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MFDS drug approval system
2013
We are dedicated to professional, individualized and market-specific solutions
to make our clients’ expansions into Korea and success in the global market
 Contents
MFDS Organization Overview
 Regulatory Infrastructure
 Review and Approval Process
MFDS : Ministry of Food & Drug Safety, it was changed from KFDA since April, 2013
www.mfds.go.kr
KFDA : Korea FDA
MFDS > KFDA
 Contents
MFDS(KFDA) Organization Overview
 Regulatory Infrastructure
 Review and Approval Process
MFDS Organization
Ministry of Food and Drug Safety
MFDS Organization
National Institute of Food and Drug Sadety Evalustion
Pharmaceutical Safety Bureau
Pharmaceutical Safety Bureau
• Drug Evaluation Department
• Pharmaceutical Safety Policy Division
• Pharmaceutical Management Division
•
Division
• Pharmaceutical Quality Division
• Narcotics Control Division
•
Pharmaceutical Standardization Division
•
Cardiovascular & Neuropharmacological
• Drug Evaluation Department
Mission of Drug Evaluation
Department is to Review to
assure quality control, safety and
efficacy of pharmaceutical drug
Drug Approval & Review Management
Drugs Division
•
Oncology and Antibiotics Division
•
Gastroenterology & Metabolism Products
Division
•
Bioequivalence Evaluation Division
Pharmaceutical Safety Bureau
 Marketing Authorization
 Clinical Trial Review
 Advertisement Regulation
 Post-Marketing Surveillance
 Quality Control
 Contents
MFDS(KFDA) Organization Overview
 Regulatory Infrastructure
 Review and Approval Process
Regulatory Infrastructure
 Regulatory hierarchy on Clinical Trials & Drug Approval
•
Pharmaceutical Affairs Law
•
Enforcement Rule of Pharmaceutical Affairs Law
•
Guideline
•
Guideline on GCP
•
Guideline on IND
•
Guideline for Accredited Clinical Institutes
•
Regulation for Review and Approval of Drugs
•
Regulation for Review and Approval for Biological Products
 Continuous legalization efforts to support Regulatory Harmonization
in order to achieve globalization
Drug Approval Evaluation Process and
Current Status
❖ Objective
To assure the safety, efficacy and quality of drug products consumed in
the domestic market
❖ Subject
Approval
Central KFDA
Items require safety efficacy
review and management
Notification
Regional KFDA
Items do not require safety
and efficacy review
 Contents
MFDS(KFDA) Organization Overview
 Regulatory Infrastructure
 Review and Approval Process
Review and Approval Process of IND & NDA
Pre-IND
Meeting
Pre-clinical
Development
IND Application KFDA Review(30 days)
Phase I
Clinical
Trial
Phase II
Clinical
Trial
Phase III
Clinical
Trial
CPAC
Consultation
NDA
Approval
Phase IV
KFDA Review (90 days)
(including pre-review for 5 days)
*CPAC : Central Pharmaceutical Affairs Advisory Committee
Sponsors have submitted application as electronic documents
through KiFDA online system since Oct. 2nd, 2006
Central Pharmaceutical Affairs Council (CPAC)

CPAC deliberates on the following;

Provide advice and experts opinion on scientific
issues

CPAC are outside experts such as physician,
researchers, pharmacologists, chemists, and
statisticians

Other important subcommittee
Drug Approval Process
Application
Preliminary Evaluation
Evaluation
Confirmation of approval
Issuing the certificate of approval
Applicant
Drug Approval &
Review Management
Division, MFDS
•Research and
development of drug
•Write a preliminary
report
•Prepare dossier for
drug approval
-Application Outline
•Review of technology by
an area
-Examine the application
-safety, efficacy data
(Article 31, 42 of
Pharmaceutical Affairs
Law )
Drug Evaluation
Department,
MFDS
•Preliminary review results
-quality
- bioequivalence and
compare clinical trials
-GMP / DMF data, etc
•Review of social impacts
Applicant
•Issuing the certificate of
approval
•Drug approval
results release
Data Requirements of NDA
Non
Clinical
Clinical
CMC
Pharmacology
GMP
ADME
Toxicology
Phase I
Phase II
Phase III
Bridging
DMF
(Foreign
New
Drug)
Safety and Efficacy Evaluation
CPP,
etc
Dossier for Safety & Efficacy Evaluation
Origin or
backgrounds leading up to discovery and development
Clinical data
A. Clinical data package
B. Bridging Data
Structure · physical, chemical and biological nature
A. Drug Substance
B. Drug Product
1
2
Stability
Stability test data
A.Drug Substance
B.Drug Product
Long-term,
accelerated,
stressed
3
4
Toxicity
A. Single dose toxicity
B. Repeated dose toxicity
C. Genetic toxicity
D. Carcinogenicity
E. Reproductive and
developmental toxicity
A. Others
antigenicity,
immunotoxicity,
local toxicity, dependency, etc.
5
6
7
8
Comparison with
domestic copies
& special features
of the drug concerned
Uses in other countries
Pharmacologic effects
A. Efficacy studies data
B. Safety or general pharmacology
studies data
B. ADME
C. Other pharmacologic effects
Bridging Concept
New
Product
“Bridging Data” = “Korean Data”
“Bridging Study” = “A trial conducted for the Korean People ”
Ethnic Factors
(Ethnic differences)
Intrinsic factor (genetic)
Approval
in Korea
Extrinsic factor
(culture, the environment)
Evaluation
Ethnic Sensitivity
Foreign Clinical Data
Bridging Data
DMF Introduction

