A Study on Drug discovery process in Fizikem pharmaceuticals A Mini Project report Submitted in partial fulfillment of requirement For the

award of the degree of

MASTER OF BUSINESS ADMINISTRATION

TECHNOLOGY MANAGEMENT
By

P Avinash

(12251304)

DEPARTMENT OFMASTER OF BUSINESS ADMINISTRATION KLU BUSINESS SCHOOL VADDESWARAM GUNTUR DISTRICT

Research and Development. The research and development (R&D, also called research and technical development or research and technological development, RTD in Europe) is a specific group of activities within a business. The activities that are classified as R&D differ from company to company, but there are two primary models. In one model, the primary function of an R&D group is to develop new products; in the other model, the primary function of an R&D group is to discover and create new knowledge about scientific and technological topics for the purpose of uncovering and enabling development of valuable new products, processes, and services. Under both models, R&D differs from the vast majority of a company's activities which are intended to yield nearly immediate profit or immediate improvements in operations and involve little uncertainty as to the return on investment (ROI). The first model of R&D is generally staffed by engineers while the second model may be staffed with industrial scientists. R&D activities are carried out by corporate (businesses) or governmental entities. Present-day R&D is a core part of the modern business world. Major decisions in firms are made on base of research and development. R &D in Business Research and development is of great importance in business as the level of competition, production processes and methods are rapidly increasing. It is of special importance in the field of marketing where companies keep an eagle eye on competitors and customers in order to keep pace with modern trends and analyze the needs, demands and desires of their customers. Unfortunately, research and development are very difficult to manage, since the defining feature of research is that the researchers do not know in advance exactly how to accomplish the desired result. As a result, higher R&D spending does not guarantee "more creativity, higher profit or a greater market share. Background New product design and development is more often than not a crucial factor in the survival of a company. In an industry that is changing fast, firms must continually revise their design and range of products. This is necessary due to continuous technology change and development as well as other competitors and the changing preference of customers. Without an R&D

program, a firm must rely on strategic alliances, acquisitions, and networks to tap into the innovations of others. A system driven by marketing is one that puts the customer needs first, and only produces goods that are known to sell. Market research is carried out, which establishes what is needed. If the development is technology driven then R&D is directed toward developing that market research indicates will meet an unmet need. In general, R&D activities are conducted by specialized units or centers belonging to a company, or can be out-sourced to a contract research organization, universities, or state agencies. In the context of commerce, "research and development" normally refers to futureoriented, longer-term activities in science or technology, using similar techniques to scientific research but directed toward desired outcomes and with broad forecasts of commercial yield. Statistics on organizations devoted to "R&D" may express the state of an industry, the degree of competition or the lure of progress. Some common measures include: budgets, numbers of patents or on rates of peer-reviewed publications. Bank ratios are one of the best measures, because they are continuously maintained, public and reflect risk. In the U.S., a typical ratio of research and development for an industrial company is about 3.5% of revenues; this measure is called "R&D intensity". A high technology company such as a computer manufacturer might spend 7%. Although Allergan (a biotech company) tops the spending table with 43.4% investment, anything over 15% is remarkable and usually gains a reputation for being a high technology company. Companies in this category include pharmaceutical companies such as Merck & Co. (14.1%) or Novartis (15.1%), and engineering companies like Ericsson (24.9%). Such companies are often seen as credit risks because their spending ratios are so unusual.

Generally such firms prosper only in markets whose customers have extreme needs, such as medicine, scientific instruments, safety-critical mechanisms (aircraft) or high technology military armaments. The extreme needs justify the high risk of failure and consequently high gross margins from 60% to 90% of revenues. That is, gross profits will be as much as 90% of the sales cost, with manufacturing costing only 10% of the product price, because so many individual projects yield no exploitable product. Most industrial companies get 40% revenues only.

On a technical level, high tech organizations explore ways to re-purpose and repackage advanced technologies as a way of amortizing the high overhead. They often reuse advanced manufacturing processes, expensive safety certifications, specialized embedded software, computer-aided design software, electronic designs and mechanical subsystems. Research has shown that firms with a persistent R&D strategy outperform those with an irregular or no R&D investment program.

Company Profile Fizikem is one of the fastest growing names in Pharmaceutical scenario catering to wide range of Therapeutic Segments with quality and affordable Ayurvedic, Generic Allopathic medicines consumer and food products along with herbal cosmetics. What started as a small ayurvedic unit in the year 1988 now emerged as an organised player in the field of health care with 2 state of the art manufacturing units in India with GMP (Good Manufacturing Practices) certifications. With its unstinted approach to quality Fizikem has earned reputation from Doctors, Distributors, Retailers and above all the end users. With strong expertise in Pharma sector. Fizikem is moving ahead to celebrate 25 years of service to the mankind and look forward to cross more milestones to establish itself as a name to reckon with in health care. Drug innovation and Development: Overview It is the mission of pharmaceutical research companies to take the path from understanding a disease to bringing a safe and effective new treatment to patients. Scientists work to piece together the basic causes of disease at the level of genes, proteins and cells. Out of this understanding emerge targets, which potential new drugs might be able to affect. Researchers work to: Validate these targets, Discover the right molecule (potential drug) to interact with the target chosen, Test the new compound in the lab and clinic for safety and efficacy and Gain approval and get the new drug into the hands of doctors and patients.

