Facility of the Year Awards: Emphasis on Excellence
Highlights from the stories of the five Category Winners and two Honorable Mentions of this year's Facilities of the Year Awards (FOYA) showcase pharmaceutical industry achievements.
ISPE’s annual Facility of the Year Awards (FOYA) competition brings out the best in the pharmaceutical industry and offers the opportunity to share advances and achievements. These mini-profiles highlight the seven organizations and projects recognized this year: winning entries in five categories and two entrants that received Honorable Mentions. View the complete profiles of the winners in the Facility of the Year Awards 2018 Facility of the Year Awards 2018 Category Winners: Spotlight on Excellence.
Facility of the Year Awards recognizes organizations large and small in the pharmaceutical, life sciences, and medical device industries. This year’s Category Winners were announced at the 2018 ISPE Europe Annual Conference in Rome, Italy. The Overall Winner will be revealed on 6 November during the 2018 ISPE Annual Meeting & Expo in Philadelphia, Pennsylvania.
Facility Integration: Shire
NEW PLASMA FRACTIONATION FACILITY FITS RIGHT IN
Building a new facility to relocate existing processes is a major undertaking. Now consider the challenge of building that facility a) within a conﬁned space, b) without disrupting existing operations, c) while staying under budget, and d) adding new capabilities. Shire, a global biotech company focused on developing treatments for underserved patient communities, especially those living with rare diseases, did just that at its campus in Los Angeles, California. The facility is one of the largest plasma fractionation sites in the world.
The campus is situated on 11.6 acres in a light industrial zone on the edge of Los Angeles. Before the new construction was commissioned in 2010, the complex was home to seven buildings and a parking garage. Building 8, a 120,000-square-foot facility, was added to house the puriﬁcation process for two commercial products. The project was also designed to improve material and personnel ﬂows.
Prior to the construction of Building 8, the puriﬁcation steps for these products were performed in Building 1, a structure that predates acquisition of the property in 1952. “Building 1 was constructed in the 1930s and was originally a warehouse,” says Brian Danahy, Engineering Director at Shire. “You can imagine that over the years, with process changes and equipment changes, along with expansion, it got to the point where the facility wasn’t the most optimal and efficient. So that is really what drove us to create Building 8, the puriﬁcation building.”
Additional challenges were space constraints in every direction (north, south, east, west, elevation, and excavation), as well as occupancy limitations, which compressed the building layout to two above-ground ﬂoors. Ongoing manufacturing operations had to continue during construction, as well, which provided multiple opportunities for creativity and innovation.
The land on which Building 8 would sit was full of underground utilities such as electrical power distribution lines, a main sewer line, and a main site ﬁre-protection distribution water line. “In the footprint of where Building 8 is now, there used to be a 100,000-gallon underground ﬁre water storage tank. There were also temporary trailers on-site and utilities running under the driveway. All of those needed to be rearranged, and some of them had to be resized,” explains Danahy. Shire used the annual plant shutdowns to relocate and reroute underground utilities.
Project execution success factors included lean construction concepts such as working in a colocated space and utilizing advanced technologies. Offices for the entire Building 8 team, including the owner, designers, construction manager, key subcontractors, and the automation contractor, were co-located to accelerate decision-making and to promote the use of the latest in design and construction technologies. This saved time, saved money, and improved quality.
The project team used building information modeling (BIM) to model systems including conduit, hanger rods, and seismic bracing. Since designers and detailers worked side-by-side in the project’s “BIM cave,” the team was able to resolve over 10,000 “clashes” per week during the design phase. Users were able to review the 3D process design weekly and could even “ﬂy through” the model to adjust equipment access and optimize process ﬂow. As a result, complex system ﬁeld installations were completed without any costly rework.
