Drug Research is a Key Strategic Driver
The business model of large bio-pharmaceutical companies has four unique aspects:
· Highly structures value chain determined by the regulatory process
· High cost of product development with associated high risks of failure
· High returns for successful product development
· Focus on innovative output
Drug research is the major innovative driver for Pharmaceutical & Biotech companies, they compete to discover and develop new drugs. To understand the structure of this value chain we need to take a closer look at the drug discovery process. To discover a new drug, laboratories have to synthesize thousands of new chemical and biological entities and test them in animals. Few compounds will survive these tests to go on to clinical studies and only a small proportion makes it to a medically and commercially successful drug.
Characteristics of drug research
The process of searching for and obtaining information on a new compound is known as “pharmaceutical research”.
The Bio-pharmaceutical value chain
There are four important steps in bringing a new chemical entity (NCE) or biological entity (NBE) to market:
· The basic research phase; pioneering to discover a new chemical entity, which has the ability to cure.
· The product development phase; practical research in animals and humans to investigate product properties, product features and possible use in human beings.
· The reimbursement phase; creation of a health & pharmaco-economic dossier to prove cost effectiveness over current treatment options.
· The product marketing phase; translation of product properties and features to benefits and added value for patients and doctors
Most pharmaceutical products start as chemicals or biological made or modified by a chemist or biotechnologist in a laboratory experiment. The scientist must be familiar with most modern ideas of organic chemistry and biomedical technologies, and he or she must also have the right mindset and “scientific nose” to be able to identify the reasons why a compound might have curing activity. With this information the molecule can be modified to increase curing potency, reduce toxicity, improve bioavailability or make the drug longer acting. It is the scientist’s main tasks to design a new compound for testing, to see if potential medicinal properties are present. To accomplish these objectives, the scientist relies on feedback from the pharmacologist who is testing the compounds in the particular animal or laboratory model. The pharmacologist creates a suitable laboratory model to evaluate the new compounds for their activity. In other words he identifies an animal species that can develop a physical condition similar to the disease under study. The lab model that may be used to test compounds may involve cellular and or animal models.
Before any compound can be tested for safety and efficacy in humans, it must show that it has some kind of related activity that can be observed in a laboratory setting. Once a compound has been identified to be of possible interest as a pharmaceutical product, the pharmacologist will study the compound more intensively in more animals or other species to establish how the compound reacts in the body. This process is known as finding the mechanism of action.
The pre-clinical phase of the research process consists of:
· Animal toxicology studies, systemic studies of the effect of the compound on the safety of an organism.
· Pharmacodynamics and pharmacokinetics studies, to determine the process by which a drug functions in the animal model once it enters the body.
· Analytical chemistry studies to study the nature and extent of the compounds impurities, its stability as a compound in the formulated state, the level in blood and other living tissue, and how and in what form it is eliminated from the body.
· Pharmaceutical formulation studies, concerning the preparation of the drug in a way that will simplify the administration of the compound to the patients.
Early animal studies will provide information as to the best routes to administer a new compound. While most drugs are given by oral route, there are many other ways a drug can be given to accomplish a particular purpose. Possible forms to prepare a product are tablet, capsule, syrup, cream, ointment, patches or solution for injection. The form also may change during the products development process.
The result of the clinical research study that are performed on a new pharmaceutical product will decide if the new drug application is ever submitted to a Board of Health (FDA for the US and EMA for the EU) for approval to market the drug. Clinical research projects are very broad in scope; they include the general strategic plan that involves:
· Finding the medical indication to be studied.
· The dosage form, strengths, and the route of administration.
· The design of the clinical protocol, case report forms, ordering of clinical supplies.
· Investigator selection, monitoring of trail conduct, data collection and data analysis.
· Reporting of the results in a form suitable for the submission to the regulatory authorities.
Clinical research the testing of the drug in humans consists of three phases:
· Phase I studies are conducted to establish a safe dose and conducted in normal healthy volunteers
· Phase II studies are conducted in persons with a disorder with the purpose to gain evidence of safety and efficacy and to establish the proper dose and dosing intervals. Safety and tolerance data are obtained in patients with the target disease to provide a measure for the drugs true effects, when used in the respective patient group
· Phase III studies are the definitive trails that will establish the safety and efficacy of the new drug in the actual population for which it is intended to be used. These trails are quite large, often involving treatment of several hundreds to several thousands of patients. Large numbers of patients are required to perform statistical analysis of the clinical data. For some diseases this may require long-term follow-up studies of at least a year. Drugs that reach this stage of development will consume the largest amount of financial and human resources.
A drug regulatory affair has influence on every aspect of the pharmaceutical research process. Once the drug is indented to be used in human beings every step in the research becomes an item that is reportable to the regulatory agency. Eventually the file is submitted for registration to the BOH (Board of Health). The biggest hurdle to take in the drug development process is obtaining approval to market the product.
Marketing identifies areas of “unmet medical needs” and as such direct the strategic research process. Examples of unmet medical need might be a new HIV drug that can be taken once a week, so that patients won’t have to worry about taking the product during their busy daily schedules. Other examples are an antibiotic that can be used safely in patients with a renal impairment or a liquid product for a group of elderly patients who have difficulty swallowing a tablet or capsule. As such marketing may influence research early in the development process that a specific modification may be requested. Positioning and differentiating the product is one of marketing’s other major responsibilities
Companies can focus their research activities on three types of products:
· A newly discovered chemical compound that has shown biological activity suggesting therapeutic efficacy (scientific driven).
· A known compound for which a medical property has recently been observed (therapeutic area driven).
· A known drug that has been prepared in a new delivery system or in combination with another product/device, where this new method of administration is believed to provide better medical properties than previously available (marketing/market driven)
Pharmaceutical and biotechnology companies must prove that their products are both safe and effective to use for the medical conditions being claimed and in patients in which the product is intended to be used. Further the information provided by the company to support the claims of the drug must contain documents that address the following aspects:
· The products chemical or biological properties.
· Observed effects on animals or in the laboratory.
· Formulation data & manufacturing information.
· Results of testing in humans under controlled conditions.
In conclusion the pharmaceutical product development process is complex, and highly regulated and at the same time it is a key strategic driver for continuation and long-term profitability of companies. Organization & structure of this complex research and development process is therefore a key strategic driver for successful innovative output and new products.