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Prospects

01/2009

BASF Relies on Solvias Chemical Hazards Monitor for Maximum Safety

Choosing a Partner for Early Drug Development

Unidentified Residues, Foreign Particles, Faulty Products: Identifying Unknown Inorganic Impurities

Intellectual Property: Rigorous Patent and Literature Searches as a Basis for Reliable Advice

News

Events




Welcome

Preface of the Head of Marketing and Sales

2

Choosing a Partner for Early Drug Development

3

BASF Relies on Solvias Chemical Hazards Monitor for Maximum Safety

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Unidentified Residues, Foreign Particles, Faulty Products: Identifying Unknown Inorganic Impurities

11

Intellectual Property: Rigorous Patent and Literature Searches as a Basis for Reliable Advice

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News

16

Events

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Publisher Solvias AG Klybeckstrasse 191 P.O. Box 4002 Basel Switzerland Tel. +41 61 686 61 61 Fax +41 61 686 65 65 info@solvias.com www.solvias.com Editor-in-chief: Silke Oeschger Tel. +41 61 686 61 41 silke.oeschger@solvias.com

Solvias Prospects 01/2009



Dear Reader and Valued Customer, The holiday period is now behind us, and I hope you all enjoyed that much-needed quality time with your families and friends. After a challenging and eventful 2008, our thoughts inevitably turn to our prospects for the new year. In both our personal and professional lives, we might reflect on how we could add more value by making better use of two of mankind’s most precious “gifts”: creativity and innovation. Coupled with close cooperation with our customers, this combination results in high-quality solutions. We hope you enjoy this edition of Prospects, which provides an insight into Solvias’ constant efforts to add value to its customers’ business, not only by extending its service range, but also by gearing its activities to the specific needs of the market. One example is the new GMP facility to be built in Basel, which complements our integrated services for chemical development up to clinical phase I/IIa, due to be operational mid-2009.

Our company can only get key insights into our customers’ needs by allowing them to express themselves. The interview with BASF highlights the essential role the Solvias chemical hazards monitor (SAM GC- 600) is playing in workplace safety – an excellent testimonial to our customized solutions. We thank you for your confidence in 2008, and look forward to continuing our inspiring partnership in 2009! With my best wishes on behalf of Solvias,

Stephan Haitz, Head of Marketing and Sales


Choosing a Partner for Early Drug Development Pharmaceutical and biotech companies must bring their drugs to market quickly to survive in a highly competitive world. One critical step in this process is the successful completion of a preclinical development program and subsequent submission of an investigational new drug (IND) to commence phase I clinical trials. Both these stages within an early drug development program (for toxicology and phase I studies) require the manufacturing of an active pharmaceutical ingredient (API) on time, according to specifications, and in conformity with quality standards and regulatory requirements. This article focuses on the main aspects to consider when deciding whether or not to outsource chemical and analytical development – including small-scale current good manufacturing practice (cGMP) API production – to support an early drug development program.

Critical Mass and Expertise in Chemical and Analytical Development Once a decision has been taken to move ahead with a new chemical entity, a costand time-efficient program needs to be established to accomplish this task efficiently, on time and within budget. Chemical development1 and subsequent cGMP manufacturing are clearly important, but other essential components of the program, such as analytical development and solid-state characterization, are sometimes neglected. A critical mass of dedicated people with high-level technical expertise and good track records is therefore needed, with the right mix, to move the project forward successfully. A ratio of analytical chemists (including experts in solid states) to development chemists of >2:1 is good because it will prevent bottlenecks between the development of analytical methods and the validation and in-process control (IPC) analysis. Many activities can be scheduled in parallel,

Figure 1: Development and validation of analytical methods



Solvias Prospects 01/2009


Figure 2: The ability to handle hazardous chemical reactions is a plus

which will be beneficial to the project and help keep to the timelines. Facilities should have sufficient manufacturing capacity available to rapidly and costeffectively manufacture the required intermediates and APIs. They should also be able to handle a wide range of chemical processes at scale. Different reactor materials and the ability to perform hazardous chemistry are a plus. It is advisable to make a site visit to get an overview of facilities.