KDMF : API registration system
(effective as of July 1st, 2002)
Background
•
Concerns about using low quality of drug substances
•
Quality control of drug substances
Scope
•
New chemical entities used as APIs
•
Phase-in of other APIs registration (designated by KFDA)
# Only drug substances registered can be used.
Common Technical Document (CTD)
Module 1
Regional
Administrative
Information
Course of development, comparison
Module 2.1
Table of Contents
with similar drugs, CPP, etc.
Standard and test procedure
(including stability data)
2.2 CTD Introduction
SE Data (excluding stability data)
2.3
Quality
Overall
Summary
2.4 Nonclinical
Overview
2.6 Nonclinical Written &
Tabulated Summaries
2.5 Clinical
Overview
2.7 Clinical
Summary
Module 3
Module 4
Module 5
Quality
Nonclinical
Study Reports
Clinical
Study Reports
Revision of KGMP Regulation
Background
•To improve the current KGMP to the international level
•Korean pharmaceutical companies could be internationally
competitive
•International collaboration on GMP like PIC/S
Major Changes
•Pre-approval KGMP (Product-based)
•Process Validation
•Site Inspection by KFDA before the product approval
Definition
 New
drug

Is a drug containing a new medicinal substance with
entirely different chemical structure or material
composition from those of drugs which have already
been approved in Korea.

Is combined preparations containing new medicinal
substances as active ingredient
Definition
 Non-new
drug requiring data submission
Is not new drug but is subject to evaluation of safety and
efficacy
 Consist of as follows;
 New efficacy
 New composition
 New formulation
 New dosage form
 New administration route

