Regulatory Affairs

REGULATORY AFFAIRS (RA)
Pipat Sriwachiropas
Research and development Manager
5 February 2014
2M(MED-MAKER) Co., Ltd.
Outline
Regulatory Affairs [ RA ]
RA

ASEAN Harmonization
Section A : Administrative data and product information
Section B : Quality Overall Summary
Section C : Body of Data
Section D : Key Literature Reference

2M(MED-MAKER) Co., LTd.
Whats RA ?
Regulatory Affairs (RA) :

() ( )
ADR

, ,
Whats RA ?
1 - Regulatory compliance :
2 - Regulatory strategy :

3 - Regulatory management system :

4 - Regulatory intelligence :


1. [ New Drugs ND ]
2. [ New Generic Drugs NG ]
3. [ Generic Drugs ]
**********************************************
(Biological Products)
(New Biological Products)
(Conventional Biological
Products)
- New Drugs
1. (New Drugs)-
(New Chemical Entities)

(New Indication)
(New Combination)
- New Drugs
New Combination
[
2 ] - New Combination
(New Chemical Entities)

New Dose
(New Delivery System)

Bioavailability
- NG
2. (New Generic Drugs) :

(New Drugs)
..2534
[ Active, Dose, Dosage form, route of administration ]
New Generic Drugs (Product Interchangeability Equivalence evidence)

(Bioequivalence
studies) / (Comparative in vitro dissolution/release studies)
(Comparative clinical studies) (Comparative
pharmacodynamic studies)
- Generic Drugs
3.(Generic Drugs)

(Active ingredients)
(dosage form)

(new indication)
** Active ingredients, **
- Biotechnology Drug
(Biotechnology Drug) :

(eukaryotic cells)
(extraction of substances
from biological tissues including human, animal, and plant tissues
(allergens)
(recombinant DNA or rDNA techniques)
( hybriddoma techniques)
(propagation of microorganisms in
embryo or animals)

(purity) (potency)
(composition) (chemical)
(physiochemical) *
- Biotechnology Drug
(New Biological Products) :
New Biological Active Pharmaceutical Ingredients

New Indication
New Combination
New Route of Administration
New Dosage Form
New strength
Genetic engineering or Other newer biotechnological
techniques
New Source of Origin -

..8
:
.. 8
..8
: ..8
..8 2
1. .. 8 / .. 8 2
2. .. 8 / .. 8
3. .. 8 / .. 8
4./ 1
Process of Generic Drug Registration

New Product

..8 / ..8
ASEAN Harmonization


1
(St andard Review)

(.. 1)
20
.. 1
30

120
.
10

30
2 10

1
(St andard Review)

( .. 1)
20
.. 1
30
120
70
10

/

30
2 80

(New Generic Drugs)

1
(Standard Review)
(.. 1 )
10

20
60
.
10
10
110
Bioequivalence report
ASEAN Harmonization
ASEAN Harmonization :
10

/( Tariff reduction/elimination )
( Non- Tariff Barrier : NTB)

impurities
NTB 190
: MOU MRA

ASEAN Harmonization
2015 2558 Health care

Free Fee Trade ( )
Barrier ( NTB ) Asean

ASEAN Common Technical Document
ASEAN Common Technical Requirements
ASEAN
ASEAN Harmonization
1 2552
ASEAN Guideline
ASEAN Common Technical Document (ACTD)

ASEAN BA BE Guideline : Malaysia
ASEAN Guidelines Stability : Indonesia
ASEAN Process Validation Guideline : Singapore
ASEAN Validation Analytical Guideline : Thailand
ASEAN Variation Guideline -
: Malaysia/Singapore
ASEAN Harmonization : Reference
ASEAN Harmonization
http://drug.fda.moph.go.th/zone_asean/introdruction.html
http://drug.fda.moph.go.th/zone_service/ser016.asp
.
http://drug.fda.moph.go.th/ ., ,
Asean Harmonization of Standards and Technical Requirements
http://www.asean.org/communities/asean-economiccommunity/item/harmonization-of-standards-and-technicalrequirements-in-asean
Pharmaceutical Technical Guidelines on Pharmaceutical
ICH Quality Guidelines
http://www.ich.org/products/guidelines/quality/article/qualityguidelines.html
ICH - International Conference on Harmonization
(US FDA)
ICH guideline
.. 2556
.. 2556
11 .. 2556
1.
2.
3.
4.
5.
6.
7.
USP34 (2011) and Supplements

BP2011 and Addenda
EP 7 and Supplements (European Pharmacopoeia)
IP 4 and Supplements (International Pharmacopoeia)
BP2011 and Supplements (Veterinary)
Thai Pharmacopoeia II, Volume I, Part 1 and
Supplements
Thai Herbal Pharmacopoeia, Volume I, II, III and
Supplements)
ASEAN Harmonization