Solvias Prospects 01/2009



Technical Expertise, Scientific Excellence and Track Record Service providers have to find their niche in a competitive market by focusing on key strengths and providing a superior service in a specific area. By investing in personnel, research or infrastructure, service providers try to create a competitive advantage in areas they believe are relevant to the industry. Companies may have strengths in different areas (for example: chiral chemistry, high potency active pharmaceutical ingredients,


continuous flow chemistry, or bioconjugates) and may offer technical expertise or scientific excellence in these areas. It is, however, also important to look at track records, to see whether the service provider’s technical expertise or scientific excellence is likely to benefit the customer’s project. Will the service provider help the project team overcome obstacles and identify the best solution in the shortest possible time? The presence of an innovations board or similar body is a good indicator that a service provider is keeping abreast of new trends in the industry and trying to improve the service offer.

Communication and Project Management Only an effective interplay between the three strands of the project (chemical and analytical development, and API manufacturing) will result in delivering the project on time and within budget. Good communication between the service provider and the project team is a prerequisite for a satisfied customer. There needs to be a project manager to effectively manage, oversee and track the progress of the project. The project manager will serve as a primary interface between the service provider and the customer, and keep the customer informed at all stages of the project. In evaluating different service suppliers, it is a good idea to inquire whether a potential partner has a dedicated customer project management team whose daily business is to track projects, manage internal resources and communicate with customers. This

management capability could make a difference to the project outcome.

Quality and Compliance A good quality system will produce good quality products. It is important for staff to be well trained and for the responsible people to review the relevant documents. In order to support subsequent filings to regulatory agencies, any partner must be fully aware of the regulatory requirements. Ignoring the regulatory requirements is likely to result in a delay in approval. A quality agreement is the basis to establish a successful business relationships and prevents misunderstandings by defining GMP responsibilities among all parties. During an audit, the customer can review documentation systems, determine GMP compliance history and inspect standard operating procedure (SOP) records. Achieving the required quality is an objective matter of instituting the proper procedures, not a subjective matter of opinion.

The Right Attitude Last but not least, it is important to work with a partner who can quickly adapt to changes and who will demonstrate a high degree of flexibility and dedication to keep to the project’s timelines. This process begins with the partner delivering a comprehensive, clear and relevant quotation on time. Responsiveness by the partner to new customer demands (for example, increasing the



Solvias Prospects 01/2009


amount of an API) is a key factor in the success of a project. The right attitude, combined with technical expertise and scientific excellence, will make it possible to overcome obstacles and will result in a successful project. Getting the right people on board is crucial to a successful outcome. It is therefore advisable to meet the partner’s team before making a commitment, and to ask for references.

What Solvias Offers as a Partner in Early Drug Development Solvias is well positioned to tackle a wide range of challenging projects for the chemical development and manufacturing of chiral and non-chiral APIs. With a new cGMP kilo laboratory to be built in Basel (planned to be operational mid-2009), Solvias is now

Figure 3: Solvias supports you at all stages of the drug development process and in the production of your APIs

Research

Preclinical

Clinical I

Discovery

Clinical II

supplementing its service offer by providing rapid, cost-effective manufacturing of APIs destined for use in phase I/IIa clinical studies. The additional manufacturing capability will complement the state-of-the-art nonGMP kilo laboratory, which was expanded in 2007. This laboratory contains multipurpose reactors and high-pressure reactors (ranging from 30 to 100 liter) able to perform cryogenic and high-temperature chemistry. Solvias’ kg-scale manufacturing facilities will leverage a strong technology base in the areas of chiral chemistry, homogeneous asymmetric catalysis, fluorination chemistry, and highpressure and hazardous chemistry. The production team is supported by our highly competent analytical laboratories, with decades of experience in method development, method validation and release testing of drug substances and drug

Clinical III

Production

Development

Drug Substance Process R & D API Synthesis Custom Synthesis

Solvias Prospects 01/2009



Launch & Marketing


Our People • Total headcount >280 employees • On average >8 years industry experience • 47% graduates / Ph. D. Manufacturing Infrastructure • Multipurpose reactors from 30–100  l scale (–70°C up to 350°C) (non-GMP and cGMP) • Multiple autoclaves up to 300 bar (0.05 to 50 l) • Reactor materials ranging from glass, glass-lined steel, stainless steel, PTFE, tantalum, Monel, and Hastelloy B and C • Chromatography up to 20 kg separation material Chemical Development • Process research and development • Salt and co-crystal screening • Process optimization • Reference substance supply

products. Our solid-state group can help in developing and characterizing the right solid form of the API. These combined services enable Solvias to provide comprehensive chemical development programs to meet the needs of the

• •

References 1 See also Prospects 01/2008: The Role of Process R&D in Early Chemical Development: Pay Now or Pay Later, by Phillip Chalabi.

