FDA Approves Flublok Vaccine for Adults

March 18, 2013
First trivalent influenza vaccine based on insect-based recombinant DNA technology
Recently, the U.S. Food and Drug Administration announced it had approved Protein Sciences’ Flublok, the first trivalent influenza vaccine made using the company’s baculovirus expression vector system (BEVS) insect-based recombinant influenza hemagglutinin (rHA) technology. Flublok is approved for the seasonal prevention of influenza in people 18 through 49 years of age. According to Protein Sciences, approval for all people 18 years and above is pending and expected later in 2013.
Unlike most contemporary flu vaccines, Flublok eschews influenza virus or eggs to produce its vaccines. Instead, Protein Sciences’ technology allows for production of large quantities of the hemagglutinin (HA) influenza virus. The FDA said that while the technology is new to flu vaccine production, it’s been used to make approved vaccines that prevent other infectious diseases.
BEVS has been characterized as the “Killer App” for vaccines, largely due to the less costly and rigorous production environment required to manufacture it compared to traditional vaccines. Protein Sciences chairman Dan Adams agrees: “I think Flublok is a great product. And it is the poster child for the underlying technology. I saw the technology as being able to produce a multitude of vaccines rapidly, safely, accurately and for low cost. Those are the key things about this technology. If you want to really fully develop the market for a vaccine, you’ve got to be able to produce it at low cost.”
Protein Sciences investment and development of BEVS and its express SF+ line will continue to deliver dividends socially and monetarily. “I think that the key is … how broadly applicable this is to all kinds of vaccines, including a whole new line of vaccines that are going to be developed by some of our biggest customers,” said Adams, offering rabies vaccine as an example: “Rabies doesn’t occur in the United States. It’s very rare. It’s just rampant in India and parts of Africa, and yet they can’t afford $300 [per dose]. Our objective is to develop a rabies vaccine you can sell for $20-$30. And using our technology, it’s feasible to do that.”
The FDA has also been relatively enthusiastic, commenting specifically on Flublok’s production scalability in its announcement: “This approval represents a technological advance in the manufacturing of an influenza vaccine,” said Karen Midthun, M.D., director of the FDA’s Center for Biologics Evaluation and Research. “The new technology offers the potential for faster start-up of the vaccine manufacturing process in the event of a pandemic, because it is not dependent on an egg supply or on availability of the influenza virus.”
Protein Sciences, a vaccine development and protein production company located in Meridan, Conn., is ramping up production capability. According to Adams, “This year we expect to produce between 3 and 5 million doses … next year, we believe we can turn out up to 10 million doses. After that, we’re probably going to need some additional capacity … we’re working hard on that right now.”
Natoli Partners with Long Island University 
Natoli Engineering and the Arnold and Marie Schwartz College of Pharmacy and Health Sciences at Long Island University (LIU) have formed a partnership to create The Natoli Engineering Institute for Industrial Pharmacy Development and Research. 
“The Natoli Institute will allow industrial scientists to join with academia to conduct meaningful research on problems associated with solid dosage forms and instrumentation,” said Professor Rutesh H. Dave, the graduate program director of industrial pharmacy and pharmaceutics at LIU Pharmacy and the principal investigator for the Institute. “It will also provide an opportunity for our students to work hand-in-hand with industrial scientists to gain real life experience.”
“The Natoli Engineering Institute for Industrial Pharmacy Development and Research will provide students access to world-class technologies and subject matter experts while providing fresh opportunities for students to investigate both long-standing and new formulations,” said Charles Kettler, Ph.D., director Natoli Scientific. “Students will be able to get hands-on experience with the tooling and get to know the ‘sticking and picking’ issues associated with low solubility molecules and other tough-to-form but common formulations like ibruprofen.” Kettler said students will also get a chance to help solve tableting and formulation issues associated with its clients’ products as well.
According to Kettler, the investment is “significant,” offering that Natoli will be funding the gutting and repurposing of one of LIU’s campus buildings and contributing a fully functioning tablet compression suite along with supporting systems to create a real-world tablet production environment. “Our contribution will include stipends and other financial support to support students and faculty,” said Kettler.
LIU Pharmacy Dean David Taft added, “This institute is a wonderful platform for our two institutions to collaboratively conduct research, develop products for brand and generic industries, and provide educational opportunities for current and future pharmaceutical scientists.”
The Natoli Institute will be located at the Brooklyn campus of Long Island University (LIU) and will be dedicated to advancing knowledge in the field of pharmaceutical solid oral dosage engineering operations and instrumentation, according to the company. Work will focus on understanding the numerous problems associated with the compression of tablets, the development of formulations for new and existing molecules, and the measurements required to ensure proper delivery of formulations to the tablet press and control of the tablet press.
Six FOYA Winners Named for 2013
The Facility of the Year Awards (FOYA) judging panel has selected six Category Award Winners in the 2013 Facility of the Year Awards program. The winning projects were chosen from 27 entries and are located in Ireland, Switzerland, the United Kingdom and the United States.
“The FOYA program is about recognizing the pharmaceutical industry’s innovation and technical advances in facility manufacturing, which ultimately is about helping patients who need and depend upon us for a reliable supply of quality medications,” said Chaz Calitri, Vice President of Network Performance at Pfizer and chair of the 2013 FOYA Judging Panel. “The six facilities honored by this year’s awards program embody innovation, exemplified by advances in areas including flu vaccine manufacturing, which is very relevant in parts of the world right now where outbreaks have occurred, threatening public health. All of this year’s honorees are to be commended for their important contributions to our industry and, most importantly, to improving people’s lives.”  
