new drug application of biotechnology products in …...example 13 pca (partial change application)...
TRANSCRIPT
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New Drug Application of
Biotechnology products in Japan
Approval Contents (i.e. Legal binding)
related to CMC part
JPMA Biopharmaceutical Committee
Technology Working Committee
Takao Kojima
CASSS CMC Strategy Forum Japan 2015
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Outline
1. Overview of relationship between Application Form
and J-CTD
– J-NDA / Application Form and J-CTD
– Approval Contents
2. Change Control for Approval Contents
– Variation Applications
– Application format for PCA and MCN
3. Issues Regarding the current Application Form
(J-M1.2) "legal Binding" for Biotechnology Products
– Description of Application Form (J-M1.2) for Biotechnology
products
4. Approaches taken at JPMA Biopharmaceutical
Committee
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1. OVERVIEW OF RELATIONSHIP
BETWEEN APPLICATION FORM AND J-CTD
AS ITS ATTACHMENT
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J-NDA / Application Form and J-CTD
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J-NDA / Application form and J-CTD
Application Form
Product Name
Ingredient and Contents
Manufacturing Process
Dosage and
Administration
Indications
Storage and Shelf life
Specification and
Testing Method
Manufacturing Sites
・・・・・・・・・・・・・・・
M1 M4M3M2 M5
Evidence
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– Module 1 is region specific and written in Japanese
– Module 2 is the primary review unit for PMDA (written in Japanese)
– M 3, 4 and 5 can be written in English.
including
Application form
Lengthier, more
contents than US
or EU version
CTD
Not
Part
of
CTD
Module 2
Basic Concept for J-CTD
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J-NDA / Application form and J-CTD
Application Form
Product Name
Ingredient and Contents
Manufacturing Process
Dosage and
Administration
Indications
Storage and Shelf life
Specification and
Testing Method
Manufacturing Sites
・・・・・・・・・・・・・・・
M1 M4M3M2 M5
Evidence
Contents provided in the
Application Form by applicants
are dealt as "matter subject to
approval."
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Approval Letter
Approval #
NDA Date
Reexamination Period
International Birth
Date
Approval Date
・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・
Contents described in Approval Letter are
"legal binding" approval matters.
Approval Contents
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Approval Contents
Module 1.2 : Application Form
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Approval contents
Product Name
Ingredient and Contents
Manufacturing Process
Dosage and Administration
Indications
Storage and Shelf life
Specification and Testing
Method
Manufacturing Sites
Application form
Any changes in the matters entered in
the Application Form
shall be addressed in administrative
regulatory procedures (PCA or MCN).
Almost all
parts are
CMC contents
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2. CHANGE CONTROL FOR APPROVAL
CONTENTS
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Variation Applications
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New Drug Application (NDA)
Required for change in the brand name, active
ingredients or their content or dosage form
Partial Change Application (PCA; sNDA)
Acceptable for change in ingredients other than
the active ingredient, their contents, dosage and
administration, indication, manufacturing method,
specification and test method, etc
Minor Change Notification (MCN)
Acceptable if proposed change is minor (no effect
to the quality, efficacy or safety of the product)
LCM regulatory system in Japan
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PCA(partial change application)
MCN(minor change notification)
1. Prior to the change
2. Regulatory review
3. Data required (basically)
1. 30 days after the change
2. Reviewed at next PCA
3. No data submitted
(US : PAS, EU : Type II ) (US : CBE, EU : Type IA)
!Change occurs
PCAMCN
prior after12M 30 days
Regulatory review
Difference between PCA and MCN
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Example
13
PCA
(partial change application)
MCN
(Minor Change notification)
1. Package form change/addition
2. Site change/addition
(DS, DP, storage, package)
3. Ingredients’ prescription change
4. Manufacturing Process change
5. Testing method change
1. Site change/addition (test)
2. Manufacturing Process change
(allowed part* : marked “ ” 『 』)
* Identified in the application form
Justification provided in the CTD
Biotechnology products
Synthetic products
PCA
(partial change application)
MCN
(Minor Change notification)
1. Package form change/addition
2. Site change/addition (DS, DP)
3. Ingredients’ prescription change
4. Manufacturing Process change
5. Testing method change
1. Site elimination
(one of several sites)
2. Site addition
(storage/package/test)
3. Manufacturing Process change
(allowed part* : marked “ ” 『 』)4. Tightening of specs
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Application format and Approval contents for
Partial Change Application and Minor Change
Notification
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Application format of M1.2 for PCA/MCN
1. General information (eg. name, address, product name....)
4. Manufacturing procedures
– Category of formulation
– Name of manufacturing site
– Manufacturing procedures ; Consists of scope, animal derived materials, procedures,
process controls
9. Manufacturing sites information with license numbers
In the case of PCA or MCN with changing of
manufacturing procedures....
Application format of PCA and MCN is different from
one of NDA.
The sections in relation to the change are only
required to submit.
Above sections would be described in M1.2, and the approval
contents in this variation would be limited to part of M1.2.
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Application format of M1.2 for PCA/MCN
Partial Change
Application Form
General information
Manufacturing Process
・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・
Process validation data,
comparability data
(characteristics,
specifications,
stability etc.), etc.
Depends upon
degree or substance
of the change
Attached Data (PCA)
Submission
Review (PCA)
Minor Change
Notification Form
General information
Manufacturing Process
・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・
Only the
changed section
is described.
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Approval contents of M1.2 for PCA/MCN
Partial Change
Application form
Product Name
Manufacturing Process
・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・
Only the
changed section
is described.
Approval Letter
PCA Date
Approval Date
・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・
Approval (PCA)
Not exist one M1.2 which is
reflected the latest approval
content of all sections.
