nwe drug development and fda

8/3/2019 Nwe Drug Development and FDA

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New Drug Developmentand

Approval Process


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NEW DRUG DEVELOPMENT PROCESSNEW CHEMICAL ENTITY

SOURCES:

Organic Synthesis

Molecular Modification

Isolation from plants

Genetic Engineering


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PRECLINICAL STUDIESIncluding

Chemistry

Physical Properties

Biological

Pharmacology

ADME

Toxicology

Preformulation


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CLINICAL TRIALS Phase I Phase II Phase III

PRECLINICAL STUDIES (Continued) long term animal toxicity

product formulation Manufacturing and controls Package and label design


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Methods of Drug Discovery

Although some drugs may be the

result of fortuitous discovery, mostof drugs are the result of carefullydesigned research programs of

screening, molecular modification,and mechanism-based drug design


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1. Random or untargeted screening

involves the testing of large numbers ofsynthetic organic compounds orsubstances of natural origin for biologicactivity

Purposes:to detect an unknown activity of the test

compound or substance

to identify the most promising compounds tobe studied by more sophisticatednonrandom or targeted screens todetermine a specific activity


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2. Molecular modification

- is chemical alteration of a known

and previously characterizedorganic compound (frequently a

lead compound) for the purpose of

enhancing its useful as a drug


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PURPOSES:1. Enhance its specificity for a particular body

target site

2. Increasing its potency

3. Improving its rate and extent of absorption

4. Modifying the advantage its time-course in thebody

5. Reducing its toxicity

6. Changing its physical and chemical properties


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3. Mechanism-based drug design

- is a molecular modification to design adrug that interferes specifically withthe known or suspected biochemicalpathway or mechanism of a diseaseprocess


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PURPOSE:The intention is the interaction of the drugwith specific cell receptors, enzymessystems, or metabolic process of pathogensor tumor cells, resulting in blocking,disruption, or reversal of the diseaseprocess


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Example of Mechanism-based drug

design

1.Enalaprilat -Vasotec - inhibits theangiotensin-coverting enzymes thatcatalyzes the conversion of AI to thevasoconstrictor substance AII. Inhibition ofthe enzymes results decreased plasma AII,

leading to decrease vasopressor effectsand lower blood pressure


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2. Ranitidine - Zantac - an inhibitor ofhistamine at the histamine H2-receptors, including receptors on thegastric cells. Used to treat gastric

ulcers

3. Sertraline - Zoloft - which inhibits

the central nervous systemsneuronal uptake of serotonin,making the drug useful in the

treatment of depression.


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Lead compound

-is a prototype chemical

compound which has afundamental desiredbiologic or pharmacologic

activity.


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Example of Lead Compound

1. Cephalosporin antibiotics - additionalH2 antagonists from the pioneer drug

Cimetidine

2. Large series of antianxiety drugs

derived from Benzodiazepine structureand the innovator drug chlordiazepine-Librium.


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3. Most drugs exhibit activities

secondary to their primarypharmacologic action.

Example: Finasteride-Proscarwas originally developed andapproved to treat benign prostatic

hyperplasia. Later, the same drug -Propeciawas approved at lowerrecommended dosage to treat malepattern baldness


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Prodrugs

-is a term used to described a

compound that requiresmetabolic biotransformationfollowing administration to yield

the desired pharmacologicallyactive compound.


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Example of Prodrug

Enapril maleate Vasotec-which, after oral administration, bioactivated

by hydrolysis to enaprilat, an ACE inhibitorused in the treatment of hypertension

Prodrug may be design preferentially for

solubility, absorption, biostability andprolonged release


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Solubility- Enabling the use of specifically

desired dosage forms and routes of

administration

Absorption- A drug may be made more water or

lipid soluble, as desired, to facilitateabsorption via the intended route ofadministration


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Biostability

- An active drug is prematurelydestroyed by biochemical or enzymaticprocess, the design of a prodrug may

protect the drug during its transport inthe body

Prolonged Release

- Depending on a prodrugs rate ofmetabolic conversion to active drug, itmay provide prolonged release and

extended therapeutic activity


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NEW DRUG - is any that is not recognizedas being safe and effective in the conditionsrecommended for its use among expertswho are qualified by scientific training andexperience.