Polymorph screening Manufacturing of – Tox material (non-GMP/cGMP) – cGMP starting materials – API for clinical phase

Analytical Development • Method development and validation (ICH) • Reference standard qualification • cGMP/GLP release testing (CoA) • Forced degradation study (ICH) • API impurity ID/characterization • Accelerated stability study Technology • Asymmetric homogeneous catalysis • CXcoupling • Chiral ligands • Fluorination chemistry (HF, SF4, F2) • Hazardous and high-pressure chemistry

pharmaceutical industry. Solvias has the competence, experience and expertise to support early drug development programs, taking account of the regulatory requirements.

Navigating your API to success.

Dr. Michael Quirmbach, Product Manager Chemical Development



Solvias Prospects 01/2009


BASF Relies on Solvias Chemical Hazards Monitor for Maximum Safety BASF PharmaChemikalien GmbH & Co. KG demands the highest standards when it comes to workplace safety. The Solvias SAM GC- 600 chemical hazards monitor plays an integral role in the safety concept at its Minden site in North Rhine-Westphalia, Germany. We interviewed Dr. Dirk Krumwiede, Deputy Manager of Multiproducts Operations, and Thorsten Bartsch, in charge of Chemical Hazards Monitoring, to find out why BASF chose this monitor and what specific requirements it meets. How did BASF find out about the Solvias chemical hazards monitor? B: It was difficult to find a chemical hazards monitor for our operations since very few manufacturers actually offer a manageable solution. We learned in 1999 through Knoll AG (now Abbott Liestal AG), of a Basel-area company that had already been using the Solvias SAM GC- 600 for quite a while. Did the SAM GC- 600 turn out to be the solution? B: Yes, we contacted Solvias and learned that this chemical hazards monitor meets our requirements exactly. It provides reliable measurements continuously and quickly. What particular substances do you monitor? K : We measure bis(chloromethyl)ether (BCME), a highly toxic substance that forms when formaldehyde reacts with hydrogen chloride. High sensitivity is a must for secure measurement results. What is the alarm limit for BCME? B: The limit for BCME is just 1 ppb. This is the same level that today’s state-of-the-art technology can detect.

Solvias Prospects 01/2009



What happens if this limit is exceeded? K: Unfortunately, this scenario cannot be prevented 100%. However, we would not immediately panic, since the installations are chambered. Production would be stopped and the installation would be pumped clean to counteract the leakage. The chambers themselves would not be entered until the correct values were restored. How does the monitoring work? B: The device is located in a separate compartment. The critical process areas are monitored via 10 separate measurement points. The results are continuously processed by software and displayed. The data are also fed to the process control system via an interface so that we can permanently monitor production. If the limit is exceeded, a light flashes or an acoustic alarm sounds. Were any other measurement methods considered? B: Actually no. The procedure recommended by the employer’s liability insurance association is very involved. For example, the samples must be collected on site, absorbed and later deabsorbed before they can be analyzed by gas chromatography. Under this system, the continuous measurement provided by the SAM GC- 600 would not be possible. Do your employees feel safe with this monitor in place? K: Employees have great faith in the measurement results. Each time the production chambers are entered, we first check to see if the air is clear of BCME. The measurement results can be displayed directly on the device or read out in the measurement con-


trol room. In addition to this, the BASF safety concept also requires employees to visit the company physician for regular preventative check-ups. Did you trust the device from the beginning? B: Yes. Before the product was delivered, two of our staff visited Solvias to see for themselves the guaranteed operational reliability of the SAM GC- 600. The methods were also tested prior to implementation. As a result, the monitor was operational immediately following installation. How important is maintenance? B: I’m responsible for daily inspection. Besides this, we have Solvias manage the semiannual maintenance and retrofitting of

the device whenever we make any changes to our production operation.

Figure 1: Thorsten Bartsch explains the results in the measurement control room

What approach would you recommend for implementing a chemical hazards monitor? B: The SAM GC- 600 is a small, compact device that is easy to install and operate. It is important to choose the right measurement points so that any possible leakages at critical points can be rapidly detected.

