The process of uncovering and developing new medicines is an extremely costly and time consuming effort. Pharmaceutical companies have to make sure that only safe and effectual medications are released to the public. At a cost of between $800 million and $1 billion, over a course of 10 to 15 years, each drug undergoes a stringent process of discovery, development, approval and finally, public use.
First: Discovery of New Medications
Pharmacologist, chemists and other scientists, working in laboratories, pinpoint genetic and cellular properties of different diseases. They then introduce biological and or chemical elements hoping to get an adverse effect on the disease cell. Following preclinical evaluations, of all the tests and discoveries, only 0.001% (5 out of 5000) is considered safe for human consumption and will be tested on volunteers.
Testing in patients continues for an additional three to six years, until one of the initial 5000 (0.0002%) is chosen and approved for public consumption as a new medicine.
The Order of Steps for developing a new medicine is as follows:
- Identifying the Target. Targets are either genetic or cellular chemicals in the body. These targets are believed to influence disease. There are numerous ways that the researchers recognize and separate targets to identify how they affect disease. Medical compounds act on targets to interrupt their function in the development of disease.
- Ranking and Authenticating Targets. Choosing which drug-target to work with involves assessing the relationship each has with the disease and how each one affects chemical and biological processes in the body. Testing determines if there is a favorable change in the disease cells by introducing a chemical compound to the drug target, thereby identifying compounds that have the desired effect.
- Identifying Leads. A lead is a combination of molecules that is thought to have the capacity to treat disease. The lead retains elements required in the new medication. Clinical researchers assess already proven substances with the new combinations to evaluate their effectiveness. To verify the success of each molecule’s effect on the drug target,analysis is performed.
- Optimizing Leads. To assist biopharmaceutical companies choose the compound, or compounds, to be developed into safe and effective drugs, lead optimization compares the properties of lead compounds with the highest probability of success. At the same time, tests to compare information on how leads are absorbed into the body and how they affect it are run. Both in vivo, in living organisms, and in vitro, in cells in test tubes, studies are conducted in a process called lead prioritization.
Before an investigational drug is tested in human volunteers:
From one to five years before an investigational drug is tested in human volunteers, the drug is in the preclinical stage and is studied significantly in laboratories to make sure of its safety. Researchers also need to know everything about the pharmaceutical make-up, how it will be produced and how it will be dispensed to the first human volunteers.
- Using in vivo and in vitro laboratory studies, researchers test and record the drug’s effect on living organisms, during the preclinical development stage.
- Pharmaceutical specialists use the findings from the preclinical stage to establish what form the drug should take for patient use. For example, in a sublingual spray or a tablet. Governing agencies who monitor drug development demand documentation of the chemical characteristics, including structure, quality, potency and purity of the active ingredient and of the final form of the drug.
- Continued pharmacological studies monitor the effects of the new drug on the human body. Potential risks are determined by toxicology tests
In the United States the FDA reviews, and must approve the tests to date, before moving on to the next step. Each country has its own regulatory agency whose guidelines must be adhered to before continuing with the drug development process.
Testing investigational drugs in humans:
Prior to testing in humans an application is presented including all the known information on the drug. Permission to begin testing on healthy human subjects is requested.
- In the United States, investigational new drug (IND), in the UK, Clinical Trial Exception (CTX), and in Australia, Clinical Trial Authorization (CTA) applications are sent to the governing agencies requesting approval to engage in clinical trials. Sometimes the research is to find new uses for a medication already an accepted standard.
An impartial committee of physicians, community advocates and others is called an independent review board (IRB). It makes sure that a clinical trial is ethical and that the rights of study volunteers are guarded. The IRB or an ethical advisory committee must accept and approve the procedure for a clinical study, as well as the informed consent, signed by the volunteers and the investigators.
There are three stages to clinical studies, Phase I, Phase II and Phase III, each involving additional study subjects.
- Phase I clinical trials are the first studies performed in humans. Usually a test group of twenty to one hundred healthy participants are administered the drug for a limited time and are observed to determine the effect of the drug on the body, how it is assimilated, circulated, processed and eliminated. These results are carefully recorded. Phase I lasts from six to nine months and is intended to confirm safety and acceptance of the investigational drug in humans.
- Phase II clinical trials continue to monitor the safety of the drug being studied, as well as evaluate its efficacy at achieving its intended purpose. In Phase II, volunteers actually have the condition for which the new drug is being tested. A few hundred patients participate in Phase II. This trial will ascertain the effective dosage amounts from minimum to maximum.
Often, a Phase II clinical trial will arbitrarily divide the recipients into two or three groups. One group will receive the investigational new drug; one group a placebo and possibly a third group will receive a standard treatment to compare it against the effectiveness of the new drug. When this is a double-blind test, even the researcher doesn’t know who received the drug or the placebo. How long Phase II lasts is contingent upon the kind of drug and the disorder that it is intended to treat. It may be anywhere from six months to three years.
- Phase III provides continuedclinical trials on the safety and efficacy of the new drug. The same randomized and blinded studies of Phase II are used in Phase III. The number of participants is again multiplied to several hundred or thousands of volunteers. This Phase may last from one to four years, depending on the condition being treated and the type of drug.
In the US: New Drug Application (NDA), and in the UK: Marketing Authorization Application (MAA) is used to apply to make a new drug available to the public. Theserequestsdetail all the data gathered during the preclinical and clinical studies, including its safety and efficacy.
Upon successfully completing the preclinical and clinical trials, the amassed documentation is presented to the Food and Drug Administration, in the US, or the governing body in the country where the study is taking place. The records will provide substantiation that the medication will perform as intended when used for the purpose for which it is prescribed. New drug approval can take anywhere from six months to two years.
Continuing studies after medication approval:
Once the regulatory agency has approved a new medication, the pharmaceutical company may continue to study in the drug in Phase III b and Phase IV. These after approval studies may continue for a few months to many years.
Phase IIIb may actually begin before the medication is approved. These trials are looking toextendpreviousstudies by delivering supplemental safety information or they may assess the approved drug for other disorders for which it may show to be beneficial.
Phase IV trials increase analysis of a proven medication to wider patient populations. Also,the effects of long-term use are studied along with the cost as compared to similar medications that treat the same disease
Post-approval studiesbroaden the possible use of an approved drug by testing in different age groups or other types of patients. The post-approval trials may also look at risks and side effects, previously undetected. All Phases of drug trials are to maintain a vigilant watch for safety and effectiveness.