Based on the development path of new molecules and biological entities approved by the FDA, we can see that the average time required to take products from clinical testing to regulatory approval is 7.2 years. However, the time from research and development to market varies among diﬀerent therapeutic areas. As shown in Figure 1, the clinical development time is relatively short as 5.2 years for AIDS antiviral agents, while it is an extraordinarily long period of 7.9 years for antineoplastic agents. Given that these products are intended to meet critical therapeutic needs and large market demands, this is an extremely long time.
Figure 1. Clinical development times (from IND filing to NDA submission) and regulatory approval times (from NDA submission to approval). *Note that the anti-infective category excludes AIDS antiviral agents. IND, investigational new drug application; NDA, new drug application.
To be competitive in today’s challenging economic, regulatory, and political environment, drug sponsors must reduce product development time, terminate unpromising candidates sooner, improve patient-recruitment capabilities, enhance the protocol design process, control development costs, maintain quality, focus on areas of high therapeutic need, and dramatically boost productivity. That’s why pharmaceutical companies are increasingly entering into functional service providers and alliance relationships with CROs to reduce overhead costs, increase efficiency, and bolster output.
No matter it is a large pharmaceutical company or a CRO and other partners, the drug development process is almost the same.
At the very beginning of this long period, thousands of compounds will be tested. Only 30 in 1000 compounds may show promising results and in those regarded as a candidate compound, just 3 can pass the first round of clinical trials, and finally only 1 can hit the market. In another words, to develop one new drug a pharmaceutical company will test thousands of compounds and discard most of them.
Before testing a drug in volunteers, the researchers must determine if it is likely to cause serious harm, also known as toxicity. There are two types of preclinical research: in vitro and in vivo. At the preclinical stage, the FDA will generally ask sponsors:
- The way it is absorbed, distributed, metabolized and excreted.
- Its potential benefits and action mechanisms.
- Toxicity studies both an acute one in at least 2 species of animals and a short-term one from 2 weeks to 3 months.
FDA also requires researchers to conduct preclinical laboratory studies using Good Laboratory Practices (GLP) as defined in the Medical Product Development Regulations. These regulations set the minimum basic requirements for the follows: study conduct, personnel, facilities, equipment, written protocols, operating procedures, study reports and a system of quality assurance oversight for each study to help assure the safety of FDA-regulated product.
Researchers will design clinical trials to answer specific research questions related to a medical product. They need to decide how to conduct the trial (a protocol) in consideration with the following questions:
- Who qualifies to participate known as selection criteria? (randomization plan)
- How many people will take part in the study? (sample size calculation)
- How long will the study last?
- Do they need a control group or other ways to limit research bias? (data validation)
- How will the drug be given to patients and at what dosage?
- What will be evaluated, when and what data will be collected? (CRF design)
- How will the data be reviewed and analyzed? (statistical strategy & SAS programming)
An Investigational New Drug (IND) application must be submitted to FDA before beginning clinical research. Then the FDA will gather a review team consists of a group of experts in different scientific fields to evaluate your protocol to protect volunteers who participate in clinical trials from unreasonable and significant risk in clinical trials. This team has 30 days to review the original IND submission. FDA responds to IND applications either approve or hold to delay or stop.
Clinical trials follow a typical series from Phase 1 studies to Phase 4 studies (Figure 2).
Figure 2. Various stages of preclinical and clinical testing with purpose and success rate at each stage.
To get an approval from FDA for a new pharmaceutical for sale and marketing in the U.S, drug sponsors need a NDA (New Drug Application) application. In NDA they must provide enough information to permit FDA reviewer to reach the following key decisions:
- Whether the drug is safe and effective in its intended use, and whether the benefits of the drug exceed the risk.
- Whether the proposed label (package insert) of the drug is appropriate and what it should contain.
- Whether the methods used in manufacturing the drug and the controls used to maintain the drug's quality are adequate to preserve the drug's identity, strength, quality, and purity.
After the FDA receives the NDA, the review team will determine if it is complete. If it is incomplete, the review team can refuse to file the NDA. If it is complete, the review team has 6 to 10 months to decide whether to approve the drug. Once approved, FDA will work with the applicant to develop and refine prescribing information.
FDA post-market drug safety monitoring (phase 4)
Although clinical trials provide important information about the efficacy and safety of the drug, complete information about the safety of the drug is not available at the time of approval. Despite the rigorous steps taken during the drug development process, there are limitations. Therefore, the real situation of product safety is actually gradually formed in months or even years, which constitutes the life cycle of products in the market. The FDA reviews reports of prescription and over-the-counter issues and may decide to add information about dosage or usage, as well as other measures for more serious problems.
In conclusion, drug development is a costly and risky affair and involves lot of money and time. We believe CD BioSciences can help you with innovative perspectives on the design and analysis of clinical trials to accelerate your development process.
If you have any questions, please feel free to contact us.
1. Kaitin, K. I. (2010) ‘Deconstructing the drug development process: the new face of innovation’, Clinical Pharmacology & Therapeutics, 87(3), 356.
2. Janodia, M. D., et al. (2007) ‘Drug development process: a review’, Pharmaceutical Reviews, 5(6), 2214-2221.