A brief presentation on the Code of Federal Regulations
Covers the following aspects -
- What is CFR?
-History of CFR
- CFR Title 21
- CFR in modern times.
- Research tools in CFR
- Whilst the realization of the CTD took many years, there is now a common format for the submission of Marketing Authorizations Applications across the three ICH regions - Europe, Japan and the USA.
- This should facilitate pharmaceutical companies to make simultaneous filings in the ICH regions as it will eliminate the extensive work previously required to convert, for example, a US dossier to an EU dossier and vice versa.
DRUG MASTER FILE
Presented by :
RUSHIKESH D MENDHE
Roll no - 511
Mpharm Ist Year
(Department of Pharmaceutics)
Content : :
INTRODUCTION
TYPES OF DMF
DMF FORMAT & ASSEMBLY
DELIVERY OF DMF TO FDA
SUBMISSION OF DMF
THE MECHANISM OF A DRUG MASTER FILE
CTD & ELECTRONIC DMFS
UPDATES TO DMF
CLOSURE OF A DRUG MASTER FILE
APPLICATION OF DMF
REFERENCE
INTRODUCTION :
A Drug Master File (DMF) is a submission to the Food and Drug Administration (FDA) that may be used to provide confidential detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of one or more human drugs.
This guideline does not impose mandatory requirements.
Objectives :
Main Objective of the DMF is to support regulatory requirements
To prove the quality, safety and efficacy of the medicinal product
TYPES OF DMF :
DMF FORMAT & ASSEMBLY :
The DMF is submitted as Original and Duplicate jackets, collated, assembled, paginated, and jacketed, using covers obtained from the government printing office and a respecifically provided for the DMFs
Multiple volumes are numbered, and the paper must be standard paper size
Paper length should not be less than 10 inches nor more than 12 inches.
Each volume of a DMF should be not more than 2 inches thick
DELIVERY OF DMF TO FDA :
DMF should be submitted at following address :
Food and Drug Administration Center for Drug Evaluation and Research Central Document Room 5901 – B Ammendale Road Beltsville, MARYLAND 20705-1266 USA
SUBMISSION OF DMF :
The DMF must be submitted in two copies, one with a blue cover and one with a red cover.
Each page of each copy of the DMF should be dated and consecutively numbered.
Each DMF submission should contain :
• A Transmittal letter
• Administrative information about the submission
• Other specific information
A. Transmittal Letter :
i) Original Submissions :
• Identification of submission: Original, the type of DMF as classified in Section III, and its subject.
• Identification of the applications, if known, that the DMF is intended to support, including the name and address of each sponsor, applicant, or holder, and all relevant document numbers.
• Signature of the holder or the authorized representative.
• Typewritten name and title of the signer.
ii) Ammendments :
• Identification of submission: Amendment, the DMF number, type of DMF, and the subject of the amendment.
• A description of the purpose of submission, e.g., update, revised formula, or revised process.
• Signature of the holder or the authorized representative.
• Typewritten name and title of the signer.
B. Administrative information about the submission:
A brief presentation on the Code of Federal Regulations
Covers the following aspects -
- What is CFR?
-History of CFR
- CFR Title 21
- CFR in modern times.
- Research tools in CFR
- Whilst the realization of the CTD took many years, there is now a common format for the submission of Marketing Authorizations Applications across the three ICH regions - Europe, Japan and the USA.
- This should facilitate pharmaceutical companies to make simultaneous filings in the ICH regions as it will eliminate the extensive work previously required to convert, for example, a US dossier to an EU dossier and vice versa.
DRUG MASTER FILE
Presented by :
RUSHIKESH D MENDHE
Roll no - 511
Mpharm Ist Year
(Department of Pharmaceutics)
Content : :
INTRODUCTION
TYPES OF DMF
DMF FORMAT & ASSEMBLY
DELIVERY OF DMF TO FDA
SUBMISSION OF DMF
THE MECHANISM OF A DRUG MASTER FILE
CTD & ELECTRONIC DMFS
UPDATES TO DMF
CLOSURE OF A DRUG MASTER FILE
APPLICATION OF DMF
REFERENCE
INTRODUCTION :
A Drug Master File (DMF) is a submission to the Food and Drug Administration (FDA) that may be used to provide confidential detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of one or more human drugs.
This guideline does not impose mandatory requirements.
Objectives :
Main Objective of the DMF is to support regulatory requirements
To prove the quality, safety and efficacy of the medicinal product
TYPES OF DMF :
DMF FORMAT & ASSEMBLY :
The DMF is submitted as Original and Duplicate jackets, collated, assembled, paginated, and jacketed, using covers obtained from the government printing office and a respecifically provided for the DMFs
Multiple volumes are numbered, and the paper must be standard paper size
Paper length should not be less than 10 inches nor more than 12 inches.
