Algeta targets breast cancer and angiogenesis through research pact with Affibody
Oslo – Norwegian targeted cancer radiotherapy specialist Algeta ASA has stepped into a global exclusive research, development and commercialisation agreement with Swedish Affibody AB (Stockholm), aimed at targeting its alpha particle-emitting thorium-227 radionuclides against Her2neu- and PDGFRβ-overexpressing tumours. Under the terms of the agreement Algeta and Affibody will determine whether two 6.5 kDa antibody mimetics, which target Her2 and PDGFRβ, can be effective carriers targeting molecules for Algeta’s thorium-227 payload. If the initial research collaboration is successful, Algeta will be responsible for all preclinical and clinical development of any development candidates that result from this collaboration, and commercialization. The companies did not publish any financial details about upfront fees, milestones or other payments to Affibody. With the agreement, Algeta will also gain access to Affibody’s Albumod platform which is designed to prevent the normally rapid renal clearance of radiolabelled Affibodies. Researchers recently published details on strategies to prolong plasma half life of radiolabelled Affibody conjugates. Algeta hopes 1st targeted radiotherapy can overcome drug-resistance mechanisms. In addition, tumour cells adjacent to those bound by the alpha-pharmaceutical may also be destroyed even if they do not bind the drug themselves. The short range of the alpha particle means that damage to healthy cells and side effects may be minimized.
Brussels – In an effort to solve the probem of asynchronous GMO market approvals, the European Commission is making another attempt to relax the current European zero-tolerance rules for non-EU approved GMOs. In May, the...
Brussels – In an effort to solve the probem of asynchronous GMO market approvals, the European Commission is making another attempt to relax the current European zero-tolerance rules for non-EU approved GMOs. In May, the Commission is to table a so-called technical solution that does not require confirmation from either the EU ministers or the European Parliament. The new rules would apply to GMO admixtures of up to 0.1% in food and feed imports.
For years, DNA fingerprinting has been celebrated as the gold standard in forensic science and crime investigation. But now it has became clear that among the 6 million DNA fingerprints taken from criminal offenders which are...
For years, DNA fingerprinting has been celebrated as the gold standard in forensic science and crime investigation. But now it has became clear that among the 6 million DNA fingerprints taken from criminal offenders which are currently stored in national databases throughout the EU, there are also full profiles from police investigators, lab researchers and staff from the manufacturers of the consumables used in DNA fingerprinting. Systematic tests by the British Forensic Science Service (FSS) suggest that DNA contamination during the production process of disposable gloves, reaction vessels, tips, and cotton swabs provide one full human DNA profile per 25,000 items. In response, the European, US and Australian forensic networks (ENFSI, SWGDAM and BASG) have proposed establishing new rules, both to prevent costly police investigations based on possibly deceptive DNA signatures and to ensure the integrity of police registries. These foresee minimising contamination during the manufacturing process, as well as the elimination of DNA traces through post-manufacturing degradation. Additionally, the institutes have called for the creation of an international “elimination database” containing the pooled profiles of staff at forensic labs, police departments and life sciences suppliers to clear false profiles before database storage.
The most spectacular case to reveal how DNA contamination can mislead police investigations was unmasked last spring in Germany. For 16 years, the police hunted for “the woman without a face” – a serial killer and burglar whose DNA profile was found at 40 different crime scenes throughout Germany, Austria and France. Last March, it became clear that there was no dastardly phantom criminal behind the crimes. The DNA found at all of the scenes was from an employee who was involved in making the cotton swabs used to collect genetic evidence. Similar links from unconnected cases have been identified previously by forensic labs in Europe, the US and Australia. Comparison of DNA profiles from the staff working in a plastic-ware factory with the profiles obtained during casework by the FSS showed that contaminations can occur in the manufacturing process of consumables used for the collection, processing, and analysis of DNA samples.