In addition to puriﬁ cation processes, Building 8 includes a full GMP pilot plant that was built using modular construction to provide an extremely ﬂexible operating environment. The HVAC, for example, allows any room to be operated at ambient to cold processing (< 0°C) temperatures. Critical utilities—WFI, compressed air, nitrogen, alcohol, and clean steam—are available via utility panels on the walls of the main production rooms. The ceiling was constructed in a grid to allow for easy relocation of lights and HEPA ﬁlters.
This pilot plant has already been used to create a bulk batch of an orphan drug. Only one bulk batch of this product is created every ﬁve years, so the ﬂexible design of the Building 8 GMP pilot plant was an ideal location to produce this product. “We plan to use that area for future products and future clinical material as well,” says Danahy. “So I think t hat is a really nice ﬂexible space that the campus will be able to use to create new products and to manufacture small batch products.”
Facility of the Future: Vetter Pharma-Fertigung GmbH & Co. KG
VETTER FACILITY SETS NEW STANDARDS
When organizations make capital investments to ensure the future, many choose to do what’s necessary. Others decide to go above and beyond. Vetter Pharma- Fertigung GmbH & Co. KG chose the latter for its Center for Visual Inspection and Logistics, a state-of-the-art storage, inspection, and material testing facility that has set new standards for the pharmaceutical industry. Vetter is a leading contract development and manufacturing organization in aseptic ﬁlling and packaging. The company supports customers from around the world from the early stages of clinical development to market launch and beyond. With industry projections pointing toward both increased demand for preﬁlled injection systems and increased global regulatory requirements, Vetter decided to build its RVW (Ravensburg Vetter West) facility.
Beyond State of the Art
Construction planning started in 2009. “We ran out of space at one of our existing sites and we needed additional capacity for growth, so the company decided to erect a completely new facility,” says Thomas Ruebekeil, Vice President, Project Management. “We also wanted to improve all processes which were implemented there. We took the opportunity to build a new facility that is more than state of the art, where we would run extremely efficient processes and be ﬂexible enough for further growth.”
The plan was to erect an autonomous site in Vetter’s headquarters city of Ravensburg, Germany, that could act as a central hub for the company’s logistical processes. The ﬁrst construction stage was commissioned in 2012, followed by the second in 2016.
The concept for RVW is a supply chain with optimized product ﬂows that incorporates perfectly harmonized processes. The site provides warehousing for cold-storage and room temperature products, capacity for freezers, constant-climate chambers, and state-of-the-art incubation chambers. Visual inspections can be performed manually or automatically.
Unlike many facilities, optimization starts from the moment materials arrive.
“We ensure the security of our customer’s products, which arrive refrigerated between 2 and 8 degrees Celsius, as we have a seamless temperature door that is also refrigerated to between 2 and 8 degrees. This is quite unique for a warehouse,” explains Michael Schmitz, PhD, Vice President Planning and Logistics.
RVW also features a lab for packaging-materials testing, storage space for auxiliary materials, a central archive, and 200 office work stations. Departments and staff from an existing Vetter building were moved into the new location in 2017.
Securing the Supply Chain
Guaranteeing cold-chain integrity for cold-storage products is crucial. Vetter achieves this through a variety of systems that are deployed and linked intelligently, guaranteeing predeﬁned temperature areas that are matched with the stringent requirements for pharmaceutical products.
The facility’s high-bay storage area is divided into two temperature zones with automatic temperature and humidity control. There are 26,500 pallet spaces for room temperature products and 7,100 for cold-storage products. This allows substances, primary packaging materials, and ﬁlled-and-ﬁnished injection systems to be stored under current good manufacturing practice (cGMP) and consistent climate conditions. “That means we have a cold zone (2–8°C) and we have a room temperature zone. And you will never ﬁnd pallets mixed in any temperature zone,” explains Schmitz.
“For the logistical ﬂow, we have short routes—direct connections between areas and automatization with conveyor belts in place,” Schmitz continues. “For example, we have a direct connection from the warehouse to the visual inspection area, which consists of manual visual inspection plus automatic visual inspections (AVI) machines. We have implemented a just-in-time process to supply the visual inspection so that we have a very limited number of pallets sitting in front of the rooms or machines; we just have one-hour stock, and when the visual inspection is ﬁnished the pallets are put back into the warehouse immediately.”