Each volume of a DMF should be not more than 2 inches thick
DELIVERY OF DMF TO FDA :
DMF should be submitted at following address :
Food and Drug Administration Center for Drug Evaluation and Research Central Document Room 5901 – B Ammendale Road Beltsville, MARYLAND 20705-1266 USA
SUBMISSION OF DMF :
The DMF must be submitted in two copies, one with a blue cover and one with a red cover.
Each page of each copy of the DMF should be dated and consecutively numbered.
Each DMF submission should contain :
• A Transmittal letter
• Administrative information about the submission
• Other specific information
A. Transmittal Letter :
i) Original Submissions :
• Identification of submission: Original, the type of DMF as classified in Section III, and its subject.
• Identification of the applications, if known, that the DMF is intended to support, including the name and address of each sponsor, applicant, or holder, and all relevant document numbers.
• Signature of the holder or the authorized representative.
• Typewritten name and title of the signer.
ii) Ammendments :
• Identification of submission: Amendment, the DMF number, type of DMF, and the subject of the amendment.
• A description of the purpose of submission, e.g., update, revised formula, or revised process.
• Signature of the holder or the authorized representative.
• Typewritten name and title of the signer.
B. Administrative information about the submission:
Abbreviated New Drug Application [ANDA]Sagar Savale
An Abbreviated New Drug Application (ANDA) contains data which when submitted to FDA's CDER, Office of Generic Drugs, provides for the review and ultimate approval of a generic drug product.
COPP/CPP it certification of pharmaceutical product for reviewing QSE i.e. Quality, Sefty,Efficacy of product. it important certification for exporting it may required by importing country.
I. INTRODUCTION
II. DEFINITIONS
III. TYPES OF DRUG MASTER FILES
IV. SUBMISSIONS TO DRUG MASTER FILES
V. AUTHORIZATION TO REFER TO A DRUG MASTER FILE
VI. PROCESSING AND REVIEWING POLICIES
VII. HOLDER OBLIGATIONS
IX. CLOSURE OF A DRUG MASTER FILE.
The presentation is about: Drug Regulatory Affairs as a profession, Scope & Responsibilities in life cycle management of a drug and role of RA in the drug approval process.
Abbreviated New Drug Application [ANDA]Sagar Savale
An Abbreviated New Drug Application (ANDA) contains data which when submitted to FDA's CDER, Office of Generic Drugs, provides for the review and ultimate approval of a generic drug product.
COPP/CPP it certification of pharmaceutical product for reviewing QSE i.e. Quality, Sefty,Efficacy of product. it important certification for exporting it may required by importing country.
I. INTRODUCTION
II. DEFINITIONS
III. TYPES OF DRUG MASTER FILES
IV. SUBMISSIONS TO DRUG MASTER FILES
V. AUTHORIZATION TO REFER TO A DRUG MASTER FILE
VI. PROCESSING AND REVIEWING POLICIES
VII. HOLDER OBLIGATIONS
IX. CLOSURE OF A DRUG MASTER FILE.
The presentation is about: Drug Regulatory Affairs as a profession, Scope & Responsibilities in life cycle management of a drug and role of RA in the drug approval process.
I have created this document with inputs from various sources. Some are taken right from slideshare. I just try to make this topic little compact and lucid, so that everybody can understand it easily
Nicely described regarding about the overview of ICH guidelines as per PCI syllabus specially for Pharmacy students not only for pharmacy student for all. It include Quality, Safety, Efficacy & Multidisciplinary guidelines and also include Common Technical Document & Electronic Common Technical Document.
The Common Technical Document (CTD) is a standardized format for regulatory submission of information on drugs, biologics, and medical devices to regulatory authorities in different countries. The CTD is designed to simplify the submission and review process by providing a consistent format and organization of information that can be easily understood by regulatory authorities in different regions.
Regulatory aspect of pharamacutical packgingvineet gupta
There is no doubt that the regulatory climate is getting more restrictive for pharmaceutical products and it is likely that packaging for pharmaceuticals will have more and more constraints placed upon it.
ICH GCP guidelines for mpharmacy 2nd sem 204T subject.
topic include the brief description regarding ICH GCP
THE GOOD CLINICAL PRACTICES AND
THE INTERNATIONAL CONFERENCE OF HORMONIZATION.
THAT INCLUDE the regulation of all pharmaceutical industries.
Pharmacovigilance is science of detection,
assessment, reporting and prevention of adverse
reactions to drug(s).
Major aims of pharmacovigilance are:
1. Early detection of hitherto unknown adverse
reactions and interactions
2. Detection of increases in frequency of (known)
adverse reactions
3. Identification of risk factors and possible
mechanisms underlying adverse reactions
4. Estimation of quantitative aspects of benefit/risk
analysis and dissemination of information needed to
improve drug prescribing and regulation.
Fixed dose combination products – rationality, status in india, development i...Dr Sukanta sen
The development of FDCs is becoming increasingly
important from a public health perspective.
