PHARMACEUTICAL & BIOTECHNOLOGY

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UNITED STATES

Cleanroom Clampdown at Lucile Packard Children’s Hospital

A new compounding pharmacy cleanroom at Lucile Packard Children’s Hospital Stanford, in Palo Alto, Calif., was slated to open in November 2019. But a number of unforeseen, yet somewhat unsurprising, factors prolonged that timeline—from improper plumbing to the COVID-19 pandemic.

“We’re in a holding pattern,” said Renee Barker, PharmD, the sterile products manager at the hospital.

Dr. Barker’s experience could provide lessons for others looking to build or remodel a cleanroom. As she learned from previous builds and remodels, a successful move into a new pharmacy cleanroom requires determination and diligence in design planning, construction monitoring and environmental testing. It also necessitates ongoing communication with everyone involved in the project.

Before the COVID-19 pandemic, Dr. Barker’s team was awaiting one of the final steps: the state board of pharmacy’s inspection of the cleanroom. When that will now happen is unclear; yet Dr. Barker highlighted informative experiences over the previous several months of construction and testing of the cleanroom, which will be part of a new fifth-floor oncology unit at the main hospital building. “Awaiting final inspections, licensing and eventual opening of our newest pharmacy is our remaining challenge,” she noted. Another cleanroom is currently compounding the oncology drugs.

Dr. Barker had been involved in a previous cleanroom construction that opened in 2017, as reported in Pharmacy Practice News (bit.ly/2S5263H). The process for that original construction began almost 10 years before the actual opening, due to the magnitude and complexity of the expansion. “The regulations surrounding sterile compounding were, and continue to be, in a constant state of flux,” she said. “A moving target of regulations is a challenge, when architectural plans require a ‘snapshot’ of regulations to set a design in place. Later requests to modify designs may or may not be able to be accommodated.”

The process for the new cleanroom has been smoother with fewer surprises, and she attributed much of that improvement to involving a subject matter expert (SME) in sterile compounding in all the meetings, logs and final sign-offs. The SME understood USP General Chapter <797> for sterile compounding and USP <800> for handling hazardous drugs, as well as state board of pharmacy regulations and FDA guidance that address sterile compounding facilities.

“I was also more directly involved with the key players—the architect, project managers, construction managers,” Dr. Barker said. “The pharmacist should have the ultimate sign-off.”

She underscored the value of keeping a timeline with a “frequent cadence for meetings.” For her team, that meant meetings on a weekly basis. “Everyone was on the phone or met in person—back when we could,” Dr. Barker said. “That was really helpful.”

A few challenges still emerged. Sterile compounding regulations, building codes and occupational safety guidelines, combined with the Americans with Disabilities Act (ADA), can “start to be mutually exclusive,” Dr. Barker said. For example, the eye wash station in the anteroom lacked a sink or catch basin for the water. The scrub sink was supposed to be deep and high, for example, yet then the eye wash could not go above it and still meet ADA requirements. Her team resolved the issue with a workflow solution. “But it’s not ideal,” she said.

The scrub sink itself posed another obstacle. The contractor purchased a stainless steel sink that had copper lining on the inside and edges of the basin. But when the entire room was treated with a triple sporicidal disinfectant cleaner, the copper parts of the sink corroded. “It looked like some beautiful fountain in Italy,” Dr. Barker recalled, but it had to be replaced, which added to the delays.

Even after construction is completed, there still may be further holdups. It can take a couple months after a request is filed for an initial inspection, she noted, adding that, based on the inspection, follow-up and physical changes may be needed.

Once inspectors pass the space, then the baton is passed on to licensing. Her team has found that this step also can take months. “That’s where we have got hung up in the past,” she said. “You can know you passed, but that doesn’t mean anything until it’s posted on the website.”

A technician and intern beginning a sporicidal cleaning of a new biological safety cabinet in the new pharmacy at Lucile Packard Children’s Hospital Stanford.

In the state of California, a pharmacy also has to request a second inspection from the California Department of Public Health. That agency then has 100 days from when the license posts and the request comes in to inspect. The pharmacy can only open after that final inspection has been signed off.

During all phases of a project, Dr. Barker recommended that pharmacies constantly review requirements and touch base with architects and construction managers. “Sterile compounding regulations speak to [how they are applied] in a building. So, you have to evaluate whether it meets requirement at all times. That means a lot of conversations.”

It also means digging into the intricacies of which USP chapters are final, which have been challenged and how much of the guidance documents can or should be enforced. “Despite the many changes to regulations, we are fortunately compliant with all current structural requirements for sterile compounding,” Dr. Barker said.