Thank you Dr. Krumwiede and Mr. Bartsch for your time. Interview: Silke Oeschger, Marketing Communications



Solvias Prospects 01/2009


BASF PharmaChemikalien GmbH & Co. KG Minden The BASF site at Minden has been producing pharmaceutical substances since 1939. Here, BASF operates the largest production facilities in the world for ephedrine, pseudoephedrine, caffeine and theophylline. Moreover, approximately 30 chemically different active ingredients and highly refined intermediates are manufactured in multiproduct installations, both for the generic pharmaceuticals market as well as those that are tailor made to specific customer requirements (custom synthesis).

SAM GC-600 Chemical Hazards Monitor

The SAM GC- 600 chemical hazards monitor is a high-performance analyzer that is based on gas chromatography technology. It is developed specifically for continuous chemical hazards monitoring, and is used where highly toxic or carcinogenic substances may be present in the productionplant air or in the workplace. Based on its high level of selectivity and sensitivity, as well as its low detection and alarm limits, the SAM GC- 600 is a reliable, robust monitor for hazardous substance exposure in the ppb to ppt range. Available detectors are FID, ECD, FPD, PID.

Outstanding Performance – Your Benefit • Early alarm triggering signals exposure to hazardous substances – warning and display already well below existing limits thanks to adjustable alarm thresholds • Highly selective and interference-free measurement – no false alarms and no resulting disruption to operations • Individual customized method development in the laboratory plus implementation and optimization on site – development of special solutions for reliable chemical hazards monitoring* • Wide bandwidth – nearly all substances having a boiling point <250°C or a vapor pressure >0.000001 mbar can be analyzed * To date, analysis methods have been developed for more than 50 substances (see separate list of substances).

Bis(chloromethyl)ether (BCME) This highly toxic substance is formed spontaneously when formaldehyde is used in the presence of hydrogen chloride (chloromethylation reaction). BCME’s workplace limit of just 1 ppb is a clear indicator of how dangerous it is. Thanks to its ability to reliably detect concentrations as low as 10 ppt, the SAM GC- 600 helps to ensure the safety of your employees.

Solvias Prospects 01/2009

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Unidentified Residues, Foreign Particles, Faulty Products: Identifying Unknown Inorganic Impurities Even when everything has been done to manufacture products of the highest quality, unwelcome surprises may still occur in practice. Approved processes can suddenly create problems. For example, unidentified contaminants, residues or foreign particles are found. This can mean halting production, announcing a recall of the medication and an urgent investigation into the nature and causes of the problem. The first phase is usually diagnosis (analytical phase), followed by an assessment of the source and the consequences of the contamination, and then finally putting measures in place to avoid such problems.

The Right Analytical Method for Rapid Results Semiquantitative X-ray fluorescence analysis – for multi-element determinations An unidentified residue or deposit can be characterized or identified by means of this non-destructive method. All elements in the periodic table ranging from magnesium to uranium, including the halogens, silicon, phosphorus and sulfur, can be detected. Figure 1: A tablet contaminated with an unidentified foreign particle Figure 2: The unidentified particle from the tablet under SEM

Time Is of the Essence Solvias has been a specialist in troubleshooting for a number of years – analyzing irregularities is one of our core competencies. No matter what the problem or analytical method, the customer can usually expect to receive initial information or even the entire solution in just one to two days.

Here are some typical problems that we solve on a routine basis: • A white crystalline active substance/tablet contains dark particles. What do these particles consist of? • A dark-brown residue was found in a reactor. What does it consist of? • A synthesis step is no longer functioning as normal. Could metallic impurities be responsible for the malfunction? • Sulfated ash levels exceed the maximum specification. Which inorganic components might be responsible for this?