•They are being used in the treatment of a wide range of
conditions and are particularly useful in the management of
human immunodeficiency virus/acquired immunodeficiency
syndrome (HIV/AIDS), malaria and tuberculosis, which are
considered to be the foremost infectious disease threats in the world today.
Prospects of incretin mimetics in therapeuticsDr Sukanta sen
Comparative trials show that there are important differences between
and among the GLP-1 receptor agonists and DPP-4 inhibitors with
respect to glycemic lowering, weight effects, and effects on systolic
blood pressure and the lipid profile.
•Nausea, diarrhea, headaches, and dizziness are common with the
available GLP-1 receptor agonists.
•Upper respiratory tract infections, nasopharyngitis, and headaches
are common with the DPP-4 inhibitors.
•Ongoing safety evaluations should provide a clear picture regarding
long-term safety.
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
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Hot Selling Organic intermediates
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
2. If you want to go fast go alone.
If you want to go far go together.
African Proverb
2
3. WILL DISCUSS ABOUT :What is CTD?
Evolution of CTD
Why CTD?
Preparing and organizing the CTD
What is the current status of CTD?
ICH – eCTD
Advantages of CTD
Limitations
Benefits
Conclusion
References
3
4. ABBREVIATIONS
CDSCO: Central Drugs Standard Control Organization
CTD: Common Technical Document
DCGI: Drug Controller General of India
eCTD: Electronic Common Technical Document
FDA: Food and Drug Administration
ICH: International Conference on Harmonisation
IND: Investigational New Drug application
NDA: New Drug Application
USFDA: US Food and Drug Administration
TGA: Therapeutic Goods Administration
EMA: European Medicines Agency
4
5.
Substantial documentation and data are required in
submissions for import/manufacture and marketing approval of
drugs for human use, resulting in large, complex applications.
Till date, applicants have used many different approaches in
organizing the information and the differences in organization of
data in each application has made reviewing more difficult and
can also lead to omission of critical data or analyses.
Such omissions can result in unnecessary delays in approvals.
Thus, a common format of submission will help in overcoming
these hurdles.
5
6. WHAT IS CTD?
Application format
The CTD is a set of specifications for a dossier for the
registration of medicines (TGA)
CTD is an internationally agreed “well structured
common format” for the organization of the technical
requirements that is to be submitted to the regulatory
authority as an application for the registration of
pharmaceuticals for human use in all three ICH regions
(U.S.A., Europe and Japan).
6
8. Prior to the advent of the CTD, regulatory reviewers received
an application from one company and spent a year or more
engaged in its review.
When the review was completed, reviewers received the next
application—most likely in a different format—and had to learn
the structure of the new application.
1996- Industry proposed CTD but ICH regulators were hesitant
disruptive to the review process
Regulators asked industry to do a feasibility study.
That study, conducted in May 1996, evaluated the time it took to
convert an FDA new drug application into an European
Medicines Agency (EMA) submission, and the reverse.
Regulators quickly saw the potential value of harmonizing
submission formats.
8
10. ORIGIN OF CTD…
ICH
EWG
WAS OFFICIALLY SIGNED
OFF IN NOVEMBER 2000,
CTD
AT 10TH ANNIVERSERY of
ICH ;
SAN DIEGO,CALIFORNIA.
10
11. CTD
CTD IS A JOINT EFFORT OF 3 REGULATORY AGENCIES:
2. Food and Drug Administration (FDA, USA) and
3. Ministry of Health, Labour and Welfare (MHLW,Japan).
CTD is maintained by ICH through EWG.
In July 2003, the CTD became the mandatory format for new drug
applications in the EU and Japan, and the strongly recommended format
of choice for NDAs submitted to the FDA.
It has been adopted by several other countries including Australia, Canada
and Switzerland (2004).
11
1.European Medicines Agency (EMEA, Europe),
12. Any guideline which is given by ICH passes through different
steps.
These different steps are called STATUS of that GUIDELINE.
STATUS
FUNCTIONALITY
Step 1
Development of Consensus
Step 2
12
Status of CTD
Text released for consultation
Step 3
Consultation outside ICH
Step 4
STEP 4 STATUS ACHIEVED IN
NOV.2000 IN 5TH ICH CONFERENCE
IN SANDIEGO..
STEP 5 STATUS ACHIEVED IN
MAY.2001 IN ICH MEETING IN
TOKYO.
ICH guideline finalized
Step 5
Implementation
GUIDANCE MADE AVAILABLE TO
INDUSTRY IN OCTOBER 16,2001 BY
FDA.
13. In 2000, the 10th Anniversary of ICH, Dr. Caroline Nutley Loew
of the Pharmaceutical Research and Manufacturers of America
(PhRMA) wrote a report, The Value and Benefits of ICH to
Industry, which detailed ICH’s creation, procedures, and
guideline development in the areas of safety, efficacy, and quality.
Her report anticipated that the CTD would revolutionize the
submission procedures for industry’s regulatory staff.