A combination of two or more old drugs or a

change in the usual proportions of drugs in anestablished combination product is considerednew if the change introduces a question ofsafety or efficacy.

FDAs Definition of a New Drug


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- A new dosage schedule or regimen, a new

rout of administration, new dosage form allcause a drug or drug products status to new

and triggers reconsideration for safety andefficacy

- A drug need not be a new chemical entity tobe considered new. A change in a previouslyapproved drug products formulation or method

of manufacture constitutes newness under

the law, since such changes can alter thetherapeutic efficacy and/or safety of a product.


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NOMENCLATURE OR NAMING OF

DRUGThe task of designating appropriatenon-proprietary names for newly found

chemical agents rests primarily with theUSANCouncil.

The official name for a drug is referredto as the drug nonproprietary orpublic name


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in contrast to the proprietary or brand

names or trademark names given bythe specific manufacturers ordistributors of the drug.

The term generic name, has beenused extensively in referring to thenonproprietary names

of the drugs.Brand nameis registered as atrademark with the United StatesPatent Office


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CATEGORY OR USE

In general, drugs exert their effects by

one of three means:

1. By exerting a physical action suchas the protective effects of

ointments and lotions upontopical application


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2. By reacting chemically outsidethe body cells.

Example: antacids counteractexcess acidity in the stomach or

antibiotics to act against invading

pathogenic microorganism.


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3. By modifying the metabolicactivity of the bodys cell.

Majority of the drugs belong

to the 3rd manner wherebrain, liver, kidney, etc. areaffected


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Proposals for NonproprietaryNames

1. Be short and distinctive insound and spelling and notbe such that it is easily

confused with existingnames


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2.Indicate the general pharmacologic

or therapeutic class into which thesubstance falls or the generalchemical nature of the substance if

the latter is associated with thespecific pharmacologic activity

3. Embody the syllable or syllablescharacteristic of a related group ofcompounds


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Pharmacology

pharmaco= drugs;

logos = study of; is thescience concerned withdrugs, their sources,

appearance, chemistry,actions, and uses.


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The term can be expanded toinclude

1. Properties2. Biological and physiologic

effects

3. Mechanism of actions4. ADME


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Pharmacodynamics = the study

of the biochemical and physiologiceffects of drugs and their mechanism

of action

Pharmacokinetics = ADME

Clinical Pharmacology = appliespharmacologic principles to the studyof the effects and actions of drugs in

humans


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Pharmacologic profile = In vitro

cultures of cells and enzymes systemsand in vivo animal models are used todefine a chemicals pharmacologic

profile

= Most animal testing is done on

small animals, usually rodents (mouse,rats) for a number of reasons includingcost, availability, the small amount ofdrug required for a study,


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the ease of administration by

various routes (oral, inhalation,intravenous) and experience withdrug testing in these species

Animal models: dog or rat -for hypertension; dog and guinea

pig - for respiratory effects; dog-for diuretic activity; rabbit - forblood coagulation; mouse andrats - for CNS studies


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Drug Metabolism

1. The extent and rate of drugabsorption from various routes of

administration, including the oneintended for human use

2. The rate of distribution of thedrug through the body and the site orsites and duration of the drugs

residence


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3.The rate, primary and secondarysites, and mechanism of the

drugs metabolism in the body

and the chemistry andpharmacology of any metabolites

4. The proportion of administered

dose eliminated from the bodyand its rate and route ofelimination


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Toxicology

Deals with the adverse orundesired effects of drugs

Not all side effects of newdrugs to be tested in animals will be

detected but the greater the

likelihood the effect will also beseen in humans

Example: headache


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Purpose of Safety Evaluation and

Toxicity Studies

1.The substances potential for toxicitywith short-term (acute effects) or

long- term use (chronic effects)

2.The substances potential for

specific organ toxicity3.The mode, site, and degree of

toxicity


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4.Dose-response relationships forlow, high, and intermediate

doses over a specified time

5.Gender, reproductive, orteratogenic toxicities

6. The substances carcinogenic

and genotoxic potential


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Acute or Short-Term Toxicity

Studies

These studies are designed

to determine the toxic effects of atest compound when administered

in a single dose and/or in multiple

dose doses over a short period,usually a single day.


