1. InEtUe rGnCaPti onal Conference on
Harmonization (ICH)
Consolidated Guidelines
Pravin Cumar
Head Academics
2. EU GCP
What is ICH?
Need to harmonies
Purpose of harmonization
Initiation of ICH
Objectives of ICH
The Structure of ICH
The process of Harmonization
ICH Guidelines – Q, S, E & M
ICH & the Future
The Impact of ICH
3. EU GCP
ICH is a unique joint initiative
involving both regulators and
industry as equal partners in the
scientific and technical
discussions of the testing
procedures which are required to
ensure and assess the safety,
quality and efficacy of medicines.
4. EU GCP
Awareness on critical evaluation of
medicinal products before market release
Medical tragedies
1960-70s:
Rapid increase in laws, regulations & guidelines
on medicinal products
Globalization of Pharmaceutical industry
But regulation of medicine remained as a
national responsibility
5. EU GCP
These changes lead to:
Duplication of work
Raising cost of health care
Escalation of R&D costs
Delay in drug development
6. EU GCP
The purpose is to make
recommendations on ways to achieve
greater harmonization in the
interpretation
Application of technical guidelines
Requirements for product registration in
order to reduce or obviate the need to
duplicate the testing carried out during
the research and development of new
medicines.
7. EU GCP
Aim to produce a single set of technical
requirements for the registration of new
drug, drug products to streamline
development.
Reduce or obviate duplicate testing
More economical use of human, animal and
material resources.
Eliminate unnecessary delays in the
availability of new medicines.
8. EU GCP
Availability of new medicines whilst
maintaining safeguards on quality, safety
and efficacy, and regulatory obligations to
protect public health.
To provide a unified standard for the
European Union (EU), Japan & United
States to facilitate mutual acceptance of
clinical data by the regulatory authorities
in these jurisdictions
9. EU GCP
Member:
Steering committee (SC):
ICH Parties - 6
ICH – Coordinators (One from each party)
Observers - 3 (non-voting)
IFPMA: Secretariat
Expert Working Groups (EWGs)
10. EU GCP
Expert working group: The SC is
advised on technical issues concerned
with harmonization topics by Expert
Working Groups.
They are nominated from the 6 Co –
Sponsors.
11. EU GCP
Participants
Six Parties: EU, EFPIA, FDA,
MHLW, JPMA, PhRMA,
Three Observers: WHO, EFTA, CanadaEuropean
Commission - European Union (EU)
European Federation of Pharmaceutical Industries
and Associations (EFPIA)
US Food and Drug Administration (FDA)
Pharmaceutical Research and Manufacturers of
America (PhRMA)
Ministry of Health, Labor and Welfare, Japan (MHLW)
Japan Pharmaceutical Manufacturers Association
(JPMA)
12. EU GCP
STEERING COMMITTEE:
Oversees the preparation for ICH and
the harmonization initiatives under
taken under the ICH Process.