The winners and their award categories are as follows:
  1.  Biogen Idec, winner of the Facility of the Year Award for Facility Integration for its Flexible Volume Manufacturing (FVM) Project in Research Triangle Park, North Carolina.
  2. F. Hoffmann-La Roche, winner of the Facility of the Year Award for Project Execution for its TR&D – Building 98 Facility in Basel, Switzerland.
  3.  MedImmune, winner of the Facility of the Year Award for Equipment Innovation for its UK Automation Upgrade Project in Speke, Liverpool, United Kingdom.
  4. Merck & Co., Inc., winner of the Facility of the Year Award for Operational Excellence for its Vaccine and Biologics Sterile Facility (VBSF) Project in Carlow, Ireland.
  5.  Morphotek, Inc., winner of the Facility of the Year Award for Sustainability for its Morphotek Pilot Plant in Exton, Pennsylvania.
  6.  Novartis Vaccines and Diagnostics, winner of the Facility of the Year Award for Process Innovation for its U.S. Flu Cell Culture Facility in Holly Springs, North Carolina.
The Facility of the Year Awards Program is sponsored by ISPE, INTERPHEX, and Pharmaceutical Processing. It is an annual program recognizing state-of-the-art pharmaceutical manufacturing projects that use innovative technologies to enhance the delivery of a superior project, as well as reduce the cost of producing high-quality medicines. For more information about the winning companies and their projects, visit www.FacilityoftheYear.org/FOYAWinners2013.
Microneedle Patch Key to DNA Vaccinations
An innovative DNA vaccine delivery system, created by a team of researchers at the Massachusetts Institute of Technology (MIT), has broken new ground employing a microneedle equipped transdermal patch in an effort to create a robust means to administer DNA-based therapies painlessly and more effectively. 
Peter C. DeMuth, biological engineering grad student at MIT and his team of material and biological science researchers recently published “Polymer multilayer tattooing for enhanced DNA vaccination,” in the journal Nature Materials. The concept represents an amazing confluence of material science and bioscience — one that will likely leave and indelible mark on the pharmaceutical industry in the coming years. 
MIT’s research demonstrated that a transdermal patch featuring microneedles is the perfect way to administer DNA-based vaccines. According to MIT, plasmid DNA (pDNA) immunization has shown poor efficacy in primate and human trials because such vaccines, to be effective, had to be carefully injected multiple times over time. One of the more promising methods for increasing the potency of DNA vaccines employed in vivo electroporation, a complicated, cumbersome and painful method that was proving completely impractical for widespread prophylactic vaccination. 
Parallel to the technical challenges of DNA vaccination, said the paper, traditional needle-based vaccine delivery has a number of inherent issues: for one, liquid formulations typically require refrigeration, increasing costs and logistical complexity especially when considering global distribution and the “cold chain.” Past that, administering injectable vaccines — especially in the developing world — is problematic, requiring staff trained to follow safe practices and other procedures associated with needle safety.
MIT’s two-pronged approach addresses both the dose and dose sequence problem and the physical challenges associated with administering vaccines for maximum effect. DeMuth explained that to create implantable vaccine coatings researchers settled on polyelectrolyte multilayers or PEMs, which are nanostructured films formed by iterative adsorption of alternately charged polymers, that can embed large weight-fractions of biologic cargos, stabilize embedded molecules in the dried state and exhibit release kinetics predetermined by the film’s architecture/composition. “We hypothesized that rapid multilayer transfer from coated microneedles into the epidermis could be achieved via an underlying polymer film designed to instantly dissolve when microneedles are applied to the skin,” said DeMuth. To produce these releasable vaccine coatings MIT employed a photo-sensitive and pH-responsive polymer PNMP (Poly(o-Nitro-benzyl methacrylate-co-Methyl-methacrylate-co-Poly(ethylene-glycol)-methacrylate), for the release-layer.
According to DeMuth, the microneedle patches efficiently transfects cells in murine skin, eliciting enhanced cellular and humoral immune responses comparable to or exceeding in vivo electroporation. In effect, the microneedles penetrate the skin at a precisely controlled depth, and like a tattoo needle and its ink, leave the multilayer vaccine behind to be released over time as the layers dissolve. Not only is the microneedle patch cheaply mass producible from common materials, the vaccine coating is resilient, and requires no refrigeration. Similarly, the logistic simplicity of the patch means immunization programs can be quickly and cost effectively administered pain free; watch out HIV.
Oncobiologics, Viropro Sign Agreement
Viropro Inc. and Oncobiologics Inc. have signed a biosimilar collaboration agreement whereby Viropro will have the rights to manufacture six monoclonal antibody products being developed by Oncobiologics for commercialization in more than 70 emerging market countries. Viropro will have exclusive commercialization rights to the six biosimilars for Malaysia. In addition, the companies will co-manage Viropro’s Penang, Malaysia Alpha Biologics biomanufacturing subsidiary. 
The six biosimilars are generic versions of Humira, Rituxan, Avastin, Herceptin, Erbitux and one other non-disclosed biotherapeutic. According to Oncobiologics, these biologics are the most popular therapies in the world for their respective cancer and immune-disease indications, representing annual global revenue of more than $40 billion with more than $6 billion in the emerging countries covered by the agreement. The partnership is planning to launch its first product by late 2014.
Published in the March 2013 issue of Pharmaceutical Manufacturing
About the Author

Steven E. Kuehn | Editor in Chief