questions in our mind.pptx

7/27/2019 questions in our mind.pptx

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Questions inour mind

By: PundalikPai


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A person asking a question is at

that moment a self-motivatedlearner i.e. a researcher. This is thebehavior we should try to nurture.

E.g. Evolution

ues ons are veryimportant


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My Question

CRO - Contract Research Organization

A Contract Research Organization (CRO) is a companycontracted by a pharmaceutical or biotechnological

manufacturer to manage clinical trials. CROs performservices such as, data management, statistical analysis,

protocol design, and final report development. e.g.Quintiles, paraxel etc.

A CRO is an independent contractor with the sponsor.

One or more of the obligations of a sponsor, e.g. design of aprotocol, selection or monitoring of investigations,evaluation of reports, and preparation of materials to besubmitted to the FDA etc. are handled by CRO.

Is there a difference between

CRO, SMO and RMO?


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SMO - Site Management Organization

A Site Management Organization (SMO) performs andmanages research for individual Investigative Sites. SMOs'

responsibilities include patient recruitment and protocol

management. e.g. many hospitals, Klintelligen, Comargo etc.

A SMO is an independent contractor with the

clinical investigator, one or more of the regulatory obligationsof a clinical investigator, e.g., preparation and maintenance of

case histories, ensuring compliance with IRB review and

informed consent requirements, AE reporting etc.

RMO - Research Management Organization A Research Management Organization (RMO) functions as a

combination of a CRO and SMO to manage research from the

conception and development of a project to the implementation

and completion at Investigative Sites. e.g. Advinus


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Hatch-Waxman Act

History- Drug approval process in 1962 Challenges for generic mfgs and innovators Need for an amendment in federal Food, Drugs and

Cosmetics act. In1984 Hatch-Waxman act as an amendment Also called Drug Price Competition and Patent Term

Restoration act1984

OBJECTIVES OF HATCH-WAXMAN ACT1. Reducing the cost associated with the approval of a

generic drug.

2. Allowing Early-Experimental-Use.3. Compensating the branded drugs manufacturers for the

time lost from the patent term because of the regulatoryapproval formality.

4. Motivating the generic drug manufacturers: Exclusivity.

My Question


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Submission options (NDA)Which act covers the submission of NDA?

Three methods of submission are available underSection 505 of chapter V of the Federal Food,Drug and Cosmetic Act:

1. 505(b)(1)

2. 505(b)(2)

3. 505(j)

Section 505(b)Provides for the submission of a New DrugApplication to support the approval of a drug

My Question


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Section 505(b)(1) the full

NDA Used for new chemical entities.

Requires complete reporting of Chemistry,manufacturing and controls, Non-clinicalpharmacology/toxicology, Clinical pharmacology.

Clinical investigations proving safety and efficacy.

Clinical trials Phase I, II, III. Filing of NDA

Phase IV (post marketing)

Right of reference

Exclusivity

Patent extension- Length of time required forregulatory process + 50% of time required forclinical trials (Time cant exceed 5yrs)


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Section 505(b)(2)- NDA Intended to encourage innovation without creating

duplicate work and reflects the same principle as the505(j) application:

it is wasteful and unnecessary to carry out studies todemonstrate what is already known about a drug

It is Considered a full NDA. Exclusivity

Reporting requirements

Same active ingredient

Previously reported safety and efficacy Information

from studies not conducted by applicant Relying on FDAs prior conclusions on safety and/or

efficacy from other NDAs

Non-clinical or Clinical Information where applicantlacks the right of reference


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Section 505(b)(2)- Contd. Examples of 505(b)(2) applications:Change in dosage form/strength/route of

administration/content of excipients.

Substitution of an active ingredient in a

combination product.Change in dosage regimen/indication

Rx to OTC switch

New combination

Modification of active ingredientNaturally derived or recombinant active

ingredient

Bio-inequivalence


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Section 505(j)- ANDAGenerics

These are the drugs which are produced anddistributed without patent protection. It may stillhave a patent on formulation but not on active

ingredient.

Are cheaper to produce and market.

Decrease the health care costs.-Can use the datafor which they dont have right of reference.

Difference between prescribablity & switchablity


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Abbreviated New Drug Application (ANDA): A type of

new drug application (NDA) in which approval of a generic

drug is based on demonstrating that it is comparable to aninnovator drug product (the RLD)

Applications are "abbreviated" because they generally do

not include preclinical and clinical data to establish safety

and effectiveness

Instead, generic applicants must demonstrate that their

product is bioequivalent (i.e., performs in the same mannerand is comparable to the innovator product in active

ingredient, dosage form, strength, route of administration,

labeling, quality, performance characteristics and intended

use)

Definition:The absence of a significant difference in the rate and extent towhich the active ingredient or active moiety in pharmaceuticalequivalents or pharmaceutical alternatives becomes availableat the site of drug action when administered at the same molardose under similar conditions in an appropriately designedstudy.

