Pharmaceutical Industry and Drug

¶ … Drug Development (From Nature to the Market) The process of drug development is a complex one. The pharmaceutical industry is required to adhere to strict governmental regulations, set out by the Food and Drug Administration (FDA), which involve numerous phases of testing and clinical trials, close monitoring of the drug's effects on users, its stability, dosage forms (the preparation), and so on. This paper will describe the drug development process, as it proceeds from nature to the market.

Drugs that eventually make it to the marketplace can come from a variety of sources -- plants, animals, microbes, synthetic chemistry, biotechnology, and even modified molecules. Years of research and billions of dollars are invested by pharmaceutical companies as they seek out new, potential drugs for the market. All of this effort has resulted in the FDA's approval of 1,200 drugs for the marketplace since 1950 (Munos 960).

The "recipes" that have gone into producing these drugs are diverse, with some changing over time in order to meet with continuingly reassessed standards and updated regulations. While drugs have been produced by societies around the world through all history, the 20th century saw the beginning of a vast, federal initiative to provide oversight of the drug industry for the first time in the U.S.

This began with the Food and Drug Act in 1906 -- the 1st law to be passed at the federal level regarding the regulation of drug standards. Various Acts throughout the 20th century amended the statutes contained in this early piece of legislation -- such as the F.D. & C. Act in 1938, the Durham-Humphrey Amendment in 1952, and the Kefauver-Harris Amendments in 1962 (all of which were passed to address issues that arose in the marketplace regarding safety of dispensation, safety of the drugs themselves, and authenticity of the drug's claims).

Today, new drugs must be sponsored in order to obtain FDA approval. Drug companies are typically the ones to sponsor new pharmaceuticals and as the sponsors, they are responsible for providing evidence that the new product is safe, effective, and does as is indicated by the product description. Moreover, as a result of the development of regulations in the industry, drug companies must also follow protocols regarding the manufacturing, packaging, labeling and shipping of drugs so that counterfeiting and mis-identification risks are reduced.

Currently, radio-frequency identification (RFID) technology is being discussed in the industry as a way for drug manufacturers to work with regulators on maintaining high standards in shipping, tracking, and receiving (Coustasse, Kimble, Stanton, Naylor). Before drugs arrive at that stage, however, there is a long process of development that begins with the preclinical stage. This is essentially the phase in which a new drug is born, conceived from natural sources, synthetic sources, or genetic manipulation.

Through the process of drug discovery, the ideal compound is identified or constructed, its biology characterized, and its pharmacological uses determined. Testing at this phase includes toxicity, carcinogenicity, mutagenicity and more (animals are typically used as test subjects in this phase). The pre-clinical phase continues with further evaluation of compounds identified as being potentially effective: the focus at this point is on providing a stable formulation of the compound through analysis of its properties (both chemical and physical).

Issues regarding stability of form include: a drug's solubility, its rate of dissolution, its partition coefficient and so on. An initial product is then created for the first clinical trial. Companies are legally obliged to ensure that this product is formulated according to the FDA's Current Good Manufacturing Practice guideline (Shukla, Vishnoi, Das). Before testing using human subjects, the drug's sponsoring company must file an Investigational New Drug (IND) application with the FDA. The Institutional Review Board must gives its approval in order for the application to be submitted.

The application is then processed by the FDA, which will take 30 days to review the application before granting or denying approval. If approved, a Clinical Hold is issued, which allows the company to proceed with its clinical trial using human subjects. There are 3 phrases of clinical investigation that a product must pass through following the FDA's approval of the IND application. Phase 1 consists of the drug being tested a small sample of healthy persons who volunteer to participate in the clinical study.

The number may range from 20 to 100 persons and the study will last for many months, as the drug's toxicity and the sample's tolerance of the drug are monitored, measured and assessed. Only 67% of drugs pass this first phase of testing, which is "primarily concerned with drug safety, not efficacy" (Pocock 3). One of the objectives here is to determine a safe level of dosage for the drug, which is determined by monitoring side effects as the subject's dosage is gradually increased over time (Pocock 3).

Phase 2 trials utilize a far larger sample with up to several hundred human subjects participating in the study, though the number is commonly between 100 and 200 participants (Pocock 3). The purpose of phase 2 trials is to measure the actual effectiveness of the drug on patients who have the problem that the drug is meant to address. Again, safety is monitored and measured in this phase as well and optimal dosage levels are ascertained. Phase 2 trials will last for 2 years and fewer than 50% of drugs successfully pass beyond this trial period.

Those that do pass phase 2 trials and are "shown to be reasonably effective" (Pocock 3) embark on the final stage of clinical testing, which is phase 3. This consists of a large-scale study that takes place at multiple centers so that effectiveness of the drug can be corroborated by more than one scientific research team and sample. This phase of testing will last for another 1 to 4 years and is "the most rigorous and extensive type of scientific clinical investigation of a new treatment" (Pocock 3).

Only 5 to 10% of all drugs produced successfully meet the required standards of phase 3 testing and proceed to market, where phase 4 testing (postmarketing surveillance) is conducted to assess the drug's impact on consumers and continue to measure safety. It may be noted that there are a variety of phase 3 trials that may be conducted in order to assess a drug's safety and effectiveness.

Randomized controlled trials are the most common methods of measuring the drug's performance over the duration of the study, as this methodological approach is consistent with the rigorous standards that must be met in order for the drug to be deemed marketable. A randomized controlled trial is a study where participants in the sample are selected at random to be the recipient of a specific intervention. Multiple interventions are utilized in the trial so as to provide the researchers with a standard of comparison.

This means that there is a control (placebo) that is designed to produce no effect at all (the control could also include no intervention whatsoever). The new drug's effect on the participants who receive it as their intervention is thus measured against the control (Bamelis, Evers, Spinhoven, and Arntz 305). Phase 4 testing refers to the marketing stage of the drug, during which time the new drug is brought to the attention of clinicians.

Its scientific value is limited as the main focus of this phase is oriented towards the business or retail side of the drug development process (Pocock 3). Nonetheless, it is still an important part of how a drug is brought to market, how it is received by clinicians and physicians, who may or may not proceed to recommend it to patients, and so on. However, the sponsor company will proceed with the New Drug Application (NDA) after the.