2 members from each of the 6 co-sponsors
Determines policies & procedures
Selects topics for harmonization
Monitors progress of harmonization
initiatives
13. EU GCP
Five-step approach
Step 1: Consensus building
Step 2: Confirmation of six-party harmonised
and consensus text released
Step 3: Regulatory Consultation and
Discussion outside the ICH
Step 4: Adoption of an ICH Harmonized
Guideline
Step 5: Implementation
14. EU GCP
Quality (Q)
- chemical & pharmaceutical QA
Safety (S)
dealing with in vitro & in vivo pre clinical
testing
Efficacy (E)
clinical studies in human beings
Multidisciplinary (M)
Terminology
Electronic Standards
Common Documents
15. EU GCP
Q 1(A-F): Stability - Photostability
Q 2: Analytical Validation
Q 3(A-C): Impurities
Q 5(A-E): Biotechnological Quality
Q 6(A,B): Specifications
Q 7: GMP for active pharma ingredients
Q 8: Pharmaceutical development
Q 9: Quality risk management
Q10: Pharmaceutical Quality System
16. EU GCP
S1: Carcinogenicity studies – Need,
Testing, Dose Selection
S2: Genotoxicity – Regulatory, Battery of Tests
S3A: Toxicokinetics
S3B: Pharmacokinetics
S4: Chronic Toxicity Testing
S5A: Toxicity to Reproduction
S5B: Toxicity to Male Fertility
S6: Preclinical Biotech derived drugs
S7A: Safety Pharmacology
S7B: QT interval prolongation
S8: Immunotoxicity for Human Pharmaceuticals
S9 : Nonclinical Evaluation for Anticancer Pharmaceuticals
17. EU GCP
E 1: Exposure to assess clinical safety
E 2: Clinical Safety Data Management
E 3: Study Reports
E 4: Dose Response Studies
E 5: Ethnic Factors
E 6: Good Clinical Practice (GCP)
E 7: Special Populations – Geriatrics
E 8: Clinical Trials Design
E 9: Statistical Considerations
18. EU GCP
E 10: Choice of Control Group
E 11: Special Populations – Children
E 12: Therapeutic categories
E 14: The clinical evaluation of QT/QC interval prolongation &
pro arrhythmic potential for non antiarrhythmic drugs
E15: Definitions for Genomic Biomarkers,
Pharmacogenomics, Pharmacogenetics, Genomic Data
& Sample Coding Categories
E16: Genomic Biomarkers Related to Drug Response:
Context, Structure and Format of Qualification
Submissions
19. EU GCP
M1: Medical Terminology
M2: Electronic Standards for Transfer of
Regulatory Information & Data (ESTRI)
M3: Maintenance of ICH guidelines for nonclinical
safety studies
M4: Common Technical Document (CTD)
M5: Data Elements and Standards for Drug
Dictionaries
20. EU GCP
IMPACT :
Enhanced patient safety
Streamline development programs
Common quality standard
Reduce resource requirements
Forum for Communication
Opportunity for Industry & Regulators to sit across
the table
Discuss drug development procedure with a
common goal of identifying best scientific
practice and applying the same uniformly across
the globe
22. US FOOD & DRUG ADMINISTRATION
The Food and Drug Administration is one of
the nation's oldest and most respected
consumer protection agencies.
www.fda.gov
23. FDA's mission
FDA's mission is:
To promote and protect the public health by
helping safe and effective products reach the
market in a timely way,
To monitor products for continued safety after
they are in use, and
To help the public get the accurate, science-based
information needed to improve health.
24. Overview
At the heart of all FDA's regulatory activities is a
judgment about whether a new product's benefits to
users will outweigh its risks.
Science-based, efficient risk management allows the
agency to provide the most health promotion and
protection at the least cost to the public.
No regulated product is totally risk-free, so these
judgments are important. FDA will allow a product
to present more of a risk when its potential benefit is
great -- especially for products used to treat serious,
life-threatening conditions.
25. FDA Departments
FDA is an agency within the Department of
Health and Human Services and consists of 9
centers/offices.
Center for Biologics Evaluation and Research
(CBER)
Center for Devices and Radiological Health
(CDRH)
Center for Drug Evaluation and Research
(CDER)
26. Contd…
Center for Food Safety and Applied Nutrition
(CFSAN)
Center for Veterinary Medicine (CVM)
National Center for Toxicological Research
(NCTR)
Office of Chief Counsel
Office of the Commissioner (OC)
Office of Regulatory Affairs (ORA)
27. CBER
CBER's mission is to protect and enhance the public
health through the regulation of biological and related
products including blood, vaccines, allergenics, tissues,
and cellular and gene therapies.
Biologics, in contrast to drugs that are chemically
synthesized, are derived from living sources (such as
humans, animals, and microorganisms), are not easily
identified or characterized, and many are manufactured
using biotechnology.