Dr. Loew characterized the CTD as “offering potential benefits
to industry far greater than any other single ICH topic,” and
predicted the CTD would afford significant savings in time and
resources as complex multiple submissions were replaced by a
single technical dossier submitted in the three ICH regions—
13
facilitating simultaneous submission, approval, and launch of new
drugs.
14.
In calling the CTD “a topic whose value to industry
cannot be underestimated,”
Dr. Loew noted that with full incorporation of the CTD and
the electronic CTD (eCTD), ICH could turn its sights to
disseminating guideline information to non- ICH countries,
yielding additional benefits to both regulators and industry.
Ten years later and in anticipation of ICH’s 20th
Anniversary, the value and benefits of ICH to regulators have
been realized.
14
15.
Moreover, implementation of the CTD in 2003 promoted the
involvement of drug regulatory authorities (DRAs) not initially
part of ICH, thereby extending ICH’s harmonized approach.
The development of the Global Cooperation Group, which
includes representatives from five regional harmonization
initiatives and the newly established Regulators Forum, created
to promote participation by non-ICH countries interested in
implementing ICH’s strategies, have also helped incorporate
the CTD into regulatory processes, creating a common
regulatory language that promotes faster access to life-saving
treatments to patients beyond ICH regions.
15
18. In ICH Region
1995: Concept of CTD proposed by Industry.
November 2000: ICH CTD guideline finalized.
September 2002: Guideline re-edited with Numbering &
Section Header changes.
Prior to July 2003: Voluntary Submission Phase in 3 ICH
Region.
July 1, 2003: Mandatory Requirement in Three ICH Regions.
In India
2009: CDSCO Adopt CTD format for Technical requirements
for registration of biological products.
October 28, 2010: CDSCO give guideline for feedback purpose
for Industry on Preparation of CTD for Import/Manufacture
and Marketing Approval of New Drug for Human Use (i.e. 18
NDA) & ask for comments and suggestion within 60 days.
20. This guidance is developed by CDSCO based on,
- The ICH Harmonised Tripartite Guideline on “Organisation of
the Common Technical Document for the Registration of
Pharmaceuticals for Human Use”. M4, Step 4 version dated
January 13, 2004, and
- Drugs & Cosmetics Act 1940 and Rules made thereunder.
20
22. OBJECTIVE OF ICH TO PREPARE THE CTD
The primary objective of the ICH is to avoid duplicative
animal and human testing and to reach a common
understanding of the technical requirements to support the
registration process in the three ICH regions.
These objectives are achieved through harmonized
guidelines and result in a more economical use of human,
animal and material resources, as well as the elimination of
unnecessary delays in the global development and
availability of new medicines, whilst maintaining
safeguards on quality, safety and efficacy, and regulatory
obligations to protect public health.
With the development of the Common Technical Document
(CTD), the ICH hopes to accomplish many of its objectives.
22
23. WHY CTD?
To provide a harmonized common format/template for the
submission of technical requirement to the regulatory
authorities (FDA) that is acceptable in all 3 ICH regions
Reduce the time and resources used to compile applications
It
will ease the preparation of electronic submissions.
To facilitate simultaneous submission in three regions.
To facilitate exchange of regulatory information.
Faster availability of new medicines
23
24. 24
Figure 1: The Drug Approval Process: Drug approval involves passing a number of steps,
including preclinical and clinical studies, and later, post-marketing research.
25. PREPARING & ORGANIZATION
OF
CTD
It is organized into: Module
1: General Information
Module 2: CTD summaries
Module 3: Quality
Module 4: Nonclinical study reports
Module 5: Clinical study reports
25
27. MODULE 1.
Administrative information and prescribing
information.
Document specific to each region.
