Selvita offers custom assay development and screening/profiling services up to 1536-well plate format. We have created a robust compound management infrastructure supporting manipulation of samples in racks, tubes and plates. We employ a fully automated HTS platform allowing testing of 10,000 compounds a day across a wide range of biochemical and cellular assay types. We operate HCS screening in support of client projects within our new state of the art HCS laboratory and are generating novel machine-learning based scripts to support enhanced image analysis in the cell types of particular interest to our clients.
Selvita has initiated the design and building of a new HTS library which will be grown and developed further to provide an excellent resource for hit identification. This compound collection is supplemented by the FideltaMacro™ library with over 1300 diverse macrocyclic molecules.
Our team is built on extensive expertise in the areas of molecular biology, biochemistry, immunology and cell biology. We have a track of record in assay development for various classes of targets, including enzymes (kinases, phosphatases, metabolic enzymes, immuno-modulatory enzymes) and protein receptors (GPCRs, nuclear receptors). Selvita’s state of art-equipment allows for a wide variety of detection modes to be implemented, adding value to your drug discovery program.
Biochemical and cell-based assays
Selvita can offer case-by-case selection of suitable cellular model/s to investigate the biological mechanism of interest (e.g. cancer cell panels of a specific type and/or with common mutation patterns). Our in-house capabilities for reagent generation include in-house production and validation of recombinant cell lines and recombinant proteins. Our assay development strategies are characterized by efficient and effective protocols. Usually, multi-factor design of experiments is employed during method development. It accelerates optimization of the assay performance, thus helping to obtain a measurement system that meets its requirements. Statistical parameters are used to support a reliable and robust assay for routine use, e.g. IC50/EC50; mRSD (mean Relative Standard Deviation); S/N ratio; Z’ factor; plate uniformity.
Medicinal chemistry is an interdisciplinary science which plays a crucial role in the drug discovery process. In medicinal chemistry we follow a highly data-and-hypothesis driven path making meaningful molecules whilst also using productive synthetic routes to bring benefit both from efficiency and from serendipitous discoveries.
We are skilled at multi-parameter optimisation based on the analysis of biological, structural and physicochemical data. We use these expanding data sets from ADME assessments, computer-aided drug design, structural biology, in vitro and in vivo biological testing, and disease models to refine our thinking and to influence the design of new iterations of molecules. In addition, the effectiveness with which the projects are executed is very dependent on the quality of the infrastructure but even more by the quality and passion of our people.
We benefit from close interactions with colleagues in the associated scientific disciplines and execute our work together under one roof in our drug discovery facilities in Krakow. Our skill in chemistry is built on years of diverse experience in small molecule synthesis and incorporates strengths in the efficient preparation of compounds across multiple chemotypes including heterocyclic synthesis, macrocyclics, peptidic molecules, steroids and nucleosides, and beyond. Our strong asset is “out-of-box” thinking and application of the latest techniques like flow-, electro- and photochemistry where classical methods reached their boundaries.
The biology offering at Selvita covers all drug discovery purposes from target validation through to preclinical candidate selection. We provide a protein-to cell approach for the development of pharmacologically active compounds.
Our in vitro pharmacology activities commence from the customized production of recombinant proteins for use as screening proteins to probe compound interaction in a panel of biochemical and biophysical methods, also in a high-throughput screening mode. In parallel, using Selvita’s considerable internal experience of protein crystallization, protein structural analyses can be performed by X-ray. Using cell-based assays, we perform small molecule activity analysis using of a large repository of cells.
These cell-based assays can also be run in a high-throughput screening mode for hit finding. Close to two hundred recombinant cell lines are available for assay development, adaptable to many pathological areas. Selvita offers the custom production of recombinant cell lines expressing the protein target of interest. In addition, primary cells, for example from human (blood) or from rodent (CNS), are available upon request for assay development. Secondary screening for pharmacological evaluation of compound characteristics is part of our Integrated Drug Discovery expertise. Mode of action, biomarkers, target engagement studies are provided for hit characterization, and for lead finding and optimization.
Multiple readouts are available from classical fluorescence, interference (TR-FRET) or biochemical-based up to bioluminescence gene reporter assays or Alpha-Lisa technology, from medium throughput to HTS, and up to 1536 well plates depending on the scalability of the assays. In vivo evaluations can be arranged by Selvita during the lead optimisation and prior to preclinical development candidate selection. We analyse tissue samples, generate and interpret PK parameters or drug and biomarker concentration for pharmacodynamic studies in many disease areas such as cancer and CNS.
