Drug development is the process of bringing a novel drug from bench to bedside. It can take 10 to 15 years for a drug to be designed, developed and approved for use in patients (Fig 1). In some circumstances, the drug development and approval process can be expedited for example, if the drug is the first available treatment for a condition, or it shows a significant benefit over existing drugs.Before a drug can reach a patient, it must go through rigorous testing to determine whether it is safe, effective at treating the condition it was developed for, and to ascertain the correct dosage and appropriate administration route.

Pharmaceutical regulatory authorities are responsible for overseeing and regulating therapeutics; including prescription and over-the-counter drugs, vaccines, cell therapies, and medical devices. They play a key role throughout the drug development process and are designed to ensure the safety, efficacy, accessibility and security of approved drugs. Throughout the development of the drug, the responsible pharmaceutical company will conduct pharmacovigilance activities.

Numerous different regulatory authorities exist worldwide. The USAs regulatory agency is the US Food and Drug Administration (FDA) and the UK equivalent is known as the Medicines and Healthcare Regulatory Agency (MHRA) every country has its own regulatory authority.

2. Preclinical Research

3. Investigational New Drug Application

4. Clinical Research

5.Regulatory Review, Approval and Post-marketing Safety Surveillance

Figure 1: An overview of the drug discovery, development and approval process.

Numerous screening approaches can be used to identify a hit compound. A hit can be defined as a compound that interacts with the target of interest. There are several strategies that can be used to discover hits including; high-throughput screening, phenotypic screening, virtual screening, fragment-based screening and structure-based design.

In phenotypic screens, the specific drug target may not be immediately evident as the approach is based on determining if a compound exerts a desired effect by observing a change in phenotype. The target underlying the observed phenotypic change may be identified later although there isnt a regulatory requirement to know the target of a drug provided it demonstrates good safety and efficacy properties.

It is extremely important that the most appropriate animal model is used at this stage, as well as considering the gender of animals to be used to prevent sex-specific bias. A drug could elicit a different response in a male animal compared to a female. You will also need to consider species-specific physiology and similarities in terms of metabolic pathways and genetics (for example 99% of all mouse genes overlap with human ones).

An IND can be categorized as either commercial or research. For an IND application there are key areas that must be covered: animal model pharmacology and toxicology studies, manufacturing information, clinical study protocols and investigator information.The IND sponsor is required to wait 30 days before starting clinical trials this delayed period gives regulators the opportunity to review the information contained within the IND application.

The clinical stage of drug development follows a series of Phases.

Study length: Typically, several months.

Primary purpose: To determine safety in humans, and to gather information on dosage. Phase I studies also guide how best to administer the drugto limit toxicity and enhance therapeutic effectPhase IINumber of participants: Several hundred. The participants will be diagnosed with the condition/ disease you a re developing the drug to treat.Study length: Spans from several months to two years.

Primary purpose: To acquire additional safety data to determine efficacy and adverse effects. This information is used to optimize the design of the larger Phase III study.Phase IIINumber of participants: 300 3000. The participants will be diagnosed with the condition/disease you are developing the drug to treat.

Study length: Spans from one to four years in length.

Primary purpose: To determine the drugs efficacy and to monitor adverse reactions. Due to the increased number of participants during Phase III, long-term or rarer side effects that may have gone undetected in Phase I and Phase II are usually detected. The greatest proportion of safety information is collected during Phase III.

The regulatory authority is responsible for the scientific evaluation of the NDA or MAA. The goal of the application is to provide the regulator with enough information gathered during preclinical and clinical studies for them to be able to determine if:

Number of participants: Several thousand. The volunteers will be diagnosed with the condition/disease that the drug is approved to treat.

The purpose of a Phase IV study is to obtain additional information about the long-term risks and benefits of taking a drug now that it is being more widely used. The real-world data can also help determine if there is scope to develop the drug further, for example:

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Exploring the Drug Development Process - Technology Networks

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