GLOBAL SUBMISSION OF IND, NDA, ANDA.pdfLokeshThakre6
It's important to note that the specific requirements and processes for INDs, NDAs, and ANDAs may vary between regulatory authorities in different countries. The descriptions provided here are general and based on the common practices in the United States.
Regulation Governing Clinical Trials In India,USA and Europe. KapilKumar198
This presentation contain detailed information about the "Regulation Governing Clinical Trials In India,USA and Europe".And about the clinical trails and medical devices regulations in India.
For better understanding of students. This will give you a detailed explanation of IND APPLICATION. Contact me through comment section if you need any assistance in understating this topic.
The United States Food and Drug Administration's Investigational New Drug (IND) program is the means by which a pharmaceutical company obtains permission to start human clinical trials and to ship an experimental drug across state lines (usually to clinical investigators) before a marketing application for the drug has been approved. Regulations are primarily at 21 C.F.R. 312. Similar procedures are followed in the European Union, Japan, and Canada
New drug application submitted by the manufacture of a drug to the FDA-after clinical trials have been completed –for a license to market the drug for a specified.
Investigational new drug application must be submitted after discovering a new drug and before beginning of clinical trials. Here given a brief note on the topic.The topics included are types of IND, criteria for application, Information in IND application, resources for IND application, laws.regulations, policies and procedures, IND forms and instructions, IND content requirements and review of IND
A brief information about the SCOP protein database used in bioinformatics.
The Structural Classification of Proteins (SCOP) database is a comprehensive and authoritative resource for the structural and evolutionary relationships of proteins. It provides a detailed and curated classification of protein structures, grouping them into families, superfamilies, and folds based on their structural and sequence similarities.
GLOBAL SUBMISSION OF IND, NDA, ANDA.pdfLokeshThakre6
It's important to note that the specific requirements and processes for INDs, NDAs, and ANDAs may vary between regulatory authorities in different countries. The descriptions provided here are general and based on the common practices in the United States.
Regulation Governing Clinical Trials In India,USA and Europe. KapilKumar198
This presentation contain detailed information about the "Regulation Governing Clinical Trials In India,USA and Europe".And about the clinical trails and medical devices regulations in India.
For better understanding of students. This will give you a detailed explanation of IND APPLICATION. Contact me through comment section if you need any assistance in understating this topic.
The United States Food and Drug Administration's Investigational New Drug (IND) program is the means by which a pharmaceutical company obtains permission to start human clinical trials and to ship an experimental drug across state lines (usually to clinical investigators) before a marketing application for the drug has been approved. Regulations are primarily at 21 C.F.R. 312. Similar procedures are followed in the European Union, Japan, and Canada
New drug application submitted by the manufacture of a drug to the FDA-after clinical trials have been completed –for a license to market the drug for a specified.
Investigational new drug application must be submitted after discovering a new drug and before beginning of clinical trials. Here given a brief note on the topic.The topics included are types of IND, criteria for application, Information in IND application, resources for IND application, laws.regulations, policies and procedures, IND forms and instructions, IND content requirements and review of IND
A brief information about the SCOP protein database used in bioinformatics.
The Structural Classification of Proteins (SCOP) database is a comprehensive and authoritative resource for the structural and evolutionary relationships of proteins. It provides a detailed and curated classification of protein structures, grouping them into families, superfamilies, and folds based on their structural and sequence similarities.
Nutraceutical market, scope and growth: Herbal drug technologyLokesh Patil
As consumer awareness of health and wellness rises, the nutraceutical market—which includes goods like functional meals, drinks, and dietary supplements that provide health advantages beyond basic nutrition—is growing significantly. As healthcare expenses rise, the population ages, and people want natural and preventative health solutions more and more, this industry is increasing quickly. Further driving market expansion are product formulation innovations and the use of cutting-edge technology for customized nutrition. With its worldwide reach, the nutraceutical industry is expected to keep growing and provide significant chances for research and investment in a number of categories, including vitamins, minerals, probiotics, and herbal supplements.
Observation of Io’s Resurfacing via Plume Deposition Using Ground-based Adapt...Sérgio Sacani
Since volcanic activity was first discovered on Io from Voyager images in 1979, changes
on Io’s surface have been monitored from both spacecraft and ground-based telescopes.
