Generic Medicinal Products:
Generic medicinal products are often not an exact copy of the original product, therefore, before a generic product is transferred to the clinical phase of development, its safety should be evaluated in animal studies. The required scope of preclinical studies should include the study of general toxic properties, including: evaluation of acute and subacute toxicity as well as local tolerance studies.

Original Medicinal Products:
Original medicinal products require a full range of preclinical studies, namely, the study of general toxic properties, including studies of acute and subacute toxicity, chronic toxicity and local tolerance studies; specific types of toxicity, including
Carcinogenicity Studies, Reproductive Performance and Developmental Toxicity Studies, Immunotoxicity Studies Genotoxicity Studies; Safety Pharmacology; Biological Activity/Pharmacodynamics of the medicinal product.

The goal of clinical development of a medicinal product is to obtain information regarding its efficacy and safety. At each stage or phase of development, the main objective is clearly and unambiguously stated. Clinical trials are categorized according to the order in which they are conducted during the clinical development of a medicinal product and/or according to their objectives.

PHASE 1: Studies of the MP Pharmacologic Properties in Humans
Phase I development is the first application of a new medicinal product to humans. Studies of this phase usually have non-therapeutic objectives and may be conducted in healthy volunteers or in specific patients’ populations. Phase I studies typically address one or more of the following objectives:

• Primary safety and tolerability assessment
• Assessment/description of PK and PD
• Study of metabolism and interactions
• Early assessment of Biological Activity

PHASE 2: Comparative Studies of Therapeutic Dosages
First attempts to determine therapeutic efficacy of a medicinal product in patients is a start of Phase II development. An important goal of Phase II studies is to determine the dose and dosing regimen for the Phase III studies. Phase II studies often utilize Dose-escalation designs to assess preliminary dose-effect data. Phase II studies typically address one or more of the following objectives:

• Early research in the target indication;
• Dose selection for further studies
• Provide a framework for pivotal research in terms of design, endpoints and methodologies

PHASE 3: Comparative Therapeutic Efficacy Study
Phase III development studies are designed to confirm the data obtained from Phase II studies, if this data indicates for efficacy and safety of the drug in the target population. The goal of these studies is to obtain data sufficient for registration. Phase III studies additionally investigate the dose-effect ratio, the possibility of using the drug in the different groups of patients, at different stages of the disease or in combination with other medicinal products. Phase III studies finalize collection of information necessary for the preparation of appropriate recommendations for the use of the medicinal product (official information on the medicinal product). Phase III studies usually accomplish one or more of the following tasks:

• Confirmation of efficacy
• Set up of a safety profile
• Provision for risk-benefit ratio assessment to support registration
• Establishment of a dose-response ratio

PHASE 4: Therapeutic Use Studies
Phase IV development begins as soon as the product is marketed and is not intended to confirm efficacy and safety as well as adjust doses. Phase IV studies can only be conducted if indications in the study are approved. These studies are not obligatory for registration, but help optimizing the product use. Phase IV studies must have a strong scientific rational. Typically, these studies provide additional information on the drug-to-drug interactions, dose-effect ratio, and safety evaluation within the approved indication (e.g., morbidity and mortality studies, epidemiologic studies). Thus, Phase IV studies typically address one or more of the following objectives:

• Refinement of the risk benefit ratio
• Identification of less frequent adverse reactions
• Optimization of dosing regimen

Bioequivalence study is a clinical study, which is carried out to determine the rate of absorption and excretion of one or more active substances and the amount of the medicinal product reaching the systemic bloodstream. Bioequivalence studies confirm equivalence of a generic product absorption to the absorption of the reference product.
The purpose of bioequivalence studies is to extrapolate the results of preclinical trials and clinical trials conducted on the reference medicinal product to the generic (hybrid) medicinal product. Such studies are usually planned within the framework of state registration of generic medicinal products.