conducted several routine and surprise audits during construction without having a single observation that could be attributed to the construction team.

The overall construction included a modular clean room system for all clean room walls, ceiling and doors. The construction team erected an independent structural steel support frame for the clean room within the existing building’s envelope. This construction strategy allowed the project to maintain the walk-ability of the modular clean room ceiling while not affecting the existing building’s structural integrity.

The project had a significant amount of support infrastructure. This included four custom AHU’s, four new chillers as well as a custom TWFI heat exchanger skid for a TWFI sub-loop that was being installed as part of the project. These systems were also tied in to the existing systems already in service at the plant. The project also included extensive modification to one of the two main WFI loops in the plant in order to reverse the flow of the loop to achieve a final design goal of their existing master plan. Throughout the installation of this infrastructure, Cyma worked with the engineering and production teams at the plant to schedule strategic shutdowns to allow the project to maintain schedule while almost completely negating the impact to production.

The project also required the retrofit of two existing Munter’s AHU’s that previously served the existing suite. The AHU’s were decontaminated, and then a thorough inspection process was performed to identify any potential failing parts for replacement. Cyma proceeded with replacing these parts in order to ensure the AHU’s fulfilled their designed role with minimal problems in the future.

The infrastructure was installed on a new two story rooftop/internal mezzanine platform system that was constructed immediately above the process space. This platform  was independently supported from the existing structure. It is important to note that Cyma also worked with the design team to ensure that this platform was completely walkable and unobstructed by any of the ductwork, piping, or other utilities being installed to support the suite below.

 

Lonza – Powder Media Upgrades

Lonza’s existing powder media suite required upgrades to achieve cGMP standards in order to continue manufacturing product. Improvements looking to be gained included improvement of process flow, congestion relief, crease facility capacity, Provide EU/FDA Compliant layout and environment and provide EU compliant airlocking. This project was scheduled for three phase in order to accommodate ongoing operations.

Phase 1 included installation of new airlocks and high speed roll up doors to properly segregate the Powder suite. Additionally, the walls of the existing room were lined with heat welded takiron and a new epoxy floor installed to provide GMP finishes throughout the suite. Completing the finish work was particularly difficult due to the existing utilities exposed within the room that could not be removed (or recessed) without adding substantial cost to the project. New ductwork was installed during this phase to prep for connection to a new AHU to be installed under the future phases. New suites were also constructed to house pre-blending operations and a relocated CIP skid.

Phase 2 included installation of new Material & Personnel Airlocks, Chemical Storage and Weigh/Dispense Suite. The Weigh/Dispense Suite was purpose built with multiple down flow booths to accommodate specific products and personnel protection. Finishes within the Phase 2 suites matched those installed under Phase 1, including takiron walls, epoxy floors and epoxy painted ceilings. Additionally, a new 15,000 CFM AHU was installed during this phase to provide the necessary air changes to accommodate the program. The AHU installation included rooftop dunnage and platforms, along with new plant utility distribution.

Phase 3 included demolition of the existing Weigh/Dispense Suite, replaced by the Phase 2 suite. This area was then converted to a Chemical Staging and Personnel In Airlock. The finishes in Phase 1 &2 were carried through to Phase 3, and the new HVAC system was extended and leveraged to provide the appropriate air changes.

Once Phase 3 was complete, the Powder Media Suite was compliant with cGMP standards, achieved uni-directional flow and was operationally optimized for the program going forward. The project was completed on time and within budget.

DPT Labs – SVP Phase 2

Cyma Builders and Construction Managers were retained by DPT Laboratories to construct a new small volume parenteral (SVP) manufacturing suite and a new compounding suite at their Lakewood, NJ facility. The project was part of an ongoing master plan being executed at the facility that involves constructing individual SVP suites to fulfill the CDMO needs of their various clients

The 7,200 SF clean room was constructed to GMP EU classification and within the footprint of an active cGMP manufacturing facility. At the onset of the project, Cyma had to take extensive precautions to ensure the construction activities would not affect the active pharmaceutical manufacturing operations that were being conducted directly adjacent to the new suite. These precautions included clean room temporary partitions, strategic placement of negative air machines to ensure the control of dust and maintain pressure, as well as a diligent clean up effort to ensure that no dust or construction debris migrated into the plant. Cyma was also directly responsible for the flow of the contractors on site and ensuring they did not deviate from approved egress pathways. The FDA, EU, and DPT’s clients conducted several routine and surprise audits during construction without having a single observation that could be attributed to the construction team.