Here, we present the highest spatial resolution images of Io ever obtained from a groundbased telescope. These images, acquired by the SHARK-VIS instrument on the Large
Binocular Telescope, show evidence of a major resurfacing event on Io’s trailing hemisphere. When compared to the most recent spacecraft images, the SHARK-VIS images
show that a plume deposit from a powerful eruption at Pillan Patera has covered part
of the long-lived Pele plume deposit. Although this type of resurfacing event may be common on Io, few have been detected due to the rarity of spacecraft visits and the previously low spatial resolution available from Earth-based telescopes. The SHARK-VIS instrument ushers in a new era of high resolution imaging of Io’s surface using adaptive
optics at visible wavelengths.
Introduction:
RNA interference (RNAi) or Post-Transcriptional Gene Silencing (PTGS) is an important biological process for modulating eukaryotic gene expression.
It is highly conserved process of posttranscriptional gene silencing by which double stranded RNA (dsRNA) causes sequence-specific degradation of mRNA sequences.
dsRNA-induced gene silencing (RNAi) is reported in a wide range of eukaryotes ranging from worms, insects, mammals and plants.
This process mediates resistance to both endogenous parasitic and exogenous pathogenic nucleic acids, and regulates the expression of protein-coding genes.
What are small ncRNAs?
micro RNA (miRNA)
short interfering RNA (siRNA)
Properties of small non-coding RNA:
Involved in silencing mRNA transcripts.
Called “small” because they are usually only about 21-24 nucleotides long.
Synthesized by first cutting up longer precursor sequences (like the 61nt one that Lee discovered).
Silence an mRNA by base pairing with some sequence on the mRNA.
Discovery of siRNA?
The first small RNA:
In 1993 Rosalind Lee (Victor Ambros lab) was studying a non- coding gene in C. elegans, lin-4, that was involved in silencing of another gene, lin-14, at the appropriate time in the
development of the worm C. elegans.
Two small transcripts of lin-4 (22nt and 61nt) were found to be complementary to a sequence in the 3' UTR of lin-14.
Because lin-4 encoded no protein, she deduced that it must be these transcripts that are causing the silencing by RNA-RNA interactions.
Types of RNAi ( non coding RNA)
MiRNA
Length (23-25 nt)
Trans acting
Binds with target MRNA in mismatch
Translation inhibition
Si RNA
Length 21 nt.
Cis acting
Bind with target Mrna in perfect complementary sequence
Piwi-RNA
Length ; 25 to 36 nt.
Expressed in Germ Cells
Regulates trnasposomes activity
MECHANISM OF RNAI:
First the double-stranded RNA teams up with a protein complex named Dicer, which cuts the long RNA into short pieces.
Then another protein complex called RISC (RNA-induced silencing complex) discards one of the two RNA strands.
The RISC-docked, single-stranded RNA then pairs with the homologous mRNA and destroys it.
THE RISC COMPLEX:
RISC is large(>500kD) RNA multi- protein Binding complex which triggers MRNA degradation in response to MRNA
Unwinding of double stranded Si RNA by ATP independent Helicase
Active component of RISC is Ago proteins( ENDONUCLEASE) which cleave target MRNA.
DICER: endonuclease (RNase Family III)
Argonaute: Central Component of the RNA-Induced Silencing Complex (RISC)
One strand of the dsRNA produced by Dicer is retained in the RISC complex in association with Argonaute
ARGONAUTE PROTEIN :
1.PAZ(PIWI/Argonaute/ Zwille)- Recognition of target MRNA
2.PIWI (p-element induced wimpy Testis)- breaks Phosphodiester bond of mRNA.)RNAse H activity.
MiRNA:
The Double-stranded RNAs are naturally produced in eukaryotic cells during development, and they have a key role in regulating gene expression .
THE IMPORTANCE OF MARTIAN ATMOSPHERE SAMPLE RETURN.Sérgio Sacani
The return of a sample of near-surface atmosphere from Mars would facilitate answers to several first-order science questions surrounding the formation and evolution of the planet. One of the important aspects of terrestrial planet formation in general is the role that primary atmospheres played in influencing the chemistry and structure of the planets and their antecedents. Studies of the martian atmosphere can be used to investigate the role of a primary atmosphere in its history. Atmosphere samples would also inform our understanding of the near-surface chemistry of the planet, and ultimately the prospects for life. High-precision isotopic analyses of constituent gases are needed to address these questions, requiring that the analyses are made on returned samples rather than in situ.
