Drug development
Drug development is a blanket term used to define the entire process of bringing a new drug or device to the market. It includes drug discovery / product development, pre-clinical research (microorganisms/animals) and clinical trials (on humans). Few people still refer to the drug development as mere preclinical development.
Contents
General
Candidates for a new drug to treat a disease might theoretically include from 5,000 to 10,000 chemical compounds. On average about 250 of these will show sufficient promise for further evaluation using laboratory tests, mice and other test animals. Typically, about ten of these will qualify for tests on humans.[1]
New Chemical Entity (NCE) development
New Chemical Entities (NCEs)(also known as New Molecular Entities (NMEs)) are compounds which emerge from the process of drug discovery. These will have promising activity against a particular biological target thought to be important in disease; however, little will be known about the safety, toxicity, pharmacokinetics and metabolism of this NCE in humans. It is the function of drug development to assess all of these parameters prior to human clinical trials. A further major objective of drug development is to make a recommendation of the dose and schedule to be used the first time an NCE is used in a human clinical trial ("first-in-man" (FIM) or First Human Dose (FHD)).In addition, drug development is required to establish the physicochemical properties of the NCE: its chemical makeup, stability, solubility. The process by which the chemical is made will be optimized so that from being made at the bench on a milligram scale by a synthetic chemist, it can be manufactured on the kilogram and then on the ton scale. It will be further examined for its suitability to be made into capsules, tablets, aeresol, intramuscular injectable, subcuteneous injectable, or intravenous formulations. Together these processes are known in preclinical development as CMC: Chemistry, Manufacturing and Control.
Many aspects of drug development are focused on satisfying the regulatory requirements of drug licensing authorities. These generally constitute a number of tests designed to determine the major toxicities of a novel compound prior to first use in man. It is a legal requirement that an assessment of major organ toxicity be performed (effects on the heart and lungs, brain, kidney, liver and digestive system), as well as effects on other parts of the body that might be affected by the drug (e.g. the skin if the new drug is to be delivered through the skin). While, increasingly, these tests can be made using in vitro methods (e.g. with isolated cells), many tests can only be made by using experimental animals, since it is only in an intact organism that the complex interplay of metabolism and drug exposure on toxicity can be examined.
The process of drug development does not stop once an NCE begins human clinical trials. In addition to the tests required to move a novel drug into the clinic for the first time it is also important to ensure that long-term or chronic toxicities are determined, as well as effects on systems not previously monitored (fertility, reproduction, immune system, etc.). The compound will also be tested for its capability to cause cancer (carcinogenicity testing).
If a compound emerges from these tests with an acceptable toxicity and safety profile, and it can further be demonstrated to have the desired effect in clinical trials, then it can be submitted for marketing approval in the various countries where it will be sold. In the US, this process is called a New Drug Application or NDA. Most NCEs, however, fail during drug development, either because they have some unacceptable toxicity, or because they simply do not work in clinical trials.
As this drug discovery process becomes more expensive it is becoming important to look at new ways to bring forward NCEs. One approach to improve efficiency is to recognize that there are many steps requiring different levels of experimentation. The early phase of drug discovery actually has components of real innovation, components of experimentation and components that involve set routines. This model of Innovation, Experimentation, and Commoditization ensures that new ways to do work are adopted continually. This model also allows the discipline to use appropriate internal and external resources for the right work.
Cost
Studies published in 2003 report an average pre-tax cost of approximately $800 million to bring a new drug (i.e. a drug with a New Chemical Entity) to market.[2][3]
A study published in 2006 estimates that costs vary from around $500 million to $2 billion depending on the therapy or the developing firm.[4]
These figures relate only to new, innovative drugs (drugs with a New Chemical Entity NCE, also called New Active Substance NAS). Each year, worldwide, only about 26 such drugs enter the market (2009: 26, 2008: 25, 2007: 18, 2006: 22, 2005: 26, 2004: 24, 2003: 26, 2002: 28, 2001: 23, 2000: 26, 1999: 33)[citation needed]. The development cost of the thousands of other drugs are much smaller. The $800 million quoted include the cost of all drug development which did not result in a new drug. It also includes some $400 million of opportunity costs.
See also
- Clinical trial
- Council for International Organizations of Medical Sciences
- Drug design
- Drug discovery
- Drug repositioning
- Generic drug
- International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, a consensus between the US, EU, and Japan.
- Pre-clinical development
References
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- Drug Development Technology Projects, companies and industry news
- CDER Drug and Biologic Approval Reports
- International Union of Basic and Clinical Pharmacologyja:医薬品開発
- ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
- ↑ DiMasi J (2002). "The value of improving the productivity of the drug development process: faster times and better decisions". Pharmacoeconomics. 20 Suppl 3: 1–10. PMID 12457421.
- ↑ DiMasi J, Hansen R, Grabowski H (2003). "The price of innovation: new estimates of drug development costs". J Health Econ. 22 (2): 151–85. doi:10.1016/S0167-6296(02)00126-1. PMID 12606142..
- ↑ Adams C, Brantner V (2006). "Estimating the cost of new drug development: is it really 802 million dollars?". Health Aff (Millwood). 25 (2): 420–8. doi:10.1377/hlthaff.25.2.420. PMID 16522582.