Setting standards to keep
forensic databases clean
An awkward aspect of the debate is that the swabs used in the German “woman without a face” case were not certified as DNA-free. However, that’s less surprising than it sounds. Up until now, there are no common standards in place to guarantee that consumables and reagents used for STR (short tandem repeats) analyses are free of detectable DNA (at concentrations below 6 pg). Together with the ENSFI, SWGDAM and BASG, the German Federal Criminal Police Office (BKA) therefore now wants to establish a raft of measures (see Forensic Science Int.: Genetics, doi: 10.1016/fsigen.2009.08.009) to keep its DNA databases free of post-incident contaminations. “The problem is not national but international,” claims Dr. Ingo Bastisch, deputy head of the DNA lab at the BKA, in a letter sent to the suppliers of consumables and materials needed to carry out the DNA analyses. In March, the BKA expert met for the first time with suppliers at the German Life Science Supplier association to discuss how to establish a standard. To prevent contaminations, the German police plan to establish a certified cachet to be used in future tender offers for consumables. The precautionary measures are backed by Bastisch (who also heads the ENFSI DNA working group), by the SWGDAM and the BASG. The forensic networks are working towards certified processes and quality assurance schemes at manufacturing sites to ensure that products are DNA-free upon delivery to the police. The proposed measures include: – automation of manufacturing lines – minimising interaction of staff with the manufacturing lines – production under cleanroom conditions (masked staff, positive airflow). – PCR-based quality control checks – physical destruction of human DNA post-production, i.e. with ethylene oxide gas, – quality controls to ensure that DNA removal was successful. Organised in the Life Science Research Group, the manufacturers who met Bastisch are generally open to the establishment of such a quality certificate. “A certificate alone cannot prevent cases like the ‘woman without a face’,” says Peter Quick, General Manager at Promega (Mannheim), “but it will clearly diminish the probability of such cases.” It’s also clear, however, that such measures will cost money – and no one yet knows who will be expected to pay for them. “The overall cost for all of the steps in the discussed quality assurance can’t yet be determined; it’s still too early,” says Quick. But according to Heinz Schmid from Greiner Bio-One, the expense involved in changing packaging and production facilities for the post-manufacture elimination of DNA can be “considerable”. And although the measures can significantly reduce the probability of systematic contamination, they cannot prevent contamination that occurs at the crime scene, nor at the forensic labs that clean up DNA, amplify it and identify its characteristic short tandem repeats.
Knowing who didn’t do it
In addition to DNA elimination in manufacturing, the ENFSI, SGDAM and BASG recommend establishing so-called “elimination databases” covering the STR profiles of everyone that could contaminate samples: forensic lab staff, cleaning personnel, manufacturing staff at suppliers, and the police involved in the case. The FSS already runs a police elimination database with 70,000 scene-going staff to ensure that obtained STR profiles are “clean”. According to a presentation by Bastisch, more and more forensic labs and police organisations are interested in setting up such a database. Discussions on the establishment of an international contamination log have begun. “Such a European elimination database – based on anonymous, company-specific data pools – (would) protect employees and their companies from the inadvertent enforcement of liability by departments in legal work,” believes Quick. “A voluntary self-commitment offers a universal concept for this.” Claudia Hoffmann from Eppendorf AG adds that since the retracing to the personal level will not be possible, this road will be easy to walk down. The question of how and where to install such a database is still under discussion.
Rising yields from biomanufacturing processes are opening up new avenues in upstream processing, especially when it comes to mammalian cell culture technology. This EuroBiotechNews biomanufacturing special (pages 32-44) trains...
Rising yields from biomanufacturing processes are opening up new avenues in upstream processing, especially when it comes to mammalian cell culture technology. This EuroBiotechNews biomanufacturing special (pages 32-44) trains the spotlight on new developments in the field, among them decreasing volume demands for biomanufacturing processes , the use of disposable materials or new media and the fresh challenges facing downstream processing . With the hype surrounding the sustainable production of fine chemicals, industrial biotechnology has continued to gain in importance – a fact demonstrated by the establishment of the first industrial-scale plant for succinic acid production to make use of a carbon dioxide consuming fermentation process.
Driven by increasing product titres of up to 20g/L, biomanufacturing scales aren’t necessarily rising – in many cases they’re actually dropping. That’s driving the move towards disposable equipment such as bioreactors, which offer the benefits of both reduced effort when it comes to cleaning/cleaning validation and lower investment costs. In areas like microbial fermentation however using disposables often limits scale. The largest systems on the market that have the necessary mass and energy transfer rates required for the cultivation of bacteria and yeasts are in the 200-500L range (wave-mixed: Biostat Cultibag RM, WaveBioreactor, stirred; XDR-DSTB microbial). The largest disposable system for animal cell culture, which is mostly used in the manufacture of recombinant proteins and antibody drugs, has a maximum volume of 2,000L (XDR-DSTB, animal). Other factors besides scalability that are currently slowing market adoption are limited experience in using such bioreactors, insufficient strength of the plastic material used, high cost for consumables, and the detection of leachables and extractables that could potentially interact with the product.