With numerous disease models developed in the past 10 years, and the experience built within the pharmaceutical industries, biotech and academia, our highly professional in vivo pharmacology team supports drug discovery projects, fully integrated with other preclinical disciplines.
The core areas of our PD expertise are inflammation, infection, fibrosis and we intend to expand into additional areas in 2021. We apply a comprehensive approach to primary and secondary pharmacodynamic profiling of the compounds to ensure generation of high-quality data relevant to human disease. Our in-depth expertise in translational biomarker selection and validation gives confidence in the smooth transition of the candidate molecule into the clinic.
Individual efficacy studies or tailored in vivo pharmacology packages can also be provided, to cover specific client needs. A full panel of automated clinical biochemistry, haematology and coagulation analyses as well as histopathology and a range of molecular biology techniques are available to support investigation of the compound efficacy.
Our toxicology group supports integrated drug discovery projects by standard and customized studies in rodents.
Our primary objective is to discharge in vivo safety liabilities through tailored study design. We offer you investigative, problem solving studies with fit-for-purpose, integrated assessment of multiple endpoints (general toxicology, pathology and DMPK endpoints).
You can benefit from our broad experience with different targets and mechanisms as it allows us to deal with unexpected findings or toxicity issues during the course of research projects.
In vivo experiments are performed at Fidelta, Selvita Group company, in AAALAC-I accredited State-of-the-Art animal facility (BSL2) with the competent veterinary personnel, technicians and hygiene personnel holding training certificates equivalent to FELASA categories A to D. Animal related research is based on the 3R principles and high-performance standards ensuring animal welfare, humane and ethical use of animals in scientific research.
Selvita offers a standard panel of in vitro ADME assays, which can be customized to fit client requirements, and provides comprehensive bioanalytical support based on our mass spectrometry platform. Our mission is to successfully support our Clients along the drug development pathway, to deliver high quality results provided by our experienced ADME specialists using state-of-the-art technologies. We provide fast turnaround times and maximum flexibility to deliver fit-for-purpose studies and achieve the specific goals of our client projects. ADME studies are offered either as stand-alone projects (fee for service model) or as a part of a collaborative Integrated Drug Discovery (IDD) program. In both cases, SLV provides a flexible approach by customizable protocols, which covers a very wide range of different needs. In addition, Selvita can propose a panel of ADME and Pharmacokinetic parameters analysis in a preassembled package which can be easily changed and customizable. The panel is ideally divided into a tiered approach depending on the drug discovery phases and then used for filtering and optimizing the ADME properties of compounds in a SAR fashion. Selvita will provide the full or partial ADME/PK package and also variants (e.g. urine analysis, tissues stability and others) following Client requests or project team decisions. Eventually, Selvita’s ADME/PK expert analysts can suggest the best compounds to be progressed into LO phase and in vivo PD experiments. Our Bioanalytical capabilities cover analyses of small molecules supporting both non-GLP as well as GLP- studies including a wide range of different activities from simple qualitative analyses to complex validation of analytical methods. Selvita also has broad experience with different sample preparation approaches using biological materials.
In-vitro Metabolism and Drug-Drug Interaction
In vitro Binding Studies:
Department of Biochemistry has long-standing expertise in supporting development of biologically active chemical compounds for multiple pharmaceutical, agrochemical and biotech companies. Extensive know-how combined with highly skilled and goal-oriented scientists is a perfect combination enabling a successful execution of your project.
Our services are dedicated to assist in multiple steps during the process of active compound development by providing high quality recombinant proteins and comprehensive structural information. Flexible pipelines employed by Selvita ensure efficient delivery of tailored protein products for various research purposes including crystallographic, biophysical, enzymatic or in vivo studies. Our X-ray services are designed to provide high-resolution structural information to support hit validation, hit-to-lead development and lead optimization in the most time/cost efficient manner.