The overall construction included a modular clean room system for all clean room walls, ceiling and doors. This system was to be integrated into the existing adjacent suite that used the same modular system. Since the existing suite was in production 7-days a week, Cyma had to perform the tie-in to the suite during a previously scheduled bi-yearly shutdown. Cyma successfully completed five separate integration points at this shutdown, when the overall suite construction was only approximately 35% complete. Using the aforementioned clean room temporary partitions, Cyma was able to ensure that the existing suite was adequately sealed and protected while the rest of the suite was completed. The suites also had a trowel applied epoxy floor system with integral cove base.

The project had a significant amount of support infrastructure. This included two custom AHU’s, a new process and HVAC chilled water system, as well as a custom AWFI heat exchanger skid for an  AWFI sub-loop that was being installed as part of the project. These systems were also tied in to the existing systems already in service at the plant. Cyma worked with the engineering and production teams at the plant to schedule strategic shutdowns to allow the project to maintain schedule while almost completely negating the impact to production.

The infrastructure was installed on a new two story rooftop/internal mezzanine platform system that was constructed immediately above the process space. This platform  was independently supported from the existing structure. It is important to note that Cyma also worked with the design team to ensure that this platform was completely walkable and unobstructed by any of the ductwork, piping, or other utilities being installed to support the suite below.

At 60% completion, Cyma was informed that the customer purchased filling line was approximately 4 months behind schedule. This delay proved devastating to the client’s overall schedule to get the suite into active production by the end of 2016. In order to help their client achieve their goal, Cyma worked with their critical subcontractors to revise the sequence of construction to minimize this impact. This allowed almost 80% of the suite to be constructed while the filling line was being completed. Once the filling line arrived, Cyma rigged the unit into place as quickly as possible so the rest of the suite could be completed. Cyma then connected all of the relevant utilities and supported the startup of the filling line.

 

 

Confidential Client – Oven Room Construction Project

Local to our west coast presence, Cyma Builders & Construction Managers completed a $500,000 Oven Room construction project for a confidential Fortune 500 Pharmaceutical firm in Vacaville, California. During this job, which consisted of 500 SQ.FT. of work and a very aggressive timeline, the client required renovation of this existing manufacturing space.

The facility owned existing ovens to cure the product; however, they had been walled off to create additional space from previous renovation. The ovens were opened back up to the existing space and two new rooms were created – a new room for the ovens as well as a transitional room from the existing space to the oven room to serve as an airlock. After years of neglect, the oven needed a complete electrical and mechanical overhaul. All the electrical, HMI and chart recorder panels were refurbished and the existing air handling units and ductwork were tested for leaks as well as received new inline HEPA filters.

In addition, new terminal HEPA filters, LED lighting, stainless steel sliding doors, and epoxy flooring were installed in the two new rooms. Due to the strict timeline, the equipment was expedited and construction activities had to be uniquely phased to meet the deadline. The project was delivered on time and under budget to meet the client’s schedule.

Confidential Client – Capacity Expansion Masterplan

Cyma Builders was selected as the construction manager by this Pharmaceutical company to implement their Capacity Expansion Masterplan. The project was driven by spatial constraint of multiple programs throughout the site, including offices, warehouse and manufacturing (not pictured). The project was design to accommodate the additional needs of all three spaces within a single building addition.

The overall project consisted of constructing a new 17,000 SF pre-engineered building structure to accommodate the new program, which was apportioned 3,500 SF office, 3,500 SF manufacturing and 10,000 SF warehouse. The project commenced with an expansive pile driving effort, which was required due to poor soil conditions and adjacency to the river, followed by concrete mat slab construction. A 2,500 SF modular Vault was then delivered and erected onsite to accommodate controlled substance storage capacity requirements. The pre-engineered metal building was subsequently delivered to site and full assembled in the field around the Vault. The design of the building was done in conjunction with Cyma’s PEMB Division and Nucor. The structure had two sections, a lower roof area to accommodate the offices and an elevated one to accommodate the manufacturing and warehouse programs. All equipment loads were coordinated heavily during the design phase so the building purchase could be expedited and comply with the critical path.

The building erection was proceeded by receipt and rigging of major rooftop HVAC equipment. The office area was supported by a new 10,000 CFM packaged, DX AHU, while the manufacturing area was served by a 27,500 CFM custom Haakon AHU, inclusive of split condensing unit and heat pipe for energy recovery from the exhaust stream. Both units were installed on the roof over the office area, with the manufacturing system ducted over to the high-bay portion of the structure. A 16,000 CFM vertical air rotation unit was utilized for the warehouse and installed on an interior pad. Office construction included a new conference room, workstations and enclosed offices. The warehouse was design to accommodate 192 total pallet positions, with the Vault design to house an additional 192. All racking was installed to achieve this and a new epoxy coating installed across the warehouse floor.

