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7/27/2019 questions in our mind.pptx
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Questions inour mind
By: PundalikPai
7/27/2019 questions in our mind.pptx
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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
M Q ti
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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
M Q ti
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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
M Q ti
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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
M Q ti
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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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