1. GMP
IN THE CURRENT REGULATORY EMVIRONMENT
Industry perspective of Japan

2. ICH Q7A (GMP for API) arrived at final agreement
and Step 4 sign off on 10Th November 2000 at
San Diego ICH-5.
The Q7A document will be enforced by April 2001
in all of three regions ( USA, EU & Japan ).
In Japan, the Q7A document is now under translation
into Japanese and
the Japanese version of the Q7A document will be
published as a notification.

3. Status of this document (Guide)
This document(Guide) is the guidance, not the regulation.
This document should be applied not only for new submission
drugs but also
for already marketed drugs.
This document should exert an influence on
all manufacturers that would supply an API to the ICH three regions.

4. Table of Content
Section Title
1 Introduction
2 Quality Management
3 Personnel
4 Buildings and Facilities
5 Process Equipment
6 Documentation and Records
7 Materials Management
8 Production and In-Process Controls
9 Packaging and Identification Labelling of APIs and Intermediates
10 Storage and Distribution
11 Laboratory Controls
12 Validation
13 Change Control
14 Rejection and Reuse of Materials
15 Complaints and Recalls
16 Contract Manufacturers (including Laboratories)
17 Agents, Brokers, Traders, Distributors, Repackers, and Relabellers
18 Specific Guidance for APIs Manufactured by Cell Culture/Fermentation
19 APIs for Use in Clinical Trials
20 Glossary

5. Scope This Guide applies to the manufacture of APIs for
use in human drug (medicinal) products.　
In this Guide “manufacturing” is defined to include
all operations of receipt of materials, production,
packaging, repackaging,labelling, relabelling,
quality control, release, storage and distribution of APIs
and the related controls.

6. The company should designate and document the rationale
for the point at which production of the API begins.
For synthetic processes, this is known as the point at
which "API Starting Materials" are entered into the process.
For other processes ( e.g.fermentation, extraction,
purification, etc), this rationale should be established on
a case-by-case basis.

7. Current Japanese GMP system
　GMP for Medical drug (API and drug product) and 　
　quasi drug [ministerial ordinance]
　 ・Regulation for Manufacturing control and
　　 Quality control (Soft)
・Regulation for Building and Facilities for
Pharmacies etc., (Hard)
　 Regulation for Quality Assurance of Imported Drugs
(GMPI) [ministerial ordinance]
In Japan, Compliance with GMP is a requirement for a marketing license and license renewal.

8. GMP(complementary) ・Biological preparation [Notification]
　　・Ethical Extract product in Kampo medicine 　　
　　　Formulation [voluntary standard]
　　・General herb medicine in Kampo Formulation
　　 　 [voluntary standard]
　　・Ethical Molded poultices [voluntary standard]
　　・in vitro Diagnostic [voluntary standard]
Other
・GMP for Drug use for Clinical trials [Notification]
・GMP for Medical excipient [voluntary standard]
・Technical Guideline for Manufacturing and Quality 　
　control of Cosmetics [voluntary standard]
・GMP for Medical Devices [ministerial ordinance]

9. After Q7A( GMP for API) enforcement
Current J-GMP
API Notification based on
(basically) ICH Q7 document
Drug product
There are some difference between current J-GMP and
ICH Q7A document, such as Quality management,
Containment,
Impurity profile,
Contract manufacturer,
API for use in clinical trials et.al.,

10. Quality management Manufacturing control manager
Product security pharmacist (Production department )
(Manufacturing manager)
Activity Quality control manager
Releasing and rejecting (Quality department)
Approving all procedure,
Specification,changing * Prescription in the
Pharmaceutical Affair Law
(Production department) Manufacturing control manager
(Quality unit)
Product security pharmacist Quality control manager

11. Containment Current J-GMP
When a drug which is easy to disperse and causes
anaphylaxis in small quantities (that means an antibiotic
of penicillin group) is manufactured simultaneously with
other drugs, its manufacturing room and air-handling
system shall be separated from those used for other drugs.
Q7A document
Dedicated production areas, which include facilities, air
handling equipment and/or process equipments, should be
employed in the production of highly sensitizing materials
such as penicillins or cephalosporins.

12. Companies'requirements in order to meet need for dedicated production area
No. companies
responding(N=44) %
Sufficient
Some remodeling/amendment
is necessary
Difficult

13. Impurity profile will be required for a marketed drug
Impurity profile data
Level of data No. companies
responding(n=67) %
All products have sufficient data
Some product(s) do not have
sufficient data:
a) Impurity is examined,
but not for an impurity profile
b) Impurity is not examined

14. Option No.of respondents
In the case of having only insufficient data
Option No.of respondents
(n=57) %
Some lots should be examined to
confirm an impurity profile
by appropriate methods
On account of the nature of the
product, it is difficult to perform
an examination of impurity profile

15. Future actions regarding impurity testing
No. of
Option respondents
(n=61)
The impurity profile is set a routine (lot) test
The impurity profile is to be certain frequency
Other(at the time of process changing,
first 3 lots et al.,)
Impossible

16. Contact manufacturer
Contract manufacturer is not available for API
on current J-GMP.
Japanese companies expect to be de-regulated after
enforcement of this ICH document.
APIs for use in clinical trials
In Japan, other GMP than medical drug should be
applied to an API for use in clinical trials.
Japanese company want to apply this document to
an API for use in clinical trials.

17. Foresight It clarifies Control items, Standards, Criteria, etc.,
GMP controlled under same standards throughout the three
ICH regions.
Increase in the level of quality assurance (include countries
out of the ICH regions)
It accelerates MRA of GMP (include countries out of
the ICH regions)
It reduces barriers for export/import, facilitating the
import/export of APIs.
Importation of major and good quality material assured