Drug Review Steps

• 1. Preclinical (animal) testing.

• 2. An investigational new drug application (IND) : outlines what the sponsor of

a new drug proposes for human testing in clinical trials.

3. Phase I- Assess the safety of a drug or device

4. Phase II- Test the efficacy of a drug

5. Phase III- Final confirmation of safety, efficacy and effectiveness.

• 6. Submission of New Drug Application (NDA) is the formal step asking the

FDA to consider a drug for marketing approval.

• 7. FDA reviewers will approve the application or find it either "approvable" or

"not approvable.“

8. Phase IV- often called Post marketing Surveillance Trials.

Phase III

Phase III is a Therapeutic confirmatory trials done in Large scale, multicentre,

Randomised, Controlled trials.

Patients: 300 to 3,000 volunteers who have the disease or condition.

Length of Study: 1 to 4 years.

Purpose: Final confirmation of safety, efficacy and effectiveness.

Only 18% Phase II clinical trials make it Phase III Clinical trial.

Approximately 25-30% of drugs move to the next phase (Phase IV).

Objectives:

To assess overall and relative therapeutic value of the new drug Efficacy,

Safety and Special Properties

• To determine optimal dosage schedule for use in general

• The dosage schedule in C.T.’s should be as close as possible to its

anticipated clinical use.

Prerequisites :

• Efficacy and dose schedule defined in Phase II studies

• No gross ADR’s

• Long term preclinical safety studies completed

• Chronic Toxicity

• Reproductive toxicity

• Carcinogenicity

• Marketing inputs favourable

• IRB and DCGI approval obtained.

Phase III Subtypes:

• Phase IIIA:

To get sufficient and significant data.

• Phase IIIB:

It allows patients to continue the treatment, Label expansion, additional safety

data.

Phase III B studies are known as "label expansion” to show the drug works

for additional types of patients/diseases beyond the original use for which the

drug was approved for marketing

• Phase IIIA:

• Prior to NDA

Generates data on safety and efficacy

• Phase IIIB :

After the NDA but prior to the approval and launch.

These may supplement or complete the earlier trials or may be directed to

Phase IV trials.

Researchers design Phase 3 studies to demonstrate whether or not a product offers

a treatment benefit to a specific population. Sometimes known as pivotal studies,

these studies involve 300 to 3,000 participants.

Phase 3 studies provide most of the safety data.

In previous studies, it is possible that less common side effects might have gone

undetected. Because these studies are larger and longer in duration, the results

are more likely to show long-term or rare side effects

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

Phase III studies involve randomized and blind testing in several hundred to

several thousand patients.

This large-scale testing, which can last several years, provides the

pharmaceutical company and the FDA with a more thorough understanding of

the effectiveness of the drug or device, the benefits and the range of possible

adverse reactions.

Once Phase III is complete, a pharmaceutical company can request FDA

approval for marketing the drug.

Phase III trials are the most expensive, time-consuming and difficult trials to

design and run, especially in therapies for chronic medical conditions.

This is sometimes called the "pre-marketing phase" because it actually measures

consumer response to the drug.

It is common practice that certain Phase III trials will continue while the regulatory

submission is pending at the appropriate regulatory agency.

This allows patients to continue to receive possibly lifesaving drugs until the drug

can be obtained by purchase.

Other reasons for performing trials at this stage include attempts by the sponsor at

"label expansion" (to show the drug works for additional types of patients/diseases

beyond the original use for which the drug was approved for marketing), to obtain

additional safety data, or to support marketing claims for the drug.

Phase III trials of chronic conditions or diseases often have a short follow-up

period for evaluation, relative to the period of time the intervention might be

used in practice

Most drugs undergoing Phase III clinical trials can be marketed under FDA norms

with proper recommendations and guidelines through a New Drug

Application (NDA) containing all manufacturing, pre-clinical, and clinical data. In

case of any adverse effects being reported anywhere, the drugs need to be recalled

immediately from the market.

Once a drug has proved satisfactory after Phase III trials, the trial results are

usually combined into a large document containing a comprehensive description

of the methods and results of human and animal studies, manufacturing

procedures, formulation details, and shelf life. This collection of information

makes up the "regulatory submission" that is provided for review to the

appropriate regulatory authorities in different countries. They will review the

submission, and, it is hoped, give the sponsor approval to market the drug.

Studies in this phase are by some companies categorized as "Phase IIIB studies.

Success rate:As of 2010, about 50% of drug candidates either fail during the Phase III trial or are

rejected by the national regulatory agency.

Phase II/III Spend:

The amount of money spent on Phase II/III trials in 2015 by Large Sponsors (R&D

$500M+) was $465,725,000 on average, while Non-Large Sponsors (R&D <$500M)

spent $13,352,000 on average.

Phase IV begins Phase III Studies :

End of Clinical Trial Activities Sponsor:

Expert Committee review of Efficacy, safety and potential sales (Profit).

• Go-No Go decision to file new drug application with DCGI

• Expert review by DCGI’s Committee

• DCGI approval

• NCE marketed