Drug Development Process - Essay Example

Drug Development Process Drug development is the process by which new therapies are created and brought to market to treat diseases. Drug should undergo a process before it will be able to approve by the Food and Drug Administration (FDA) and before it will be marketed. The Food and Drug Administration ensures the safety and efficacy of the drug being marketed. The FDA requires examining the efficacy of the drug thru well-controlled trials, the effectiveness of the drug should be determined and the safety of the drug to be developed is checked before approving the medication for market. The Drug Development Process includes 12 steps; 1) Disease State 2) Metabolic Pathway / Gene Pathway, 3) 3) Molecular Specificity, 4) 4) Quantitative Structure - Activity Relationship (QSAR), 5) 5) Structural information using-NMR database and X-ray crystallography, 6) Synthesis of Compound 7) In Vitro and In Vivo Testing 8) Metabolism and Toxicity Testing 9) Pharmacokinetics 10) Clinical Trials 11) Formulation of Product 12) Approval Each step should follow the guidelines provided by the Food and Drug Administration. Product for development which has been marketed or studied previously will undergo the same steps. According to the February 1993 report by the Congressional Office of Technology Assessment, one company costs $359 million in U.S. To be able to get one new medicine from the laboratory testing to the pharmacist's shelf, the process usually takes 12 years on the average and only 5 in 5,000 will make it to human testing. And only one of the 5 will be approved.(FDAreview.org).. The Process of Development 1) Disease State The first step is to analyze the target to be developed. Before developing a drug, you must identify first the state of the disease and the symptoms to which the development of drug will be base to. It is important to identify the target. The key decision if whether the target for therapeutic intervention is one that will have a positive effect on managing the disease in question. There are some companies who want to further develop their product. For example, a drug for diabetes will be developed; the company should specify what would be the added pharmacological action on their drug. This will be the basis for the clinical testing that the new product should undergo. 2) Metabolic Pathway/ Gene Pathway Metabolic pathway is a new approach in addressing and developing enhanced disease, understanding platforms with the potential to design significantly more effective drugs against many human diseases, including cancer. (Schimdt , 2004). There are several factors that controls the level of drug in the individual patients, including environment, patient compliance and genetic differences. . The metabolic pathway will give insight on the possible kinetic problems that may occur by providing which specific enzyme the drug is metabolized. In this step the drug manufacturer will be able to identify the isozymes responsible for the metabolism in humans. Nowadays, there is several computer aided system in testing the metabolic pathways of a drug. 3) Molecular Specificity In this step the molecules to be added in the drug should be specified for further analysis. Added molecules in a drug can alter the potency and efficacy of a drug. To be able to identify the molecules to be added, there are several new technology which can be of help to be able to shorten the period of this test. One molecule can affect the phamacological action of a drug, for example one molecule added to morphine can increase its painkilling effect. 4) Quantitative Structure-Activity Relationships (QSAR) The Quantitative Structure - Activity Relationship or QSAR predict and analyze the drug activity. The QSAR represent an attempt to correlate structural or property descriptors of compound with activities. In QSAR the hydrophobicity, topology, electronic properties, and steric effects, are determined empirically, or more recently by computational methods. Activities used in QSAR include chemical measurements and biological assays. It is applied in many discipline, with many pertaining to drug design and environmental risk assessment. 5) Structural information using-NMR database and X-ray crystallography NMR database and X-ray crystallography are used to identify the structural information of a drug. Proteins are the primary targets for most drug discovery efforts. Proteins have become increasingly important as therapeutic agents Only X-ray crystallography and nuclear magnetic resonance (NMR) can give localized, high-resolution structural information on proteins. Nuclear magnetic resonance (NMR) techniques are being applied to determine the structure and dynamics of proteins, nucleic acids and protein-nucleic acids complexes in solution. X-ray Crystallography Databases play an important role in drug discovery and in biotechnology and biological research. This has improve significantly when freezing of crystals at liquid nitrogen temperature (cryofreezing), multiple-wavelength anomalous dispersion phasing, robotisation, automated data collection and the use of synchrotron beamlines where adopted as standards. 6 ) Synthesis of Compound In this step the drug are subjected to further analysis of its compound. The process of identifying the added molecules with the potential desired change in a biological system. The new molecules can be produced through artificial synthesis or extracted from natural sources. Nowadays, increasing the throughput assay of the drug can be determined using the chemistry or the technology or the combination of both. Compound can be synthesized using the modern technology to shorten the period of drug development. Synthesis of a compound is important to evaluate the effect of the added molecule in the human body. However testing should be done first using the in vitro or in vivo testing before it will be tested to human. 