1. GLOBAL SUBMISSION OF IND & NDA
NON CLINICAL DRUG DEVELOPMENT
REGULATORY AFFAIRS
Presented by
Chitrang R Patil (M23027)
F.Y.M.Pharmacy
Guided by Miss. Ashwini Bhoir Mam
Pharmaceutics
Konkan gyanpeeth rahul dharkar college of pharmacy, karjat
2. PRECLINICAL INVESTIGATION
The testing of new drugs in humans cannot begin until there is solid
evidence that the drug product can be used with reasonable safety in
humans. This phase is called "preclinical investigation."
Goal of preclinical investigation is to assess potential therapeutic effects
of the substance on living organisms and to gather sufficient data to
determine reasonable safety of the substance in humans through
laboratory experimentation and animal investigation
A preclinical investigation usually takes one to three years to complete.
3. INTRODUCTION
The INVESTIGATIONAL NEW DRUG APLICATION (IND) is the formal
process by which a sponsor requests approval for testing of a drug in humans.
It includes information developed during preclinical testing regarding safety
and effectiveness.
A pre- IND meeting can be arranged with the FDA to discuss a number of
issues
The design of animal research, which is required to lend support to the clinical
studies.
The intended protocol for conducting the clinical Trial.
The chemistry, manufacturing, and control of the investigational drug.
4. Includes an investigational brochure that ensures that clinicians
conducting the trial and their institutional review board(IRB) are
adequately informed about possible effect of the drug.
If the FDA accepts the IND request within 30 days of submission,
clinical testing of new molecule on human may begin by the
investigator.
If at any time during clinical testing, the data furnished to FDA
indicate the IP to be toxic under the criterion of FDA's Benefit/Risk
ratio, FDA can terminate clinical trial and its actions are not subject to
any judicial review.
INTRODUCTION
5. TYPES OF IND
Investigator IND- submitted by a physician who both initiates and
conducts an investigation, and under whose immediate direction the
investigational drug is administered or dispensed.
Emergency Use IND-allows the FDA to authorize use of an experimental
drug in an emergency situation that does not allow time for submission of
an IND in accordance with 21CFR, Sec. 312.23 or Sec. 312.20.
Treatment IND-is submitted for experimental drugs showing promise in clinical
testing for serious or immediately life- threatening conditions while the final
clinical work is conducted and the FDA review takes place.
6. THE IND APPLICATION MUST CONTAIN
INFORMATION IN THREE BROAD AREAS
Clinical
protocols and
investigator
information
Animal
pharmacology
and toxicology
Manufacturin
g information
7. REGULATORY AND ADMINISTRATIVE
COMPONENTS
The content 21CFR part 312. and format of IND application is laid out in
Cover sheet -312.23(a)(1)(FORM FDA 1571)
Table of contents-313.23(a)(2)
Introductory statement and a general investigational plan -312.23(a)(3)
Investigators brochure-312.23(a)(5)
Clinical Protocols-312.23(a)(6)
8. REGULATORY AND ADMINISTRATIVE
COMPONENTS
Chemistry, manufacturing and control information- 312.23(a)(7)
Pharmacology and Toxicology information-312.23(a)(18)
Previous human experience with the investigational drug- 312.23(a)(9)
Other relevant information like no of IND submissions- 312.23(a)(10)
Number of copies to be submitted (1+2)
Protocol amendments, any changes in the protocol.- 312.(a)(11)
9. IND APPLICATION PROCESS
Compile the components of the IND Application.
Items with original signatures should be scanned as PDF files.
Refer to FDA website for submission addresses.