ASEAN Harmonization
Part 1: Administrative data and product information

product
Part 2: Quality Document
Quality Overall Summary, Body of Data, Key Literature References
Part 3: Non-Clinical Document

Nonclinical Overview, Nonclinical Summary, Nonclinical Study Report,
List of Key Literature References
Part 4: Clinical Document

Clinical Overview, Clinical Summary, Tabular Listing of All
Clinical Studies, Clinical Study Reports, List of Key Literature
References
Pharmacology : PK [A,D,M,E]
PD receptor
ASEAN Harmonization

ASEAN Harmonization
Part 1: Administrative data and product information

product
Part 2: Quality Document
Section A : Table of Content
Section B : Quality Overall Summary
Section C : Body of Data
Section D : Key Literature Reference ( )

(Product Interchangeability Equivalence evidence)
ASEAN Harmonization

Part 1(Section A)
information
Part 2(Section B)
Part 3(Section C)
Part 4(Section D)
ASEAN Harmonization
: Administrative data and product

: Quality Overall Summary
: Body of Data
: Key Literature Reference ( )
ASEAN Harmonization : Section A

Part 1 : Administrative data and product information
Part A Part 1
... A1 ... AR :

.1 :
, , release product,
, Appearance,
Pharmacopoeia, Finished Product Spec
ASEAN Harmonization : Section A

Part 1 : Administrative data and product information

,
, GMP,
-

( )
Package insert
..8/..8 ( / )
....

ASEAN Harmonization : Section B

Part 2 : Quality Overall Summary

... A2

2 Substance [S] 7
Product [P] 9

S. (Drug Substance) 7
S1 (General Information)
1.1
(Nomenclature) : Chemical name

1.2 (Structure) : Molecular formula,
Molecular Weight, Structure Formula
1.3 (General Properties) :
( Description ), Solubility

S2 (Manufacture)
2.1 (Manufacturer (s))

API
1 Second

Source [ Second Supplier ]

COA
Source


S3 (Characterization)
3.1 (Elucidation of
Structure and Other Characteristics)

Pharmacopoeia

Synthetic partway Impurities
3.2 (Impurities)
Pharmacopoeia
Barrier

Synthetic Pathway
Pack
Purity&Safety
Stability Physio-Chemical
properties
ICH Guildline Part ICH Q3A
(R2), ICH Q3B (R2)

S4 (Control of Drug Substance)
4.1 (Specification)
(Certificate of Analysis - COA)
Monograph Pharmacopoeia
reference
COA Supplier API
COA Supplier S2.1
Xerox Monograph
Related
Substance

:
Standard
4.2 (Analytical Procedures)

Test Description
Chromatogram
4.3 (Validation of Analytical
Procedures)
Pharmacopoeia Validation
Assay identification

S5 (Reference Standards or
Materials)
API Reference Standard
COA Reference Standard
Working Standard
S6
API API


S7 (Stability) : API
Protocol ASEAN Guidelines Stability
COA

-
Lab

,

Minimum Shelf-life
Manufacturing

P. (Drug Product) 9 Part
P1 (Description and Composition)

( Physical appearance )
% Each gram contains Urea 100 mg (10% W/W)

BP2010, p.1159
Overage
Overage Loss on Process
P2 (Pharmaceutical
Development) :

Dosage form
2.2 (Components of the Drug Product) :

2.3 (Finished Product) :
Finished Product Specification Monograph
Pharmacopoeia
2.5 (Container Closure System) :
Product

P2 (Pharmaceutical Development)
(Microbiological Attributes) :
Total Microbial Count, Test for pathogen
, Preservative Efficiency
2.7 (Compatibility)
- [ Handbook of
Exipients 12. Incompatibilities ]
-
,
2.6
P3 (Manufacture)
3.1 (Batch Formula) :
- - Batch Formula
- Overage Overage
3.2 (Manufacturing
Process and Process Control)
-
- Flow Chart
P3 (Manufacture)
3.3 (Control of
Critical Steps and Intermediates)
- intermediate
- in-process control
- Bulk Product
P3 (Manufacture)
3.4 /
(Process Validation and/or Evaluation)
- Follow ASEAN Process Validation Guideline
Process Validation
4
1. Prospective Validation :
2. Concurrent Validation :
3. Retrospective Validation :
4. Re-Validation :

P3 (Manufacture)
Process Validation
1 Validation Report Production Batch 3

Batch
2 Development Pharmaceutics Report

Process Validation Report Pilot Batch 1 +
Validation Scheme ( )
3
reference agency
declaration statement
P4 (Control of excipients)
4.1 (Specifications) :
Pharmacopoeia Xerox