Solid expertise of our scientific team with a broad range of target proteins make a strong basis for meeting Client expectations. Our offer includes:
Structural studies using X-ray crystallography are driven by a team with many years of international experience. Altogether, we have determined 200+ high-resolution structures and published 60+ research papers. Our services include:
NMR in Drug Discovery
Computer-Aided Drug Design Selvita’s computer-aided drug design (CADD) centre was created to foster collaborative research between medicinal chemists, biologists, biophysicists, structural biologists and computational scientists. In a drug discovery campaign, CADD is usually used for three major purposes:
CADD depends on the extent of structure and other information available regarding the target (enzyme/receptor/protein) and the ligands. The latest advancements like AI, QSAR, combinatorial chemistry, different databases and available new software tools provide a basis for designing of ligands and inhibitors that require specificity and novelty.
At hit identification, hit-to-lead or lead optimization stage our CADD can apply the following methods:
Most notably, our computational and medicinal chemists are working seamlessly together in interactive molecular design sessions, in order to rapidly generate hypotheses for molecular drug designs that are immediately assessed in suitable in silico models before molecules are prioritized and selected for syntheses in our laboratories or purchasing. Using a diverse set of available computational chemistry tools that are applicable for a given project, we assist the medical chemists in order to minimize the time, synthetic efforts and detours along the transformation process of a hit compound into a candidate.
AI-driven Drug Discovery
At Selvita not only we use traditional CADD but we also employ methods based on artificial intelligence (AI) or machine learning (ML). Those methods are especially useful for designing focused screening libraries, as a support in properties optimization process or to predict ADMET properties. Since the main task of the AI-based methods is to find associations between seemingly unrelated data, they are also very useful in target deconvolution process. All tasks related to AI and ML are performed in collaboration with ARDIGEN – SELVITA GROUP company specializing in this area.
Development and optimization phases during the drug life cycle are crucial. We’re fully aware of that fact, and we work in an efficient and flexible manner, using the best industry practices, in order to support our clients at this important stage of the process. Our team consist of industry experts with a thorough understanding of the process and long-standing expertise in the field, complemented with appreciation of the latest trends in analytical and bioanalytical chemistry.
At this stage we develop and test new analytical and bioanalytical methods. When do we develop a new method? We usually do this in several cases: when the existing method described in the guidelines is obsolete or does not meet the clients’ requirements; for new medicinal product when there is no efficient method for purity determination or assay; when the final product is a mixture of different active ingredients.
For method development we use either HPLC or UHPLC. Our analytical department is equipped with liquid chromatographs Agilent 1260 Infinity II and 1290 Infinity II (Agilent Technologies), Ultimate 3000 RS UHPLC and Ultimate 3000 SD HPLC (ThermoFisher Scientific) with DAD-UV, PDA, FLD, CAD, ELSD detectors.
Once the method is developed and optimized it can be validated, which is mandatory if the method will be potentially used for testing of a drug product. The implementation of a new method to the analytical laboratory is crucial in the method life cycle and is therefore under supervision of the laboratory management and quality assurance unit.
Validation is always conducted according to approved protocols which can be prepared either according to Selvita’s standard operating procedures (SOPs) or client’s SOPs. When the validation is complete, all results are described in the validation report which then should be approved by the client. The process of transferring a method from the company to another laboratory is also closely supervised. Transfers and validations of the methods are conducted in accordance with the current GMP regulations and approved protocols.
All the experiments required for these operations are conducted by our experienced analysts and supervised by the laboratory management. This guarantees that the analytical method works accurately and correctly in any workplace it is implemented.
Selvita offers a comprehensive set of services related to the stability studies for different formulations, drug substances or drug product with different dosage forms. The scope of stability studies offered includes preparation of a stability study protocol, study monitoring and a complete analytical testing needed for particular drug, continuous and summary reporting of stability results.
The test conditions available on site are: 25°C/60% RH, 30°C/65% RH, 30°C/75% RH and 40°C/75% RH and comply with the ICH requirements. Upon client’s request, we can also conduct stability studies in other conditions in the Binder stability chambers. In addition to stability studies, we also carry out photostability, accelerated stability and forced degradation studies.
The physical and chemical stresses include especially: exposure to heat, exposure to light (UV/VIS), acidic, alkaline and oxidizing stresses, exposure to elevated temperatures and humidity of the environment. Accelerated stability and forced degradation studies are usually part of development of a new method, but they can also support stability studies for different formulations of a drug product.
Quality control is an integral part of the drug production process. Selvita specializes in the final stage of quality control of pharmaceutical products (small and large molecules) – routine analyzes of batches for release (release testing).
