New service in outsourced drug disposition
and toxicology

sp2 - Sep 2004

Midwest BioResearch is a new US company formed by pharmaceutical industry professionals to provide drug disposition and toxicology services for late-stage drug discovery and early-stage development. Tom Mulligan spoke to Mike Schlosser, the company’s president, to find out more.

In October of last year Midwest BioResearch, LLC (MBR) was established as a speciality contract research organisation to provide outsourced drug disposition and toxicology services to the biotechnology and pharmaceutical industries. The company, which was founded by former scientists, managers and directors from Pfizer, Pharmacia, and Searle, provides a personalised service to help researchers select and progress their protein or small-molecule therapeutics out of discovery and through development.

When Pfizer bought Pharmacia in 2003, it closed down Pharmacia’s Chicago research and development facilities, displacing over 1,500 employees. One of these facilities provided safety assessment of new drugs. MBR was formed from this unit in October 2003, initially with seven people, and has rapidly expanded to now employ 17 people. “There is a need in the industry for expertise in the areas of drug disposition and toxicology for early drug candidate selection through to registration, and MBR was founded to meet this need,” says Dr Mike Schlosser, the company’s president. “We are interested in supporting the overall development cycle of drug candidates and are not just a company supplying laboratory services. We believe in partnerships. We offer guidance and strategic approaches for our customers.”

The company’s management team has extensive experience in protein and small-molecule bioanalysis, structure identification, genetic toxicology, safety assessment, and risk management in both discovery and development within the pharmaceutical industry.

“Our team has contributed to one of the healthiest drug pipelines in the industry and to the registration of novel blockbuster drugs,” says Schlosser. “By focusing on key areas of drug development and providing personal service and strategic advice, we offer a formula that can save biotechnology and pharmaceutical companies time and money.”

Laboratory services combined with consultancy

MBR provides both laboratory and programme services and support. The company’s facility, located at Evanston, Illinois, is GLP-compliant and contains state-of-the-art equipment ranging from fully automated sampling and data recording systems to API LC/MS/MS instrumentation. In addition, the company has access to a wide variety of modern analytical equipment for structure identification and non-GLP work through the Analytical Services Laboratory at Northwestern University. The company also has an established network of scientists, associates and CROs that can provide strategic advice and partnering for programme milestones as needed.

MBR has a team with significant experience in the preparation and review of regulatory summary documents including INDs, NDA/BLAs, and CTDs. “Our programme services group is experienced at rapidly incorporating study results, with expert interpretation, into summary documents, while providing a thorough safety risk analysis tailored to the stage of development and target population,” says Schlosser. “We have direct experience in ICH-CTD format/philosophy, and in working within multi-disciplinary teams to produce high-quality summary regulatory documents that can withstand regulatory scrutiny.

“When a preclinical issue arises in drug development, it is of utmost importance to correctly manage that risk. We have extensive experience in managing development issues within speciality areas and in working with regulatory agencies to resolve these issues. We’re experienced with both proteins and small molecules at all stages of drug development. If the need arises, we work with global experts in various fields to ensure critical, rate-limiting issues are adequately addressed,” he says.

“As R&D budgets decrease and the need for novel therapeutics increase, outsourcing key functions in drug discovery and development is the viable alternative to efficiently develop commercial drugs,” Schlosser states. “However, we have found in our years of experience, that there is much more to just outsourcing experiments. Our goal is to carefully integrate our years of experience in drug disposition and toxicology testing with the critical personal attention and responsiveness needed to meet objectives, timelines and budgets.”

Overcoming drug failures through drug disposition and toxicology studies

It is estimated that nearly 86 per cent of drug failures are a result of either inadequate blood levels or unacceptable toxicity 28 SEPTEMBER and side effects. The ability to identify and understand drug disposition and toxicology is critical in compound selection and in the management of risk during development programmes. MBR aims to streamline compound selection and product development to improve cycle times, lead quality, and efficiency by offering expertise in assay design, method development, and validation for both proteins and small molecules analysed in a variety of biological matrices, including tissues. The company has the experience and technology to rapidly generate results for making decisions at the late-discovery and early-development phase; generate regulatory-compliant results from a large number of samples from either clinical or preclinical projects; and determine key pharmacokinetic, toxicokinetic, and pharmacodynamic parameters for understanding behaviour of a drug or metabolite.

Specific assays that can be conducted to either GLP (development focus) or non-GLP (discovery focus) include dose formulation assays, metabolic stability, metabolite profiling, protein binding, method development and validation, antibody characterisation (eg, epitope mapping), pharmacokinetic and toxicokinetic analyses, cell culture bioassays (eg neutralising activity), and blood compatibility testing (RBC osmotic fragility).

MBR is also capable of structure determination of metabolites and other organic compounds and their impurities. In addition, its toxicologists can perform impurity risk assessments to support clinical trials and registration of new products. The company also has extensive experience in using a tier strategy for genetic toxicity testing, and can provide strategic advice and perspective on findings generated within each tier:

• Tier 1 includes an evaluation for structural alerts coupled with rapid and efficient mutagenicity and clastogenicity screens. Screens can be tailored to a customer’s specific screening needs.

• Tier 2 includes regulatory-compliant studies conducted to meet worldwide requirements for drug/chemical registration

• Tier 3 involves follow-up investigative studies conducted to understand the mechanism of an equivocal or positive response and/or human relevance of the findings.

Supplying a specialised service

“There is a need in the industry for specialised niche companies like ours,” says Schlosser. “We have partnered with several companies, acting as the extension of the laboratories of small biotechs, as well as providing strategic advice in drug development. We are also working with larger pharmaceutical companies. The majority of our clients are US-based companies, but we are currently in negotiations with UK companies. We also have a strong relationship with Evanston’s Northwestern University which houses a variety of state-of-the-art analytical equipment for structure identification.

“We’ve had a big increase in the number of people we employ plus a large expansion of our lab facilities. Since our inception, we have expanded our lab facilities by 25%. Last year, we were able to purchase state-of-the-art equipment from Pfizer R&D and moved it to our new premises at Evanston to set up our GLP laboratory facilities. We now have five LC/MS/MS instruments, automated liquid-liquid and solid-phase extraction equipment, ultracentrifuge, several automated plate readers including fluorescence, HPLC systems, radiolabel detection devices, and bacterial and mammalian cell culture facilities. In addition, we have placed large emphasis on compliance-related activities, including assurance of data integrity, process improvement, and training.

“Our future prospects are based on establishing strong collaborations with Big Pharma and with growing biotech companies. Due to Big Pharma’s stagnant growth relative to number of compounds coming through their pipeline, it’s increasingly the case that they need the types of services we offer,” says Schlosser. “The European market is also very important for us. The new Clinical Trials Directive has created a number of regulatory hurdles within the EU. We believe we can help by providing top-quality preclinical services and strategies to efficiently and safely allow initial human testing in the US within timeframes more rapidly than in Europe.

“Through MBR’s expertise in pharmaceutical drug discovery and development and in proactively working with regulatory agencies, the MBR team can generate novel preclinical strategies that achieve early and successful milestones,” says Schlosser. “These strategies not only take into account the critical elements of drug candidates, which we can help define in our laboratories, but those of the drug target, clinical endpoints, and intended use. The earlier in the drug discovery and development process a company can merge its preclinical and clinical strategies, the more time and money that company will save in the achievement of major milestones,” he concludes.

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