Remote Tech Helps Hospital Pass Certification

Jerry Siegel, PharmD, the vice president and managing partner of Safe Medication Management Associates Inc., is consulting for a new hospital pharmacy seeking certification in Ohio. The COVID-19 pandemic, he noted, has “added some additional and unusual wrinkles to the process.”

The state board of pharmacy determined that they were not going to send an inspector before opening the new pharmacy cleanroom suites. “Instead they wanted us to send a video tour of the facility highlighting the key features to meet USP <797> and USP <800> standards,” Dr. Siegel explained.

They created a video that showed, among other features, interlocking sliding doors and the ability to monitor and control temperature, humidity, pressures, and air exchanges from a central system in the pharmacy. It was enough to earn approval from the board. Dr. Siegel noted an unexpected benefit: The certification company was “available at a moment’s notice,” given a reduced workload.

“The pharmacy has now passed certification and will be ready for opening,” he added. “Plans for conservation of PPE [personal protective equipment], re-sterilization of PPE with UV-C lights, and alternate plans for cleaning supplies have already been developed.”

Dr. Siegel reported a financial relationship with BD.

What About the Cost?

As far as finding the funds for cleanroom renovations, “It’s not as if you can have a bake sale!” Dr. Barker said. “I have been fortunate that this institution is dedicated to meeting requirements. This is also part of the vision phase, to determine what is needed for compounding, and then design to meet the requirements. The costs vary tremendously depending on the location in which you are building.”

She added a note of caution: “There definitely is a danger in cutting corners; it will probably show up as a deficient [compliance area] in the future, and making changes in an existing cleanroom can cause downtime, vendor testing, etc. This is expensive in terms of money, time and patient care.”

More Construction Cues

Asked to comment on strategies for successful cleanroom and pharmacy renovations, Gene Decaminada, RPh, the manager of compounding compliance for Option Care Health, highlighted a few critical construction considerations. These include installing a hands-free anteroom sink, window ledges that are slanted or flush to the wall, ledge-free floor coving that is flush with the wall, and sealed wall panels and ceiling light fixtures. He also underscored the importance of making a line of demarcation large enough in both the anteroom and negative pressure room to accommodate cleanroom staff.

Stevanato Preparing to Open Technology Excellence Center in Boston (US TEC)

The new center will provide a full-service approach to support biopharmas along their drug development journey, from the early phase to commercialization and lifecycle management.

Since 2013, an interdisciplinary team of researchers and scientists in Italy have been conducting a wide range of testing, from container performance to chemical analysis. Through the years, the company also strengthened its analytical capabilities with a network of collaborators and partnerships, such as with Pfeiffer Vacuum for Container Closure Integrity Testing.

Set to open its doors in late September, US TEC will support biopharma drug development throughout the lifecycle, helping them overcome the challenges of the container-closure system.

The technology and knowledge transfer from the Italian laboratory will be finalized in the fall. Leveraging the Group's knowledge in material science of glass, plastics, and rubber, US TEC will support one of the most binding decisions for biopharma industry players: how to select the optimum glass container. Making the right choice during the early-stage of product development ensures two-fold compatibility: Drug and Container Closure System, as well as Container Closure System integration into drug delivery devices.

By partnering at an early stage, US TEC can anticipate challenges and present viable, well-informed solutions to its biopharma customers, saving development time and resources.

"R&D represents a key driver for Stevanato Group's growth. From its outset, the US TEC will advise on materials science, chemistry, and engineering performing many added value analytical tests focusing on container closure characterization as well as fill&finish development and optimization. In the second phase, we will be adding customized solutions dedicated to product development and functional testing of primary containers and drug delivery devices. Located in the cradle of biotech, US TEC can easily integrate within the product development team and the value chain of our local customers,” said Paolo Patri, Stevanato Group Chief Technology Officer.

"As pharma companies are under pressure to find more effective and safer treatments rapidly, more clinical trials take place, and new emerging therapies are developed and tested. Being in the US, we can offer timely solutions for robust product development for these therapies. With our dedicated team of subject matter experts, we work as a single point of contact coordinating internal resources and our best-in-class network of partners and consultants", said Abizer Harianawala, Site Leader at Stevanato Group's US TEC.

Berkshire Sterile Manufacturing Expands Facility

Berkshire Sterile Manufacturing (BSM) has secured $16.5 million in financing from Berkshire Bank and Lee Bank to expand its operations in Lee, MA. This financing will be used to add manufacturing capabilities including an additional robotic line for producing sterile drug products in vials, syringes, and cartridges. BSM will also install a new pharmaceutical-grade water system, add additional testing capabilities in their microbiology and analytical labs, expand their warehouse, and double the size of their cleanrooms.

