Drug Development process

By Snigdhadeb Dey Tamara Ray Supervisor : Dr Karabee Chatterjee Apollo Gleneagles, Kolkata

Drugs
Broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. In pharmacology, a drug is "a chemical substance used in the treatment, cure, prevention, or diagnosis of disease or used to otherwise enhance physical or mental well-being. Drugs may be prescribed for a limited duration, or on a regular basis for chronic disorders.

Drug Development In a nutshell

Human Clinical Trials
Pre-Clinical Animal Testing

Approval Process

Drug Discovery

Post Marketing Surveillance

Drug Discovery
Program selectionIdentification of the problem-disease

A single continuous layer of flat-to-cubodial mesothelial cells covering the ovary is considered to be the tissue of origin of EOCs (Epithelial Ovarian cancer)

OSE

EOC

LEAD
Lead is a compound which from a series of compounds have some desirable biological activity First foothold of the drug Compound library- collection of compounds, variety or diversity of the compounds will vary

Discovery- Lead,Compound Library, Combichem

Gly Lead optimization
Ser Tyr (His)
Leu (Trp)

Arg (Tyr)

Compound library

Trp

Pro

His

GlyNH

Combichem
pGlu

Preclinical Testing

In-vitro cell studies Cell migration assays

In-vivo drug validation studies

depending on the design, technology, and performance of your device, we may recommend additional pre-clinical evaluation.

A. Test Protocols
We recommend the test protocol describe clearly defined test objectives and a rationale in support of your belief that the endpoints and pass/fail criteria are meaningful and clinically relevant.

B. Test Methods and Conditions

We recommend you provide a clear description of the test methodology and actual test conditions. We recommend you conduct pre-clinical testing, where appropriate and feasible, in an environment that simulates actual clinical conditions.

C. Actual Device Evaluated

We recommend you indicate whether you used a neurothrombectomy device fabricated by representative manufacturing process. Otherwise, we recommend you submit a rationale explaining your belief that the device you used in testing will provide a sufficient assessment of the final finished device.

D. Statistical Analysis
We recommend you provide your sample size justification. We recommend the results you report include, where appropriate: number of samples range of values mean

standard deviation 95% confidence interval. We also recommend you provide a probability measure that is indicative of the statistical significance of any comparisons you make to other devices or control groups.

IND
CDER offers a Pre-Investigational New Drug Application (IND) Consultation Program6 to foster early communications between sponsors and new drug review divisions in order to provide guidance on the data necessary to warrant IND submission. Animal pharmacology, toxicology studies Evidences of previous exposure/use on human Manufacturing details Clinical protocol and investigator information

Lets the FDA understand the level of initial exposure

Must be updated on annual basis

Amendments can be filed anytime Sites can be contacted, timelines may become an issue

Human Clinical Trials

P
PhaseI Human/Clinical Pharmacology Immunogenic Potency MTD

Phase II Explanatory Trials efficacy and safety. Phase III Confirmatory trials Phase IV Post Marketing Trials

Healthy volunteers(15-30) using clinical, physiological and biochemical observations. At least 2 subjects should be used on each dose. MTD,Pharmaodynamics, pharmacokinetics, adverse reactions of the Study drug

Patient pool = homogenous population selected by ( < 100,relatively narrow criteria)

Determination of dosage for stage III and regimen

Wider patient pool is recruited(100-1000), generally in comparison with a standard drug and/or a placebo as appropriate Compare treatment with the std(ethnic and socioeconomic groups comes under the drug trial) Further studies with the drug-dosage relationship.Extended drug exposure studies conducted as well. These data completes the prescribing information

Study end points , therapeutic regimens (including concomittant medications)

Examining subsets of data, multiple end points included

Cytotoxic drugs are studied in patients

Investigators requires specialized facilities for the conduction of the trials

Marketing Approval Product License

Regulatory Organization

FDA

DCGI ICMR

MHRA

Filing the NDA (New Drug Application) Initiation and conduction of Phase IIIB and IV trials

Purpose of phase IIIB trials- gathering additional safety data, additional indication of the study drug, assess its use in geriatric and pediatric patients

Phase IV
Studies performed after drug approval, especially on the basis of the product characteristics on which the marketing authorization was granted

Goes beyond prior demonstration of drugs safety, efficacy and dose determination,sometimes used for getting the physician get familiar with the medicine

Conduction of this depends on the discretion of the licensing authority (optimizing the drug) Additional drug-drug interaction studies, dose response or safety studies, approved studies such as mortality/morbidity studies, epidemiological studies

NDA

Approval Guidelines
MHRI/DCGI/FDA
Product is of adequate quality for its intended use, it is sufficiently safe and effective. Preferred for new marketing authorization (MA) applications is the electronic Common Technical Dossier (eCTD). Summary of Product Characteristics (SmPC) will need to be prepared using the Word template. Validation-completeness and appropriate signatures. full toxicological, pharmacological and clinical data would be expected.

Professional assessmentAssessorsAdvisory bodiesRenewals and variations to licenses

Post Marketing Drug Surveillance

Closemonitoringforclinicalsafety(PSUR) PSUR==RRSI Coveronly intervaldata Onein6months ,lateroneinayear SUARmustbereportedasapwithin15daysofinitialreporting Newsafetystudiesinformation describedinPSUR

Structured PSUR
Title page Introduction Current world wide marketing status Update of actions taken for the safety information Estimated patient exposure Presentation of individual case histories Studies Over all safety evaluation Conclusion Appendix providing documents pertaining to indications, dosing, pharmacology and other related documents

Conclusion

References