10. IND APPLICATION SUBMISSION
FDA will send an acknowledgement via email and in a letter with the
following information:
Date of IND receipt
IND number
Contact name
Phone at FDA for questions
Address and instructions for future submissions of the IND
FDA has up to 30 days in which to respond to the sponsor- investigator
regarding the IND if there are clinical, regulatory, or other concerns
11. IND SUBMISSION: THE FIRST 30 DAYS
• IND arrives to the Central Document Room
If electronic: loaded in the Electronic Document Room (EDR)
If paper: Sent to the White Oak Document Room
Data entered into DARRTS (Document Archiving, Reporting, and Regulatory
Tracking System
• IND forwarded to CPMS (Chief, Project Management Staff)
• PM (Project Manager) assigned
• Review Team assigned
12. IND SUBMISSION: THE FIRST 30 DAYS
The Review team will determine within 30 days of receipt of your IND
whether your study is "safe to proceed" or will be placed in clinical hold
13. FDAADMINISTRATIVE ACTIONS
• Comments Or Requests For Modifications
FDA communications to the sponsor-investigator within the 30-day window
following FDA receipt of the IND must be answered promptly Updated
materials submitted to the FDA in response to a request for
changes/information should be submitted in the same manner as the original
IND.
• Approval of IND
Research may commence 30 days following of receipt of the IND if the FDA
has not made any request for additional information or changes to the IND
Application as submitted.
FDA Approval of the IND will be sent electronically and in a letter to the
sponsor investigator.
14. IND PROCESS IN INDIA
No clinical trial for new drug for any purpose be conducted without
permission, in writing, of the Licensing Authority(DCGI).
Application for conducting clinical trials in India require submission by the
sponsor on Form 44 along with fee(Rs 50K) and documents as provided
under Schedule Y to Drugs and Cosmetic Act 1940.
15. Data to be submitted along with the application on Form44 to conduct clinical
trails (2 hard copies and 2 soft copies)
1.Application on Form44
2. Introduction of the drug
3.Fee Rs 50K through challan form
4.Chemical and pharmaceutical information as per Appendix I of Schedule Y.
5.Animal pharmacology as per Appendix IV
6.Animal toxicology as per Appendix III.
7.Human/clinical pharmacology data as per Appendix I.
8. Regulatory status in other countries as per Appendix i.
16. After receiving the
application, the
Central Drug
Standard Control
Organisation
(CDSCO)
Headquarter in
New Delhi refer it
to
The New Drug
division where it is
reviewed by IND
committee. The
committee submits
its report to
DCGI along with
its
recommendations.
If the report by
committee is
favorable, DCGI
approves the
INDA.
17.
18. New Drug Aplication
The New Drug Application is the vehicle through which the drug sponsors formally propose
FDA or DCGI to approve a new investigational drug for sale and marketing after Phase IIIA
Pivot trials.
The official definition of New Drug is in Sec 20 l(p) of Federal Drug, Food and Cosmetics
Act as;
Any new drug , the composition of which is such that it is not recognized among expels
qualified by scientific training as safe and effective tor use under prescribed, recommended or
suggested conditions.
19. Any drug the Composition of which is such that it as a result of investigations
to determine safety and efficacy for use has become recognized, but which
has not, otherwise in such investigations been used to a material extent .
The following letter codes describe the review priority of the drug;
S-STANDARD REVIEW: For drugs similar to currently available drugs
P-PRIORITY REVIEW : For drug that represent significant advances over
existing treatments
20. Classification of drugs in NDA
Center of drug evaluation and Research(CDER) classifies new drug
applications according to the type of drug being submitted and its intended
use:
A. New molecular entity
B. New salt of previously approved drug
C. New formulation of previously approved drug
D. New combination of two or more drugs
E. Already marketed drug product- Duplication (i.e., new manufacturer)
F. New indication (claim) for already marketed drug (includes switching
marketing status from prescription to OTC)
G. Already marketed drug product ( no previous approved NDA)
21. In US following 4 types of applications are submitted for
approval of drug for marketing depending upon the type
and nature of the drug:
A. New Drug Application (NDA)
B. Biological License Application (BLA)
C. Application u/s 505(b)(2)-Paper NDA
D. Supplemental New Drug Application (SNDA)
22. FORMAT AND CONTENT OF NDA
The application is required to be submitted in common technical document format with
the following different sections:
FDA Form 356h
User Fee Cover Sheet (FDA Form 3397)
Cover letter (Comprehensive table of contents for Modules l to 5)
Summary
Chemistry, Manufacturing and Control
Samples, Method Validation, Package and Labeling
The application is required to be submitted in common technical document format with
the following different sections:
23. Nonclinical Pharmacology and Toxicology
Human Pharmacokinetics and Bioavailability
Microbiology (For anti-microbial drugs only)
Statistical methods and analysis of Clinical Data
Safety Update Repos (typically submitted 120 days after NDA submission)
Statement regarding compliance to IRB and Informed Consent requirements
Case Report Tabulations
Case Report Forms
Patent information and certification
Other information.