This whole process takes an average of 10-15 years.

Understand the disease Before any potential new medicine can be discovered, scientists work to understand the disease to be treated as well as possible, and to unravel the underlying cause of the condition. They try to understand how the genes are altered, how that affects the proteins they encode and how those proteins interact with each other in living cells, how those affected cells change the specific tissue they are in and finally how the disease affects the entire patient. This knowledge is the basis for treating the problem. Researchers from government, academia and industry all contribute to this knowledge base. However, even with new tools and insights, this research takes many years of work and, too often, leads to frustrating dead ends. And even if the research is successful, it will take many more years of work to turn this basic understanding of what causes a disease into a new treatment. Target Identification Choose a molecule to target with a drug Once they have enough understanding of the underlying cause of a disease, pharmaceutical researchers select a target for a potential new medicine. A target is generally a single molecule, such as a gene or protein, which is involved in a particular disease. Even at this early stage in drug discovery it is critical that researchers pick a target that is drugable, i.e., one that can potentially interact with and be affected by a drug molecule. Target Validation Test the target and confirm its role in the disease. After choosing a potential target, scientists must show that it actually is involved in the disease and can be acted upon by a drug. Target validation is crucial to help scientists avoid research paths that look promising, but ultimately lead to dead ends. Researchers demonstrate that a particular target is relevant to the disease being studied through complicated experiments in both living cells and in animal models of disease. Drug Discovery Find a promising molecule (a lead compound) that could become a drug. Armed with their understanding of the disease, scientists are ready to begin looking for a drug. They search for a molecule, or lead compound, that may act on their target to alter the disease

course. If successful over long odds and years of testing, the lead compound can ultimately become a new medicine. There are a few ways to find a lead compound: Nature: Until recently, scientists usually turned to nature to find interesting compounds for fighting disease. Bacteria found in soil and moldy plants both led to important new treatments, for example. Nature still offers many useful substances, but now there are other ways to approach drug discovery. High-throughput Screening: This process is the most common way that leads are usually found. Advances in robotics and computational power allow researchers to test hundreds of thousands of compounds against the target to identify any that might be promising. Based on the results, several lead compounds are usually selected for further study. Biotechnology: Scientists can also genetically engineer living systems to produce disease-fighting biological molecules. Perform Initial Tests On Promising Compounds Lead compounds go through a series of tests to provide an early assessment of the safety of the lead compound. Scientists test Absorption, Distribution, Metabolism, Excretion and Toxicological (ADME/Tox) properties, or pharmacokinetics, of each lead. Successful drugs must be: absorbed into the bloodstream, distributed to the proper site of action in the body, metabolized efficiently and effectively, successfully excreted from the body and demonstrated to be not toxic.

These studies help researchers prioritize lead compounds early in the discovery process. ADME/Tox studies are performed in living cells, in animals and via computational models. Pharmacological aspects of drug development. Of the about 5,000 to 10,000 drug candidates screened during the drug discovery stage, about 250 will typically make it to the preclinical research stage.20 During this phase, the pharmacological concerns of toxicity, bioavailability,21 and efficacy are investigated. In addition, at this point, an investigational new drug (IND) application is filed with the Food and Drug Administration (FDA), patents are applied for, and efforts are started to develop economic and quality manufacturing processes. Safety testing takes place in animals that are administered ever increasing doses to look for onset of toxicity. Also, a key feature of this stage is to determine the best method of delivery (e.g., oral, intravenous, etc.). A drug with a low bioavailabilityat or near zero either must have its dosage increased when administered orally or it must be administered in some other way. Other tests include determining a drug candidates shelf lifetime and shipping durability. Phase 1 Clinical Trial Perform initial human testing in a small group of healthy volunteers. In Phase 1 trials the candidate drug is tested in people for the first time. These studies are usually conducted with about 20 to 100 healthy volunteers. The main goal of a Phase 1 trial is to discover if the drug is safe in humans. Researchers look at the pharmacokinetics of a drug: How is it absorbed? How is it metabolized and eliminated from the body? They also study the drugs pharmacodynamics: Does it cause side effects? Does it produce desired effects? These closely monitored trials are designed to help researchers determine what the safe dosing range is and if it should move on to further development. The first step in preclinical pharmacological testing is to determine toxicity, including the relationship between dosage and toxicity, how those effects vary over time, the organs affected, and the reversibility of any effects. To determine how the effects change over time or whether there are long-term toxic effects, extended tests are performed. They usually last more than a year and attempt to determine a number of factors in addition to a cataloging of any risks of long-term use. Included are tests to determine dosage range, maximum dosage for no side effects, and largest tolerable dosage. In parallel, carcinogenicity studies, involving various dosage levels and lasting up to two years, are carried out. Other conditions studied include local side effects, allergenic reactions, and effects on reproduction.