E.g. Application form
Proposed label for use in the region
27
28. MODULE 1: GENERAL INFORMATION
1.1 Covering letter & comprehensive table of contents (modules 1
to 5)
1.2 Administrative information
1.2.1 Brief introduction about the applicant company
1.2.2 Duly filled and signed application in Form 44 and Treasury
Challan
1.2.3 Legal and Critical Documents
1.2.3.1 Copy of Clinical Trial/BE. No Objection letters issued by
CDSCO
1.2.3.2 For import and marketing of finished products
a. Copy of drug sale license in Form 20B / 21B
b. Copy of Free Sale Certificate (FSC) and/or Certificate of
Pharmaceutical Products (CPP) issued by the Regulatory
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Authority of the country of origin
29. c. Batch release certificate issued by National Regulatory
Authorities
d. Copy of Form 11 for imported drug product for testing purpose
1.2.3.3 For manufacture and marketing of finished products
a. Copy of existing manufacturing license in Form 25 / 28 / 26
b. Copy of Form-29
1.2.3.4 Undertaking or Declaration as per Annexure II
1.2.3.5 Certificate of Analysis
29
30. 1.2.4 Coordinates related to the application
1.2.4.1 Name, address, telephone, fax, e-mail of applicant of drug
product
1.2.4.2 Name, address, telephone, fax, e-mail of manufacturer of
drug substance
1.2.4.3 Name, address, telephone, fax, e-mail of the responsible
official
1.2.4.4 Name, address, telephone, fax, e-mail of other manufacturer(s)
involved in the production process
1.2.4.5 Name, designation, address, telephone, fax, e-mail of the
official responsible for releasing batches of drug product
1.2.4.6 Name, address, telephone, fax, e-mail of the authorized agent in India:
(for imported drug products)
1.2.4.7 Name, address, telephone, fax, e-mail of the manufacturing premises
holding Market Authorization of the drug product (for imported drug 30
products)
31. 1.3 GENERAL INFORMATION ON DRUG PRODUCT
1.3.1 A brief description of the drug and the therapeutic
class to which it belongs
1.3.2 Non-proprietary name or generic name of drug
1.3.3 Composition (As per label claim)
1.3.4 Dosage form
1.3.5 Strength per dosage unit
1.3.6 Dispensing requirements
1.3.7 Route of administration
1.3.8 Commercial presentation
1.3.9 Conditions of storage or conservation
1.3.10 Full Prescribing Information (Package insert)
1.3.11 Product Labeling: Proposed draft labels and cartons have to be
provided.
1.3.12 Summary of the packaging procedures for Indian shipments
31
32. 1.4 SUMMARY OF TESTING PROTOCOL(S) FOR
QUALITY CONTROL TESTING together with a complete
impurity profile and release specifications for the product should
be submitted.
1.5 Regulatory status in other countries
1.5.1 List of countries where proposed drug is Marketed
1.5.2 List of countries where proposed drug is Approved for
Marketing
1.5.3 List of countries where proposed drug is Approved as IND
1.5.4 List of countries where proposed drug is Withdrawn (if any,
with reasons for withdrawal)
1.5.5 Details of any restrictions on use, in any country where it is
marketed /approved
32
33.
1.6 Domestic price of the drug followed in the countries of
1.7 A brief profile of the manufacturer’s research activity
1.8 A brief profile of the manufacturer’s business activity in
domestic as well as global market
1.9 Information regarding involvement of experts, if any
1.10 Samples of drug product
1.11 Promotional materials
33
35. Module
Content
2.1
Common technical document table of contents (Modules 2–5)
2.2
CTD introduction
2.3
Quality overall summary
2.4
Nonclinical overview
2.5
Clinical overview
2.6
Nonclinical written and tabulated summaries
Pharmacology
Pharmacokinetics
Toxicology
2.7
Clinical summary
Biopharmaceutic studies and associated analytical methods
Clinical pharmacology studies
Clinical efficacy
Clinical safety
Literature references
Synopses of individual studies
35
36. 2.3 QUALITY
OVERALL SUMMARIES
In general, the Quality Overall Summary (QOS) is an outline of
data presented in Module 3.
Please do not provide the entire information present in Module 3
corresponding sections, but, provide brief information picked
from relevant sections.
This QOS normally should not exceed 40 pages of text,
excluding tables and figures.
36
37. 2.3.S Summary of drug substance
2.3.S.1 General Information (name, manufacturer)
2.3.S.2 Manufacture (name, manufacturer)
2.3.S.3 Characterisation (name, manufacturer)
2.3.S.4 Control of Drug Substance (name, manufacturer)
2.3.S.5 Reference Standards or Materials (name, manufacturer)
2.3.S.6 Container Closure System (name, manufacturer)
2.3.S.7 Stability (name, manufacturer)
2.3.P SUMMARY OF DRUG PRODUCT
2.3.P.1 Description and Composition of the Drug Product (name, dosage form)
37
38. 2.3.P.2 Pharmaceutical Development (name, dosage form)
2.3.P.3 Manufacture (name, dosage form)
2.3.P.4 Control of Excipients (name, dosage form)
2.3.P.5 Control of Drug Product (name, dosage form)
2.3.P.6 Reference Standards or Materials (name, dosage
form)
2.3.P.7 Container Closure System (name, dosage form)
2.3.P.8 Stability (name, dosage form)
2.3.A appendices
38
39. 2.4 NON-CLINICAL OVERVIEW
Nonclinical overview should present an integrated and critical
assessment of the pharmacologic, pharmacokinetic, and
toxicological evaluation of the pharmaceutical.
In general, it should address the interpretation of data, the
clinical relevance of findings, cross-linking with quality aspects
of the pharmaceutical, and the implications of nonclinical
findings for the safe use of the pharmaceutical.