24. General requirements for filing NDA
• The new NDA regulations require the application tobe submitted in 2 copies:
A. An Archival Copy- lt is a complete copy of application submission that
serves as its permanent record.
B. A Review Copy- It is divided into 6 technical sections:
i. Chemistry, Manufacturing and Controls (CMC)
ii. Non clinical Pharmacology and Toxicology
iii. Human Pharmacokinetics and Bioavailability
iv. Microbiology (if required)
v. Clinical data
vi. Statistical
25. • On receipt of NDA, the CDER stamps with a receipt date to enable FDA to
forward action within 180 days called ‘Review Clock’ under Review Time
Frames (21 CFR 314.1OO). The FDA assigns the application for review.
• The FDA has to intimate the applicant if it is incomplete within 60 days
according to Filing Time Frames (21 CFR 314.101).
• FDA notifies the sponsor of its completion/ incompletion and if complete sends
it for secondary review process. FDA inspects the manufacturing facilities for
the drug, It may also inspect sample of clinical trial locations to verify the
accuracy of data submitted
26.
27. • Throughout the process FDA and sponsor communicates through in person
meetings, telephone conferences, fax etc. to seek clarification if necessary.
Once all reviews are complete; the Divisional Director evaluates the reviews
and makes FDA’s decision. The FDA may:
• Approve the drug for marketing.
• Approve the drug with condition when problem exist with the application that
needs to be addressed before approval.
• Refuse to approve the drug, when it may require additional research or
reformulation of the drug product.
28. NDA PROCESS IN INDIA
• In India, New Drug is defined under Rule 122-E of Drugs and Cosmetics Act
as:
A. A drug which has not been used in the country to any significant extent under
various conditions
B. A drug already approved by DCGI for certain claims which is now proposed
to be marketed with new claims like indications, dosage, dosage form etc.
C. A fixed dose combination of two individually approved drug being combined
for the first time in a fixed ratio or new already marketed combination.
29. D. All vaccines are considered as new drugs.
E. A new drug continues to be considered as new drug for a period of 4
years from its approval or its inclusion in Indian Pharmacopoeia.
F. After successful finishing of clinical trials, the applicant seeking for
approval to manufacture a new drug requires to submit application on
Form44 along with data as given in Appendix I to Schedule Y Of
Rules 1945 to DCGI who grants its approval in Form 46 or 46-A.
G. In his name while applying to manufacture a new drug to State
Licensing Authority. Thus the applicant is required to obtain necessary
approval from DCGI as well as SLA for manufacturing a new drug for
sale purposes in India.
H. The approval issued is ‘manufacture for sale’ rather than ‘marketing
approval’ as per the practice world over.
30. PERMISSION TO MANUFACTURE A NEW
DRUG:
Brief introduction of the new drug
Chemical and pharmacological information
Animal pharmacology and Toxicology
Human/ Clinical Pharmacology (Phase I)
Exploratory Clinical Trials (Phase II)
Confirmatory Clinical Trial s(Phase III)
Bio-availability, dissolution and stability study data
Regulatory status in other countries
Application for test license
Marketing information
31.
32. References
1. Chakraborty R, Yadav K (2018) Drug approval process in US, Europe and India
and its regulatory requirements: A Review 6: 31-39.
2. Mahapatra AK, Sameeraja NH, Murthy PN (2014) Drug Approval Process In
United States of America, European Union and India : A Review. AcrcTra 1:
13-22.
3. https://www.jpsr.pharmainfo.in/Documents/Volumes/vol9Issue10/
jpsr09101759.pdf
4. Gupta NV, Reddy CM, Reddy KP, Kulkarni RA, Shivakumar, et al. (2012)
Process of Approval of New Drug in India with Emphasis on Clinical trials
13: 17-23.