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Animals are observed: eating anddrinking habits; weight changes; toxic

effects; psychomotor changes; fecesand urine are collected.

Animal death: recorded; study on

histology; pathology and statistically

evaluated on the basis of doseresponse


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Subacute or Subchronic Studies

Animal toxicity studies of aminimum of 2 weeks of daily drug

administration at three or moredosage levels to two animal species

are required to support the initial ad

ministration of a single dose inhuman clinical testing.


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Chronic toxicity studies

The initial human dose is

usually one-tenth of the highest

nontoxic dose (in milligrams perkilogram of subjects weight) shownduring the animal studies. For drugs

intended to be given to humans for a

week or more, animal studies of 90to 180 days must demonstrate

safety.


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If the drug is to be used for a chronichuman illness, animal studies 1 year orlonger must be undertaken to supporthuman use.

Compare the strain, sex, age, doselevels and ranges, routes ofadministration, duration of treatment,

observed effects, mortality, body weightchanges, food and water consumption,


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physical examination(electrocardiography, ophthalmic,examination), hematology, clinical

chemistry, organ weights, grosspathology, neoplastic pathology,histopathology, urinalysis, ADME

data


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Carcinogenicity Studies

Usually component of chronic testingand is undertaken when compound hasshown sufficient promise as a drug to enter

human clinical trials.Carcinogenicity studies are long term

(18-24 months), with surviving animals killedand studied at defined weeks during the testperiod


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Data on the causes of animaldeath, tumor incidence, type and

site, and necropsy findings are

collected and evaluated

Preneoplastic lesions and/or

tissue-specific proliferationeffects are important findings


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Reproduction Studies

Reproduction studies areundertaken to reveal any effect of an

active ingredient on mammalian

reproduction

Included in these studies are

fertility and mating behavior; earlyembryonic, prenatal, and postnatal

development, multigenerational

effects, teratology


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In these studies, the maternalparent, fetus, neonates, and

weaning offspring are evaluated for

anatomic abnormalities, growth, anddevelopment. The animal used in

other toxicity studies in reproductive

studies, usually the rats.


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In embryotoxicity studiesonly, a second mammalian species

traditionally has been required. The

rabbit is the preferred choice forpractically and the extensivebackground knowledge

accumulated on this species.


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Genotoxicity or Mutagenicity

Studies

Performed to determine whether

the test compound can affect genemutation or cause chromosome orDNA damage. Strains Salmonella

typhimurium are routinely used inassays to detect mutations.


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Early Formulation Studies

- As a promising compound ischaracterized for biological activity, it is

also evaluated with regard to chemicaland physical properties that havebearing on its ultimate and successful

formulation into stable and effectivepharmaceutical product


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- This is the area of responsibilityof pharmaceutical scientists and

formulation pharmacists trainedin pharmaceutics


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Preformulation Studies

- Each drug substance has intrinsicchemical and physical characteristic that

must be considered before thedevelopment of a pharmaceuticalformulation

-Among these are the drugs solubility,partition coefficient, dissolution rate,physical form, and stability


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Drug Solubility

- A drug substance administered by anyroute must posses some aqueoussolubility for systemic absorption and

therapeutic response- Poorly soluble compounds (exampleless than 10mg per ml aqueous

solubility) may exhibit incomplete,erratic, and or slow absorption and thusproduce a minimal response at desired

dosage


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Partition Coefficient

-A drug partition coefficient is a measureof its distribution in a lipophilic-hydrophilic phase system and indicates

its ability to penetrate biologicmultiphase system

Dissolution Rate

- Is the speed at which a drug substancedissolves in a medium


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Physical Form

-The crystal or amorphous forms and or theparticle size of a powdered drug can affectthe dissolution rate, thus the rate and extentof absorption, for a number of drugs