RVW also has freezer capacity used for active pharmaceutical ingredients (API). There are seven chambers for storing raw materials, enough space for a total of 317 chest freezers. Each chest has a volume of 556 liters and storage temperatures that range from –20 to –80°C. The highly sensitive and very valuable pharmaceutical substances are stored in these chests under strict safety standards. To make sure the freezers are always in operation, RVW offers multiple emergency power supplies and backup chests.
To ensure the round-the-clock integrity of all products and processes within the facility, the Vetter team implemented an energy-supply system with an incredible six levels of backup. The facility’s basic power comes from two separate connections to the public grid. In the event of a failure, autonomous standby units can power the entire facility. Should these also fail, additional standby units, including a mobile 400-volt power unit, are available to supply all temperature-critical areas.
RVW was built with modular components, and has space available for future expansion, if required. “When we constructed and planned the facility, we looked at future trends, such as digitalization or smaller batch sizes, as well as trends from the regulatory side,” says Ruebekeil. “What we have here at RVW is for the next 30 years, and I would say we can fulﬁll the upcoming requirements. But we don’t want to stop now; we are looking to see where we can further improve our processes.”
Operational Excellence: Shire
STATE-OF-THE-ART QC LAB
Determined to deliver faster and more economical results and to instill a lasting culture of continuous improvement, global biotechnology company Shire is reinventing its world-class plasma manufacturing campus in Los Angeles. As part of that initiative, the company relocated its quality control (QC) lab to another building to thoroughly examine and reﬁne its QC processes and design a next-generation lab that may set a benchmark for the pharmaceutical industry.
Founded in 1986, Shire focuses on developing treatments for underserved patient communities, especially those with rare diseases. The Los Angeles campus, which manufactures treatments for primary immunodeﬁciency, hemophilia A, ﬂuid imbalance, emphysema, and infant botulism, is one of the largest plasma-fractionation sites in the world. The complex and sensitive nature of these processes means that the company is highly dependent on its internal quality control capabilities.
With the existing QC lab located in a building slated for demolition, the company selected a 16,000-square-foot area within an office building as its new home. The new location will permit future expansion. In addition to supporting the Los Angeles manufacturing operations, this QC lab will support other Shire facilities.
To enable this capability, Shire has fully decoupled the QC lab from Los Angeles manufacturing operations and infrastructure.
Deconstructing All Processes
From the project’s inception in April 2015, the goal of the Shire QC team was clear: Redesign their QC operation to deliver faster and more economical results while instilling a culture of continuous improvement.
Under the mentorship of their Lean Six Sigma Master Black Belt, the team went through a series of kaizen* events to map out current operational ﬂows, identify improvement areas, and eliminate wasteful practices. Together, the team developed the guiding principle that all processes had to be simple and clear, with direct customer-supplier connections.
“There are three main areas of our QC lab—a biochemistry lab, a micro•biology lab, and lab support, which supports the incoming samples materials and how they ﬂow,” says Bert Chai, Associate Director of Engineering at Shire. “We looked at how many samples we needed to test. We looked at how samples arrive, in what format, and by what transportation method, and then recorded how many samples are coming in at a time, how much space we needed, and so on. We painstakingly analyzed every step of the process.”
Construction began in January 2017 and was completed in seven months. The design was developed with exceptionally clear lines of sight, offering increased safety, quality, and efficiency. Management stations at a central hub in the transparent facility enable management to identify and respond to issues rapidly.
While the traditional isolated, low-visibility laboratory concept required the use of a two-person “buddy system” to ensure safe operations, the new design allows team members to pursue individual tasks while being visually connected to the entire group.
Not only do these connections promote a shared sense of pride in team accomplishments, but the natural light and breathtaking views of the city and hillsides elevate the work environment.