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Solvias Prospects 01/2009


A distinction is drawn between major constituents, minor constituents and trace impurities. A metallic residue can be clearly identified. This method can also be used to identify inorganic impurities responsible for elevated levels of sulfated ash. Scanning electron microscopy with energy dispersive X-ray analysis – for small particles Unidentified small particles can be examined with a microscope. Elementary identification is accomplished using scanning electron microscopy (SEM) with energy dispersive X-ray analysis (EDX detector). To illustrate: In this example, particles were observed in a tablet and were subsequently identified, from the Fe, Cr, and Ni content, as steel abrasion (refer to Figures 1–3). ICP-OES – especially for heavy metal impurities If the problem has already been narrowed down to heavy metal impurities in the test substance, for example steel abrasion or corrosion residue, ICP-OES can be used to perform a quantitative analysis of 21 typical metals in the trace range. From the ratios of metals, e.g. Ni, Cr, Mo, Co, Cu and Fe, found,

the type of steel responsible for this contamination may even be identified. Other options Inorganic elemental mass spectrometry (ICP-MS) can be used for more specialized analyses, extended to include traces of all metals in the periodic table. Anion and/or cation screening using ion chromatography are another specialty. The selection of the methods discussed for an analysis of this kind depends on various parameters, such as the specific question posed or the available quantity of the respective material for analysis. Whatever the method, Solvias delivers results as rapidly as possible, so as to keep possible production downtimes to a minimum.

Applicability to Quality Control: Scope for GMP Release The methods listed here can be used for more than troubleshooting. ICP-OES method has been validated for the quantitative determination of 21 heavy metals and is therefore suitable for use in release analysis under GMP.

Dr. Bertold Gercken, Senior Lab Manager Figure 3: Determination of the composition of the contaminant particle based upon the EDX spectrum

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Intellectual Property: Rigorous Patent and Literature Searches as a Basis for Reliable Advice Patents are used by inventors and companies to protect their intellectual property. Patent and literature searches are essential both to assess the novelty of an invention before applying for a patent, and to prevent patent infringement by ensuring that no relevant patent exists or that the knowledge is in the public domain. The information obtained from a patent and literature search provides a basis for deciding how to proceed.

Need for Comprehensive Searches Decisions taken on the basis of search results are important, so patent and literature searches must be comprehensive and thorough. Clearly, the services of a professional searcher are needed to obtain a reliable result.

Professional searchers are scientists who are specialists in the field which is to be investigated. They have specific training and experience in database searching and in analyzing the content of documents. In particular, they must have:

• Excellent communication skills to discuss search inquiries and reports with customers • Systematic knowledge of databases, search interfaces, query languages and retrieval techniques • Knowledge of the technical field in which the search is to be conducted • Basic knowledge of the patent system in regard to patent expiry, equivalents, pending applications, granted patents, etc.

Value of Searches In the early stages of the patenting process, state-of-the-art and patentability searches are used to assess novelty and non-obviousness of the invention. The results should cover all publications from any sources which may describe all or part of the invention. These are essential aids for patent attorneys and inventors who want to draft patent applications, and for examiners during the granting process.

Figure 1: Database search

Another type of search focuses on possible infringement of patents and on freedom to operate. Infringement and freedom-to-operate searches are used to assess the potential of new products or processes to infringe an existing patent. These searches identify patents that might be infringed, or publications

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Solvias Prospects 01/2009


disclosing technical knowledge that is in the public domain and that therefore can be applied freely. Based on the results of such searches, a patent attorney can provide an expert opinion on product clearance.

Search Workflow A search involves several steps, as shown in the flowchart (Chart 1).

Scoping the search

Analyzing the search results

Scoping the Search – Input Determines Output The search question must first be specified in detail. In a direct discussion with the customer, the searcher needs to develop an understanding of the question the customer wants to search. The question determines the type and extent of the search. Direct contact between customer and searcher will help to eliminate any misconceptions concerning the scope of the search.

Chart 1: A typical search workflow

Solvias Prospects 01/2009

Preparing and executing the database search

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Preparing and Executing the Database Search – Definition of the Right Strategy The next step is to develop a database search strategy to respond to the customer’s question. The question is categorized into different concepts, each capturing a single aspect. These concepts, together with a list of databases selected by the searcher and rated as appropriate for the search constitute the search strategy. Concepts may

Compiling the search report

appear as a list of keywords (synonyms) or, in the field of chemistry, as a chemical structure. For the database search, the searcher needs to combine the different concepts to reflect the search question, and to translate the combination of concepts into the specific query language for each database and retrieval system. The searcher will then run the query and retrieve a list of documents from the databases.


Analyzing the Search Results Not all documents retrieved by the database search will be relevant, so the searcher will analyze titles, abstracts, indexing and, if necessary, the full texts of publications to rate the relevance of the document in regard to the search question. For certain searches, the searcher will also analyze patent families and legal status data. For example, in an infringement search, only valid patents in selected countries will be relevant.