This type of testing is based on the approved specification of the drug product. Selvita does not have a GMP production line but holds GMP certificate and manufacturing license which allow to perform release testing by our GxP laboratories. Selvita also holds the import license which is required for release testing of batches that were produced outside the EU.
Selvita’s portfolio of methods for release testing is very extensive. We offer the following physico-chemical methods: HPLC, UHPLC, RP-HPLC, SEC, IEX, IF, CE, GC, IEF, LC/MS, SDS-PAGE, AAS, ICP-OES, ICP-MS, disintegration time, dissolution, and also biological methods: microbiology testing: sterility, purity, endotoxins, cell culture based bioassays: proliferation assays based on different read-outs, ADCC, CDC, apoptosis assays, reporter gene assays, potency assays. We are proud to be the EU release testing laboratory for the world’s largest pharmaceutical manufacturers.
In addition to laboratory work, Selvita can also support its clients in other areas. Our team of experts can provide our clients with help in many regulatory aspects such as: Chemistry Manufacturing and Controls (CMC) documentation preparation, filling in the quality module in the Common Technical Documentation (CTD), as well as, batch certification (certificates of analysis and certificates of confirmation) confirmed by the Qualified Persons employed by Selvita.
Process chemistry can be considered as a bridge connecting small, laboratory scale synthesis with industrial scale processes taking place in pharmaceutical, agrochemical, or petroleum, industries. Process chemists take the synthesis from the milligram scale to the manufacturing scale. This may involve several activities:
Selvita supplies a unique blend of practical knowledge and experience based on numerous success stories Feasibility studies /Route scouting & development Hunt for novel, patentable and cost-effective synthetic routes begins with exploring state of the art through literature and patent searches, which is made possible by our access to world-class chemical databases and online journals. This combined with the experience and creativity of Selvita’s chemists puts us in a unique position to meet our Clients’ expectations.
The generated ideas are examined by bench chemists and the successful routes move to an advanced stage of development. Process optimization, parameterization and scale-up Process optimization means finding a balance between yield, cost and the number of steps. Reaction yield often depends on a number of parameters such as temperature, pressure, dilution, reagent excess, reaction time, drying method, etc. Parameterization studies determine optimal ranges for all important variables, so that the best set of conditions can be selected for the further scale up studies.
Further support including in silico studies As part of an integrated service Selvita offers analytical support necessary for both technology transfer to production and product registration (impurity identification, isolation and synthesis, impurity profiling, etc.).
We can also generate in silico prediction of likely toxicity profile for a compound if needed for registration or regulatory purposes. Technology transfer Technology transfer is an ultimate step of process development at Selvita. Our chemists have experience with several successful transfers to industry. Some of these run now on thousands kilogram scale. During transfer the Client will receive detailed documentation including process description, analytical methods, reports on impurities, and safety issues discussion.
Selvita offers preparation of active substances for pharmaceutical (both API and NCE) and agrochemical research (AI) on a mg- up to kg-scale. Furthermore, we specialize in synthesis of key intermediates and building blocks, including optically active materials.
Being aware that the chemical industry is undergoing dynamic change under the influence of global competition and constantly changing regulations, we endeavor to translate the knowledge, experience and creativity of our scientists into practical solutions that will meet the criteria of innovation and competitiveness. We are seeking ways to increase the competitiveness of products on the world market, primary by the following means:
We approach each project individually and seek a tailored solution, simultaneously ensuring clear, commercial and application-driven criteria for the project’s success. Our strengths are flexibility, integrity, punctuality, and above all an innovative and multifaceted approach to a problem.
Selvita is an experienced partner with a good track record of successful R&D projects performed for different Polish and multinational agrochemical companies.
For companies that produce and register plant protection substances, we offer a scope of services that includes:
Analytics under GLP/GMP conditions
Using many years of our experience in drug development, we can participate in projects aimed at introducing innovative pesticides to the market offering expertise in the following areas:
Selvita employees are also familiar with various aspects of the petrochemical and and heavy organic synthesis, including amongst others:
On top of that we offer synthesis of isotopically labelled compounds. We have significant experience in compound labelling with “cold” isotopes such as deuterium, 13C and 15N. We can also establish a synthetic route suitable for labelling with hot isotopes to be executed at another lab.