Trend to stirred disposable
Stirred systems are the gold standard with classic stainless steel bioreactors, and market adoption of stirred disposable bag bioreactors has been very strong since its late market entry in 2006. Aside from stirred systems for small and mid-scale production such as the S.U.B., Biostat Cultibag STR, Nucleo Bioreactor and XDR-DSTB, wave-mixed systems such as the Biostat Cultibag RM Wave Bioreactor are available up to 500L, and are dominating seed inoculum production. New systems with two-dimensional platform movement promise to improve the volumetric oxygen transfer rates, and thus expand the disposable bag systems to processes with even higher oxygen demands. The new developments in upstream processing and formulation are proving a challenge for current product purification methods. It remains to be seen whether in the longer term other techniques such as protein crystallisation will augment current standards like chromatography and filtration.
he increasing maturity of the biopharmaceuticals market – together with a rising number of biosimilar developments and market applications – is leading to a sharper focus on the cost of goods (COG) for biomanufacturing....
he increasing maturity of the biopharmaceuticals market – together with a rising number of biosimilar developments and market applications – is leading to a sharper focus on the cost of goods (COG) for biomanufacturing. Discussions about COG generally lead to reflections on the economy of scale, i.e. decreasing costs by manufacturing more of a given product. However, there are several other factors that can lead to decreasing volume demands for biomanufacturing processes, and these can counteract the economy of scale argument. Examples for these parameters include: higher manufacturing yields, lower dosages in therapy, and the development of projects for smaller niche markets. Any or all of these can go hand-in-hand with decreased demand for a product. This article gives a short overview on the trends leading to smaller fermentation scales, particularly in microbial manufacturing processes.
In recent years, improved process technologies have significantly increased production efficiency. The most obvious improvement is the use of optimised expression systems combined with optimised fermentation characteristics. Together, these aspects can lead to fermentation titres exceeding 20g/L, as was recently reported by Richter-Helm BioLogics for an E. coli inclusion body process (Fig. 1). A thorough process optimisation program starting with a basic fermentation scheme in 1L reactors, yielding a recombinant protein titre of 1.8g/L, led to a more than 10-fold increase through parameter optimisation and up-scaling. The initial fermentation harvest titre of 1.8g/L was already well in the range of actual commercial manufacturing processes (half of these yielding <1g/L with an overall average of approximately 2.2g/L). However, for the subsequent transfer to a commercial manufacturing facility, this would mean a possible reduction in scale by the optimisation factor, assuming all subsequent step yields remained the same.
The increase in yields in upstream processing has changed the focus in today’s process development programmes. Existing purification schemes based on large-scale columns that employ expensive resins are no longer matching these yields. There is thus a need to develop and establish new solutions for the purification of biologicals. Several technologies are available today, some of which – like membrane chromatography – are employing analogous purification functions for a lower price. Others are reducing costs by applying purification steps that combine several classical purification steps. An example for this approach is the implementation of expanded bed adsorption (EBA) chromatography, which combines cell debris separation and capture chromatography in a single step. The implementation of EBA technology with “Streamline SP” resin in a project for the manufacturing of a chimeric molecule (fab + effector molecule) at Richter-Helm BioLogics led to a significant improvement by reducing process and CIP times without a negative impact on yield. As a direct result, the utilisation rate for the project at the multipurpose facility was reduced, freeing up the resource pool to handle more customer projects per year in that facility. And as the number of necessary process steps dropped, efforts for additional activities – including QC testing and QA record review – fell as well, along with the consumption of process media such as WFI, steam, buffers, etc. (Fig. 2). In a collaborative effort, Richter-Helm BioLogics and Upfront Chromatography A/S were able to improve these initial results even further. The final process yield in total, purified product per fermenter volume was increased 1.8-fold, thus significantly reducing the COG per final purified product and making smaller scale manufacturing feasible.