Bioequivalence

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Para Filings? Under the provisions of the HWA a generic drugs firm must

certify its intentions with respect to each patent associated withthe generic drug it seeks to market.

For a generic drug manufacturer to submit ANDA, fourpossibilities exist under HWA:

1. That patent information on the drug has not beenfiled i.e. no patent information appears in theorange book.

2. That the patent has already expired.

3. The date on which the patent will expire.

4. That the patent is invalid or will not be infringed bythe manufacture, use or sale of the drug for whichthe ANDA is submitted.

These certifications are termed as paragraph I, II, III,and IV certifications respectively.

My Question

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ReferencingOrange Book

Whats in the name?

List of Approved drug products and theirtherapeutic equivalence evaluations.

Abbreviations in the book AA, AB, AP AN?Office of generic drugs (OGD)

OGD recommendations?

Home page (FDA.gov)

Drugs Guidance compliance & regulatoryinformation

Bioequivalence recommendations for specific products

My Question

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Format/guideline for

submission of applicationWhat is a Dossier? Dossier is a well compiled file document submitted to the respective regulatory as a

requirement for the approval of a drug product.What is a CTD? The Common Technical Document (CTD) is a set of specification for application

dossier for the registration of Medicines and designed to be used across Europe,Japan and the United States. It was developed by the European Medicines Agency(EMEA, Europe), the Food and Drug Administration (FDA, U.S.) and the Ministry ofHealth, Labour and Welfare (Japan). The CTD is maintained by the InternationalConference on Harmonisation of Technical Requirements for Registration ofPharmaceuticals for Human Use (ICH).

What is eCTD? The electronic Common Technical Document (eCTD) is an interface for the

pharmaceutical industry to agency for transfer of regulatory information. The contentis based on the Common Technical Document (CTD) format. It was developed bythe International Conference on Harmonisation (ICH) Multidisciplinary Group 2 ExpertWorking Group (ICH M2 EWG). As of January 1, 2008, the U.S. Food and DrugAdministration announced that the eCTD is the preferred format for electronicsubmissions.

How to submit a Dossier? The regulations require three copies named as Archival ( Blue), review ( Red) and

Field (Burgundy/purple) copy in case of USA, and one copy ( Binding color is notspecified) for Europe.

My Question


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Organization of CTD

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How to consent pediatric patients in

clinical trials? According to the Good Clinical Practice guideline

(ICH-GCP E6), Informed consent is a process by which

a subject voluntarily confirms his or her willingness to

participate in a particular trial (voluntariness), after havingbeen duly informed of all aspects of the trial, its nature,

significance, implications and risks that are relevant to the

decision-making process (information/disclosure) in a way

that the patient can comprehend and understand therelevant information (understanding).

My Question


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four elements are required for a fully valid consent:

1. competency,2. information/disclosure,

3. understanding and

4. voluntariness.

Competency is a legal term used to indicate that a

person has the ability and is mentally capable to make

and be held accountable for his/her decisions

(competency).

According to the Declaration of Human Rights, a childis to be considered as a person with all basic human

rights from the day ofbirth.


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According to the note for guidance ICH Topic E11, paediatricage groups are separated into the following categories mainly

based on physiological and developmental similarities and

pharmacological parameters:1. Preterm newborn infants (


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Differences in assent process

among different age groups


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Parent information sheet

The structure and content of the

parent information sheet and theparent informed consent formfollows the same international rulesas for an adult patient informationsheet and informed consent form.

Both parents need to give consentand sign the informed consent form

Important elements to beconsidered when obtainingparental consent

1. Complete, balanced andUnderstandable information

The need and purpose for clinicalstudies

Rationale for experimentaltreatment

Background information on thedisease

Detailed information on the studydrug

Condition under study.

2. Thorough risk and benefitassessment

3. Measures taken to preservechilds safety

4. Rights of parents and child

5. Consider childs presumed will /Voluntariness of participation

6. Enough time for parents to

consider the options availableand discuss with family

7. Investigator and site staffavailable to answer questions

8. Keep parents informedthroughout the study


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Questions

& Answers


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References

Federal Food Drug and Cosmetic ActChapter V,

Section 505(b)(2)

21 USC 355(b)(2)

21 CFR 314.50NDAs

21 CFR 314.54505(b)(2) applications

21 CFR 314.108Exclusivity DRAFT Guidance for

Industry: Applications covered by section 505(b)(2).

Challenges and practicalities of obtaining parental

consent and child assent in paediatric trials,Regulatory RapporteurVol 7, No 6, June 2010


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questions in our mind.pptx