Dr. Andrea Wagner, senior vice president business development, said, "We are pleased that Berkshire Bank and Lee Bank were able to provide the financing we need to double our capacity to serve the needs for clinical manufacturing of sterile injectable drugs for COVID-19 and other diseases. We expect to hire an additional 60 employees over the next two years to support our growth."

The company, founded in 2014 with financing from Berkshire Bank and MassDevelopment, received a TIF from the town of Lee with a promise to create 60 new jobs in 5 years. "Six years from its founding, BSM employs more than 150 people at its Lee manufacturing facility in high paying career jobs, and we are continuing to hire staff," said HR director, Jennifer Moriarty.

Michael Ferry, Senior Vice President Berkshire Bank, commented, "Berkshire Bank is proud to continue its support of BSM's growth. We were there for BSM as they grew in the last 5 years significantly helping the local economy.”

BSM is placing orders for the new equipment which is being built by companies in the U.S. and Europe. The new equipment will arrive over the next year and a half and will be fully operational by early 2022.

WuXi Biologics to Open Clinical Mfg. Facility in Cranbury, NJ

WuXi Biologics has signed a 10-year lease for a clinical manufacturing facility (MFG18) in Cranbury, NJ.

The new facility will install total 6000 L bioreactors, Process Development (PD), Quality Control (QC) labs, along with supporting functions. The 66,000-sq.-ft. facility is expected to become operational in late 2020 and will add as many as 100 jobs to the region.

WuXi Biologics' also recently purchased land to build a new 107,000-sq.-ft. clinical and commercial manufacturing facility in Worcester, MA, and leased a 33,000-sq.-ft. site to establish a process development lab in King of Prussia, PA.

"We are excited to announce our third site in the United States and proud to become a member of the New Jersey community. Cranbury is a growing hub for the biotech and biopharma industries, and we look forward to working with and serving our partners in the area to benefit patients worldwide," said Dr. Chris Chen, CEO of WuXi Biologics.

Crusader Community Health Planning New Clinic

Crusader Community Health is planning the construction of a two-story, 50,000 sq. ft. health clinic in Rockford. It is being designed by Hagney Architects. The project is valued at $15 million. They have been in the process of taking bids for the project.

Bluebird Opens Gene Therapy Plant as EMA Backs Gene Therapy

The EMA has recommended approving Zynteglo, bluebird bio’s one-off treatment for beta-thalassaemia. Meanwhile the cell and gene therapy firm has cut the ribbon on a 125,000-square-foot facility in Durham, North Carolina.

The EMA’s Committee for Advanced Therapies (CAT) recommended Zynteglo (autologous CD34+ cells encoding βA-T87Q-globin gene) – also known as LentiGlobin – paving the way for bluebird bio to bring its gene therapy product to market.

The product uses a lentiviral viral vector to add functional copies of a modified β-globin gene into a patient’s own stem cells, addressing the underlying genetic cause of patients for whom a related donor for stem cell transplantation is not available.

The European Commission (EC) will now review the product before granting bluebird marketing approval or not. The Committee for Medicinal Products for Human Use (CHMP) meeting was the first to be held in Amsterdam following the EMA’s arrival in the Netherlands due to the current Brexit debacle.

NC manufacturing plant

In November 2017, bluebird bio acquired a facility in Durham, North Carolina and after investing $80 million in the site, the firm has now cut the ribbon on the lentiviral vector facility.

The plant will support bluebird’s cell and gene therapy candidates including bb2121 and bb21217 for the treatment of multiple myeloma and LentiGlobin for the treatment of transfusion-dependent β-thalassemia (TDT) and sickle cell disease.

The 125,000 square-foot facility is the first inhouse production site for bluebird, which has relied up to now solely on contract development and manufacturing organizations (CDMOs) and services firms including Brammer Bio, Novasep and MilliporeSigma. The new plant will not affect these multi-year contracts, the firm has said.

The facility is “a crucial step toward our mission of bringing a new generation of treatments to people living with severe genetic diseases and cancer,” said bluebird CEO Nick Leschly.

Seqirus Goes Fully Cell-Based for Seasonal Flu Vaccine

Seqirus’s vaccine offering for the future will be uniquely cell-base, but the firm says traditional egg-based production still plays a role in fighting influenza.

Provided each year by the World Health Organization (WHO) Global Influenza Surveillance and Response System (GISRS), candidate vaccine viruses (CVVs) are the basis for the development and production of seasonal influenza vaccines.