The manufacturing area was designed to accommodate two (2) new Finishing Suites, only one of which was constructed and built out as part of the project. Additional support spaces included a Wash Room and Weigh/Dispense/Re-Pack Area. The proposed Finishing Suite included installation of existing mill and sifter equipment for bulk API processing; however, a new stack-up was required in order to accommodate their reuse. Cyma Builders led the procurement effort to purchase the new stack-up complete with new IBC’s, post lift, static butterfly valves, blender, and pack out equipment surrounded by a multi-tier stainless steel mezzanine. Additional process equipment purchases were also coordinated to accommodate the program including roller conveyors and floor scales.

The office and warehouse area were turned over on time and within budget in October 2015. the manufacturing suite is currently on schedule and within budget currently projected to conclude in the first quarter of 2016.

DPT Laboratories – Washroom Prep Suite

Cyma Builders & Construction Managers was selected by DPT Laboratories for construction a multi-component project to build a new Wash Prep Suite along with a Critical Utility Plant in support of ongoing operations and future expansion plans.

The Equipment Wash Prep Suite ($5,250,000.00/5,000 SF) involved the construction of a new wash room to support current and future filling operations as well as the construction of new utilities to support the future expansion needs of the facility. The wash room was constructed using the AES modular clean room system, and includes Grade C and D spaces. A new 13,500 CFM AHU was installed on roof level dunnage, along with all associated supply/seturn distribution and terminal HEPA filtration.  Process utility distribution include new clean steam and WFI piping to points of use and washroom equipment connections.  The challenges in constructing the suite involved installing a large amount of ductwork, re-circulation fans, and other HVAC & Process utilities in a mechanical space above the suite while maintaining a clearly designated walking path on the ceiling for maintenance and testing access. This effort required extensive coordination between the subcontractor, Cyma, architect and engineer to ensure an acceptable end product. Cyma also tied the new wash suite into an existing production suite during a compressed shutdown schedule to accommodate the client’s need to maintain production.

The new wash suite required the installation of several new pieces of equipment to allow for the proper operation of the room. Two Steris parts washers and Belimed Autoclaves were installed in the suite and integrated into the AES wall system and integrated with stainless steel closure panels.

The Critical Utility Infrastructure ($3,600,000/4,000 SF) upgrades to the production facility were extensive during the Equipment Prep & Wash project. Cyma performed a complete upgrade of two of the existing electrical services during this project, which served almost all of the major production and storage areas at the plant. This shutdown required an extensive, coordinated shutdown that was performed over a weekend. Cyma and the client worked together to ensure that all critical areas were supported with emergency power, and to make sure that the transfer of the loads from the old switchboards to the new substations were performed without issue.

Other infrastructure upgrades include major modifications to the plant’s water for injection (WFI) capabilities.  A new 8,000 gallon Feldmeier holding tank was installed, along with a custom distribution skid to support the new WFI loop that was installed as part of this project as well as the existing loop that was currently in service. Cyma installed a new MECO Vapor Compression Still and Pretreatment system to perform the WFI generation on this new system. In addition to this infrastructure, Cyma also purchased and installed a new Digital Analysis Waste Neutralization system to treat any waste before releasing it to the township drainage system.  All work was performed strategically to avoid impact to any active manufacturing operations.  Architectural room construction followed equipment installation to define the boundaries of the newly complete Critical Utility Plant.

OSD Manufacturing Facility

Cyma Builders was selected as the construction manager for a Weigh/Dispense/Blend Suite to facilitate relocation of OSD manufacturing operations to a California facility location.

Working with CRB as the design lead, the client considered the numerous approaches and technology to achieve the throughput required for the space. Cyma Builders assisted in cost analysis of the options and coordinated the bid process for all process equipment , specifically Downflow Booth and Blender equipment, and assisted with management of the submittal process.

The footprint of the new Weigh/Dispense/Blend Suite was carved out of an existing TSA Warehouse, requiring heavy coordination with daily operations. Concrete pits were sunk into the existing slab at three (3) locations to allow flush mounted scales to be installed for tote weighing. A new steel frame was erected to support an AHU platform and process equipment structural requirements, while the remainder of the Suite was built with structural/seismic considerations using cold formed metal framing. The walls/lid of the Suite were rated to provide a walkable surface for maintenance of MEP systems serving the space. A new Buffalo air handling unit was installed, along with air valves and terminal HEPA filters to comprise the HVAC system. Plumbing utilities were extended off existing site distribution and infrastructure, including Purified Water, Compressed Air and Potable Water. A new 200 A bus duct plug was installed to support the new HVAC, process and general distribution electrical loads for the space. All shutdowns of plumbing and electrical systems were carefully coordinated with the active site to avoid any impact to active manufacturing operation and production schedules.