Exception of Safety and Efficacy Data

Drugs may be excluded evaluation for safety and efficacy.
 Drugs listed in the followings;
 Pharmacopia (KP, USP, JP, BP, EP, Deutsches
Arzneibuch and Pharmacipee Francaise)
 Pharmaceutical compendia published in the past 3 yrs
(US PDR, Drugs in Japan, ABPI Data Sheet
Compendium, Rote Liste, VIDAL, L'iniformatore
Farmaceutico, Arzneimittel Kompendium der
Schweiz, Compendium of Pharmaceuticals and
Specialties )
NDA Filing
1. Origin, background of discovery and development
2. Structure, physicochemical properties, and biological properties
3. Stability
a. Long-term storage or accelerated testing b. Stress testing
4. Toxicology
a.
Acute toxicity
b.
Subacute and chronic toxicity
c.
Reproductive and development toxicity
d.
Inhaling toxicity,
e.
Genetic toxicity,
f.
Immunological toxicity
g.
Carcinogenetic toxicity
h.
Local toxicity
5. Pharmacology
a.
Efficacy
b.
General/Safety Pharmacology
c.
Pharmacokinetics
6. Clinical data
a. Safety and Effectiveness b. Bridging data
7. Usage in foreign countries
8. Comparison with similar drugs that are currently available in Korea
Stability
•
Data that are prepared from test in according to Guidelines
for Stability of drugs (MFDS Notification 2000) or ICH
guidelines
a. Long Term Storage testing is ;
– Study under the recommended storage condition, for the retest period or shelf life proposed (or approved) for labeling
– 25℃ / 60% RH
b. Accelerated testing
– 40℃ / 75% RH
c. Stress testing (photostability)
– 50 ℃, -20 ℃, light, acid/base solution
Toxicology
• Data that are prepared from test in according to Guidelines for
Toxicity test of drugs (MFDS Notification 1999)
• Tested under Good Laboratory Practice guidelines for toxicity
test of drugs
• Test methods and evaluation standards are appropriately found
to be scientific and rational.
• Categories
a. Acute toxicity
b. Subacute and chronic toxicity
c. Reproductive and development toxicity
d. Inhaling toxicity,
c. Genetic toxicity,
f. Immunological toxicity g. Carcinogenetic toxicity
h. Local toxicity
Pharmacology
Data shows pharmacological action and mechanisms of
drugs
Categories
a. Efficacy
b. General Pharmacology or Safety Pharmacology
c. Pharmacokinetics (Absorption, Distribution,
Metabolism, and Excretion)
Clinical Trials
Data are prepared in according to Korea GCP or ICH
GCP
Clinical data was therapeutic confirmatory study that is
to ascertain the safety and efficacy of the test drug in a
large number of selected patients in order to determine
the indication, dosage & administration and precaution
in human use
NOTIFICATION
APPROVAL
Requirement related to safety and efficacy
New drug
Data submission
Drug
Generic Drug
Reference Compendia
listed Drug
Any drug product never approved in Korea.
New Chemical Entity.
New indication, composition, formulation, dosage
form, and New administration route
Major
claims
Medium
claims
A drug product that is comparable to brand/reference
listed drug product in dosage form, strength, route of
administration and intended use.
Minor
claims
Drug product is listed in Reference Compendia and
Korean Pharmaceutical Codex.
Waived
APPROVAL
Requirement related to safety and efficacy
-New drug
New drug
• Any drug product never
approved in Korea. New Chemical Entity.
• New tests; stability data, total pharm/tox
Data submission
Drug
data, clinical data
NOTIFICATION
• Labeling
• New indication
Generic Drug
Reference Compendia
listed Drug
• New dosage and administration
APPROVAL
Requirement related to safety and efficacy
- Data submission Drug
New drug
• New indication, composition, formulation,
dosage form, and New administration route
of previous marketed drug products
Data submission
Drug
• Required new tests; part of pharm/tox data,
NOTIFICATION
clinical data according to claims level
• Labeling
Generic Drug
• Indication, dosage & administration with
appropriate evidentiary support
Reference Compendia
listed Drug
APPROVAL
Requirement related to safety and efficacy
- Generic drug
New drug
• Same API, dosage, formula
• Required for Bioequivalence test or
Data submission
Drug
comparative clinical test
NOTIFICATION
• Labeling
• Same with Pre-Approved product
Generic Drug
Reference Compendia
listed Drug
APPROVAL
Requirement related to safety and efficacy
- Listing Drug
New drug
• Reference Compendia
• KP, USP, JP, BP, EP, Deutsches Arzneibuch
Data submission
Drug
and Pharmacipee Francaise
NOTIFICATION
• the Manufacturing Standards of Pharmaceuticals
• Not required new test; pharm/tox data,
Generic Drug
clinical data
• Labeling
Reference Compendia
listed Drug
• Pre-Approved product
Establishment of Pharma Spec.
Standards of strength or potency
1. General standard
A. Pharmaceutical ingredients: not less than 99.0%
B. Single preparations: 95.0-105.0% (for externally applied preparations, 90.0-110.0%)
C. Multiple preparation : 90.0-110.0%
2. Antibiotic preparations: 90.0-120.0%
3. Vitamins
A.Vitamin multiple preparation (except injections) and vitamins and metal elements
added in the vitamin multiple preparation: 90.0-150.0%
B.Vitamin single preparations and vitamin injections: 90.0-130.0%
C.Vitamin
4. Volatile substances of the pharmaceutical: 90.0-130.0% (e.g., menthol, thymol,
camphor, ethanol, etc.)
Establishment of Pharma Spec.
5. Single and multi nucleic acids: 90.0-130.0% derivatives preparations: 90.0-130.0%
6. Enzyme preparations
A. Pharmaceutical ingredients: not less than 100.0%
B. Digestive enzyme preparations: not less than 90.0%
C. Anti-inflammatory enzyme preparations: 90.0-130.0%
7. Single or multi amino acids and their derivatives preparations: 90.0-130.0%
8. Lactic acid bacteria preparations and other probiotics: not less than 90.0%
9. Disinfectants: 90.0-110.0%
10. Protein∙organ extracts (hydrolysis) preparations
A. Pharmaceutical ingredients: not less than 100.0%
B. Drug products: not less than 90.0%
Establishment of Pharma Spec.
11. If it is impossible or unnecessary to determine the content of active
pharmaceutical ingredients and so, the specification of content is not established,
the efficacy test, performance test, or pharmaceutical test may be conducted
instead (e.g., medicinal carbon: absorption capacity test).
Establishment of Pharma Spec.
Test standards for other quality control
1.pH: ± 1.0 as for actual statistical values
2.Specific gravity: ± 0.05 as for actual statistical values
3.Residue on evaporation: Upper limit shall be established on the basis of actual
statistical values.
4.Alcohol number: This test shall be established for oral preparations containing not
less than 4% of ethanol and the limit shall be not less than 90.0% of t
5.Preservatives test: This test shall be established for drug products containing
preservatives. In this case, the preservative shall be identified and the content shall
be not more than the labeled value. As for all preparations except oral solutions, the
amount of the content shall be 80.0-120.0% of the labeled value. If necessary, other
appropriate ranges may be established separately. he labeled value.
Establishment of Pharma Spec.
Test standards for other quality control
6. Uniformity of dosage units: Korean Pharmacopoeia and Specification & Test
Methods for Mass (Volume) Variation of Pharmaceuticals, etc. (KFDA's
Notification) shall be applied.
7. Microbial limit test: Specification & Test Methods for Microbial Limit Test
of Pharmaceuticals, etc. (KFDA's Notification) shall be applied.
8. Adhesive strength: When tested according to the Adhesive strength method
described in the adhesive plaster of the Korean Pharmacopoeia, plasters and
pressure sensitive adhesives, and cataplasmas shall have the adhesive strength of
not less than 42 g per 12 mm wide.
9. Texture (length and width): When tested according to the Texture described
in the adhesive plaster of the Korean Pharmacopoeia, the length and width shall
be not less than 98.0% of the labeled values.
Establishment of Pharma Spec.
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