Stability

- The chemical and physical stability of a

drug substance alone, and when combinedwith formulation components, is a critical topreparing a successful pharmaceuticalproduct


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Initial Product Formulation and

Clinical Trial Materials

- Prepared for Phase 1 and Phase 2

for clinical trials

- Phase 1 studies, for orallyadministered drugs, capsules areemployed containing the activeingredient alone, withoutpharmaceutical excipients


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-Phase 2, the final dosage form is selected and

developed for Phase 3 trials, this is the formulationthat is submitted to the FDA for marketing approval

Clinical Supplies or Clinical Trial

Materials

- Comprise all dosage formulations used in theclinical evaluation of a new drug

- This includes the proposed new drug, placebos(inert substances for controlled studies) and drugproducts against which the new drug is to becompared (compactor drugs or drug products)


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Blinded Studies

-Are controlled studies in which at leastone of the parties (example, patient,

physician) does not know whichproduct is being administered

= Some studies are open label, inwhich case all parties may know whatproducts are administered


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In all clinical study programs, the packagelabel of the investigational drug must bearthe statement Caution: new drug limitedby federal ( or United States) law toinvestigational use

- Blister packagingis commonly used inclinical studies, with intermediate labelscontaining the clinical study or protocol number,patient identification number, sponsor number,directions for use, code number to distinguishbetween investigational drug, placebo, and orcompactor product, and other relevantinformation


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NEW DRUG APPLICATION (NDA)

Submission

FDA Review

Pre-approval Plant inspection

FDA action


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INDApplication for permission to administer a

new drug to humans

Outlines the proposal to use the newdrug for human testing in clinical trials

Studies in humans can only begin after

IND is reviewed and approved by the

FDA and an institutional review board

(IRB)


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INVESTIGATIONAL NEW DRUG

1.Full description of new drug

2.Where and how it is manufactured

2.All quality control information andstandards

4.Stability


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5. Analytical method

6. Pharmacology

7. Toxicology

8. Efficacy in animals

9. Persons who will do the clinicalstudies


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Clinical drug evaluation & Authorization

Investigational new drug (IND) submission

-the rationale for the drug and

patient group to be treated-all pre clinical safety and efficacy data

-detailed plan for clinical development

-CIB( clinical investigators brochure)

Submitted to FDA for review and permission toproceed.


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Ethics

Declaration of Helsinki-1964

The clinical trial must minimize the riskfor participants

Provision for care of the patients

Terminate the trial when the risk

becomes incompatible with the goals ofthe trial

Adverse events to be reportedimmediately to an ethical committee


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Ethics Committees

The ethics committee reviews a protocol beforethe study is allowed to start. Their job is toensure that the risks of being in the study are

not greater than the potential benefit.


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IRB( Institutional Review Board)IEC (Independent Ethical Committee)

To ensure the rights and welfare of theparticipants

FDA regulations mandates to review theclinical trial protocols for ethical and legal

issues

Also has the authority to approve, modify ordisapprove it


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Informed Consent

Participation in clinical trials is alwaysvoluntary.

No, thank you, Idrather not participate.

Yes, I wouldlike to

participate.


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Clinical Trials & Research 70

Informed Consent

Purpose

Medicine to be

studied Procedures and

schedule

Risks

Potential benefits

Alternatives toparticipation

Confidentiality

Wh t i Cli i l T i l?


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What is a Clinical Trial?

Identify a health question.

Develop a plan.

Enroll volunteers and follow the plan.

Study the information collected.

Share the results with others.

Improve treatment.


