Aptuit provides drug development services to pharmaceutical and biotechnology companies worldwide. Our development services are based upon state-of-the-art facilities and timely delivery of quality data. A wealth of experience allows Aptuit to help you define the best strategy for the development of your compound. All of this is driven by your ultimate goal – getting to market faster.

Since all drug development activities depend on the reliable supply of the Active Pharmaceutical Ingredients (APIs), a foremost Aptuit capability is its comprehensive global API service. These services span post discovery to commercial production of API, making Aptuit the single solution provider of API development and manufacture.

The cellular and biochemical mechanisms involved in biotherapeutic function are inherently complex, requiring an in-depth characterization of the mechanisms of action of biotherapeutics to successfully support preclinical development to fi rst in man. As part of our clients’ early development programs, Aptuit can provide specifi c support to evaluate mechanisms of action, effi cacy and PK/PD assays, in addition to our comprehensive range of standard safety pharmacology and toxicology studies and in vivo effi cacy models.

Aptuit’s dedicated immunoanalytical team can provide comprehensive and innovative approaches to immunoassay studies. Our scientifi c knowledge and academic and industry expertise can be applied across a range of therapeutic areas. The immunoanalytical group supports assay development and validation with applications in discovery, preclinical/clinical sample analysis and immunogenicity testing.

Since Biotherapeutics have the potential to elicit an unwanted immune response, a strategy to characterize this response must be in place for clinical trials. Indeed, consideration of immunogenicity is initially developed in the preclinical phase in order to assess the potential effect such a response may have on drug activity and PK. Aptuit employs a three stage approach, as recommended in the EMEA guideline on immunogenicity assessment of biotechnologyderived therapeutic proteins (EMEA/CHMP/BMWP/14327/2006).

Potential immunotoxicity of therapeutic compounds is a major consideration in drug development. Aptuit’s Applied Immunology group can conduct immunotoxicology studies in state-of-the-art AAALAC accredited facilities. These studies can be supplemented by analysis of a range of immunological parameters appropriate to the drug’s mechanism of action.

Aptuit’s acquisition of GlaxoSmithKline’s Medicines Research Centre in Verona, Italy expands and bolsters Aptuit’s integrated scientific capability and expertise for the benefit of our customers globally.

Aptuit’s facility in Verona, Italy expands and bolsters Aptuit’s integrated scientific expertise and operational capabilities for the benefit of our global customers.

Our pharmacometrics team provides planning and analysis support for a wide range of clinical studies as well as entire clinical plans from First-Time-In- Human through to proof of concept clinical trials.

Aptuit’s strategy is to work with our clients to develop innovative, robust, and cost-effective chemistry solutions for any of their medicinal or computational chemistry needs from hit identification (hitID) through to candidate selection.

The challenge of the development in new drugs from candidate selection to launch resides in the high clinical attrition rate. In fact, only 8% of new drugs will successfully make it up to launch and the attrition rate for new molecules entering clinical development is on average 85%. The probability of success for compounds in Phase I & II has a significant impact on overall development costs, in a way that clinical development accounts for approximately 60% of the cost for each new drug.

Pathology is the integrative discipline by definition, with a long tradition of integrating structure and function of disease. Pathology possesses a unique skill, microscopic interpretation that can be applied to the evaluation of the expressed phenotypes in both humans and animals. Pathology uses multiple and irreplaceable tools, particularly histology, ultra structure techniques and biomarkers.

Pharmacology and Safety Pharmacology can support all phases of the Drug Discovery process from Target Validation to Candidate Selection, FIM and beyond, in a fully integrated manner with other preclinical disciplines. Our fully integrated approach, working closely with colleagues in Medicinal Chemistry and DMPK, allows us to produce high-quality candidates and reduce candidate attrition rates. We have experience and expertise in a wide variety of target types including: GPCR targets, ion-channels, transporters and enzymes.

Aptuit Verona offers unique integrated analytical capabilities and expertise. It delivers complete and high quality packages of analytical services for drug discovery and development of chemical entities customized for each phase, from early definitions through a fully validated GMP environment to analytical tech transfer. This translates in to benefits for our customers and is assured by a seamless transfer of knowledge and methods from one phase to the other.

Aptuit provides chiral and achiral method development as well as sample analysis services. Chromatography experts offer a wide range of analytical and preparative support for chiral and achiral compounds, using both HPLC and SFC technologies.

Clinical Sciences includes activities such as discovery medicine, clinical trial management, data management, pharmacokinetics and statistical services, which span from the design and implementation of multi-faceted projects up to proof of concept, through the design and implementation of single areas within the client’s clinical development plan.

The ICH S7B guidelines highlight the importance of understanding the consequences for development of a drug candidate with a potential to prolong QT interval. Cardiovascular assessment in vivo along with in vitro assessment at the HERG channel is recommended. If results from these two tests are equivocal then further investigation in other models are advised. Aptuit provide a fully comprehensive package of studies to cover ICH S7B regulatory requirements, which can be monitored for GLP compliance.

