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. 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 USA’s regulatory agency is the US Food and Drug Administration (FDA) and the UK equivalent is known as the Medicines and Healthcare products Regulatory Agency (MHRA) – every country has its own regulatory authority.
Stages of Developing a Drug
- Early Drug Discovery
Investigational New Drug Application
Regulatory Review, Approval and Post-Marketing Safety Surveillance
An overview of the drug discovery, development and approval process.
1. Early Drug Discovery
There are several core “steps” that are carried out during drug discovery. Academic and industry scientists collaborate to identify potential druggable targets for a specific disease. They work to discover and optimize drug compounds that can elicit an effect on a specific biological target implicated in a disease – in the hopes of treating it. Work at this stage is performed in the laboratory using in vitro and animal models.
2. Preclinical Research
Preclinical testing is designed to deliver important information about a drug candidate’s efficacy and safety before it is tested in human subjects. Both in vitro and in vivo models are typically used to provide evidence of a candidate’s biological effect. Preclinical studies are required by regulatory authorities such as the FDA and MHRA before submitting an investigational new drug application (IND) which is required to progress to clinical development.
3. Investigational New Drug Application
The FDA groups INDs into three different types:
This is submitted by the physician responsible for initiating and investigating. The same physician will manage the administration and/or dispensing of the investigational drug. This type of application is typically requested for the study of an unapproved drug, or an approved drug for use of the drug in an unlicensed indication, or a different patient population.
An emergency use IND enables the regulator (FDA) to authorize the use of an investigational drug in an urgent situation, without the obligation to submit an IND in accordance with 21 CFR, Sec. 312.23 or Sec. 312.20. This type of application is used for patients who do not meet existing clinical study criteria, or in situations where an approved clinical protocol doesn’t actually exist.
This type of IND application is submitted to gain access to an experimental drug that has shown promise in clinical trials for treating a serious or life-threatening condition, whilst the final clinical work is completed, and the new drug application is reviewed by the FDA.
4. Clinical Research
Clinical trials are designed to answer specific research questions related to an investigational drug. The trials must follow a study protocol – a document that describes exactly how the clinical trial will be conducted. It details key study objectives, study design, and statistical considerations, to ensure the safety of participants and the integrity of the data collected during the study.
The attrition of compounds as they move through the drug development process
5. Regulatory Review, Approval and Post-Marketing Safety Surveillance
New Drug Application
The application process for marketing authorization in the USA is known as a New Drug Application (NDA). In the European Union and other countries worldwide, this same process is referred to as a Marketing Authorisation Application (MAA).
Biologic License Application
The approval of biological products in the USA falls under the provisions of the Public Health Service (PHS) Act. The Act requires the manufacturer of the biologic to hold a license for that product. A Biologics License Application (BLA) must be submitted for therapeutic biological products including (but not limited to); monoclonal antibodies (for in vivo use), cytokines, growth factors, enzymes, immunomodulators, proteins, and non-vaccine therapeutic immunotherapies.
Once the drug receives approval from the relevant regulatory authority, numerous activities will need to be initiated to prepare for the launch of the product.
Post-marketing Safety Surveillance
Post-marketing safety surveillance is the term used for the monitoring of a drug after it has received approval and has reached the market. It is designed to evaluate the long-term safety and efficacy of a drug, potential “real-world” problems with formulation, and use for unapproved conditions or “off-label” (e.g. use in an age group or at a dosage outside of that advised in the product label).