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Clinical trials have a long history even if not

acknowledged as Clinical trials

Formal record of clinical trials dates back to the

time of the Trialists:

Dr. Van Helmonts proposal for a therapeutic trial of

bloodletting for fevers [1628]

Dr. Linds, a ship surgeon, trial of oranges & limes for

scurvy [1747]

NY/VI AETC


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Review of scientific background

Written hypothesis/hypotheses to betested

Study design-type-study population

-statistical analysis-enrollment of subjects-intervention-follow up of subjects

Organization

PROTOCOL


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Phase 0


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Phase 0

Recent designation as per FDA-2006 guidelines

First in humans

100th of the pharmacological dose

Early PK and PD data

Minimal pre clinical study

Adv : unreliable in vitro and animal study

Disadv : safety/efficacy


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Phase 1

Participants (fewer than 100 healthy people)

Dose

Determines safety of the drug

Involve dose ranging studies to determine toxicity

and major adverse effects

May provide early evidence of efficacy

End point- toxicity


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Phase 2

Evaluate efficacy and therapeutic benefit

Involve 80-100 Patients

Identify common short term side effects

Establish dosing regimen and dose

optimization

Validate the design of phase 3

Duration : 1-2year


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Phase 2A

Pilot study

Dose defining and dose form

Safety and efficacy

PK/PD data

Risk benefit ratio


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Phase 2B

Controlled pivotal study

Placebo Double blind

Safety and efficacy

Phase 3


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Phase 3

Large multi-center Randomized study

Involve 1000-3000 patient volunteers

Placebo controlled blind studies to clearly demonstrateefficacy, safety and therapeutic benefit

Package insertion and labeling

Adverse drug reactions

Duration: 2-3 years


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No fixed time and population

The purpose is usually to support the marketingcampaign

Rare ADRs

Drug interaction

New clinical indication (Phase 5)


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The Impact of Clinical Trials-

Successful Some clinical trials have been critical to patient

health & provision of health care

For instance:

o Protocol 076: HIV perinatal transmission

1st trial of AZT

o Various cancer treatmentso Development of other HIV related medications like

PIs


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The Impact of Clinical Trials-Unsuccessful

Medications did not work as in pre clinicalstudy

Loss of Follow-Up

Harmful substance

Unethical & poorly conducted study (Ex:Gene Replacement Study)


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APPROVAL

Once all clinical data has been submitted,reviewed and approval is granted to license inmarket

Post marketing surveillance

Approval takes 6 months to 2 years


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POST MARKETING TRIALS

Phase IV Clinical Trials

clinical pharmacology/Toxicology

additional indications

Adverse Reaction Reporting

Product Defect Reposting

Product Line Extension


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Content of the IND

The content of an IND is prescribed inthe Code of Federal Regulations and issubmitted under a cover sheet (Form FDA-

1571):

Name, address, and telephone number ofthe sponsor of the drug

Name and title of the person responsiblefor monitoring the conduct and progress ofthe investigation


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Names and titles of the persons

responsible for the review and evaluationof information relevant to the safety of thedrug

Name and address of any contractresearch organization involved in thestudy

Identification of the phase or phases ofthe clinical investigation to be conducted


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Introductory statement and general

investigational plan

Description of the investigational plan

Brief summary of previous humanexperience with the drug (domestic orforeign)

Chemistry, manufacturing, controlinformation

Pharmacology and toxicology information


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If the new drug is a combination ofpreviously investigated components, acomplete preclinical summary of thesecomponents when administered singly andany data or expectations relating to the

effect when combined

Clinical protocol for each planned study

Commitment that an Institutional ReviewBoard has approved the clinical study andwill continue to review and monitor theinvestigation


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Investigator brochure

Commitment not to begin clinicalinvestigations until the IND is in effect,the signature of the sponsor orauthorized representative, and thedate of the signed application


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Clinical Protocol

As a part of IND application, clinicalprotocol must be submitted to ensure theappropriate design and conduct of the

investigationClinical Protocol include:

Statement of the purpose and

objectives of the study Outline of the investigational plan andstudy design


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Estimate of the number of patients to be

involved

Basis for subject selection, with inclusionand exclusion criteria

Description of the dosing plan, includingdose levels, route of administration, andduration of patient exposure

Description of the patient observations,measurements, and tests to be used


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Clinical procedures, laboratory tests,

and monitoring to be used inminimizing patient risk

Names, addresses, and credentials ofthe principal investigators and coinvestigators

Locations and descriptions of theclinical research facilities to be used


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FDA Review of an IND

Application

To protect the safety and

rights of the human subjects andto help ensure that the study

allows the evaluation of the drugs

safety and effectiveness.