For the 2019/20 season, Seqirus had decided to use a cell-based CVV for all four influenza strains recommended by the WHO for its quadrivalent influenza vaccine, Flucelvax.

“While production for Flucelvax Quadrivalent will be exclusively cell-based for the 2019/20 season, traditional egg-based production process plays a critical role in the fight against influenza, and we continue to manufacture and distribute egg-based vaccines globally,” said a Seqirus spokesperson. Egg-based vaccines work and have been proven to be safe and effective, but there has been a shift to cell-based production to help ensure manufacturers can meet global demand for vaccines.

“There are several studies highlighting the potential benefits of cell-based influenza vaccines compared to egg-based vaccines. An analysis by S. Rajaram evaluated antigenic match between the circulating H3N2 influenza virus and the cell-derived or egg-derived virus used in influenza vaccines and showed that egg-derived vaccine viruses have consistently higher levels of mismatch than cell-derived vaccine viruses.

“Two independent studies, one conducted by the US FDA/CMS and the other by Kaiser Permanente Northern California, found cell-based influenza vaccines to be more effective than egg-based influenza vaccines during the 2017/18 season.”

The firm would not, however, comment on the cost differences between egg and cell-based vaccine production and the knock on for payors and patients.

“We do not discuss pricing for future seasons, which is determined by a number of factors, including but not limited to anticipated demand.

Seqirus is a division of Australian firm CSL Limited, established in 2015 following CSL’s announcement to acquire Novartis’ global influenza vaccine business. The deal went through in 2016.

According to the spokesperson, the firm is the largest cell-based influenza vaccine producer in the world and supplied more than 20 million vaccine doses of quadrivalent influenza vaccine (QIVc) in the US during the 2018/19 influenza season.

And the firm continues to invest in process improvements and capacity to meet demand.

“We have scaled up our plant at Holly Springs significantly – quadrupling production over the last three years.” The $140 million (€124 million) expansion in North Carolina, announced last November, will create 120 jobs once completed next year.

“With continued investment in process improvement, such as the FDA approval of our next generation cell-based manufacturing process, and the $140 million expansion of our manufacturing facility, we are in a strong position to meet year on year increases in global demand.”

Cambrex Completes Highly Potent API Manufacturing Facility at Charles City, IA

Cambrex Corporation (NYSE: CBM), the leading small molecule company providing drug substance, drug product and analytical services across the entire drug lifecycle, announced that it had completed the construction of a $24 million highly potent API (HPAPI) manufacturing facility at its site in Charles City, IA. The 6,000 sq. ft. facility is currently undergoing validation. The production area will operate to an occupational exposure limit (OEL) down to 0.1µg/m3 and contain 4 reactors ranging from 200 to 1,000 gallon capacity enabling manufacturing campaigns of batch sizes up to 300 kg. With the completion of this new facility, the Charles City site now has the flexibility to support all phases of development and offer all scales of HPAPI manufacture across the full OEL band spectrum.

“Across our sites, Cambrex has a strong reputation in the handling and supply of potent molecules, and this investment allows us to increase the capacity we can offer our customers,” commented John Andrews, VP, Operations & Site Director, Cambrex Charles City. “We have seen an increased number of molecules in the clinical pipeline being designated as potent and highly potent, so having the flexibility within our manufacturing network to scale up with existing customers as projects progress, as well as accommodate new projects, is crucial to meet those market needs.”

Cambrex’s Charles City, Iowa facility employs over 370 people and is located on a 45-acre site. The site is part of the company’s Drug Substance business unit and manufactures a wide range of APIs and pharmaceutical intermediates, including highly potent molecules and controlled substances.

About Cambrex:

Cambrex is the leading small molecule company that provides drug substance, drug product and analytical services across the entire drug lifecycle. The company provides customers with an end-to-end partnership for the research, development and manufacture of small molecule therapeutics. With over 35 years’ experience and a growing team of over 2,000 experts servicing global clients from sites in North America and Europe, Cambrex is a trusted partner in branded and generic markets for API and dosage form development and manufacturing.

Cambrex offers a range of specialist drug substance technologies and capabilities including biocatalysis, continuous flow, controlled substances, solid state science, material characterization and highly potent APIs. In addition, Cambrex can support conventional dosage forms including oral solids, semi-solids and liquids and has the expertise to manufacture specialist dosage forms such as modified-release, fixed dose combination, pediatric, bi-layer tablets, stick packs, topicals, controlled substances, sterile and non-sterile ointments.