During the safety testing, animals are used for studies of toxicity including chronic toxicity.The drugs cancer-causing potential is also investigated by examining how it may damage the animals DNA. Pregnant animals are used to look at the drugs effects on pregnancy. Animal testing is opposed by some, however, and their methods are being sought, including the use of tissue cultures, bacteria cells, and computer models. Many of these methods are now used for preliminary screening to reduce the number of animals used in safety testing.

Phase 2 Clinical Trial Test in a small group of patients. In Phase 2 trials researchers evaluate the candidate drugs effectiveness in about 100 to 500 patients with the disease or condition under study, and examine the possible short-term side effects (adverse events) and risks associated with the drug. They also strive to answer these questions: Is the drug working by the expected mechanism? Does it improve the condition in question? Researchers also analyze optimal dose strength and schedules for using the drug. If the drug continues to show promise, they prepare for the much larger Phase 3 trials. Phase 3 Clinical Trial Test in a large group of patients to show safety and efficacy In Phase 3 trials researchers study the drug candidate in a larger number (about 1,0005,000) of patients to generate statistically significant data about safety, efficacy and the overall benefit-risk relationship of the drug. This phase of research is key in determining whether the drug is safe and effective. It also provides the basis for labeling instructions to help ensure proper use of the drug (e.g., information on potential interactions with other medicines). Phase 3 trials are both the costliest and longest trials. Hundreds of sites around the United States and the world participate in the study to get a large and diverse group of patients. Coordinating all the sites and the data coming from them is a monumental task. During the Phase 3 trial (and even in Phases 1 and 2), researchers are also conducting many

other critical studies, including plans for fullscale production and preparation of the complex application required for FDA approval. New Drug Application (NDA) and Approval: Submit application for approval to FDA Once all three phases of the clinical trials are complete, the sponsoring company analyzes all of the data. If the findings demonstrate that the experimental medicine is both safe and effective, the company files a New Drug Application (NDA) which can run 100,000 pages or more with the FDA requesting approval to market the drug. The NDA includes all of the information from the previous years of work, as well as the proposals for manufacturing and labelling of the new medicine. FDA experts review all the information included in the NDA to determine if it demonstrates that the medicine is safe and effective enough to be approved (see sidebar How does the FDA decide to approve a new drug?). Following rigorous review, the FDA can either 1) approve the medicine, 2) send the company an approvable letter requesting more information or studies before approval can be given, or 3) deny approval. Review of an NDA may include an evaluation by an advisory committee, an independent panel of FDA-appointed experts who consider data presented by company representatives and FDA reviewers. Committees then vote on whether the FDA should approve an application, and under what conditions. The FDA is not required to follow the recommendations of the advisory committees, but often does. Manufacturing Going from small-scale to large-scale manufacturing is a major undertaking. In many cases, companies must build a new manufacturing facility or reconstruct an old one because the manufacturing process is different from drug to drug. Each facility must meet strict FDA guidelines for Good Manufacturing Practices (GMP). Making a high-quality drug compound on a large scale takes great care. Imagine trying to make a cake, for example, on a large scale making sure the ingredients are evenly distributed in the mix, ensuring that it heats evenly. The process to manufacture most drugs is even more complicated than this. There are few, if any, other businesses that require this level of skill in manufacturing. Ongoing Studies and Phase 4 Trials Research on a new medicine continues even after approval. As a much larger number of patients begin to use the drug, companies must continue to monitor it carefully and submit

periodic reports, including cases of adverse events, to the FDA. In addition, the FDA sometimes requires a company to conduct additional studies on an approved drug in Phase 4 studies. These trials can be set up to evaluate long-term safety or how the new medicine affects a specific subgroup of patients. Conclusion The discovery and development of new medicines is a long, complicated process. Each success is built on many, many prior failures. Advances in understanding human biology and disease are opening up exciting new possibilities for breakthrough medicines. At the same time, researchers face great challenges in understanding and applying these advances to the treatment of disease. These possibilities will grow as our scientific knowledge expands and becomes increasingly complex. Research-based pharmaceutical companies are committed to advancing science and bringing new medicines to patients.