…are driving trends to reduce manufacturing scales
On the same process technology note, another issue driving the trend to reduce manufacturing scales is the move towards disposable equipment for biopharmaceutical manufacturing. Disposable equipment offers the benefit of reduced effort for cleaning and – even more important in some cases – reduced workload when it comes to cleaning validation. However, using disposables also often limits scale. This is most critical in microbial fermentation, where to date no bioreactor is available in several litres scale which can generate the mass and energy transfer rates required for the cultivation of bacteria and yeast. Even disposable bags to hold buffer and media in biomanufacturing are limited to approximately 2,000L. Technology improvements and increased process yields in upstream and downstream processing, however, are not the only factors contributing to lower manufacturing scales. The trend is also being driven by a decrease in demand for state-of-the-art biologic therapeutics. As biopharmaceuticals are often developed for rare or previously untreatable diseases, the total number of patients – and thus the total amount of active substance that must be produced – is often relatively low. In addition, the product amount per dosage remains low, as the potency of biotech products is generally relatively high. Some good examples for microbial-derived products with low product amount per dose are Interferon alfa-2a (each dose contains 11.1µg of recombinant protein, leading to a yearly administration of only 1.7mg per patient), Interferon beta-1b (each dose contains 0.25mg of protein, leading to a yearly administration of just 46mg per patient) and Somatropin (just 0.2mg of protein in one dose, leading to a maximum yearly administration of 70mg). Taking into account the average yield mentioned above of 2.2g/L after fermentation and a reasonable total process yield of 25%, the resulting total fermentation volume required per year could easily be met by a facility having no more than 1m3 of fermentation volume. Thus a multipurpose facility like that shown in Fig. 3 today provides sufficient capacity to supply the demand for several commercialised products.
References  Kaiser et al., Steigerung von Qualität und Ausbeute in der Wirkstoffproduktion; Laborwelt 11 (3), 18-22, 2010  HighTech Business Decisions; Biopharmaceutical Contract Manufacturing 2009: Expanding Markets, New Capacities and Improved Performance; Report 2009  Gottschalk; Large-Scale Chromatography, What Lies Ahead?; Pharma Focus Asia, 2007  May; Improving DSP Productivity: Reduction of Processing Operations using EBA Technology; Presentation 2nd Biomanufacturing Symposium, 2009  efpia; The Pharmaceutical Industry in Figures, Report 2008  Full prescribing informations, Roche, Bayer Healthcare, Sandoz
Brussels – An internal EU paper outlines European Commission plans to give more power to the EU member states to independently decide whether GMOs can be planted on their territories. According to Reuters, the Commission does not...
Brussels – An internal EU paper outlines European Commission plans to give more power to the EU member states to independently decide whether GMOs can be planted on their territories. According to Reuters, the Commission does not want to change existing centralised rules for market authorisation of GMOs, but proposes that member states revise their co-existing guidelines in such a way that GMO cultivation is blocked. The Bulgarian Parliament adopted similar regulations in March with a GMO law that establishes a 10-kilometre GMO cultivation ban around environmentally sensitive areas (so-called ‘Natura 2000’ areas) and organic fields, which result in a de-facto ban of GMO acreage. According to the paper, the Commission is alternatively considering limiting applications to specific countries or territories or to account for socio-economic factors. Together, the centralised authorisation procedure and the increased subsidiarity regarding GMO cultivation is expected to have positive impact on biotechnology- and seed companies. The Commission now wants to discuss this model with the biotech industry, environmental NGOs, and farmers.
Brussels – The European Commission has set out its plans to simplify the procedures for taking part in EU-funded research projects. 'I want researchers to spend more time in the lab and less time in the office,' stated EU...
Brussels – The European Commission has set out its plans to simplify the procedures for taking part in EU-funded research projects. 'I want researchers to spend more time in the lab and less time in the office,' stated EU research Commissioner Máire Geoghegan-Quinn at the end of April, the European Commissioner for Research, Innovation and Science. 'Our proposals aim to minimise administrative burdens in Europe's research programmes.“ The simplification strategy, is split into three parts. The first part concerns changes such as better user support, easily understandable documents, user-friendly IT (information technology) tools and optimised business processes) that are reduces the time taken to award grants and make payments. Additionally the Commission plans to investigate how prizes can be used to attract top researchers and investments. The second strand of the simplification plan is devoted to more radical changes to the current financial rules. Both the European Parliament and Council must give the green light in order for these changes to take place. Ideas put forward here include a wider use of 'average cost methodologies', which would free projects from accounting separately for each small item of expenditure. The third part of the Communication concerns changes which could be implemented under future framework programmes. Here the Commission plans to explore options which would work on a 'payment by results' principle. 'The Court of Auditors itself has asked whether instead of the current system of 'payment by input', we could move towards 'payment by output',' explained Commissioner Geoghegan-Quinn. 'Agreed objectives would be set in return for funding. Payment of full amounts would be linked to whether those objectives are achieved.' Commissioner Geoghegan-Quinn emphasised that simplification could be achieved without compromising on financial control. 'I am a former member of the Court of Auditors,' she pointed out. 'I can tell you that multiplying different and overlapping procedures equals confusion. Clear and simple rules, consistently applied, equal good financial control.'
