Drug development process

Prepared By Pawan Dhamala
RR College Of Pharmacy
Bangalore

1. PAWAN DHAMALA B.PHARMACY RR COLLEGE OF PHARAMCY DRUG DEVELOPMENT PROCESS

2. Not every compound that is tested in laboratory is marketed ; it has to undergo several stages of development called drug development. In this process new drug candidate get high standard for its regulatory approval. Drug development is an uncertain pharmaceutical activity with risks. In the drug development process, an innovator first has to screen through many compounds that show hopeful results.

3. This is costly process as many compounds that are tested are thrown away at the preliminary stage only. To innovate a new drugs a company needs to begin with many thousands of compounds. The development of new drugs is a complex and costly process. Cost of biopharmaceuticals are higher. R & D task involves discovery(preclinical studies) and development (clinical studies) of New Chemical Entities(NCEs)/(NMES).

4. About 10,000 NCEs investigated to potentially treat disease , only 250 make it to animal testing stage, and approximately 5-10 would qualify for testing in humans. Only 1-2 products of the original 10,000 NCEs result in a marketable product. STAGES OF DEVELOPMENT OF A NEW DRUG Preclinical stage: The preclinical stage involve on animals to find out various parameters for a potential drug candidate under the process of development.

5. In this stage, innovator evaluates the drug’s toxic and pharmacological testing through in vivo & in vitro laboratory animal testing. In this stage USFDA minimum requirement is to develop pharmacological profile of the drug; determine toxicity and conduct short term toxicity studies. 2) Clinical stage It is commonly conducted in 4 phases: Phase 0 ( Microdosing ) Phase 1 Phase 2

6. 4. Phase 3 5. Phase 4 (Post Marketing surveillance)

7. Phase 0 = This is an exploratory phase of a clinical trial. Phase 0 trail is done with very small number of people, usually fewer than 15. Investigators use a very small dose of medication to make sure it isn’t harmful to humans before they start using it in higher doses for later phase. Phase 1 = Phase 1 are carried out in a small number of healthy volunteers usually 20 to 100.

8. The purpose of Phase 1 is to identify the metabolic and pharmacological effects of the drug in human and side effects associated with increasing doses. The purpose of Phase 1 studies is to determine the safety profile. During Phase 1, sufficient information about the drug’s pharmacokinetics and pharmacological effects is required. Approximately 70% of drugs tested in this stage move to the next phase.

9. Phase 2 = Phase 2 clinical trials conducted to obtain some preliminary data on the effectiveness (efficacy) of the potential drug to treat disease or condition. In this phase it helps to determine the common short-term side effects and risks associated with the drug under testing. These studies are typically well-controlled, closely monitored, and performed on larger groups of patients , usually 20-300. Duration of this phase ranges from several months to 2 years. Approximately 33% of drugs tested at this phase move to next phase.

10. Phase 3= Phase 3 are expanded, controlled and uncontrolled trials. The purpose of this study is to gather information about the effectiveness and monitoring of adverse reaction. Phase 3 includes 300 to 3,000 volunteers who have disease or condition. To obtain approval from USFDA there must be at least 2 successful phase 3 clinical trials. The length of the study is about 1 to 4 years where approximately 25-30% of drugs move to the next phase.

11. Phase 4 = It is also known as Post Marketing Surveillance(PMS). It is carried out once a candidate drug is approved as a drug and marketed as a medicinal product. This phase aims is to find out the drug safety profile in a large patient pool across the world and to establish its safety profile. It helps to detect rare or long-term adverse effect of the drug over a large patient population. Several thousand volunteers who have the disease or condtion are involved in this phase of the trial.

12. Time Required for Developing a New Drugs: Drug development process is very slow process. A candidate drug is examined at every stages of development by regulatory authorities before it is launched in market. According to PhRMA (Pharmaceutical Research and Manufacturers of America, A pharma industry trade group of America ), it may range between 12 to 15 years to develop a new drug. It may take about six and half years of discovery ; preclinical testing and toxicity testing; 1.5 years of Phase 1; about 2 years in Phase 2; about 3.5 years in Phase 3 and about 1.5 years of regulatory authority review and approval. Once a drug get approval it may undergo Phase 4 to collect more safety and efficacy data.

13. Cost of Developing New Drug: Drug development requires a huge investment from pharmaceutical companies. According to various sources that the cost of developing a single new drug varies from US$ 800 million to US$ 1.7 billion. The money invested by the pharmaceutical company for such unsuccessful molecules in sunk cost and cannot be recovered. 3) Regulatory approval: IND: Once the candiate drug is tested in animals (preclinical testing ), a sponsor files IND with the regulatory authorities for testing it in humans.

14. The IND application includes information such as: result of previous experiment i.e : how ,where , and by whom the new studies will be conducted; the chemical structure of the candidate drug ; how it works on the body ( mechanism of action); toxic effects found in the animal studies; and how it is manufactured. IND must be reviewed by Institutional Review Board (IRB). IND application contain information such as : Animal pharmacology and toxicology studies. Manufacturing information of candidate drug Clinical protocols and investigator information.

15. B) NDA NDA application is the medium through which the new drug sponsors purpose regulatory authority to approve this drug for sale and marketing in the country of approval. The goal of NDA are to provide enough information to permit regulatory reviewer for following key decisions: Whether the drug is safe or effective Whether the labelling of new drug is appropriate Whether the methods used in manufacturing the new drugs and control used to maintain its quality are adequate to preserve its identity, strength, quality, and purity. The document submitted in NDA describes the whole picture of new drugs.

16. After completion of all phases of clinical trials , sponsor files NDA with regulatory authority to show safety and efficacy of the compound. NDA describes all relevant scientific information related to the new drug that is gathered during the investigations. As NDA is a huge information submitted, regulatory authorities requires enough time to review every details of information submitted. Thank you !