Compiling the Search Report The search report should contain the search question, a description of the search strategy, the number of relevant references retrieved, and a listing of those references. The description of the search strategy should cover the databases and other tools used for searching, and list the concepts and keywords searched. Optionally, the searcher will add a comment to each reference explaining why it was considered relevant. The searcher might also note any salient points or describe difficulties encountered when searching.

knowledgeable in these technical fields as well as in the field of patents, and who has excellent communication skills. Although the Solvias search service is part of the patent department, it maintains close contact with other departments. Searches can thus be offered along with other Solvias products and services. Searches may be part of a larger project, for example in the field of chemical synthesis or polymorphism. Such collaborative efforts are also available within the patent department, for example a stateof-the-art search together with the drafting of the patent application by a patent attorney, or a freedom-to-operate search together with a written legal opinion concerning product clearance.

Dr. Dieter K端ry, Information Scientist

The Solvias Search Service Solvias offers patent and literature searches in the fields of chemistry and pharmaceuticals. Search requests are processed by an experienced professional searcher who is

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News

Solvias Acquires Exclusive License for Homogeneous Catalysis Technology Solvias has acquired an exclusive license from Evonik Degussa GmbH, Essen (Germany), to develop, manufacture, and market two ligand product lines: catASium ® and cataCXium ®. “The license agreement boosts the metal-mediated homogeneous catalysis technology capabilities at Solvias. The integration of Evonik’s ligands will add yet more diversity to our product portfolio and will help solve the toughest catalysis problems,” says Dr. Garrett Hoge, Product Manager Catalysis at Solvias. Solvias is already a center of excellence for homogeneous catalysis and high-throughput screening. Adding the new Evonik license will add to Solvias’ capability.

catASium ® is a line of chiral ligands for asymmetric hydrogenation, consisting of highly varied chiral ligands and their associated Rh complexes. Asymmetric hydrogenation reactions allow the effective synthesis of a large variety of chiral building blocks and intermediates, and are extensively used by the pharmaceutical, fragrance, and agrochemical industries. This technology has successfully been applied to the manufacture of pharmaceuticals (in both small and large volumes), as well as to the production

Solvias Prospects 01/2009

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of chiral agrochemicals in quantities of up to 20,000 tons per year. The catASium ® portfolio complements the successful Solvias approach of using ligand diversity and highthroughput screening to find catalysis leads for our customers. cataCXium ® is a line of CX-coupling ligands with proven success in solving CX-coupling problems in the pharmaceutical, agrochemical, and specialty chemicals industries. CXcoupling reactions (bond formation of carbon with sulfur, nitrogen, oxygen, or other carbon atoms) produce very high yields and use relatively inexpensive starting materials, such as primary and secondary amines or imines, or aryl halides and sulfonates. Adding cataCXium ® ligands extends the Solvias range of industrial pallada-cycle catalysts and the CN-coupling technologies using Josiphos ligands developed by Professor John Hartwig at Yale University.

Solvias Offers New Flexible Arrangement for Asymmetric Hydrogenation High-Throughput Screening With a new flexible arrangement for highthroughput screening, Solvias offers customers a choice of six 96-well standardized plates designed for six general substrate


types. For added flexibility, customers can also modify the standard plate in any way they choose. This flexible arrangement is one of the fastest ways to identify a chiral catalyst lead for your chemical process.

Pre-designed high-throughput screening plates are available for the following general substrate types:

• Acrylic acid: classic substrate • Enamide: classic substrates including α- and β-dehydroamino acids • Simple ketone: typically methyl aryl ketones, alkyl aryl ketones, and ketones that lack a second transition metal coordinating functional group • Functionalized ketone: classic α- or β-keto ester substrates or close relative • Simple olefin: tri- or tetra-substituted • Unprecedented: substrates that have little or no precedent in the literature

Solvias views this research service as an extension of the customer’s laboratory. Solvias’ aim is to fit into the customer’s drug development process with maximum flexibility, so that customers can achieve quick results at a competitive cost.