39
40. 2.4.1 Introduction and GLP statement
A brief introduction about the contents of this section and a
comment on the GLP status of the studies submitted should be
provided
2.4.2 Overview of the Non Clinical Testing Strategy
2.4.3 Pharmacology
2.4.4 Pharmacokinetics
2.4.5 Toxicology
2.4.6 Integrated Overview and Conclusions
2.4.7 List of Literature References
40
41. 2.5 CLINICAL OVERVIEW
Summary and analysis of the clinical data
Provide a brief overview of the clinical findings, including
important limitations (e.g., lack of comparisons with an
especially relevant active comparator, or absence of information on
some patient populations, on pertinent endpoints, or on use in
combination therapy).
Analyse the benefits and risks of the medicinal product in its
intended use based upon the conclusions of the relevant clinical
studies
41
42.
Address particular efficacy or safety issues encountered in
development, and how they have been evaluated and resolved.
Explore unresolved issues, explain why they should not be
considered as barriers to approval, and describe plans to resolve
them.
Explain the basis for important or unusual aspects of the
prescribing information
42
43.
2.5.1 Product Development Rationale
2.5.2 Overview of Biopharmaceutics
2.5.3. Overview of Clinical Pharmacology
2.5.4 Overview of Efficacy
2.5.5 Overview of Safety
2.5.6 Benefits and Risks Conclusions
2.5.7 Literature References
43
44. 2.6 NON-CLINICAL SUMMARIES
Summary of pharmacokinetic, pharmacological and
toxicology studies – in-vivo/in-vitro, species, route
and duration
Appropriate age and gender related effects
44
45. 2.6.1 Introduction
2.6.2 Written Summary of Pharmacology
2.6.2.1 Brief Summary
2.6.2.2 Primary Pharmacodynamics
2.6.2.3 Secondary Pharmacodynamics
2.6.2.4 Safety Pharmacology - defined as those studies that
investigate the potential undesirable pharmacodynamic effects
of a substance on physiological functions in relation to
exposure in the therapeutic range and above.
2.6.2.5 Pharmacodynamic Drug Interactions
2.6.2.6 Discussion and Conclusions
2.6.3 Tabulated Summary of Pharmacology
2.6.4 Written Summary of Pharmacokinetics
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46. 2.6.4 Written Summary of Pharmacokinetics
2.6.4.1 Brief Summary
2.6.4.2 Methods of Analysis
2.6.4.3 Absorption
2.6.4.4 Distribution
2.6.4.5 Metabolism
2.6.4.6 Excretion
2.6.4.7 Pharmacokinetic Drug Interactions
2.6.4.8 Other Pharmacokinetic Studies
2.6.4.9 Discussion and Conclusions
2.6.4.10 Tables and Figures
2.6.5 Tabulated Summary of Pharmacokinetics
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47. 2.6.6 Written Summary of Toxicology
2.6.6.1 Brief Summary
Study type and
duration
Route of
Species
administration Compound
Compound
administered*
Single-dose toxicity
po and iv
Rat and mouse
Parent drug
Single-dose toxicity
po and iv
Rat and mouse
Metabolite X
1 month
po
Rat and dog
Parent drug
6 months
po
Rat
“
“
9 months etc.
po
Dog
“
“
Repeat-dose toxicity
47
48. 2.6.6.2 Single-Dose Toxicity
2.6.6.3 Repeat-Dose Toxicity (including supportive toxicokinetics
evaluation)
2.6.6.4 Genotoxicity
Studies should be briefly summarised in the following order:
in vitro non-mammalian cell system
in vitro mammalian cell system
in vivo mammalian system (including supportive
toxicokinetics evaluation)
o 2.6.6.5 Carcinogenicity (including supportive toxicokinetics
evaluations)
Short- or medium-term studies
Long-term studies
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2.6.6.6 Reproductive and Developmental Toxicity
2.6.6.7 Local Tolerance
49. 2.7 CLINICAL SUMMARIES
This section is intended to provide a detailed, factual
summarization of all of the clinical information in the CTD.
This includes:
information provided in clinical study reports;
information obtained from any meta-analyses or other cross-
study analyses for which full reports have been included in
Module 5; and
post-marketing data for products that have been marketed in
other regions
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50.
2.7.1 Summary of Biopharmaceutic Studies and Associated
Analytical Methods
2.7.1.1 Background and Overview
2.7.1.2 Summary of Results of Individual Studies
2.7.1.3 Comparison and Analyses of Results Across Studies
2.7.2 Summary of Clinical Pharmacology Studies
2.7.2.1 Background and Overview
2.7.2.2 Summary of Results of Individual Studies
2.7.2.3 Comparison and Analyses of Results Across Studies
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2.7.2.4 Special Studies
51.
