Clinical drug trials involve 4 phases - Phase 1 tests drug safety in healthy volunteers, Phase 2 assesses effectiveness in patients, Phase 3 expands trials to gather more safety/efficacy data, and Phase 4 studies occur after approval to further monitor safety. The FDA approval process begins with an Investigational New Drug application to begin human testing, followed by a New Drug Application providing all trial results. If approved, post-marketing surveillance further monitors the drug's safety after market entry. On average, only 20% of initially studied drugs are ultimately approved by the FDA.

1. Clinical Trials

2. Clinical Trial
New Drug Development Timeline
Source: FDA/Center for Drug Evaluation and Research
www.fda.gov/Drugs/DevelopmentApprovalProcess/SmallBusinessAssistance/ucm053131.htm

3. Clinical Trials
Research and Development
R&D involves initial synthesis and analysis of a
promising pharmaceutical OR development and
analysis of a biopharmaceutical produced in living
cells.
On upcoming slides, the word “drug” applies both to
pharmaceuticals and to biopharmaceuticals.

4. Clinical Trials
Investigational New Drug
Application
The application to the FDA to request permission
to begin human testing is called an Investigational
New Drug application or IND.
The IND permits the use of an investigational new
drug for the sole purpose of conducting clinical
trials.

5. Clinical Trials
Phase 1
Drug is tested for its interaction with
the human system.
 How is the drug absorbed
 How is the drug distributed in the body
 How is the drug metabolized by the body
Trials usually involve normal, healthy
volunteers and take about a year to
complete.

6. Clinical Trials
Phase 2
Pilot student to begin to define
the effectiveness and safety of
the drug in patients with the
disease or condition to be
treated, diagnosed or prevented.
Testing the various doses of the drug and dosing regimens

7. Clinical Trials
Phase 3
Expanded clinical trials
Designed to …
Gather additional evidence of
effectiveness for specific interactions
Better understand safety and drug-related
adverse effects

8. Clinical Trials
Phase 4
Studies that occur after a drug has received
approval from the U.S. Food and Drug
Administration to be marketed
 Performed to determine the incidence of
adverse reactions
Determine the long-term effect of the drug
 To study a patient population not previously
studied
 For marketing comparisons against other
products and users

9. Clinical Trials
Testing in Humans
For example, of 100 drugs for which investigational new drug applications are submitted to the FDA, about 70 percent will clear Phase 1 and go on to Phase 2. About 33
of the original 100 drugs will clear Phase 2 and go on to Phase 3. About 25 to 30 of the original 100 drugs will clear Phase 3 and go on to Phase 4. Finally, on average, 20
of the original 100 drugs ultimately will be approved for marketing. www.centerwatch.com/clinical-trials/overview.aspx

10. Clinical Trials
New Drug Application (NDA)
Submitted to the FDA if Phase 1, 2 and 3 trials indicate
the drug is safe and effective
Comprehensive statement with information about the
drug’s chemical structure, scientific rationale and
purpose of the drug therapy, preclinical and other
laboratory results, all human clinical testing data, drug
formulation and production details, and proposed
labeling
1000s of pages…which are submitted electronically.

11. Clinical Trials
New Drug Application (NDA)
 FDA has 60 to conduct a preliminary review and decide if it has
enough information to proceed with the NDA review
 FDA required to make a decision within 180 days of the date the
NDA is submitted
 FDA and company can create a mutual agreement to lengthen the
time frame
 NDA decision-making process can take anywhere from 2 months
to 7 years — the average time is 2 years
May require minor or major changes of the NDA or additional
clinical studies and may inspect the production, testing and
packaging facilities to ensure they are compliant with regulations

12. Clinical Trials
Post-marketing surveillance
Monitor the ongoing safety of marketed drugs by
reassessing drug risk based on …
New data collected after the drug is marketed
By recommending ways of trying to most
appropriately manage that risk
 Includes adverse reaction reporting by the medical
community of the pharmaceutical company that
markets the drugs
 Periodic sampling and testing of the drug
 Periodic inspections of the manufacturing and
distribution process