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FDA Drug Classification System

By Chemical Type

Type 1 New Molecular entity, not

marketed in USType 2 New ester, new salt, or otherderivative of an approved active moiety

Type 3 New formulation of a drugmarketed in US


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Type 4 New combination of two ormore compounds

Type 5 New manufacturer of a drugmarketed in US

Type 6 New therapeutic indication

for an approved drug


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By Therapeutic Classification

Type P Priority review, a

therapeutic gain

Type S Standard review, similar to

other approved drugs


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Additional Classification

Type AA For treatment of AIDS

or HIV-related disease

Type E For life-threatening orseverely debilitating disease

Type F Review deferred pendingdata validation


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Type G Data validated,removal of F rating

Type N Nonprescription drug

Type V Drug having orphandrug status


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Drug Dosage and Terminology

The safe and effective dose of a drugdepends on different FACTOR:

1.Characteristics of the drug substance

2.The dosage form and its route ofadministration

3.Variety patient factors - age, bodyweight, general health status, pathologicconditions

4. Concomitant drug therapy


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Usual adult dose - the amount ofdrug that will produce the desired effectin most adult patients.

Usual Dosage range - indicatesthe quantitative range or amounts of thedrug that may be prescribed safely

within the framework of usual medicalpractice.


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Underdosage / Overdosage -

doses falling outside of the usual range

Usual Pediatric dose - doseusually given to children

Schedule of dosage or Dosageregimen - determined during the clinicalinvestigation and is based largely on a

drugs inherent duration of action, itspharmacokinetics, and characteristics ofthe dosage form


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MEC Minimum Effective

Concentration -An average blood serumconcentration represents the minimumconcentration that can be expected toproduce the drugs desired effects in a

patient

MTC Minimum toxic

Concentration - The second level ofserum concentration of drugs expected toproduce dose-related toxic effects in the

average individual


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MED Median Effective Doseof adrug is the amount that will produce

the desired intensity of effect in 50%of the individuals tested.


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MTD Median Toxic Dose - is the

amount that will produce a defined toxiceffect in 50% of the individuals tested

The relationship between thedesired and undesired effects of a drugis commonly expressed as theTherapeutic index and is defined asthe ratio between a drugs median toxic

dose and its median effective dose,TD50/ED50.


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Some factors of patients considered indetermining a drugs dose in clinical

investigations and in medical practice includethe following:

Age

Body Weight

Body Surface Area

Sex Pathologic State

Tolerance

Therapeutic and Toxic Blood Level Concentrations of Some Drugs

Drug Substances concentration, mg/L DrugS b t Th ti T i L th l


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Substance Therapeutic Toxic Lethal

Acetaminophen 10-20 400 1500

Amitriptyline 0.5-.20 0.4 10-20

Barbiturate

Short Acting 1 7 10Intermediate 1-5 10-30 30Long Acting ~10 40-60 80-100

Dextropropoxyphene 0.05-0.2 5-10 57

Diazepam 0.5-2.5 5-20 :50

Digoxin 0.0006-0.0013 0.002-0.009 --

Imipramine 0.05-0.16 0.7 2

Lidocaine 1.2-5.0 6 --

Lithium 4.2-8.3 13.9 13.9-34.7

Meperidine 0.6-0.65 5 30

Morphine 0.1 -- 0.05-4

Phenytoin 5-22 50 100

Quinidine 3-6 10 30-50

Theophylline 20-100 -- --


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Therapeutic Indices For Various Drug Substances