2.7.3 Summary of Clinical Efficacy
2.7.3.1 Background and Overview of Clinical Efficacy
2.7.3.2 Summary of Results of Individual Studies
2.7.3.3 Comparison and Analyses of Results Across Studies
2.7.3.3.1 Study Populations
2.7.3.3.2 Comparison of Efficacy Results of all Studies
2.7.3.3.3 Comparison of Results in Sub-populations
2.7.3.4 Analysis of Clinical Information Relevant to Dosing
Recommendations
2.7.3.5 Persistence of Efficacy and/or Tolerance Effects
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52. 2.7.4.2.1.3 Other S2.7.4 Summary of Clinical Safety
2.7.4.1 Exposure to the Drug
2.7.4.1.1 Overall Safety Evaluation Plan and Narratives of Safety Studies
2.7.4.1.2 Overall Extent of Exposure
2.7.4.2 Adverse Events
2.7.4.2.1 Analysis of Adverse Events
2.7.4.2.1.1 Common Adverse Events
2.7.4.2.1.2 Deaths
erious Adverse Events
2.7.4.2.1.4 Other Significant Adverse Events
2.7.4.2.1.5 Analysis of Adverse Events by Organ System or Syndrome
2.7.4.2.2 Narratives
2.7.4.3 Clinical Laboratory Evaluations
2.7.4.4 Vital Signs, Physical Findings, and Other Observations
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Related to Safety
53. o
2.7.4.5 Safety in Special Groups and Situations
o
2.7.4.5.3 Drug Interactions
o
2.7.4.5.4 Use in Pregnancy and Lactation
o
2.7.4.5.5 Overdose
2.7.4.5.6 Drug Abuse
2.7.4.5.7 Withdrawal and Rebound
2.7.4.5.8 Effects on Ability to Drive or Operate Machinery or
Impairment of Mental Ability
o
o
o
2.7.4.6 Post-marketing Data
2.7.5 Literature References
2.7.6 Synopses of Individual Studies
53
54. MODULE 3 QUALITY
The Quality section of the Common Technical Document
(M4Q) provides a harmonised structure and format for
presenting CMC (Chemistry, Manufacturing and Controls)
information in a registration dossier.
Module 3 content
Module
Content
3.1
Module 3 table of contents
3.2
Body of data
3.3
Literature references
54
55. 3.2 BODY OF DATA
3.2.S DRUG SUBSTANCE(S)
3.2.S.1 General information (name, manufacturer)
3.2.S.1.1 Nomenclature (name, manufacturer)
3.2.S.1.2 Structure (name, manufacturer)
3.2.S.1.3 General Properties (name, manufacturer)
3.2.S.2 Manufacture of Drug Substance (name, manufacturer)
3.2.S.2.1 Manufacturer(s) (name, manufacturer)
3.2.S.2.2 Description of Manufacturing Process and Process Controls
(name, manufacturer)
3.2.S.2.3 Control of Materials (name, manufacturer)
3.2.S.2.4 Controls of Critical Steps and Intermediates
3.2.S.2.5 Process Validation and/or Evaluation (name, manufacturer)
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3.2.S.2.6 Manufacturing Process Development (name,
manufacturer)
56. 3.2.S.3 Characterization of Drug Substance
3.2.S.4 Quality control of Drug Substance
3.2.S.5 Reference Standards or Materials
3.2.S.6 Container Closure System
3.2.S.7 Stability of Drug Substance
3.2.P DRUG PRODUCT (NAME, DOSAGE FORM)
3.2.P.1 Description and Composition of the Drug Product
3.2.P.2 Pharmaceutical Development
3.2.P.3 Manufacture of Drug Product
3.2.P.4 Control of Excipients
3.2.P.5 Control of Drug Product
3.2.P.6 Reference Standards or Materials
3.2.P.7 Container Closure System
3.2.P.8 Stability of drug product
56
57. MODULE 4: NON-CLINICAL STUDY REPORTS
Module 4 describes the format and organisation of the nonclinical
(pharmaco-toxicological) data relevant to the application.
4.2 STUDY REPORTS
4.2.1 Pharmacology
4.2.2 Pharmacokinetics
4.2.3 Toxicology
4.3 literature references
57
58. MODULE 5: CLINICAL STUDY REPORTS
Module 5 describes the format and organisation of the clinical
data relevant to the application.
5.3.1 Reports of Biopharmaceutical Studies
5.3.2 Reports of Studies Pertinent to Pharmacokinetics Using
Human Biomaterials
5.3.3 Reports of Human Pharmacokinetic (PK) Studies
5.3.4 Reports of Human Pharmacodynamic (PD) Studies
5.3.5 Reports of Efficacy and Safety Studies
5.3.6 Reports of Post-Marketing Experience
5.3.7 Case Report Forms and Individual Patient Listings
5.4 literature references
o
58
59. GUIDANCE FOR THE INDUSTRY
Divided in 4 guidance document
M4Q
M4
CTD
59
60. ECTD
6 months behind CTD
May, 2001, Tokyo, Step 2 of the eCTD ICH process was
agreed by Multidisciplinary Group 2 Expert Working Group
(ICH M2 EWG).