Successful FDA Inspection Solvias was inspected by the American Food and Drug Administration (FDA) on November 3 and 4, 2008. The inspection by the US health authority was prompted by the submission of two new drug applications (NDAs) by one of our customers. The scope of the inspection was the analytical activities pertaining to heavy metal release associated with four active pharmaceutical ingredients used in the two NDAs. After the two-day inspection, the investigator concluded that Solvias has a very good quality system. It was confirmed that the analytical activities for the two NDAs are performed according to cGMP requirements. No 483 report was issued by the investigator. Following the successful FDA inspection in 2005, when no 483 report was issued either, this recent inspection validates the success of our ambitious efforts to continuously improve the quality of our services. We would like to express our thanks to all concerned for their excellent preparation and performance in regard to the inspection.

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Professor Walter Baratta Wins Solvias Ligand Contest 2008 The annual Solvias Ligand Contest challenges researchers all over the world to submit new and improved applications of Solvias ligands and catalysts. To pick the winner the jury takes account of novelty, scientific rigor and originality, as well as practical applicability in organic synthesis. This year, the jury awarded the prize to Professor Walter Baratta of the Dipartimento di Scienze e Tecnologie Chimiche, Università di Udine (Udine, Italy), for his paper “Osmium and Ruthenium Complexes as Efficient Catalysts for the Asymmetric Reduction of Ketones,” describing the application of Solvias ligands in the area of asymmetric catalysis. The citation of the jury reads: “In recognition of the development of a remarkably efficient new class of catalysts based on Os-Josiphos complexes. The novel catalysts as well as the analogous Ru complexes exhibit very good enantioselectivities, very high turnover numbers and turnover frequencies for the hydrogenation of aromatic ketones. In addition there is potential for further development.”

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The award ceremony, including a presentation of the prize-winning papers, took place during the seventh Solvias Science Day, November 18, 2008, at the Congress Center in Basel. Around 120 participants from academic and industrial laboratories attended the event.

Cooperation with Patheon Provides Integrated Development Services In a new cooperation, Solvias’ excellence in preformulation and solid-state chemistry will be combined with Patheon’s experience and expertise in formulation development to offer integrated development services to pharmaceutical and biotechnology companies. “For Solvias, the alliance with Patheon is an ideal fit with our existing integrated approach to the development of drug substances. It expands the range of services we can offer our customers to include formulation of APIs for early clinical phases. We believe that the ability to provide fully integrated chemical development services,


from early stage drug development through formulation, is of clear benefit to our customers, as it will result in greater efficiencies, reduced interfaces, and better information flow. Customers’ development timelines will be significantly shortened,” says Phillip M. Chalabi, Vice President of Business Development at Solvias Inc. (US). The partnership between Patheon and Solvias will provide customers with flexible and integrated early development services, including API characterization, salt selection and co-crystallization, polymorphism screening, solubility determination, and excipient compatibility and formulation. Patheon’s innovative Quick to ClinicSM program will be implemented for rapid Phase I development, and to optimize programs for special molecules such as those with low solubility

or challenging solid-state properties. As this is a non-exclusive cooperation, the customer has a free choice of service provider for development activities. According to Wes Wheeler, Chief Executive Officer and President of Patheon, “Patheon’s vision is to be the best provider of services. This alliance with Solvias is an example of how Patheon is committed to providing and expanding these turnkey solutions for the most integrated, value added service offering for our customers.” Patheon is a leading provider of contract development and manufacturing services to pharmaceutical and biotechnical companies. Patheon’s technologies and services range from pre-clinical development to manufacturing a full array of dosage forms.

Get in touch Tel. + 41 61 686 61 61 Fax + 41 61 686 65 65 info@solvias.com Solvias AG Marketing and Sales WRO – 1078.3.05 P.O. Box 4002 Basel Switzerland


Events

Meet Us at the Following Exhibitions and Conferences WCBP 2009 January 12–14, 2009 Booth T3 San Francisco, CA, USA www.casss.org

Modern Synthetic Methods & Chiral USA May 11–13, 2009 Chicago, Il, USA www.scientificupdate.co.uk

Informex 2009 January 28–30, 2009 Booth 1712 San Francisco, CA, USA www.informex.com

Achema May 11–15, 2009 Booth D19–E19 Frankfurt, Germany www.achema.de

IQPC-Polymorphism & Crystallization March 11–13, 2009 London, UK www.iqpc.com

Bio 2009 May 18 –20, 2009 Atlanta, GA, USA www.bio2009.org

biotrinity 2009 April 2–3, 2009 Oxford, UK www.biotrinity.com

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