Vienna /Brussels – EU Health Commissioner John Dalli has called on agriculture companies for full transparency in GMO research. During a meeting at CropLife International, the Commissioner said that every research result relevant...
Vienna /Brussels – EU Health Commissioner John Dalli has called on agriculture companies for full transparency in GMO research. During a meeting at CropLife International, the Commissioner said that every research result relevant to GMO approval and safety, whether positive or negative, should be immediately reported to the EU Commission or the European Food Safety Authority (EFSA). The Commissioner stated that confidentiality of this type of information cannot be granted in every single case, even if market relevant know-how is involved. More transparency could create a greater acceptance from the public. Dalli added that he expects a clear communication from the agro-industry when it expects to finish of the use of antibiotic resistance markers. The reaction of the public after the EU approval of BASF’s GM potato Amflora demonstrated what a sensitive issue GMO cultivation remains, said the Commissioner. He invited the industry to participate in a debate on a viable long-term, coherent and responsible use of GMOs. Biotech companies should see this as an opportunity to explain their products to the general population in a better way.
New York - A federal judge in New York on Monday struck down patents on two genes linked to breast and ovarian cancers. Insiders say that the decision against Myriad Genetics could have a lasting impact on medical research and...
New York - A federal judge in New York on Monday struck down patents on two genes linked to breast and ovarian cancers. Insiders say that the decision against Myriad Genetics could have a lasting impact on medical research and development of treatments by the biotechnology industry in the US, Europe and elsewhere. In a 152-page ruling, Judge Robert Sweet upheld challenges to Myriad's patents by the American Civil Liberties Union (ACLU), genetic researchers and several women who suffered from breast or ovarian cancers. The ACLU and the Public Patent Foundation argued that genes found in human bodies which control hereditary characteristics are products of nature and not subject to patents granted by the federal government. The ACLU said in a statement that the ruling "marks the first time a court has found patents on genes unlawful and calls into question the validity of patents now held on approximately 2,000 human genes." Peter Meldrum, president and CEO of Myriad, said the company will appeal the ruling but that it would not have a marked impact on its operations or earnings. "We're confident the court of appeals will reverse this decision and uphold the patent claims," he said in an interview. Myriad was formed in 1991 by University of Utah researcher Mark Skolnick. The University of Utah Research Foundation licensed several of the patents to Myriad, and also was sued by the ACLU. The lawsuit claimed that patenting the BRCA1 and BRCA2 genes stifled research and development of alternative tests by other scientists and companies. Myriad has successfully marketed tests that cost about $3,000 to detect the presence of mutations of the BRCA1 and BRCA2 genes. The company's shares were down about 8 percent, or $2.17 a share, in after- hours trading on the Nasdaq stock market.
Strasbourg – Members of the European Parliament have adopted an action plan (Strategic Energy Technology (SET) Plan) bringing EU investments of EUR 2 billion per year in low carbon technologies, including investments into...
Strasbourg – Members of the European Parliament have adopted an action plan (Strategic Energy Technology (SET) Plan) bringing EU investments of EUR 2 billion per year in low carbon technologies, including investments into renewable resources and bioraffineries. The MEPs called for 'the urgent establishment of a funding timetable by the Commission and the Member States of the resources they will commit to ensure that funds start flowing from 2010.' The European Parliament also asked the European Investment Bank (EIB) to increase its lending to energy projects and calls on it to prioritise projects that will raise the viability of low carbon technologies. MEPs pointed out that small and medium-sized enterprises (SMEs) are the drivers behind the development of many low carbon energy technologies. With this in mind, they are calling for a 'significant share' of EU funding under the SET-Plan to be made available to SMEs, insisting that these funding schemes be 'designed in an SME-friendly manner'
Lonza Group Ltd (Basel) has enlisted Roche‘s former Global Head of Research, Prof. Dr. Jonathan Knowles, as its new Scientific Advisor. Knowles will be mainly shaping Lonza‘s LIFT initiative, which is designed to deliver...
Lonza Group Ltd (Basel) has enlisted Roche‘s former Global Head of Research, Prof. Dr. Jonathan Knowles, as its new Scientific Advisor. Knowles will be mainly shaping Lonza‘s LIFT initiative, which is designed to deliver long-term technology breakthroughs and new business platforms across all Lonza divisions.
7th Berlin Conference on IP in Life Sciences: Big Data, Big Drugs
The health care industry faces significant transformation, driven by a boom in knowledge within biomedical sciences and breakthrough technologies such as gene sequencing. The management of "big data“ will change the understanding of diseases, development of drugs and treatment of patients. more