In addition to the Weigh/Dispense/Blend upgrades, modifications were required to a second floor tablet press dump stations to accommodate installation of new compression equipment. The existing second floor space was a combination of charging suites, ovens and staging areas, making the unification difficult from and architectural and HVAC standpoint. Also, temporary protections had to be devised to isolate an existing dump station that had to remain active for portions of construction due to ongoing qualification runs. Following demolition of all existing equipment and architectural components, a new HVAC system was installed served by a roof mounted Buffalo air handling unit. Electrical and plumbing utilities were extended off existing site distribution/infrastructure. Heavy coordination was required with the two (2) new tablet presses being installed on the first floor. The second floor slab was cored at strategic locations for installation of new stainless steel dump chutes and process control panels. Finishes were then patched at the suite below to restore them to original condition.

Both spaces were finished with DensArmor walls/ceilings, epoxy paint, Stonhard epoxy floors and stainless steel bumper/corner guards. Chase SS sliding doors were installed at most new airlocks and suite, while ASI high speed roll-ups were installed for access to the Downflow Booth and Warehouse airlock. Specialty systems installed for the space included door interlock/security controls, PA system and fire alarm system.

Jacobus – OSD Manufacturing Facility

Cyma Builders & Construction Managers have been retained by Jacobus Pharmaceuticals, Inc. to provide Pre-Construction, Construction, and Post-Construction services for their Oral Solid Dosage production facility upgrades in Plainsboro, NJ. The overall facility upgrade program includes complete renovation of (2) existing drug production processes from raw material entry and bulk API generation through final tableting and coating. In addition, several of the overall facility support functions will be renovated and expanded to support expanded capacity and improved circulation, as well as replacement and upgrade of existing building infrastructure. The facility is to remain operational throughout construction, including manufacturing areas, requiring a strategically planned approach to phasing to minimize operational shutdowns.

Construction scope includes renovation and expansion of existing API generation, processing, and tableting suites to improve manufacturing efficiency and production environment quality. Non-GMP and cGMP corridors and air locks will be modified to allow for better facility circulation. New non-GMP and GMP staging areas will be created. Replacement and upgrades of HVAC, Electrical, and non-process utility systems will be completed as necessary to support the renovations. Upgrades to process utility systems and controls will be completed to support the new manufacturing equipment. A central cold storage box will be installed to support all OSD functions. A new receiving dock will be constructed for receipt of raw materials, along with a new hazardous material storage containment area. Removal and modifications of existing process equipment to improve efficiency in loading and transfer of materials. Installation of new process equipment will includes Reactors, Centrifuges, Charcoal Settlers, Dryers, Presses, Coaters, Mixers and Misc. Production and Packaging Equipment. Final installation of interconnecting process utilities and controls for material transfer will complete the project.

DPT Laboratories – SVP Suite

Cyma Builders & Construction Managers were retained to provide pre-construction and construction management services for DPT Laboratories new Small Volume Parenterals manufacturing suite at their Lakewood, NJ Facility. The SVP Suite was the first phase of a multi-phase manufacturing expansion and capacity upgrade. The program was constructed within an existing cGMP manufacturing area, requiring strategic implementation of construction and interface with existing utilities.

Work commenced with construction of temporary containment systems with negative air equipment to ensure adjacent manufacturing operations would not be compromised, followed by demolition of the existing program. A new concrete vault was constructed below the existing concrete slab to hold a process waste collection tank, cooling system, and transfer pump assembly. A network of Stainless steel process waste collection pipe and drain points were installed to support the manufacturing waste. In order to accommodate process support and HVAC equipment a structural steel mezzanine was constructed in the interstitial space and a platform was constructed at the roof level.

Modular construction was chosen for all clean room walls, ceilings, and doors. A ¼” troweled applied epoxy floor system with integral cove base was used throughout as a common floor finish.

Two custom air handling units were installed at the roof level and were supported by a common make up air unit to pre-condition the intake of outside air. Several custom exhaust fans were provided to relieve excess air. An HVAC chiller plant was implemented , consisting of an air cooled chiller, holding tank, and circulation pump. A humidification steam boiler was installed at the roof level with a series of humidification coils placed strategically in the supply duct stream. Supply, return, and exhaust ductwork was distributed and constructed in accordance with each room’s ISO classification. A new BAS control systems instituted to support all new HVAC equipment.

Clean utilities for the new process consisted of USP water, process chilled water, compressed air, and nitrogen. With the exception of process chilled water all clean utilities existed at the site, but required a very strategic approach for tie-ins and distribution to the SVP suite, due to the fact they supported business critical manufacturing. A new process chiller was installed at the roof level to support the process cooling. Utility panels were utilized to serve as centralized use points for all clean utilities with stainless steel hoses from panels to equipment.

The main substation had adequate capacity to support the new manufacturing program, however a new breaker was required to feed secondary 480V distribution gear. Several transformers and power panels were installed at the mezzanine level for process, HVAC, lighting, and general loads. A UPS was provided for back up of critical loads. All new lighting was clean room grade.

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