Paragon to Build Second GMP Mfg. Facility

On the heels of its acquisition by Catalent, Paragon Bioservices, the biologics contract development and manufacturing organization (CDMO), is forming a wide-ranging partnership in gene therapy manufacturing with Sarepta Therapeutics. The two companies will seek to establish additional dedicated facilities for manufacturing Sarepta's gene therapy candidates.

Prior to the news, Catalent unveiled its intent to acquire Paragon for $1.2 billion. With the future support of Catalent and the opening of its new, state-of-the-art commercial manufacturing center near the Baltimore-Washington International Airport, Paragon is positioned to advance gene therapy products including Sarepta's Duchenne muscular dystrophy (DMD) gene therapy candidate. The new large-scale production campus—now combined with a recently leased second building which will be built out for commercial GMP manufacturing—has the potential for more than 425,000 square feet of manufacturing space upon completion of construction. The facility will offer individualized manufacturing suites specially designed to handle the needs of gene therapy products.

Sarepta has developed proprietary manufacturing capabilities for the development, scale-up and purification of its gene therapy candidates for clinical development and commercialization.

"With the recent grand opening of our new manufacturing facility, the expansion of our relationship with Sarepta, and the anticipated transaction with Catalent, Paragon is positioned to be the premier leader in gene therapy manufacturing," said Pete Buzy, president and chief executive officer, Paragon. "Paragon's level of expertise and experience in this area is unparalleled. That together with our high caliber partners and customers will allow us to meet the manufacturing demands of the double-digit growth in the gene therapy market."

Paragon and Sarepta will use their respective strengths in gene therapy manufacturing, as well as the related development techniques including bioanalytics, to take viral vector manufacturing to the next level. The partners will explore the potential for a joint venture in manufacturing new gene therapy candidates in a dedicated facility.

Douglas S. Ingram, president and chief executive officer, Sarepta, said, "We are excited to begin work on this new venture with Paragon and ultimately Catalent. Sarepta has had a long and fruitful relationship with both Paragon and Catalent, one of Sarepta's current PMO drug manufacturers, and we are particularly pleased to expand our relationship with both companies. Catalent is a well-resourced innovator with an outstanding reputation for operational excellence, product quality, and reliable supply. By making our expertise available to Paragon and Catalent, we can ensure the success of our own manufacturing programs and explore potentially new and enhanced techniques to drive innovation in gene therapy manufacturing."

"The unmatched expertise of both Paragon and Sarepta in developing and overseeing the manufacture of potentially transformative gene therapy technologies will be a tremendous asset to Catalent," said John Chiminski, chief executive officer, Catalent. "We are delighted to have this opportunity to work together with Sarepta in this high-growth and life-saving field of medicine."

G-CON PODs Selected as Supplier for Just – Evotec Biologics

G-CON Manufacturing announced the company will support Just – Evotec Biologics, a wholly-owned Seattle-based company of Evotec SE, with their construction of a late-stage clinical and commercial manufacturing facility for biologics in Redmond, Washington. The news comes shortly after the announcement of the construction of Just – Evotec Biologics’ first J.POD® facility in North America, creating the “Facility of the Future” to provide flexible and modular, larger scale manufacturing of clinical and commercial-stage biologics.

Just – Evotec Biologics’ J.POD® technology features small intensified bioprocessing operations housed inside G-CON cleanroom PODs. G-CON will design and fabricate the PODs for cGMP manufacturing suites that require mobility and reconfigurability to meet current and future needs. The one-of-a-kind cGMP biomanufacturing facility includes six J.PODs® for upstream and downstream processing, totaling 8,825 sq. ft. of cleanroom space using the G-CON POD product. A key feature of the facility is its flexible platform design with the ability to scale out with additional PODs in the future without interrupting existing processes, resulting in zero operational scale-up risks.

The facility is part of Just - Evotec Biologics’ plan to provide flexible, high-quality manufacturing while de-risking drug discovery and development, not only for Just – Evotec Biologics, but also for Evotec’s partners.

“We treasure the partnership with Just – Evotec Biologics, a company supporting the shared vision of highly flexible and readily deployable manufacturing sites,” said Maik Jornitz, CEO of G-CON.

Amicus Opens New Gene Therapy Center of Excellence

The new center expands the company’s R&D capabilities and will help it advance its portfolio of rare disease gene therapy programs.

On March 5, 2020, Amicus Therapeutics announced the official opening of its new Global Research and Gene Therapy Center of Excellence in Philadelphia, PA, to advance its portfolio of rare disease gene therapy programs. Amicus and the University of Pennsylvania (Penn) had earlier announced a major expansion to their gene therapy collaboration in 2019, which provides Amicus with disease-specific worldwide rights to Penn’s next-generation gene therapy technologies from Wilson Lab. The gene therapy technologies focus primarily on lysosomal storage disorders as well as twelve additional more prevalent rare diseases, including Rett Syndrome, Angelman Syndrome, and select other muscular dystrophies.

