Spotlight December 2015

New Sandoz Biosimilar Drug-Product Facility

Workers in a compounding room at the new Sandoz facility

In September 2015, Sandoz (the generics and biosimilars business of Swiss drug maker Novartis) opened its BioInject biomanufacturing facility in Schaftenau, Austria. Over €150 million of investment is creating 100 highly skilled jobs in a state-of-the-art facility for manufacturing prefilled syringes and devices for both biosimilars and novel biologics. Staff can fill 18,000 syringes/hour and package 100 syringes/minute.

In welcoming guests at the opening, Carol Lynch (global head of biopharmaceuticals and oncology injectables at Sandoz) said that BioInject will be central to a Novartis biomanufacturing network that includes facilities in Slovenia, Singapore, and France. The company has invested €2.2 billion in Austria since 1996, with more than 4,600 employees at four Austrian sites.

In September, Sandoz became the first company to introduce a biosimilar for the US market. It has several biosimilars in different stages of development, including five in phase 3 clinical trials and filing preparation.

EU Supports Nanomedicines in Development

Nanomedicine in Europe is transforming academic research into technology with the help of the European Technology Platform on Nanomedicine (ETPN) based in Grenoble, France. Patrick Boisseau is head of the nanomedicine program at Leti, the nanotechnology institute of the French Alternative Energies and Atomic Energy Commission, as well as ETPN’s chair. In his October 2015 reelection to that post, he said that the organization will help European companies bring innovative nanomedicines to market.

Renamed the ETPN Association, the organization plans to help companies receive clinical validation for their products and get access to target markets, in addition to providing education and training to their employees. Having coordinated for the past three years with Horizon 2020 (an EU research-and-innovation support program), the association also has established a Nanomedicine Translation Hub to help companies develop new nanomedicines for regulatory approval. ETPN is also involved in international cooperation projects, especially with the United States.

Increasing focus on industrialization began with its 2013 white paper (www.etp-nanomedicine.eu/public/press-documents/publications/etpn-publications/etpnwhite-paper-H2020), which identified primary bottlenecks in nanomed development and offered recommendations to eliminate them. Most of those have been or are being implemented, including establishing an EC–US joint nanomedicine characterization laboratory; building three pilot lines for scaling up nanomedical manufacturing of clinical batches; creating a translation advisory board to help entrepreneurs in nanomedicine; and funding innovative nanomed companies.

The European Commission has positioned nanomedicine as a key enabling technology (KET), an EC designation for technologies with significant potential to fuel economic growth. Other KETs are nanoelectronics, industrial biotechnology, advanced materials, photonics, and advanced manufacturing technologies. Nanomedicine could help launch a new generation of smart systems for diagnostics, therapies, and patient monitoring. To that end, Boisseau promised “dedicated actions to support education and training, clinical validation, market access, reimbursement, and new regulations, as well as industrial development.”

Europe Clarifies Supplementary Protections

In early October 2015, the Court of Justice of the European Union (CJEU) handed down a landmark ruling to end industry uncertainty over the duration of supplementary protection certificates (SPCs). These critical intellectual property rights are granted to innovators whose path to market is delayed by essential regulatory processes involved in marketing approval. The European SPC system seeks to compensate patentees by granting standalone rights that last for a maximum period of five years after patent expiry.

In this legal case, Seattle Genetics had applied for and been granted by the Austrian Patent Office (APO) an SPC based on its basic patent for brentuximab vedotin (Adcetris). The APO calculated the SPC term to begin on the date that marketing authorization was granted; Seattle Genetics challenged by stating that it should have used the date the company was notified of that approval (common practice in some EU member states, but not Austria). Until now, the CJEU had not publicly weighed in on the correct calculation. Its decision confirms that the term of an SPC should begin on the date that market approval is communicated to the innovator rather than the date of the decision to grant that approval.

Mike Gilbert is a partner at Marks & Clerk Solicitors, a British intellectual property law firm specializing in biotechnology. He applauds the CJEU’s decision. “Both common and commercial sense have prevailed,” he said. “The SPC system was expressly set up to compensate innovators whose products could not be placed on the market without first undergoing an often lengthy and expensive regulatory procedure. These processes limit effective patent protection for products because the 20-year period of patent protection is dramatically cut short by delays in bringing products to market.”

Gilbert explains that this decision recognizes the compensatory effect as a fundamental principle of the SPC system. Calculating the duration of an SPC not by the date from which an innovator can start marketing its product but from any earlier date runs counter to that intention. “There is often a short delay between the granting of market approval and notification of it given to the innovator,” Gilbert explains. “The effective date of a marketing approval plays an important role in determining the duration of an SPC — the later the date, the longer the duration of the SPC.”

The difference may be only a few days at most, but those few days can amount to millions of euros in sales of valuable products across all EU member states where SPCs are in force. In this specific case, the decision effectively adds five days of SPC protection. Gilbert said, “This decision will have wide ramifications for innovators and generic manufacturers alike, providing for greater commercial certainty.”

US Biodefense Study Emboldens Biotech

In late October, the Blue Ribbon Study Panel on Biodefense in the United States released its final report (www.biodefensestudy.org) recommending new approaches to developing medical countermeasures more quickly for emerging infectious disease threats. Led by former US senator Joseph Lieberman and former governor and Homeland Security secretary Thomas Ridge, the panel discussed improving US health security and strengthening the country’s ability to prepare for and respond to biological threats — both naturally emerging and human caused. The report calls out the crucial role of drug and vaccine medical countermeasures and the need for significant government funding and innovative thinking to ensure that such products are made available before threats arise.

Biotech companies are applauding these ideas. The panel urges creation of a medical countermeasures program for infectious-disease threats with pandemic potential. Certain vaccine and therapeutic product candidates would be developed using platform technologies up to the point of initial clinical studies, with commercial-scale manufacturing capacity made ready to be called upon when a disease emerges.

“Many nations possess stockpiles of medical countermeasures against specific biological and chemical threats,” commented Paul Chaplin, president and CEO of Bavarian Nordic in Denmark. “But significant gaps remain in the research and development of products needed to protect against a number of other infectious diseases, both current and potential.” His company serves an example of that preparedness model for preparedness. “In response to the recent Ebola crisis, our company went from a small discovery project to large-scale manufacturing and phase 3 studies with our partner Janssen in under 12 months. This rapid advancement was made possible by initial investments from US government and Bavarian Nordic in validating the MVA-BN vaccine platform.”

GE Healthcare’s First KUBio Facility Goes Up

The world’s largest biomanufacturing plant based on single-use technology has been constructed for JHL Biotech at the Biolake science park in Wuhan, China. Based on GE Healthcare’s KUBio modular construction concept, the facility is made up of 62 modules that were constructed in Germany and transported by container ship and river barges through Shanghai and up the Yangtze River. It took about two years from project initiation to complete turn-key construction on site. Next comes Xcellerex FlexFactory hardware — including several 2,000-L single-use, stirred-tank bioreactors — which JHL has experience with already at its biomanufacturing plant in Taiwan.

The Biolake site is designed to accommodate increasing local demand for biosimilars and innovative biopharmaceuticals. The science park itself includes space for offices, support functions such as a quality-assurance laboratory, and a local fill–finish plant. The JHL site is set up to add a second KUBio facility, should demand make such an addition necessary. CEO Racho Jordanov says, “Industry-wide, there is a clear focus on cost of goods and how this directly impacts final pricing. By designing a facility to support multiple KUBios, we are ideally positioned to aggressively address this issue — while still maintaining the speed to market and necessary quality for meeting US and EU regulations.”