“We are very pleased with the end result of how the physical lab came together,” says Chai. “We are pleased with the aesthetics of the lab—it is very bright, open, and cheerful—as well as its efficiency. We use a just-in-time process, so anything that we don’t need in this lab can be stored in the warehouse or at our supplier’s warehouse. So we really don’t have a lot of waste.”
The QC team also evaluated the space required for each analyst. “Rather than each person having their own dedicated lab space, we decided to give everybody a laptop and have them share workspaces. Since this is a 24/7 operation, once analysts’ shifts are done, they take their belongings and laptops home with them.” This reduced capital investment and reinforced teamwork while conserving space and maintaining the showcase appearance of the new lab.
The results have been well received by all involved in the lab’s day-to-day functioning.
A benefit not initially envisioned by the project team is increased capacity. “When we ﬁrst started discussing this move,” says Sam Kitchell, Vice President of Engineering at Shire, “in the context of the lab, we were concerned about whether or not we could handle the capacity for just that location. By changing the way we work, we not only met existing capacity needs but created additional capacity through efficiency. For me, that’s one of the tangible outcomes that makes me most proud.”
*Kaizen (Japanese: “change for better”)—the practice of continuous improvement; industrial or business techniques for implementing continuous improvement; “kaizen events” are short-duration projects with a speciﬁc aim for improvement.
Project Execution: BioMarin Pharmaceutical, Inc.
KEEPING THE FAITH: GENE-THERAPY FACILITY COMPLETED IN 11 MONTHS
Based in Novato, California, biotechnology company BioMarin Pharmaceutical is a leader in the development and commercialization of biopharmaceuticals for rare diseases with genetic causes. Its pipeline is robust, with several therapies at various stages of development and trials.
In the summer of 2016, as development of their investigational gene therapy for hemophilia moved forward, the company embarked on a project to construct a new manufacturing facility within a seemingly impossible time frame. The resulting facility, built and commissioned in only 11 months, demonstrates that the impossible can be achieved with dedicated people, a solid plan, and the right amount of faith.
On a Fast Track
The company launched Project FAITH on 2 August 2016. One year later, BioMarin announced that valoctocogene roxaparvovec, its AAV-factor VIII vector investigational gene therapy for hemophilia A, was ready for Phase III trials. The building project was fast-tracked for both business and therapeutic reasons, with the new facility targeted to support clinical trials before the end of 2017. To meet this goal, BioMarin elected to repurpose their existing office/warehouse building in Novato.
Because therapies such as valoctocogene roxaparvovec have life-changing potential, the Project FAITH team understood the need to work quickly while keeping their eyes on longer-term objectives. “Although it has a speciﬁc purpose right now, the intent is that this facility will be ﬂexible and able to expand to meet not only our current manufacturing needs but also our future needs for other gene therapies,” said Carl Albertson, Director of Capital Projects at BioMarin.
While many gene-therapy ﬁrms farm out virus production, the ﬁerce demand for these specialized services often results in delays. To avoid these problems, BioMarin plans to use the facility to manufacture viruses for its products, said Dr. Robert Baffi, BioMarin’s Executive Vice President of Technical Operations, in a 2017 New York Times article. “The new facility also will give the company complete control over manufacturing,” he added.
An Impossible Time Frame
BioMarin’s project team was tasked with developing a plan to repurpose the existing office/warehouse building within the desired time frame. The new facility would include allocations for manufacturing and quality control testing, as well as ﬁlling and packaging suites. It also included new utilities, material staging, a loading dock and site-access modiﬁcations. To accomplish this, several parallel critical paths were swiftly set into motion.
“We held a kickoff meeting and then the next day we started demolition drawings, which were completed in two weeks,” explained Logan Kelley, Senior Project Manager at BioMarin. “By the third week we had started demolition, and at that point, we’d already started our structural drawings and our underground drawings to complete the core and shell. We had those done in approximately six weeks and submitted them to the city so we could start the work.”