The 75,000-ft2 center is located on the top three floors of the new building and consists of office and state-of-the-art laboratories. It will ultimately house approximately 200 researchers and drug developers focused exclusively on gene therapies.

“This is a remarkable advancement in the history of Amicus and further strengthens our great collaboration with Dr. Jim Wilson and the Gene Therapy Center at Penn. Philadelphia is a magnet for talent in gene therapy and an engine for innovation. This new global research center located in the ‘cradle of liberty’ will become part of the ‘cradle of cures’ as we move many gene therapy programs forward toward patients in need. With exclusive global rights to 50 rare diseases in collaboration with Dr. Wilson’s team we hope to be able to alleviate an enormous amount of human suffering with the great science work that will be done in this new facility,” stated John F. Crowley, chairman and CEO of Amicus, in a company press release.

REST OF WORLD

Rigenerand Receives Regulatory Approval for Gene Therapy Production

Authorization has enabled Rigenerand to enter into clinic, offer CDMO services and consultancy, and plan to expand cleanroom capacity

Rigenerand, a biotech company that both develops and manufactures medicinal products for cell therapy applications, primarily for regenerative medicine and oncology, has announces it has received authorization from the Italian Medicine Authority (AIFA) to produce gene therapy medicinal products for clinical purposes.

This authorization enables Rigenerand to manufacturer its own autologous gene therapy medicinal product (RR001) for the treatment of pancreatic cancer. It also authorizes the company to start its phase I first-in-man clinical trial of RR001, now expected to start in Q1, 2021.

RR001 has been granted Orphan Drug Designation (ODD) by both the US FDA and European Commission COMP (Committee for Orphan Medicinal Products). This ODD offers the opportunity for Rigenerand to request an accelerated assessment procedure and quicker development pathways towards a marketing authorization in the US and EU.

Rigenerand will also now offer direct GMP CDMO services to international and Italian partners in clinical development of cell and gene therapy products (ATMPs). The company will utilize its experience from its drug development and diagnostic arms to deliver a science-based approach to its GMP manufacturing services and cell-based medicinal products development.

Rigenerand plans to expand its manufacturing facility from five sterile cleanrooms suites. This will be by implementing further closed system and isolator technology in pre-designated areas in its facilities.

The five sterile cleanrooms are within the Rigenerand GMP facility, which contains a Biosafety Level 3 (BSL3) negative pressure area, suitable to handle genetically modified microorganisms (MOGM), viruses and Risk Group 3 microorganisms, as well as a Biosafety Level 2 (BSL2), positive pressure area: suitable to manipulate non-infectious cell based products and Risk Group 2 microorganisms. Rigenerand's cleanroom technology offers the flexibility to scale-up the processes from academic / hospital laboratories, and the feasibility of technology transfer of manufacturing processes from other cell factories in order to expand their process capability.

In addition, Rigenerand is now authorized to deliver consultancy to biotechnology and pharmaceutical companies on cell and gene therapy development and manufacturing. This consultancy includes expanding process capabilities and developing early-stage cell and gene therapy medicinal products for clinical purposes.

As the cell and gene therapy sector continues to grow, with increased numbers of therapies moving through clinical development and onto commercialization, demand for CDMO services will continue to grow. There is an increased demand for global networks of CDMO GMP cell and gene therapy manufacturing. This calls for an improved capacity to treat patients whilst reducing logistical complexities, issues, risks, and costs.

"The regulatory approval for Rigenerand to produce gene therapies for clinical development now enables Rigenerand to enter the clinic with its own gene therapy product to target pancreatic cancer," said Massimo Dominici, scientific founder, Rigenerand. "Combined with the Orphan Drug Designation, the approval will enable Rigenerand to choose an accelerated pathway to bring a gene therapy approach to pancreatic cancer patients with little alternative therapeutic option."

"The authorization is also essential in allowing Rigenerand to offer its much needed GMP CDMO services to the wider cell and gene therapy sector," said Giorgio Mari, Rigenerand CEO. "We will be expanding our CDMO facility to cater for increasing demand. Operating as both a developer with a clinical pipeline as well as a CDMO has resulted in an unrivalled blend of expertise for us to offer to partners and the wider cell and gene therapy industry."

Oxford Biomedica Adds Two Suites to Manufacture AZ Vaccine

Oxford Biomedica teams up with VMIC to expand capacity for AZ’s vaccine candidate for COVID-19.

