There is still a very bright future for the plasma fractionation industry. That was one of the conclusions reached when the 9th Plasma Product Biotechnology (PPB) meeting ended on the beautiful island of Sardinia, Italy in mid-May. This meeting series, which is a joint organization by CSL Behring and Cytiva, has been going on since 1999, when the very first PPB meeting was organized in Australia. Since then, several different islands have hosted successful PPB meetings.
The 9th PPB meeting in May 2015 was no exception –140 participants from 25 different countries and representing 50 different companies or institutes – were treated to a full program with six scientific sessions focusing on issues and possibilities around manufacturing, development, and clinical use of plasma products in general. In addition, a poster session allowed for an open discussion around some of the latest trends and innovations within the industry in combination with excellent networking opportunities.
The meeting was opened with a much appreciated keynote lecture given by Paul Perreault, CEO and managing director at CSL Ltd, on the topic “Global Healthcare Evolution and the Participation of the Industry.” Perreault started by quoting Jeff Bezos, founder and CEO of Amazon: “What’s dangerous is not to evolve.”The investment in biotech was said to be impressive with $51Bn in 2013, but there are still many changes and improvements that need to be made. Some of the examples given by Perreault were in the area of recombinant plasma proteins, disruptive technologies, and especially improved diagnosis of patients and better access to therapeutics. Perreault stressed that even with the ever-growing cost pressure on healthcare and treatment costs, one needs to be balanced when looking at how to handle that cost pressure, even if “biopharma is an easy target.” The cost of medicines was said to account for a small and declining share of the healthcare spending growth in the US, so there is a need to look at the entire healthcare system, even if it is complex. Perreault continued to discuss the focus on rare diseases, as plasma protein-based therapies are heavily focused on rare diseases. Even if the diagnosis and treatment options are increasing for rare diseases, the great majority of conditions still have no treatment. There is also a vast difference between the developed and emerging markets. According to Perreault, there is a strong need for global policies and actions to support development, diagnosis, and treatment of rare diseases.
The first session in the PPB conference program was Manufacturing Perspectives, which remains to be the top pick of the meeting participants when asked which session they liked the most. Several novel -- or maybe better described as technologies still under development – were reviewed and some progress can now be seen in some cases. Expanded bed adsorption (EBA) technology, precipitate protein isolation by membrane electrophoresis (PrIME+), and the affinity cascade (PPPS) all demonstrate progress in different parts or in different situations. Improvements in more established process operations, such as filter press operation and chromatography processes, were also reported.
Among the quality and regulatory trends, Quality-by-Design (QbD) remains to be a popular topic. Philippe Paoloantonnacci presented a QbD approach for a new LFB IVIg product, with identification of Product Quality Attributes (PQAs) and Critical Quality Attributes (CQAs). Process risk analysis was carried out to establish linked process parameters, and after robustness studies, the critical process parameters (CPPs) were determined. The advantages of this QbD approach were claimed to be better information for process design, clear justification of the process and product specifications, and well-structured process and product knowledge for the regulatory filings.
One of the conference presentations that received a significant amount of attention, and also onsidered to be one of the most memorable topics according to the meeting survey, was from BaxAlta’s (former Baxter). Christophe Carnewal presented their work on qualified small-scale models to reduce the number of conformance batches and a simplified regulatory submission for upscaling and process validation activities. However, some meeting delegates still expressed some concerns if this would be fully acceptable from regulatory authorities.
Day two of the PPB meeting started with the Pathogen safety session, chaired by Hannelore Willkommen. Three opening presentations dealt with the Hepatitis E Virus (HEV) issue from a risk, regulatory, and safety point of view. The take-home message was that the efficacy of plasma manufacturing steps for inactivating/removing HEV provides good assurance regarding the safety of the final plasma protein product.
Another highlight of the conference is as always the focus lecture. This time it was given by Dr. Andrew Nash from CSL Behring on the topic of new generation of long-acting coagulation factors. With these new types of therapies, the hemophilia patients can reduce the number of weekly prophylactic infusions and significantly simplify the treatment burden. In March 2014, Biogen received its recombinant Factor IX-Fc fusion protein (Alprolix™) approved by FDA, and in December, CSL Behring also submitted a biologics license application (BLA) for the marketing authorization of its long-acting fusion protein linking recombinant coagulation Factor IX with recombinant albumin (rIX-FP). Also in the clinical pipeline, one can find long-acting recombinant Factor VIII and Factor VII. Dr. Nash concluded by stating that potentially an even bigger impact on the treatment of hemophilia patients could come from bispecific antibodies. These molecules might prevent development of inhibitors in hemophilia patients, which today is causing some therapies ineffective. One example being the announcement from Chugai/Roche in November about the results from studies on “ACE910,” an anti-factor IXa/X humanized bispecific antibody.
The third and final day of the conference covered both market trends and new products and innovations in plasma processing. Global aspects on the manufacturing, supply, and hemophilia care in the rapidly growing markets of Asia, such as China and India, were presented by Ranjeet Ajmani from PlasmaGen and Jeff Davies from Centre for Biopharmaceutical Excellence, Australia. Ajmani explained that the rapid economic growth in several Asian countries has led to an increased focus on critical care and rare genetic disorders, where plasma protein therapeutics find a majority of their applications. This trend, combined with the large population, means that Asia could become the largest consumer of plasma protein therapeutics. However, still a large extent of the population remains to be non-diagnosed. Davies, the former Executive Vice President of CSL, focused his talk on China. There is a strong demand for plasma products in China, especially considering that ever since 1985 China has banned importation of almost all blood products, due to the concern for HIV epidemic. There are 20 plasma fractionation companies in China, and to meet the demand currently there is a significant investment ongoing in their facilities.
In a global perspective, it is still IVIG that is the main growth driver for the entire plasma fractionation industry. But in China, there is also a strong growth for albumin; 32% growth in sales 2009-2012. Albumin is also – probably for that reason -- exempt from the import ban. Main clinical application is treatment of liver diseases. The renaissance of albumin was also the topic of another presentation during the plasma conference, given by John More at BioProducts Laboratory. Albumin was the very first therapeutic protein to be recovered from human plasma at an industrial scale, and was the main target product in the original Cohn process. Over the years, albumin has been connected with several controversies and even medical research fraud scandals. Now the future for albumin looks brighter, according to More, and not only in China.
In the final New Products & Innovation session, there were several new opportunities to improve the plasma fractionation industry on the agenda. One of the major trends in biopharmaceutical manufacturing overall is continuous processing. This was introduced by James Higgie at CSL Behring as a future option. An alternative precipitation approach using polyacrylic acid (PAA) instead of ethanol was also discussed. Karl McCann, also from CSL Behring, talked about the continuation of this concept that was first presented by Cytiva at the last PPB meeting, now with more results on the chromatography steps following the PAA precipitation. Interesting with new concepts in the field of plasma fractionation, as the business is still considered to be fairly conservative.
In summary, the 2015 PPB meeting series was considered to be one of the most interesting plasma meetings ever, judging from the feedback from several returning conference visitors. In a survey, 69% of the attendees rated the conferences as Excellent and 30% as Good. All of the survey respondents wanted to have a new plasma conference in 2017. So the conference organizers have already started the search for a new island that could host next meeting.