Much of the existing facility was gutted, with only about one-third of the office space maintained. The roof was reinforced to support new HVAC requirements and the building shell was strengthened to surpass seismic codes for the area, which is prone to earthquakes.
While the exterior work and site access were still under construction, the building’s interior was outﬁtted and connected to the good manufacturing (GMP) utility systems. This enabled the process development team to commence their critical test runs in May 2017; these included two process development runs, an engineering run, and three successful media ﬁlls, followed by GMP release for production in August 2017.
“A key piece of our success was that we had an overarching vision; we knew we needed to separate the packages to stagger design and construction activities, so they could overlap each other and we could achieve our aggressive schedule,” said Kelley.
Deﬁning a New Process
“We dedicated all our key resources and co-located them in the same area with the contractors and consultants, so that everybody just focused on talking to each other as opposed to emailing or calling or trying to set up a meeting. We could make decisions and communicate on the ﬂy and have morning huddles to make sure everybody knew what everyone else was doing,” said Albertson.
“And while we were constructing the building, we were concurrently doing manufacturing for process development and testing in the same facility. So we had to coordinate the activities and keep everyone safe while we were doing multiple tasks in this building.”
Bringing BioMarin’s ﬁrst-ever sterile ﬁlling and packaging suite online in the prescribed time frame presented its own unique technical challenges. The operational readiness team met this challenge head-on, hiring and training new staff in parallel while construction took place. Operators were trained on the ﬁlling equipment as it was being installed, and were given a full-scale wooden model of the isolator to help them reﬁne their procedures while preparing for the ﬁnished equipment train.
In keeping with industry trends, the validation team quickly set to work as design documents were developed, allowing factory and site acceptance testing to be leveraged. BioMarin also quickly formed strong relationships with their raw materials suppliers, which helped them understand and overcome challenges in setting up critical supplies for start-up testing as well as GMP runs. In total, BioMarin developed and approved 1,546 GMP documents to support the fully operational facility in under eight months!
Final cost for the project came in at an amazing 1% above the approved budget. According to Kelley, the key to the project’s notable success was about getting everyone involved and moving in the same direction.
Sustainability: Wyeth Pharmaceuticals Co., a Pﬁzer Company
OSD FACILITY: WORLDWIDE MODEL FOR SUSTAINABILITY
Pﬁzer Consumer Health has manufactured oral solid dosage (OSD) pharmaceutical and health supplement products at its facility in Suzhou, China since 1995. In recent years demand for the Caltrate and Centrum health supplements manufactured there has increased rapidly. To meet the demand and to plan for future growth, the company decided to build a second manufacturing facility in Suzhou. The new facility has become a model for sustainable design, not just for China and not just for Pﬁzer, but the pharmaceutical industry as a whole.
Committed to Sustainability
From the beginning of the project, the project team highlighted environmental sustainability as a key driver, in alignment with Pﬁzer’s corporate objectives.
In its 2017 Annual Review, Pﬁzer Inc. reiterated its commitment to protecting the environment through its Environmental Sustainability Council, which focuses on three cores areas: “mitigating climate change and its impact through reductions in our greenhouse gas emissions; reducing waste through the lifecycle of our products; and reducing water use.”
Paul Chiu, Global Engineering, explained that “at Pﬁzer, Senior Management in the United States pushes all sites to think about sustainability, and they want to see it reﬂected in facility design. Very early in the project, we set an initial objective to achieve LEED (Leadership in Energy and Environmental Design) Gold for the site, for both the manufacturing building and for the office building.”
Project leaders also recognized the potential to set a new benchmark for the industry in a region with serious sustainability and environmental challenges. “On one side we are responding to Pﬁzer’s objectives, but in parallel we are also responding to the Chinese government’s expectations of how Western companies in China should be performing,” says Chiu. “It is not unusual for the government to expect Western companies like Pﬁzer to set a higher standard in the hopes that we will inﬂuence the local companies to follow.”