Oxford Biomedica and the Vaccines Manufacturing and Innovation Centre (VMIC) have agreed a partnership for the manufacture of viral vector-based vaccines.

The deal represents the first industry partnership for VMIC, which is a non-profit organization set up to advance the UK’s vaccine development and manufacturing capability.

Both partners will work immediately on AstraZeneca’s adenovirus vector vaccine candidate, AZD122 – after the two organizations had previously aided early work conducted by the University of Oxford.

As part of the agreement, VMIC will acquire the manufacturing equipment necessary to equip two manufacturing suites. VMIC will then deliver the equipment to Oxford Biomedica’s commercial manufacturing center, Oxbox, where the latter company will produce the potential vaccine for AZ.

At present, AZ’s vaccine candidate is regarded as one of the most promising for use against the novel coronavirus. It is likely that the candidate is one of five selected by the US government for additional support and accelerated development.

AZ has partnered extensively to enable it to build the capacity for two billion doses of the vaccine candidate in 2021, with Oxford Biomedica being one such partner.

Oxford Biomedica confirmed that the suites will be used to scale the capacity for AZD1222, but also stated that they could also be utilized for additional viral vector vaccine candidates.

In return, the company will provide VMIC staff members training and technical assistance in the operation of a manufacturing facility producing vaccines.

The training will ready VMIC employees whilst the organization’s permanent facility is completed at the Harwell Campus, in Oxford. VMIC’s manufacturing plant is expected to be completed in mid-2021, after which it will be able to produce up to 70 million vaccine doses in four to six months.

In the longer term, the agreement ‘provides a framework’ for commercial scale manufacturing capacity for additional novel viral vector vaccine candidates for the UK population, ‘when needed’.

SUSupport Expands to Bring in Indian Partner

The Austrian startup provides its single-use equipment to PharmNXT in India.

Single Use Support is based in Tyrolean, Austria, and is specialized in providing single-use equipment to the biopharma industry.

The startup aims to supply equipment to ‘close the gap’ between downstream processing and the fill & finish process.

According to the company, the aim is to provide a secure logistics process for single-use bags, which includes fully automated filling and freezing, refrigerated transport, thawing and emptying of the drugs.

PharmNXT, based in Mumbai, has developed a collaboration with SUSupport to acquire its product portfolio, which it will add to its own capabilities to provide end-to-end equipment for the production of biologics.

According to co-founder of SUSupport, Johannes Kirchmair, the Bulk.Stream process allows for a reduced risk of product loss, as the ‘complete solution’ minimizes the potential for bio-contamination.

As part of this process, up to 20 bags can be filled in parallel to achieve a total volume of up to 200L, with a ‘Freeze-Thaw’ platform allowing the product to be frozen, after which the product can then be transported with SUSupport’s containers.

According to the startup, the expansion into the Indian market follows on from also receiving orders for its products in Europe, the US and China.

FUJIFILM Investing $928M in Denmark CDMO Site

Will double the site's current drug substance manufacturing capacity and will expand capabilities to include fill/finish.

FUJIFILM Corp. is investing approximately $928 million in the Denmark site of FUJIFILM Diosynth Biotechnologies, a CDMO for biologics and advanced therapies. The investment will double the Denmark site's current drug substance manufacturing capacity, and will expand capabilities to include fill/finish, and enhance its current assembly, labeling and packaging services.

The investment will expand production lines for bulk drug substance with the addition of a further six mammalian cell bioreactors, bringing the total to 12 x 20,000-liter bioreactors by fall 2023. The development will also include the addition of the Denmark site's first fill/finish production line (added by summer 2023), with a fully-automated system capable of producing up to approximately 35 million units per year for large-scale production. In spring 2022, a new packaging line equipped with facilities to assemble multiple types of auto-injectors as well as automatic labeling, will be added.

"Our culture of innovation and reputation of manufacturing excellence ensures our rapid growth to better serve the healthcare community," said Takatoshi Ishikawa, executive vice president, general manager of bio-CDMO division, FUJIFILM Corporation. "Since the acquisition of the Denmark site last year, the facility's strong manufacturing track-record, coupled with FUJIFILM Diosynth Biotechnologies' technologies enabling a stable supply of high-quality biopharmaceuticals, has led to new orders not only from existing clients, but also new clients, contributing to our rapid business expansion."

Pall Corp. Establishes Biotech CoE in Shanghai

New facility will provide bioprocess engineering consultancy, technology demonstration, testing and training for China

Pall Corp. has established a Biotech Integrated Solutions Center of Excellence (CoE) in Shanghai, China. The CoE is a new facility for bioprocess engineering consultancy, technology demonstration, testing and training for China and broader Asia.

