Preclinical Studies in Drug Development

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Hi Friends, my first blog for this month is regarding Preclinical studies in Drug development. After its discovery in the laboratory every New Chemical Entity NCE)should face a series of challenges/trials to make its way into the market successfully. The entire drug development process can be divided into the following steps: [1] 1. Preclinical Studies/Trials 2. Investigational new drug application (IND) 3. Clinical Studies/Trials 4. New Drug Application (NDA) 5. Approval A preclinical study is the processes by which researchers test drugs and other medical devices to see whether they are safe and effective for use in humans [2]. This stage aims to obtain data related to the toxicity and pharmacological efficacy of the drug and determination of the bioactivity, safety and efficacy of the drug through in vitro and in vivo animal testing. These studies are both short and long-term. It takes about an average of 61/2 years for preclinical studies to complete. [3] This process include studies regarding [4] A. Chemistry B. Physical properties C. Biological i. Pharmacology ii. ADME iii. Toxicology D. Preformulation Usually these studies are conducted extensively on animals like rodent and non-rodent models because a drug may affect different species in different ways. [3] By performing animal testing one can get information regarding [3] 1. The bioavailability of the drug 2. Metabolic pathway of the drug 3. Toxicity of drug and its metabolites 4. Rate of excretion of the drug and its metabolites by the body During the preclinical studies the preclinical toxicology testing is of main importance as it decides the eventual success of the drug. In drug development programs toxicity studies are conducted to determine [4] a. Substances potential toxicity with short term (acute effects) or long term (chronic effects) use. b. Potential for specific organ toxicity c. Mode, site, degree of toxicity d. Dose-response relationships for low, high and intermediate doses over a specified time e. Gender, Reproductive or teratogenic toxicities f. Substances carcinogenic and genotoxic potential Various stages in Preclinical Toxicology testing are [5] -Acute studies -Repeated Dose Studies -Genetic Toxicity Studies -Reproductive Toxicity Studies -Carcinogenicity Studies -Toxicokinetic Studies After the drug is evaluated for its toxicity profile and getting positive results it is then subjected to Preformulation studies to determine its intrinsic physical and chemical characteristics like solubility, partition coefficient, rate of dissolution, stability. [4] With the available data after the Preformulation studies, an initial product is formulated with the consideration of the dose or doses, dosage form and route of administration desired for clinical studies and proposed marketed product. Finally under the Food, Drug and Cosmetics Act the sponsor/principle researcher of the new drug should file with the FDA an Investigational New Drug (IND) application for further testing in human volunteers under clinical studies.[6] THIS BLOG DOES NOT CONTAIN PLAGIARIZED MATERIAL References: 1. http://www1.pointcross.com/source/ddg/steps/index.html (Accessed on 12.03.2011) 2. http://www.wisegeek.com/what-are-preclinical-studies.htm (Accessed on 12.03.2011) 3.http://www.peri.org/distance_tour/decision/html/preclinical.html (Accessed on 12.03.2011) 4. Ansel's Pharmaceutical Dosage Forms and Drug Delivery Systems, 8th Edition, Pg: 39-40, Published by Lippincott Williams & Wilkins. 5. http://www.pacificbiolabs.com/drug_stages.asp (Accessed on 12.03.2011) 6. Leon Shargel's Comprehensive Pharmacy Review, 7th Edition, Pg: 01, Published by Lippincott Williams & Wilkins.
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Gangadhar Hari's picture
Author: Gangadhar Hari

Comments

Sudha Thamarapalli's picture

Gud one. Could you pls clarify me on the sentence in ur blog 'These studies are both short and long-term.' What does this actually mean?

Regards,

Sudha.T

Gangadhar Hari's picture

Thank You madam for your invaluable feedback. Coming to your query, the sentence signifies that long term toxicity studies continue to take place throughout the entire drug development program from preclinical studies through clinical trials and into post marketing surveillance. To get information regarding toxicity profiles of drug's on long term use and the subsequent effects. [4]
Gangadhar Hari's picture

Thank You madam for your invaluable feedback. Coming to your query, the sentence signifies that long term toxicity studies continue to take place throughout the entire drug development program from preclinical studies through clinical trials and into post marketing surveillance. To get information regarding toxicity profiles of drug's on long term use and the subsequent effects. [4]
Siva Mavuduru's picture

Sir Nice blog But there is wide genetic and physiological variation between human and rodents. isn't it? How can we consider tests done on the rodents as the basis for the drugs intended for human use?
Gangadhar Hari's picture

As you have said the direct extrapolation of toxicity and safety data obtained in preclinical studies to humans is difficult because of species variation and different dose response relationships, immunologic differences and others but "the greater the number of animal species tested that demonstrate a toxic effect , the greater the likelihood that the effect will also be seen in humans".[4] Thank You, Keep Blogging...
VOLETI VIJAYA KUMAR's picture

Can you tell,which animals are to be selected for conducting toxic studies? And How the animals are selected for these studies?

VIJAYA KUMAR.VOLETI M.Pharmacy

Asst Professor

Raos college of Pharamcy

Nellore

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