“I commend our team in China for their thoughtful approach to this project, incorporating energy conservation and environmental protection technologies, including highly efficient equipment, solar power generation, a water recycling system, a heat recovery system, and a smart rainwater harvesting system,” said Kirsten Lund-Jurgensen, President, Pﬁzer Global Supply.
Led by Yuyi Meng (Engineering Leader) and Jianlong Xie (Utilities Leader), the local team worked closely with Pﬁzer’s subject matter experts in the United States and Europe. Corporate practices advocate that all Pﬁzer engineering projects include good engineering practices (GEP) for environmental sustainability.
For the Suzhou facility, these included but were not limited to:
- Energy-efficient mechanical equipment, such as chillers, cooling towers, air compressors, and air handlers
- Efficient water-conservation equipment, such as cooling towers, laundry washers, toilets, and shower ﬁxtures
- Air, water, and steam discharge systems to maximize energy recovery, such as steam condensate heat recovery to preheat hot water for processes and domestic use
- LED lamps throughout the facility
- Parameters that challenge the air-conditioning systems to allow for the widest possible temperature and humidity ranges without compromising GMP or product requirements
As the plant becomes operational, energy and water utilization will be reviewed for additional opportunities in design and operational practices.
To push the boundaries of sustainable design, Meng and his team consulted with employees from the ﬁrst Suzhou facility. “The idea was to get the entire plant staff to be engaged in support of an energy-saving design,” explains Chiu. “The team received many submissions from employees making suggestions on how we could make contributions. However, the goal was not just to solicit ideas but also to make them feel that they are part of a very noble effort.” Many employees’ ideas were adopted in the new facility design.
As the team ﬁnished their design, they realized that in surpassing GEP, they were also able to move beyond their initial target of LEED Gold certiﬁcation. Chiu said, “We received LEED Platinum certiﬁcation in the fourth quarter of last year as the project came close to completion.”
Both the manufacturing and the office and laboratory building were certiﬁed, making the Pﬁzer Suzhou facility the world’s ﬁrst LEED Platinum certiﬁed pharmaceutical manufacturing campus. It also received the China Two Star Energy certiﬁcation for a manufacturing site, with requirements very similar to LEED Platinum.
While the new site is destined to produce health supplements, Chinese regulations classify it as a pharmaceutical plant, no different than if it were producing prescription drugs.
“Our sustainable design has enabled us to reduce carbon emissions by 4,000 tons per year, which is equivalent to planting 235,000 trees,” says Meng. “In addition, our water consumption is reduced by 40,850 tons per year.”
Chiu believes that it was the passion of senior management and the local team that allowed the project to go the extra mile to achieve LEED Platinum certiﬁcation. And it was well worth the effort: “Some people think that you have to spend a lot of extra money to achieve that Platinum standard, but I don’t think we spent more than 0.5% of the project budget to achieve this certiﬁcation.”
The new Pﬁzer Suzhou facility has been producing performance lots since October 2017; it expects to receive certiﬁcation from the Chinese authorities to enter full production in the second quarter of 2018.
“What was unique about this project,” says Chiu, “is that it was 100% built by the local team. I am not sure if I know of any other greenﬁeld facilities in China built by Western companies that are 100% entirely built by the local team.”
Honorable Mention: Emergent BioSolutions, Inc.
NEW FACILITY PROTECTS AGAINST PUBLIC HEALTH THREATS
Since 2000, the United States has endured biological attacks with anthrax-laden letters; natural outbreaks of diseases like severe acute respiratory syndrome, Ebola, and Zika; as well as inﬂuenza pandemics. In response to such national emergencies, the Biomedical Advanced Research and Development Authority (BARDA) in the Office of the Assistant Secretary of Preparedness and Response within the US Department of Health and Human Services, set out to enhance the government’s ability to develop and manufacture medical countermeasures to address these and other threats using the public-private partnership model.
