Taab biostudy services conducts BA/BE study as per CDSCO (Indian FDA) as well as ICH (E3)/ EMA/ASEAN/US FDA etc. guidelines as desired by the sponsor. For conducting BA/BE study the protocol is being prepared in consultation with the sponsor and clinical pharmacologist.The CDSCO approves the protocol and issues the NOC to conduct BA/BE study at a particular CRO which is mentioned in the protocol.
The sponsor supplies the reference and test drugs, API and COA for method development along with the NOC from DCGI,New Delhi.The healthy human volunteers (24/36) are accommodated in a air-conditioned CPU(Clinical Phamacological Unit) of TAAB at 77/2/1B/1 Bade Raipur Road Kolkata-700032 for preclinical study.
The video-recording of informed consent processing is being carried out in presence of principal investigator,
study co-ordinator,nurse and other related staff prior to BA/BE study.
The TAAB collects the blood samples from the volunteers as per the blood sampling points stated in the protocol and stored in a deep freezer at -20°C .The drug is then extracted from the plasma either by suitable solvent (liquid-liquid extraction) or protein precipitation.
Finally the concentration of the drug in plasma is analysed by suitable, sensitive and validated bioanalytical method with help of LCMS/MS at bioanalytical lab of TAAB at 76/D Ibrahimpur Road,Kolkata-700032.
The outcome of LCMS/MS helps to evaluate the Pharmacokinetics parameters (Cmax, Tmax, AUC, Kel, T½ etc) of individual volunteers which are presented graphically as blood-concentration and time profile.
The statistical analysis of the plasma-concentration data are computed in a winnonlin software to prove whether the test product is bioequivalent or not with the reference product based on the scale of 0.8 < AUCtest/AUCref < 1.25 or the same ratio for Cmax .
Pharmacokinetics is the application of mathematical calculation and modelling techniques to the time course of absorption, distribution, metabolism, and excretion of drugs in the body.It is primarily concerned with the analysis of concentration and rate of drug availability to the required receptor site.
Sample analysis will target concentration of drug as time progresses, resulting in the production of a ‘plasma drug concentration-time curve’.Plasma drug concentration time curve can be obtained after a single oral dose of a drug by measuring conecentration of drug in plasma samples taken at various intervals of time and plotting the concentration of drug in plasma (Y-axis) vs corresponding time at which plasma samples were collected (X-axis).Pharmacokinetics parameters are calculated from this graph, most commonly,
- Maximum plasma concentration (Cmax)
- Time to maximum plasma concentration (Tmax)
- Area under the plasma concentration curve (AUC): a calculation to assess the bodies total exposure to a drug over a given time
- Half life (t½) : the time taken for the plasma concentration to fall by 50%
Pharmacodynamics refers to the relationship between drug concentration at the site of action and the resulting effect, including the time course and intensity of therapeutic and adverse effects. The effect of a drug present at the site of action is determined by that drug’s binding with a receptor. For most drugs, the concentration at the site of the receptor determines the intensity of a drug’s effect.
The “dose-response curve” is used to describe the relationship between the concentration of drug at the site of action and the intensity of pharmacological effect caused. Graphs can then be used to analyse individual drug activity, or be compared with other graphs to assess, for example, potency (the amount of drug needed to produce similar effects) or maximal efficacy (concentration of drug required to produce maximum effect).
Stability studies are an essential component of pharmaceutical development, allowing evaluation of active pharmaceutical ingredient (API) stability or drug product stability under the influence of a variety of environmental factors such as temperature, humidity and light. In accelerated stability study, a product is stored at elevated stress conditions.In general case, the accelerated storage condition must be > 15° C above ambient storage condition i.e. 40°C ± 2°C/75 % RH ± 5 % RH. Accelerated testing should be done atleast 3/6 months and it suggests sampling point of 0, 3, 6 months. Temperature is probably the most common acceleration factor used for chemicals, pharmaceuticals, and biological products.Humidity and pH can be used along with temperature to accelerate degradation.
The dissolution performance test is required test for all solid oral dosage forms for product release testing. It is also commonly used as a predictor of a drug product invivo performance. To meet dissolution requirements, the United States Pharmacopeia (USP), Indian Pharmacopeia (IP),
British Pharmacopoeia (BP) etc provide information in the way of a general chapter on dissolution. The TAAB follows those guidelines on development and validation of dissolution procedures.
The TAAB has Dissolution apparatus (Electrolab Dissolution Tester USP I/II) equipped with Fraction Collector and Temperature regulator. The TAAB has already carried out dissolution study of several drugs according to the guidelines of USP, IP, BP etc. At different pH values of 1.2,6.8 etc.
TAAB also conducts the following types of dissolution tests:
- Similarity factor (f2 ) test:
- Based on Time points
- Based on Dissolution medium pH
Dissolution Kinetic Study is carried out on multiple time points .