Specifications developed by ICH M2 EWG
Maintained by eCTD IWG
Electronic submission from applicant to regulator
60
61. M2 EWG – developed change control process to monitor
implementation process & provide solutions and added flexibility
found necessary during implementation
Addressed and resolved
- study report structure
- lifecycle management
- consistency with CTD
61
64. ECTD:ELECTRONIC
-
CTD
Developed by M2 EWG (Multidisciplinary 2 Expert
Working Group) of ICH.
64
Industry <-----> Message <------> Agency
Paper submission has
been replaced by electronic
submission
/ 19
65. CHARACTERISTICS OF ECTD:1. Files Referenced in the XML Backbone(s)
65
(Extensible Markup Language)
REASONS:
1.It manages the large data for the entire submission and for
each document within the submission.
2.This XML backbone allows the eCTD submission to be
viewed via a web browser and can be loaded on a Web
server.
/ 19
66. 66
2.The file formats that can be included in
the eCTD are Portable Document
Format (PDF) and XML.
However other formats can be used for graphs and
images.
JPEG
PNG
GIF
-may be used for higher resolution.
/ 19
67. 3. All eCTD Submissions Include Module 1
67
Module 1 Identifies following important information:
Company Name
Drug Name
Submission Type
Submission Date
Application Number
Sequence Number
/ 19
68. NOMENCLATURE FOR FILES AND ECTD
SUBMISSION.
EXAMPLE:- MODULE 2 FILE NOMENCLATURE AND eCTD
submission
Description
File Name
2.2 introduction
22-intro
2.3 Quality overall summary
23-qos
2.4 Non clinical Overview
24-nonclin-over
2.5 Clinical Overview
25-clin-over
2.6 Non clinical Written and
Tabulated Summaries
26-nonclin-sum
2.7 Clinical summary
27-clin-sum
68
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70. ADVANTAGES OF CTD
To make the reviewing of each application more easy and
also to avoid omission of critical data or analyses. Omissions
of such data can result in unnecessary delays in approvals.
To save time and resources
To facilitate regulatory review and communications
Appropriate format for the data
Easy to understand and evaluation of data
Applicable to all types of products (NCE,
radiopharmaceuticals, vaccines, herbals, etc.)
70
71. SILENT BENEFITS OF THE CTD
More “reviewable” applications
Complete, well-organized submissions
More predictable format
More consistent reviews
Easier analysis across applications
Easier exchange of information
Facilitates electronic submissions
71
72. LIMITATIONS………
CTD is only a format, its not a single dossier with a single
content.
Legal requirements differ in the different regions
ICH guidelines have not yet harmonized in all requirements
Pharmacopoeias are not harmonized
Applicant may have regional preferences.
72
73. •The eCTD has proved critical to improving application
submission efficiencies as well as reviewer efficiency.
•Besides delivering submission material to the reviewer in an
expedited manner, the eCTD format has made it easier to
develop standardized reviewer e-templates and review tools for
each of the review disciplines.
73
74. IS CTD MANDATORY FOR ALL TYPE OF
SUBMISSIONS?
CTD is mandatory for all.
Import and/or manufacture and marketing approval of new
drugs (New chemical entity, new indication, new dosage
forms, new route of administration etc.), as a finished
pharmaceutical product, for first time submission and for
subsequent applications until 4 years.
Modified release formulations (even after 4 years of
approval by CDSCO)
Fixed Dose Combinations under item (a) of Appendix VI
of Schedule Y of Drugs and Cosmetics Rules 1945.
74
75. CONCLUSION
Whilst the realization of the CTD took many years, there is
now a common format for the submission of Marketing
Authorizations Applications across the three ICH regions Europe, Japan and the USA.
This should facilitate pharmaceutical companies to make
simultaneous filings in the ICH regions as it will eliminate the
extensive work previously required to convert, for example, a
US dossier to an EU dossier and vice versa.
75
76. REFERENCES
1. Molzon J; “The Common Technical Document: the changing face of New Drug
Application”; Nature Reviews – Drug Discovery; Volume 2, January 2003;Page 7174.
2. “Guidance for Industry on Preparation of Common Technical Document for Import /
Manufacture And Marketing Approval Of New Drugs For Human Use (New Drug
Application – NDA)”. Available at http://cdsco.nic.in/CTD_Guidance%20-Final.pdf
3. Roth I R; “Preparing the Common Technical Document for Registration of
Pharmaceuticals for Human Use (CTD) – Insight and Recommendations”; Drug
Information Journal; Volume 42; 2008; Page149-159.
4. “The Common Technical Document- Quality (CTDQ)”. Available at
http://www.ema.europa.eu/ .
5. “Guideline M4: The Common Technical Document”. Available at
http://www.ich.org/products/ctd.html
6. Smith C G, O’donnell J T; “The Process of New Drug Discovery & Development”;
2nd Edition; Informa Health Care USA, Inc.; Page 477.
7. “ICH Harmonised Tripartite Guideline: Organisation Of The Common Technical
Document For The Registration Of Pharmaceuticals For Human Use M4”.
Available at http://www.ich.org/fileadmin
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