Less Than 5 Between 5 and 10 Greater Than 10

Amitriptyline Barbiturates Acetaminophen

Chlordiazepoxide Diazepam Bromide

Diphenhydramine Digoxin Chloral hydrate

Ethchlorvynol Imipramine Glutethimide

Lidocaine Meperidine Meprobamate

Methadone Paraldehyde Nortriptyline

Procainamide Primidone Pentazocine

Quinidine Thioridazine Propoxyphene

Routes Of Drug Administration


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TERM SITE

oral mouth

peroral (per os, p.o.)gastrointestinal tract via mouth

sublingual under the tongue

parenteral other than GIT (by injection)

intravenous veinintraarterial artery


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intracardiac heartintraspinal/intrathecal spineintraosseous bone

intraarticular jointintrasynovial joint-fluid areaintracutaneous/intradermal skinsubcutaneous beneath the skin

intramuscular muscle

TERM SITE


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TERM SITE

epicutaneous (topical) skin surface

transdermal skin surface

conjunctival conjunctiva


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intraocular eyeintranasal noseaural ear

intrarespiratory lungrectal rectumvaginal vagina

urethral urethra

TERM SITE


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Drug Product Labeling (Package

Inserts)

1. Description of the product

2. Clinical Pharmacology

3. Indications and usage

4. Contraindications

5. Warnings


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6.Precautions

7.Adverse reactions

8.Drug abuse and Dependence

9.Over dosage

10.Dosage and Administration

11. How supplied


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Some products, however, have

been approved and later removedfrom the market for safety reasons,

including the following:

Grepafloxacin HCL (Raxar)

Brofenac sodium (Duract)

Cisapride (Propulsid) Alosetron HCL (Lotrovec) Fenfluramine HCL (Pondimin)


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Dexfenfluramine HCL (Redux) Terfenadine (Seldane) Cerivastatin (Baycol) Mibefradil (Posicor) Astemizole (Hismanal)

Troglitazone (Rezulin)

Preclinical Clinical NDA Review Post Marketing Research andResearch and Development Surveillance Development

Initial synthesis Adverse


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and reactioncharacterization Phase 1

Phase 2 Surveys/sampling

testing

Phase 3

Animal testing

Short term

Long term Inspection

Average 61/2 Average 7 years Average 1 1/2years years

FDA 30-day safety review NDA submitted NDA approval

Average of approx. 15 years from initial synthesis to approval of NDA


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Drug Discovery and Drug Design

- R and D activities on new Rx drugs for human

- OTC drugs, generic drugs, biotechnologyproducts, animal health care drugs,

diagnostic products, and medical devices

- development of new agents, such asvaccines to protect against poliomyelitis,measles, and influenza


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New pharmacologic categories of drugs including oral

hypoglycemic drugs effective against certain types ofdiabetes mellitus

- Antineoplastic or anticancer drugs,

- Immunosuppressive agents to assist thebodys acceptance of organ

transplant- Contraceptives to prevent pregnancy

- Tranquilizers and antidepressantdrugs to treat the emotionallydistressed


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New and Important Innovative Therapeutic

Agents Approved by FDA

1. Efavirenz - Sustiva - to treat AIDS2. Didanosine - Videx EC - to treat AIDS

3. Tenofovir - Viread - to treat AIDS4. Leuprolide acetate - Eligard prostate cancer5. Triptorelin pamoate - Trelstar - prostate cancer6. Lovastatin - Mevacor - hyperlipidemic

7. Treprostinil sodium - Remodulin - pulmonaryarterial hypertensive

8 M ifl i HCl A l i f i di


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8. Moxifloxacin HCl - Avelox - infectious disease9. Montelukast sodium - Singulair - chronic

asthma10. Tegaserod maleate - Zelnorm - irritable bowel

syndrome in women11. Sodium oxybate -Xyrem - cataplexy in patient

with narcolepsy12. Galantamine HCl - Reminyl - dementia withAlzheimers disease

13. Fondaparinux sodium - Arixtra - deep veinthrombosis

14. Voriconazole - Vfend - infectious disease

S l t l Abb i t d d


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Supplemental, Abbreviated, and

Other Applications

Supplemental New Drug Application

Abbreviated New Drug Application

Biologics License Application

Animal Drug Applications

nwe drug development and fda

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