7) In Vitro and In Vivo Testing There two testing methods in analyzing the pharmacological effect of the drug being developed. In vitro methods (using cells and tissues outside the body in an artificial environment) are routinely used to determine the safety or effectiveness of a drug or ingredient. In vitro testing appears simple. Cells from the body of a living organism are grown with a chemical soup that provides the nutrients needed for the cells to survive outside the body. These cells are exposed to ingredients, and each ingredient is analysed to understand metabolism. The cells are analysed to understand the concentration of the ingredient that makes the cells unhealthy. In vivo tests are carried out in several animal species for the development of drugs, food additives, pesticides, and industrial chemicals, and in humans primarily for drugs. In vivo studies range in duration from short-term dosing to lifetime exposure. They include studies to assess the potential for inducing birth defects, as well as multigenerational studies for assessing adverse reproductive outcomes. 8) Metabolism and Toxicity Testing Metabolism and toxicity testing step is one of the most important step in drug development. A major step in assessing the toxicity of a drug is the prediction of the entry fate of the compound in human metabolism. In this stage the new product are being tested for its risk factor to human and the environment. The added molecules in a drug will be tested either in vitro or in vivo for further analysis of the said product. Tests provide information on the dose-response pattern of the compound and its toxic effects. The chemical changes that take place in the product are further tested for the possible toxicity of the developed product. 9) Pharmacokinetics Pharmacokinetics includes the absorption and disposition of a drug in a human body. Pharmacokinetics has many applications in drug therapy. Pharmacokinetics will help the pharmaceutical company in making their formulation. The amount of drug released from different formulations may vary. Pharmacokinetics will be able differentiate one drug from another. Each drug has its own pharmacokinetics. Pharmacokinetics includes the administration, distribution, metabolism and excretion of drug. 10) Clinical Trials (Phases 1,2,3,4) In this step a pharmaceutical company conducts laboratory and animal studies to show biological activity of the compound against the targeted disease, and the compound is evaluated for safety. These tests take approximately three and one-half years. (fdareview.org) Clinical Trials, Phase I. The first phase involves 20 to 80 healthy volunteer and this phase takes about a year. The coverage of these phase are as follows: drug's safety profile, including the safe dosage range, the absorption, metabolism, and excretion of the drug on study. Clinical Trials, Phase II. In this phase, the number of volunteer for study has increased to about 100 to 300 sick people. This phase will determine the effectivity of the drug on study. The duration of the study usually takes 2 years. Clinical Trials, Phase III. The effectiveness and the adverse reaction of a drug are being identified in this phase. The study is usually conducted in a hospital or clinic with strict monitoring of the doctor for possible adverse reaction. The FDA and the pharmaceutical representative discuss the development of the drug. Clinical Trials, Phase IV. In evaluation the long term effect of a drug, FDA requires the pharmaceutical company for additional studies. This phase is applicable to those medicines with questionable effects to human during the clinical tests. 11) Formulation of Product The last step in drug development before the approval is the formulation of a product. In this step the pharmaceutical company will make the active compound into the possible strength and form suitable for human use. This will include the dosage form of the drug either if the product is in liquid, tablets, capsules, ointments and others. The formulation includes the active ingredient, excipients, and additional flavoring. The process of turning an active compound into a form and strength suitable for human use. The formulation includes the possible adverse reaction, the indication and other side effects of the drug. Upon completion of the above tests, the pharmaceutical company will now apply for a New Drug Application or NDA. 12) Approval The last step in drug development before it reaches the market is the approval of Food and Drug Administration. In assessing the New Drug Application or NDA, the FDA consult advisory committee composed of experts to obtain range of advised regarding the drug safety, effectiveness and labeling. Upon the approval of the FDA, the developed drug will now marketed, with the strict compliance with FDA's guidelines in labeling. If the approved product shows adverse effects that would harm the human seriously, the FDA has the right to withdraw the said product in the market. Reference: 1. Schimdt, C. (2004) Metabolomics takes its place as latest up and coming "omic" sciences, J. Natl. Cancer Inst. 96, 732-734 2. . Liotta L. Petrocoin E; Molecular profiling of human cancer. Nat Rev. Genet 2000, 1:48-56 3. Lisa Russel , "Drug Design", 2003 http://www.chemsoc.org/ExemplarChem/entries/2003/nottingham_russell/6.html 4. Congress of the United States, Office of Technology Assessment. Pharmaceutical R&D: Costs, Risks and Rewards: 1993; pp. 4-5. Based on Pharmaceutical Manufacturers Association Annual Survey 5. Alliance Phases of Product Development , http://www.allp.com/drug_dev.htm 6. http://www.fdareview.org/approval_process.shtml Read More