In 2012, BARDA entered into a 25-year partnership with Emergent Bio-Solutions, a global life sciences company that provides specialty products to address accidental, intentional, and naturally occurring public health threats. Emergent was designated one of three national Centers for Innovation in Advanced Development and Manufacturing (CIADM), a network of sites designed to provide development and manufacturing capabilities for rapid deployment in response to public health emergencies.
“Our FOYA project was centered around being able to make 50 million doses of pandemic ﬂu vaccine within four months of pandemic declaration [by the World Health Organization],” says Scott Battist, VP, General Manager and Site Head for Emergent’s Bayview site. “We knew we needed a facility with signiﬁcant capacity that could run a wide range of processes, but we didn’t know on which speciﬁc expression platform (microbial, mammalian or insect cell culture, viral vector, etc.) the pandemic ﬂu vaccine would best be developed.” This upstream uncertainty demanded ﬂexibility to handle a wide range of downstream processing requirements.
Designing for the Unknown
In mid-2013, the Emergent team began conceptual design for a 56,000-square-foot CIADM facility to be built adjacent to its existing Bayview facility in Baltimore, Maryland. Design and site work began in 2014, followed by construction in the summer of 2015. As of early 2018, the facility is in the ﬁnal stages of commissioning and qualiﬁcation. In engineering this building, Emergent deﬁned a new type of biotech facility: one that is operationally agile enough to change product campaigns quickly, with minimal limitations. The iterative design process was instrumental in delivering the ﬂexible, responsive, process-agnostic platform that BARDA demanded while still giving Emergent a facility that could meet internal needs.
Flexibility is a key design feature. Unlike most pharmaceutical production facilities, Emergent did not design for a speciﬁc process, but instead considered a variety of processes that it could potentially run in the future. “It could be anything covering microbial, cell culture, or viral expression systems to produce the bulk vaccine,” says Battist.
As a result, the facility’s scalable space, coupled with a singular focus on single-use technologies, can accommodate varied process platforms and is ready for the plug and play of current standard cGMP equipment trains. If demand and supply timelines require higher downstream throughput, for example, the operations team has the capacity to run parallel units to meet the required productivity. The utilities and space are available, and in most cases, existing equipment can be moved to accommodate any necessary new equipment.
BARDA’s partnership with Emergent requires the company to react quickly to declared emergencies. “If a flu pandemic were declared, we would receive notiﬁcation from BARDA to start vaccine manufacture and would be expected to produce 50 million ﬁlled, ﬁnal doses of vaccine within four months, with ﬁrst doses being delivered within 12 weeks of the notiﬁcation from BARDA,” says Battist.
Once a platform is validated, the pandemic production schedule includes:
- Bulk antigen production
- Bulk antigen quality control release
- Final ﬁlling
- Final drug product release
BARDA’s partnership also requires that the government keep the CIADM facility busy for six months of each year. This includes work on inﬂuenza viruses as well as other clinical trial material. “In addition to pandemic ﬂu vaccines, the facility is also capable of manufacturing other medical countermeasures for the US government under the same CIADM contract with BARDA. To date these have included production of anti-Ebola therapeutic monoclonal antibodies from a CHO (Chinese hamster ovary) cell line. This facility-ﬂexible approach also allows the site to accept contract manufacturing work as well as produce its own products, and has been building a strong business around all three sources of work. The facility is capable of manufacturing products from a variety of platforms including microbial, cell culture, and viral/cell culture for their customers and stakeholders,” explains Battist.
The company recently adapted the facility in response to its acquisition from GSK of raxibacumab, the only monoclonal antibody therapeutic licensed by the US Food and Drug Administration to treat and prevent inhalational anthrax. This product, which will serve as the site’s anchor commercial product, will be produced using Emergent’s ﬁrst-in-kind 4,000-liter single-use bioreactors, an equipment capability that was neither considered nor discussed during facility design. It was easily accommodated, however, by the ﬂexible nature of the facility, which allows these systems to be installed with minimal utility distribution systems modiﬁcations and no necessary changes to building architecture, structure, or infrastructure.