At our GMP manufacturing facilities in Kansas City, MO, our AutoDose’s Powdernium™ can significantly improve your drug development timelines and decision-making process by accelerating your drug to First-in-Man studies. The system offers great flexibility by dispensing drug substance directly into capsules, vials or bottles. It also minimizes early formulation development, drastically decreases the amount of drug substance needed to get to First-in-Man, and reduces analytical development costs. Aptuit customers can access this technology within the security of Aptuit’s GMP facility located in Kansas City, Missouri.

Identification and Authentication Peptide mapping procedures (e.g. peptide mass fingerprinting) are used to identify the protein. Comparability Testing This service is used to assess whether process changes have had an effect on the properties of a protein drug substance. Separation We offer a full complement of chromatographic as well as electrophoretic separation techniques as listed below. Related Substance Isolation and Characterization Related substances may include such variants as oxidized forms,

Development of new therapeutic entities can be a complex process requiring the development of a sound strategy and a detailed project plan. These are essential for progression of a compound through the different phases of preclinical and clinical testing in a timely and cost-effective manner. Aptuit Consulting is an independent group

Development of new medical products for regulatory approval is complex, costly, and time-consuming. There is a myriad of external providers capable of undertaking work to achieve the discreet steps within this process, but coordinating these steps within an appropriate regulatory framework requires considerable skill and experience.

Pharmaceutical development is one of the most challenging aspects of pharmaceutical and biopharmaceutical innovation. It involves navigating the complexities of pharmaceutical science and manufacturing, while achieving regulatory compliance. Aptuit recognizes that rising to today’s challenges requires a network of highly skilled specialists and global, integrated pharmaceutical development capabilities. With more than 500 scientists operating out of 330,000 sq. ft. of state-of-the-art GMP/GLP laboratory and manufacturing capacity, Aptuit is the global leader in pharmaceutical sciences. Aptuit offers solutions tailored to our customers’ exacting needs

Mapping and Image Studies On a micron or sub-micron scale, solid samples such as powders, pressed tablets or cast films typically exhibit non-homogeneous mixing of components. This results in regions that are disproportionately more concentrated in individual components, which can have major impact on stability, delivery and other physical properties of the product. Our powerful analytical techniques provide a wealth of chemical and physical information on specific microscopic regions of solid samples. Some of the most prominent techniques are:

Preparation of Amorphous or Disordered Materials We have experience with a broad range of methods of preparation of amorphous and disordered materials including an amorphous screen (see screening section). These methods are optimized based on the drug substance of interest.

Crystallization of Difficult Materials and Scale-up Crystallization is the critical step in solid form control. We can help you define a process that ensures the solid form you manufacture is the one you want. Crystallization Process Development and Scale-up We have wide-ranging experience in all areas of crystallization. We can take your compound through the stages of generating the first crystals, polymorph screening, salt or cocrystal form selection and

With over 20 years’ experience of drug discovery and development, Aptuit’s Efficacy Group has outstanding pharmacological expertise covering a broad range of therapeutic areas. These services can be used to screen test substances for lead candidate selection, and to test pharmacological efficacy in a range of models. Protocols are individually designed to meet the requirements of the Sponsor and studies are conducted in a GLP environment (and may be monitored by QA if

Aptuit understands that manufacturers of generic pharmaceuticals are challenged by budget constraints and shortened timelines. At Aptuit’s site in Verona, Italy, a dedicated bioequivalence (BE) team integrates clinical, pharmacokinetic and statistical expertise with formulation development and manufacturing and bioanalytical capabilities. Our strength in these competencies enables Aptuit to meet specialized needs and deliver customized solutions for generic drug development. In this way, the key steps in generic development can be supported, exploiting fully the “critical path opportunities” (as cited in the FDA Document, May, 2007) and the scientific knowhow that allow accelerated development and approval of the generics. The range of products for which generic versions are available is thereby expanded while high standards for quality, safety and effi cacy are maintained. The physicians and scientists that form Aptuit’s team bring more than 15 years experience in clinical pharmacology studies, including their work in BE studies in healthy volunteers and patient populations.

Aptuit’s position as a long standing supplier of Active Pharmaceutical Ingredients (APIs) in the industry includes our ability to develop, manufacture and handle highly potent and cytotoxic compounds on three continents. An expert team of Aptuit scientists, with more than twenty-fi ve years of experience in synthesizing HPAPIs, ensures the delivery of consistent and reliable high potency and cytotoxic APIs.

The advent of automated patch-clamp recording and subsequent launch of Rapid ICE has revolutionized the use of electrophysiology in drug discovery and development. Rapid ICE screening of compounds for activity at the hERG ion channel has proved to be an invaluable early safety assessment assay.

For over 20 years, pharmaceutical companies have relied on SSCI for solid state development and improvement of drug products and substances. Through the acquisition of SSCI in 2006, Aptuit is considered the industry leader in solid state chemistry services.

Advancements being made in genomics, proteomics and systems biology are transforming the drug discovery and development process, while facilitating our understanding of the molecular underpinnings of disease. Translational, or “bench-to-bedside,” research involves expediting the translation of these scientific discoveries in to clinical practice.