Investigational New Drug Application (IND)
In the paragraphs that follow, we will provide an overview of the FDA process and highlight the position of Samaritan Pharmaceutical’s lead therapeutics within the process. This should enlighten the reader about the future of Samaritan and the global benefits offered by its therapeutics.

Perhaps the greatest challenge for those interested in biopharmaceutical drug development companies is the understanding of the U.S. Food and Drug Administration (FDA) process. This is because the FDA process runs counter to conventional thinking. In particular, we mistakenly tend to view the FDA as an authorization organization that not only approves the safety and efficacy of new drug entities, but also issues approval of the various methods pharmaceutical companies use to develop such drugs. To the contrary, the FDA’s charge is to prevent the marketing of therapeutics and biologics it views to be unsafe based on a series of scientific observations and known human experience.

Understanding the difference between our perception and the reality of the FDA’s function is essential for the appropriate evaluation of a company as it negotiates the FDA process.

Pre-IND Requirements
The first major milestone associated with the FDA drug development process is the Investigational New Drug Application (IND). However, the process of drug discovery and development begins long before the IND submission is conceived. First, a potential therapeutic is discovered either by accident or as a result of diligent research. This discovery is typically followed by some form of intellectual property protection, which is usually manifested as a patent application. Simultaneously, additional research is conducted in order to properly characterize the physical and biological properties of the therapeutic. These studies are accompanied by a series of in vitro investigations designed to further evaluate the potential efficacy of the therapeutic.

Once these issues are established, researchers seek to determine the potential safety of the therapeutic through a series of in vitro toxicity studies. If the results of these investigations prove promising, researchers then focus on the efficacy and safety of the therapeutics in vivo and ex vivo. Here animal models and/or human cell cultures are used to evaluate the therapeutic.

Assuming success upon completing this series of preclinical examinations, the question of whether or not this promising therapeutic can actually be recreated to consistently meet standards of purity, stability, and beneficial activity is addressed. In brief, we need to know that the drug can be made and administered without sacrificing quality and effectiveness and without requiring an inordinately burdensome dosing regimen.

If all of these pre-IND requirements are satisfied and the therapeutic continues to demonstrate promise, then the drug becomes an eligible candidate for an IND submission. It is important to note that pre-IND costs can run as much as $75 million to $198 million according to the therapeutic.

IND DRUG DEVELOPMENT PROCESS
As stated above, IND submission is considered the first major milestone in the drug development process. The FDA’s primary concern in evaluating IND submissions is the safety of potential therapeutics such that the therapeutic does not present unreasonable health risks to humans. Efficacy and dose response concerns are secondary considerations that the FDA requires biopharmaceutical companies to address after they've established, to the greatest extent practical, the drug’s safety.

There are nine major sections in the IND
1.	Introductory Statement and General Investigational Plan: Information requested here is intended to place the drug development plan into perspective and help the FDA anticipate sponsor needs.
2.	Investigator’s Brochure: Researchers investigating the safety, tolerability, efficacy, and dose response of the investigational drug are informed as to the drug’s physical and biological properties and any results from previous investigations in this document.
3.	Protocol: Protocols establish how each proposed clinical trial will be conducted. There are four primary clinical trial phases. Phase I investigations generally evaluate drug safety and tolerability in healthy human volunteers. Phase II investigations further evaluate safety and tolerability as well as dose response and efficacy in a small sampling of humans suffering from the target disease or infliction. Phase III investigations replicate and expand upon Phase II investigations in a much larger sampling. Finally, Phase IV investigations are typically post market approval investigations that continue to study the therapeutic to determine long-term implications of its use.
4.	Chemistry, Manufacturing, and Controls: These requirements are designed to assure the proper identification, quality, purity, and strength of the investigational drug.
5.	Pharmacology: This section describes the drug’s physical and biologic effects in animals and its mechanism of action.
6.	Toxicology: This section describes the toxic effects of the drug in animals and in vitro.
7.	Previous Human Experience:
8.	Additional Information:
9.	References: Completion of the IND process consists of successful matriculation through Phase I, Phase II to Phase III investigations leading to submission of a New Drug Application (NDA). The entire process may take as long as 15 years and cost as much as $1 billion.

NDA PROCESS
The goal of every biopharmaceutical company is to attain approval to market its beneficial therapeutic or biologic. Submission of an NDA represents the culmination of that pursuit. The NDA submission is reviewed by six separate divisions within the FDA Center for Drug Evaluation and Review (CDER): Medical, Biopharmaceutical, Pharmacology, Statistical, Chemistry, and Microbiology. Should each of these divisions indicate that they are satisfied with the data submitted, the document is forwarded to an advisory committee that in turn organizes meetings with the sponsor and eventually determines the marketing fate of the drug.