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Application form
Product Name
Ingredient and Contents
Manufacturing Process
Dosage and
Administration
Indications
Storage and Shelf life
Specification and
Testing Method
・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・
Approval Letter
Approval #
NDA Date
Reexamination Period
International Birth
Date
Approval Date
・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・
Approval contents of M1.2 for PCA
Partial Change
Application form
Product Name
Manufacturing Process
・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・
Approval Letter
PCA Date
Approval Date
・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・
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Product Name
Ingredient and Contents
Manufacturing Process
Dosage and Administration
Indications
Storage and Shelf life
Specification and Testing
Method
Manufacturing Sites
Application form
Product Name
Ingredient and Contents
Manufacturing Process
Dosage and
Administration
Indications
Storage and Shelf life
Specification and
Testing Method
・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・
Approval letter
Approval #
NDA Date
Reexamination Period
International Birth
Date
Approval Date
・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・
Approval contents of M1.2 for PCA
Partial Change
Application form
Product Name
Manufacturing Process
・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・
Approval Letter
PCA Date
Approval Date
・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・
Manufacturing Process
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Application form
Product Name
Ingredient and Contents
Manufacturing Process
Dosage and
Administration
Indications
Storage and Shelf life
Specification and
Testing Method
・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・
Approval Letter
Approval #
NDA Date
Reexamination Period
International Birth
Date
Approval Date
・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・
Approval contents of M1.2 for MCN
Minor Change
Notification Form
General information
Manufacturing Process
・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・
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Product Name
Ingredient and Contents
Manufacturing Process
Dosage and Administration
Indications
Storage and Shelf life
Specification and Testing
Method
Manufacturing Sites
Application form
Product Name
Ingredient and Contents
Manufacturing Process
Dosage and
Administration
Indications
Storage and Shelf life
Specification and
Testing Method
・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・
Approval letter
Approval #
NDA Date
Reexamination Period
International Birth
Date
Approval Date
・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・
Approval contents of M1.2 for MCN
Manufacturing Process
Minor Change
Notification Form
General information
Manufacturing Process
・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・
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3. ISSUES REGARDING THE CURRENT
APPLICATION FORM (J-M1.2)
"LEGAL BINDING"
FOR BIOTECHNOLOGY PRODUCTS
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Description of Application Form (J-M1.2)
for Biotechnology products
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Application form
Product Name
Ingredient and Contents
Manufacturing Process
Dosage and
Administration
Indications
Storage and Shelf life
Specification and
Testing Method
・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・
Module 2.3
Pick out
Module 1.2
Raw data
Summarize
Module 3 Module 3
NDA Documents - CMC part -
Description of Application Form (J-M1.2)
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The matters entered in the application form (J-M1.2)
After approval, any changes in the matters shall be
addressed in administrative regulatory procedures
(PCA or MCN).
MCN items are evaluated during the review as to
whether it can be accepted.
Critical target or set values cannot be set as MCN
items.
However, in the case of biotechnology products ...
Almost all of the changes in the matters shall be
required PCA.
Description of Application Form (J-M1.2)
for Biotechnology products
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what should be the
approval content ?
which items should be
described in
Application Form ?
The matters entered in the Application Form (J-M1.2)
of NDA should be described with consideration for
future life-cycle management.
To ensure quality required for assuring efficacy and
safety of drugs
Which items could
be controlled as
MCN ?
Therefore....
Description of Application Form (J-M1.2)
for Biotechnology products
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M 1.2
Application
Form
Current Description of Application Form (J-M1.2)
for Biotechnology products
M 2.3
QOS
M 3
Quality Reports
Module 2.3
Equal
Module 1.2
Application
Form
Aren't the items, which should be
controlled under GMP, included for
biotechnology products ?
Isn't there overlap in description?
GMP Documents
- product master formula,
production instructions, SOPs...
Manufacturing Process
Specification and Testing Method
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It is described the detailed procedure for the operation.
Current Description of Manufacturing Process
Manufacturing sites
Manufacturing procedures
Describe process up to starting materials, cell culture,
purification and storage.
Raw materials, animal derived materials and reagents that are
likely to affect the quality.
Major equipment, important process parameters (temperature,
pH, time) and in-process control tests.
Each process parameter should be defined as major/minor by
brackets.
Test items, analytical methods and criteria if in-process test
are required for critical processes.
Storage condition and period for critical intermediates.
For Biotechnology products, too much details are to be described from the previous time, and different contents are described from the company or requested by PMDA etc.
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Description of Specification and Testing Method
In principle, use the test listed in JP.
When a test is not listed as general testing methods in JP,
detailed testing method including criteria needs to be
described.
Description needs to be compliant with JP.
Reagents name including supplier name, and whole kinds of
test solution needs to be described.
Unlike description in the column for manufacturing process,
specification and testing method including reagents and test
solution are subject to PCA in principle.
Usually it is described which shows the whole procedure.
Test name
Specifications and testing methods
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4. APPROACHES TAKEN AT JPMA
BIOPHARMACEUTICAL COMMITTEE
TECHNOLOGY WORKING COMMITTEE
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what should be the approval content as
a legal binding in the manufacturing
process in order to ensure quality
required for assuring efficacy and
safety of antibody drugs?
Conducted research and discussion for the
description of each manufacturing process,
parameter, control tests etc.
J-M1.2 MOCK-UP preparation
Preparation of mock-up draft of Manufacturing
Process for drug substance of antibody drugs.
Based on risk evaluation information,
experience and knowledge ....
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Discussion between PMDA and Industry
In the near future, we intend to exchange
views with PMDA regarding the specific
description examples of the column for
manufacturing process for drug substance of
antibody drugs in Application Form.
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