The Breakdown of Drug Discovery & Development

Novel drugs do not just appear overnight, rather, they are borne from the ceaseless sacrifice of dedicated researchers.

Step 1 Discovery

The story starts with understanding the pathology of a certain disease that the researcher aims to eradicate; or with the identification of a biological target responsible for the pathology of a disease. Doing so will enable them to know its nature, i.e.: how it spread, why it happened, and where it originated.

 

 

Afterwards, the researcher can begin to identify the mechanism/s of action required for a substance to stop or reverse the adverse effects of the disease. They will then study a wide array of compounds to check which can prove to be beneficial to their study.

There are also instances wherein a promising molecular compound will appear first and will undergo extensive analyses to check its chemical or biological composition. Once researchers establish it, they can easily understand, and possibly foresee, how and what that compound will target once it reaches the circulatory system. Based on these information, researchers can develop a drug against a specific type of illness.

There is a possibility that in this phase of scientific study numerous compounds, with varying health effects, may arise. But early testing as well as modification, optimization, and purification can help decrease that list.

 

Step 2 Preclinical Research

 

 

Once an active pharmaceutical ingredient is purified and formulated into a drug - easily taken in by patients - it is time to move towards Preclinical testing. This is where the dosing and the toxicity levels of the drug is studied; to verify the safety of the drug before proceeding towards human subjects.

This phase involves two types:

  • In Vitro: refers to procedures done in a controlled environment outside a living organism.

  • In Vivo: experiments utilizing a whole, living organism. These tests are often preferred rather than the latter, since researchers can readily observe the effects of the compound with a living subject.

 

The Food and Drug Administration (FDA) requires researchers to use good laboratory practices (GLP):

  • Study conduct

  • Personnel

  • Facilities

  • Equipment

  • Written protocols

  • Operating procedures

  • Study reports

  • System of quality assurance

All these assure that the safety and integrity of FDA-regulated products are maintained.

 

Step 3 Clinical Research

Clinical trial or clinical research is the next phase; this focuses on the ways that the drug will interact with the human body.

 

 

Prior to the start of the clinical trial, researchers must design their own clinical study based on what they want to accomplish on the different clinical research phases, and these are as follows:

Phase

Study Participants

Length of Study

Purpose

1

*Approximately 70% of drugs move to the next phase

20 to 100 healthy volunteers with the disease/condition.

Several months

Safety and dosage

2

*Approximately 33% of drugs move to the next phase

Up to several hundred people with the disease/condition.

Several months to 2 years

Efficacy and side effects

3

*Approximately 25-30% of drugs move to the next phase

300 to 3,000 volunteers who have the disease/condition.

1 to 4 years

Efficacy and monitoring of adverse reactions

4

Several thousand volunteers who have the disease/condition.

 

Safety and efficacy

Table 1 is referenced from: http://wcms-internet.fda.gov/patients/drug-development-process/step-3-clinical-research

 

Clinical trials must follow a specifically designed study plan or protocol developed in-house. This where they must review all previous studies or information of the drug to formulate research questions and objectives. Only then can they decide on:

  • The selection criteria for the population

  • The number of people that will take part

  • How long the study will last

  • Ways of limiting research bias, i.e.: control group

  • The dosage and drug delivery form of the drug during patient administration

  • What information will be collected and based on what tests

  • Method of data analysis

Afterwards, the drug developers would need to submit to the FDA an Investigational New Drug (IND) application before they could begin with the clinical research proper. The application is comprised of:

  • Information on animal studies with toxicity data

  • Manufacturing process information

  • Clinical protocols for all planned studies

  • All data from previous similar human researches

  • Investigator information

Researchers will be able to ask the FDA for help during the process development to help enhance the study. Final approval of the clinical trial design will be given once it passes the FDA review, which can last at least 30 days. This process aims to protect volunteer participants from unreasonable risks of the trials.

 

Step 4 FDA Review

 

 

Once the drug developer collected enough proof on the drug's safety and efficacy from the preclinical and clinical trials, they can file an application to market the drug.

This is where the New Drug Application (NDA) comes in; it tells the full story that the drug has gone through. This application must include the reports on all studies, such as:

  • Proposed labelling

  • Safety updates

  • Drug abuse information

  • Patent information

  • Institutional review board compliance information

  • Directions for use

When the FDA approves this, it is a necessity that they work with the drug developers to refine prescribing information; this is known as 'labeling'. This procedure provides information on the optimal use the drug.

When alarming questions arise that needs careful consideration, the FDA can allow the public to make comments, as well as get an expert advise from one of its Advisory Committees.

 

Step 5 FDA Post-Market Safety Monitoring

After years of rigorous and delicate studies to ensure the safety and efficacy of a drug, there are still limitations that make it impossible to obtain a complete data on it. Thus, the ultimate safety of the product must be well observed even after years of its arrival in the market.

 

 

Should there be any report of unforeseen adverse reactions, it is the duty of both the drug manufacturer and the FDA to make necessary actions.

 

References:

  1. 1. The Marshall Protocol Knowledge Base.(2018). Differences between in vitro, in vivo, and in silico studies. Retrieved on 25 April 2019. Retrieved from: https://mpkb.org/home/patients/assessing_literature/in_vitro_studies

  2. 2. US FDA.(2018). The Drug Development Process. Retrieved on 25 April 2019. Retrieved from: https://www.fda.gov/ForPatients/Approvals/Drugs/default.html

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