The facility is equipped with advanced bioprocessing equipment and automation platforms, and technological solutions for biomanufacturing, including single-use cell culture solutions, cell clarification using acoustic wave technology, chromatography using automated packing techniques, viral clearance, tangential flow filtration and mixer / container modules. It is designed to lead customers through the sequential stages of process flow and will serve as a center for new technologies, as well as a training facility for customers and Pall employees.

“As the biopharmaceutical industry moves from traditional batch or single-use processing to continuous bioprocessing solutions, Pall is poised to help customers reduce process development and production costs and drive significant improvements in efficacy and productivity,” president of Pall Corp., Jennifer Honeycutt, explained.

“Our investment in the new Shanghai Centre of Excellence is designed to give Pall customers options ranging from batch to single use and continuous bioprocessing solutions, depending upon where customers are in their journey. The goal is to provide technology solutions that meet their current needs, while offering some of the most progressive technological solutions for the future.” added Honeycutt. “By opening this state-of-the-art facility, we hope to unlock new opportunities for our customers based in China, and for any global customers looking to enter or expand their operations in the Asia Pacific region.”

HALIX to Expand Production of Proteins, Viral Products at New cGMP Facility

HALIX, a Dutch contract development and manufacturing organization (CDMO) focused on clinical and commercial proteins and viral products, has marked the interim completion of a new cGMP facility within Leiden Bio Science Park in the Netherlands. The new facility will specialize in developing and producing biopharmaceutical drug substances. [HALIX]

The new 6,700 m2 (72,118-square-foot) cGMP facility is located within Leiden Bio Science Park, which houses the largest number of bioscience start-ups in the Netherlands among its 103 dedicated medical life sciences companies and institutions, which include Leiden University and Leiden University Medical Center (LUMC).

Construction on the cGMP facility began in July 2018.

“After a construction time of just 12 months we are now able to start production of viral products and protein production will follow soon,” Alex Huybens, HALIX COO, said in a statement. “This milestone aligns with our growth and expansion strategy that will enable us to accommodate the growing market demand as well as our clients’ demands.”

HALIX has said it plans to expand its scope of services for therapeutic proteins and viral vaccines. The company specializes in GMP manufacturing of biologics, by manufacturing drug substance on eucaryotic cells, and by performing aseptic fill and finish and lyophilization services.

Full-scale operational production at the new facility will begin in the fourth quarter, HALIX added.

The five-level production facility contains a manufacturing line for viral vaccines and viral vectors, and a separate protein manufacturing area with a capacity up to 1,000 L single-use bioreactors. Lab space will be available for process development, analytical development, and quality control.

All cleanroom areas have a unidirectional process flow and are designed to allow commercial manufacturing of biopharmaceuticals products, according to HALIX.

“This new facility offers our current and future clients capacity and flexibility for future expansion and will allow for cGMP manufacturing solutions for viral products, proteins, gene therapy, and client-specific new technologies,” added Roland Hecht, HALIX’s chief customer officer.

The cost of the facility has not been disclosed.

Based in Leiden, the Netherlands, HALIX was founded in 2012 and is a 100% owned subsidiary of HAL Allergy Group. Both companies are owned by Droege Group, a family-owned investment firm specializing in long-term, equity-financed direct investments in medium-sized companies or corporate subsidiaries as a majority shareholder.

HALIX says it offers its clients end-to-end drug development services from the start of commercial production after successful registration of products.

Biotechpharma Expands Manufacturing Capacity

Biotechpharma UAB, a biopharmaceutical CDMO, has invested more than €50 million to further expand its fermentation capacity to 5,000 L, along with a new process development lab.

Dr. Vladas Bumelis, chairman of the board, said, “The expansion comes amid growing global demand for flexible and responsive outsourcing partners that are able to support the full product lifecycle, from upstream and downstream process development and optimization to GMP manufacturing of drug substance and formulated drug product.”

“We are thrilled to announce this latest expansion of our infrastructure, as it will allow us to better support our customers’ biological development programs with quality, speed and flexibility of service,” said Giedrius Žunda, chief executive officer of Biotechpharma.

The new plant located at the company’s site in Vilnius, Lithuania, will contain a new line of bioreactors for microbial fermentation at 5,000 L scale and the necessary equipment for downstream processing operations. The flexible facility design will also allow for increased mammalian cell culture production capacities in addition to the existing two lines of 1000-L and 2000-L scale for mammalian cell production, both equipped with single-use bioreactors. Completion of the plant, which should be operational in 4Q20, will result in an increase in volume capacity by nearly double.

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