4.2 (Analytical Procedures)

COA Supplier
4.3 (Excipients of Human

or Animal Origin)

P5 (Control of Finished Product)
5.1 (Specification) (Certificate

of Analysis)
Finished Product Specification
Pharmacopoeia Xerox Pharmacopoeia
Spec Meet the requirements, Comply with

90.0 -100.0 %
Related Substance %
Range of mean weight
Shelf-Life Storage Condition Stability Study

(Analytical Procedures)
- Finished Product Specification
- Chromatogram
- Pharmacopoeia Method
Verification (Specificity, Accuracy, Precision)
5.2
Validation (Specificity, Accuracy, Precision, Linearity,Range)

(Validation of Analytical
Procedures )
5.3
- ASEAN Validation Analytical Guideline

Verification (Specificity, Accuracy, Precision)
Validation (Specificity, Accuracy, Precision, Linearity&Range)

(Batch analyses)
- [ Chromatogram ]
- HPLC System Suitability
-
- COA
5.4

(Characterization of
Impurities) : Pharmacopoeia
5.5
Standard Related Substance

Related Substance Detection Limit
Spec Toxicology
Spec

Impurities 3
1. API intermediated ( )
API By product ( )
2. Formulation API Hydrolysis Degradation Product (
)
3. API
Related Substance = Degradation Product + By product + intermediated
P6 (Reference Standards or
Materials)
Part S5
API Reference Standard
COA Reference Standard

P7 (Container Closure system)

Finished
Product
Specification Packaging

P8 (Stability)
ASEAN Guidelines Stability Long term
Accelerated studies
Lot.

Assay 5%
Degradation Product
pH
Dissolution

ASEAN Stability Guildline
4.5 : Testing Frequency

Storage Condition
Products
Real time
NCE, NG, Generic and

0, 3, 6, 9, 12, 18, 24
Variation (MaV and MiV) months and annually
through the proposed
shelf-life
Accelerated
NCE , NG, Generics

and Variations
(MaV and MiV)
Testing Frequency
0, 3 and 6 months
4.7 : Storage Condition

4.7.1
General case
TYPE OF CONTAINER/STUDY
STORAGE CONDITION
Long term (products in primary containers

Semi-permeable to water vapour )
30 oC +2 oC
75 %RH +5 %RH
Long term (products in primary containers

impermeable to water vapour )
30 oC +2 oC
RH not specified
Accelerated studies
40 oC +2 oC
75 %RH +5 %RH
Stress studies
40 oC +2 oC
75 %RH +5 %RH
or at more stressful conditions
4.7 : Storage Condition

4.7.3
Drug Products (Aqueous based) packaged in

Semi-permeable containers condition for water loss
TYPE OF
CONTAINER/STUDY
STORAGE CONDITION
Duration
Long term
30 oC +2 oC
35 %RH +5 %RH
12 months
Accelerated studies
40 oC +2 oC
Not more than 25 %RH
6 months
P9 (Product
Interchangeability Equivalence Evidence)
(Bioequivalence
Study Data) AZT, ,
Sustained release

(Bioequivalence study Report)
ASEAN Harmonization : Section C
Part III : Body of data -

Section C Section B
Pharmacopoeia

Specification
Protocol Stability Protocol, Method Validation,
Process Validation
Result Stability Validation
Certificate of Analysis
Certificate of Standard reference

ASEAN Harmonization : Section D
Part IV : Key Literature Reference

Section D

.. 2556
.. 2556
11 .. 2556
1.
2.
3.
4.
5.
6.
7.
USP34 (2011) and Supplements

BP2011 and Addenda
EP 7 and Supplements (European Pharmacopoeia)
IP 4 and Supplements (International Pharmacopoeia)
BP2011 and Supplements (Veterinary)
Thai Pharmacopoeia II, Volume I, Part 1 and
Supplements
Thai Herbal Pharmacopoeia, Volume I, II, III and
Supplements)
ASEAN Harmonization
ASEAN Common Technical Document (ACTD)

ASEAN BA BE Guideline.
ASEAN Guidelines Stability
ASEAN Process Validation Guideline
ASEAN Validation Analytical Guideline
ASEAN Variation Guideline
Regulatory Affairs
Regulatory Affairs (RA) :

()
Research& Development
Pre-Clinical Clinic
ADR

Life cycle Product ( )
THANK YOU
Pipat Sriwachiropas
086-016-8008
2M(MED-MAKER) Co., Ltd.

Regulatory Affairs

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REGULATORY AFFAIRS (RA)

2M(MED-MAKER) Co., Ltd.

2M(MED-MAKER) Co., LTd.