28. CBER
These products often represent cutting-edge
biomedical research and, in time, may offer the
most effective means to treat a variety of
medical illnesses and conditions that presently
have few or no other treatment options.
29. CDRH
More than 20,000 firms worldwide produce over
80,000 brands and models of medical devices for
the U.S. market, ranging from contact lenses and
blood sugar monitors to implanted hip joints and
heart valves.
The FDA's Center for Devices and Radiological
Health (CDRH) makes sure that new medical
devices are safe and effective before they are
marketed.
30. Contd…
Many of these devices are the first of a kind,
such as a robotic arm that can operate a variety
of surgical tools with tremendous precision.
Other high-tech devices are designed to
prevent, diagnose or treat cancer, heart disease,
impaired vision and hearing, and other health
problems.
31. Contd….
The center also monitors devices throughout
the product life cycle, including a nationwide
postmarket surveillance system.
And it assures that radiation-emitting products,
such as microwave ovens, TV sets, cell phones,
and laser products meet radiation safety
standards.
32. CDER
The FDA's Center for Drug Evaluation and
Research (CDER) promotes and protects the
health of Americans by assuring that all
prescription and over-the-counter drugs are
safe and effective.
CDER evaluates all new drugs before they are
sold, and serves as a consumer watchdog for
the more than 10,000 drugs on the market to be
sure they continue to meet the highest
standards.
33. Contd…
The center routinely monitors TV, radio, and
print drug ads to ensure they are truthful and
balanced.
CDER also plays a critical role in providing
health professionals and consumers
information to use drugs appropriately and
safely.
34. CDER regulates-
Prescription Drugs: Prescription medicines
include any drug product that requires a
doctor's authorization to purchase.
Generic Drugs: A generic drug is a drug
product that is equivalent to brand name
products in terms of quality and performance.
Over-the-Counter Drugs: OTC drug products
are available to consumers without a doctor's
prescription.
36. Introduction
Title 21 is the portion of the Code of Federal
Regulations that governs food and drugs within
the United States for the Food and Drug
Administration (FDA), the Drug Enforcement
Administration (DEA), and the Office of
National Drug Control Policy (ONDCP).
37. It is divided into three chapters:
Chapter I — Food and Drug Administration
Chapter II — Drug Enforcement
Administration
Chapter III — Office of National Drug Control
Policy
38. Chapter I
• Most of the Chapter I regulations are based on the
Federal Food, Drug, and Cosmetic Act.
• Notable sections:
• 11 - electronic records and electronic signature
related
• 50- Protection of human subjects in clinical trials
• 56- Institutional Review Boards that oversee clinical
trials
• 58- Good Laboratory Practices (GLP) for nonclinical
studies
39. The 100 series are regulations pertaining to food:
101, especially 101.9 — Nutrition facts label related
106-107 requirements for infant formula
110 cGMPs for food products
170 food additives
190 dietary supplements
40. The 200 and 300 series are regulations
pertaining to pharmaceuticals :
202-203 Drug advertising and marketing
210 cGMPs for pharmaceuticals
310 Requirements for new drugs
328 Specific requirements for over-the-counter
(OTC) drugs.
41. The 500 series are regulations for animal feeds
and animal medications:
The 600 series covers biological products (e.g.
vaccines, blood):
The 700 series includes the limited regulations
on cosmetics:
The 800 series are for medical devices:
42. The 900 series covers mammography quality
requirements enforced by CDRH.
The 1000 series covers radiation emitting
device (e.g. lasers, cell phones) requirements
enforced by CDRH.
The 1200 series consists of rules primarily
based in laws other than the Food, Drug, and
Cosmetic Act:
43. Chapter II
1308.11 — List of Schedule I drugs
1308.12 — List of Schedule II drugs
1308.13 — List of Schedule III drugs
1308.14 — List of Schedule IV drugs
1308.15 — List of Schedule V drugs
44. Chapter III
1405 Government wide requirements for drug-free
workplaces