Honorable Mention: Government Pharmaceutical Organization (GPO)
GMP FACILITY SECURES A SUSTAINABLE SUPPLY OF HIV MEDICINES
Despite much progress, HIV/AIDS continues to be a global health issue. The problem is particularly severe in Thailand, which accounts for approximately 9% of cases in the Asia–Paciﬁc region. Out of a national population of 66 million in 2016, an estimated 450,000 people were living with HIV and 6,400 died of AIDS-related illnesses. The situation is compounded by the high cost of importing HIV drugs as well as the difficulty of producing enough medicine domestically.
The Government Pharmaceutical Organization (GPO) has responded to the challenge by building a new facility that follows international best practices to greatly increase its ability to produce cost-effective, high-quality, much-needed HIV drugs.
Adopting Best Practices
GPO is the largest pharmaceutical producer and distributor in Thailand. GPO purchases API from countries such as India, China, and the EU to produce and package drug products, then distributes them to hospitals, clinics, and its own retail outlets.
The company’s desire to boost capacity at its 50-year-old production site in Bangkok led to a major construction project: a new medicine manufacturing facility north of the capital in Rangsit. The plant, which follows Association of Southeast Asian Nations (ASEAN) alignment to PIC/s international good manufacturing practices (GMP), has become a key part of the Thai government’s efforts to control and treat HIV infections. The plant produces antiretroviral (ARV) medicines, in addition to other drug products.
While the existing Bangkok facility still uses paper-based processes, the Rangsit facility has integrated IT systems that allow an entirely paperless and compliant operation. “When we created the new facility, we looked at how we could reduce the paperwork and how to easily track every batch of every medicine we produce,” explains Dr. Mukdavan Prakobvaitayakit, Deputy Managing Director of GPO. “We integrated key systems, including MES (manufacturing execution system) for managing the process, eQMS (electronic quality management system) for managing documents and training, and LIMS (laboratory information management system) for managing the laboratory, in addition to the legacy ERP (enterprise planning system).”
“GPO produces more than 5,000 batches per year, and we wanted to gain more efficiency out of the system,” says Mr. Teerapong Cheepchol, Deputy Managing Director of Factorytalk Co., Ltd., the IT solutions supplier on the Rangsit project. “We looked into systems like MES batch recording and LIMS systems to make sure that all information is highly integrated and we are able to transfer back to the originator. No one else in the region has this high integration of their systems; this is a case study for the industry here in Thailand to see the beneﬁt using IT systems.”
Its alignment with PIC/s GMP, coupled with GAMP® best practices, has made the Rangsit facility able to supply local HIV medicines at a price 20 times lower than imported medicines, while still achieving global quality standards. In 2017, the facility’s production capability was 1.5 billion tablets/ capsules. According to Dr. Prakobvaitayakit, expansion of the facility is imminent, which will increase annual production capacity to 4.5 billion tablets/capsules by 2020.
“The technology is very important because it helps us to reduce our costs,” she says. “We serve many patients at the public hospitals, and this means that we can serve more people in Thailand for this price. It makes us proud because this project is for the patients who gain access to specialty medicines. We worked so hard to have this factory and now our hard work has been fruitful.”
The Rangsit facility has been inspected by the World Health Organization (WHO) and found satisfactory, since GPO submitted the HIV dossier for HIV drugs to the WHO Prequaliﬁcation Program—the ﬁrst plant in Thailand to achieve such status. “We love that we can supply medicines to our Thai patients, and now elsewhere in the region, like Myanmar and Cambodia,” says Dr. Prakobvaitayakit. “The government pharmaceutical factory in Myanmar also want us to do a technology transfer, so we are happy that our project can be shared with the other nearby countries; that makes us very proud.”