Informative translation

Operational Communication
May 30, 2011

To: The Health Department (Bureau) Pharmaceutical Affairs Section of each Prefecture

Compliance and Narcotics Division, Pharmaceutical and Food Safety Bureau

Ministry of Health, Labour and Welfare

Questions and Answers (Q & A) on the Relationship between the QMS Ministerial
Ordinance1 and ISO13485: 2003

“Ministerial Ordinance on Standards for Manufacturing Control and Quality Control

for Medical Devices and In-vitro diagnostic reagents” (Ministerial Ordinance No. 169 of
the Ministry of Health, Labour and Welfare in 2004; hereafter referred to as the “QMS
Ministerial Ordinance”) was prepared in keeping with ISO13485:2003 (hereafter
referred to as “ISO13485) in order to seek international harmonization and that
article-by-article explanation was provided in Chapter 4.3 of Yaku-Shoku-Kan-Ma
Hatsu Notification No. 0330001 “Enactment, Revision and Abolishment of Ministerial
Ordinances and Public Notices pertaining to the Manufacturing Controls and Quality
Controls (GMP/QMS) of Medicines and Medical Devises, etc. accompany the
Enforcement of Acts partially revising the Pharmaceuticals Affairs Law and the Law
concerning the Regulation of Drawing of Blood and the Service of Supplying Donated
Blood” dated March 30, 2005 (hereafter referred to as “enforcement notice”). Now, from
the perspective of securing international harmonization, we have, in order to make even
clearer the relation between the QMS Ministerial Ordinance and the ISO 13485, put
together the following attachment regarding that point of view and hope that it will
serve as a reference for operations.

1 NOTE by TÜV SÜD Japan, MHS

The “Ministerial Ordinance No. 169 of the Ministry of Health, Labour and Welfare in
2004” is referred to as the “QMS Ministerial Ordinance” in Japan.
“J-GMP” is used as an abbreviation of the Ordinance within TÜV SÜD group, in
order to avoid confusion between “QMS”, which is well known as an abbreviation of
Quality Management System, and “QMS Ministerial Ordinance”, which is one of
Japanese regulation.

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 Attachment

(General)
Q1
Is it correct to think that the QMS Ministerial Ordinance and the ISO13485 are
completely the same?
A1
The QMS Ministerial Ordinance was enacted taking into consideration ISO 13485 from
the perspective of securing international harmonization and matches ISO 13845,
excluding Chapter 3 which is applicable to packaging, etc. manufacturers, etc., the
requirements of Chapter 4 which is applicable to Animal / human origin medical devices,
etc. manufacturers, etc. and a portion of the additional requirements, etc. of Chapter 2
which is applicable to medical devices manufacturers, etc. Please refer to the Q & A
below concerning the details of the additional requirements, etc. pertaining to Chapter
2.

Q2
In the article-by-article explanation of Chapter 4.3 of the enforcement notice it is noted
that “this article corresponds to “XXX” of ISO 13485” or that “this article corresponds to
part of “XXX” of ISO 13485, but what does this mean?
A2
Regarding the former, there are no modified requirements and have the same
requirements as ISO 13485 (JIS Q 13485:2005) and, regarding the latter, additional
requirements under the Pharmaceutical Affairs Law (Law No. 145 of 1960) are
included.

(In relation to Article 5 (Requirements pertaining to Quality Management Systems))

Q3
In Paragraph 4 it is written that “Where the manufacturer, etc. choose to outsource any
process that affects the conformity with the product requirements, the manufacturer,
etc. shall ensure the control over such processes” and processes which are the subject of
manufacturing licenses or the accreditation of foreign manufacturers are excluded.
When processes are subject to licenses or accreditations are outsourced, the control over
this outsourced manufacturer, etc. shall be undertaken by the marketing authorization
holder pursuant to “Ministerial Ordinance on Standards for Quality Assurance for
Drugs, Quasi-drugs, Cosmetics and Medical Devices” (Ministerial Ordinance No. 136,

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2004 of the Ministry of Health, Labour and Welfare; hereafter referred to as the GQP
Ministerial Ordinance), but is it acceptable for the manufacturer, etc. which receives
the outsourcing of the marketing authorization holder to undertake this control or to
jointly undertake this control with the marketing authorization holder?
A3
Either method is acceptable. However, contract (including QMS Ministerial Ordinance
Article 29) with the manufacturer, etc. pursuant the GQP Ministerial Ordinance shall
be clearly documented. Additionally, it shall be kept in mind that ultimate
responsibility for quality pertaining to the outsourced processes lies with the marketing
authorization holder. Namely, the provisions of paragraph 4 shall not impede the
execution of the control of a manufacturer, etc. which has obtained a license or
accreditation to execute outsourced processes having clearly documented contract with
the marketing authorization holder pursuant to the GQP Ministerial Ordinance by the
outsourcing manufacturer, etc.

(In relation to Article 6 (Documentation of Quality Management Systems))

Q4
In paragraph 2 the preparation of Seihin Hyojun Sho is required. When in an overseas
manufacturing facility a DMR (Device Master Record), etc. is prepared corresponding to
the laws and regulations of the respective nations, is it necessary to separately prepare
the Seihin Hyojun Sho required in the Pharmaceutical Affairs Law? Also, with respect
to those details, is it necessary to note the marketing approval (certificate) number, etc.
indicated in the enforcement notice?
A4
While Seihin Hyojun Sho is required to be prepared for each product, it is acceptable
from the perspective of international harmonization to deem that a Seihin Hyojun Sho
has been prepared when “a document which prescribes required matters pertaining to
the specification and quality management systems for each product” is prepared
pursuant to the regulations, etc. of each nation with the objective of appropriately
controlling quality management documents. Additionally, when Seihin Hyojun Sho is
prepared in foreign manufacturing facilities, it is acceptable not to note the marketing
approval (certificate) number, etc.

(In relation to Article 8 (Control of Documents))

Q5
Although it is noted in the enforcement notice that “this Article corresponds to part of

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ISO 13483 “4.2.3 Control of documents,” what are the differences in this Article?
A5
The difference in this Article is the retention period of obsolete quality management
documents or those copies prescribed in paragraph 4. In ISO 13485 it is required that
documents used in manufacture or inspections have a retention period of at least the
lifetime of the medical device determined by the organization (however, that period
must not be shorter than the retention period of all records obtained as a result or the
period prescribed in related regulatory requirements). However, in the QMS Ministerial
Ordinance the retention period (however, documents pertaining to training is 5 years)
set forth as follows from the date of the obsolete of the relevant quality management
documents is required. However, it is sufficient to, at the least, store documents used in
the manufacture of products or in tests and inspections so that the relevant documents
can be used during the retention period of records pertaining to the relevant products
prescribed in Article 9.
(1) Products pertaining to specified maintenance control medical devices prescribed in
Article 2, Paragraph 8 of the Pharmaceutical Affairs Law: 15 years (however, in
respect to relevant products on which the notation of the validity period or
expiration date (hereafter simply referred to as the “validity period”) is required,
when the period to which 1 year is added to that validity date is longer than 15
years, the period to which 1 year is added to the relevant validity period)
(2) Products pertaining to medical devices other than specified maintenance control
medical devices: 5 years (however, in respect to relevant products on which the
notation of the validity period is required, when the period to which 1 year is added
to that validity date is longer than 5 years, the period to which 1 year is added to the
relevant validity period)

(In relation to Article 9 (Control of Records))

Q6
Although it is noted in the enforcement notice that “this Article corresponds to part of
ISO 13483 “4.2.4 Control of records,” what are the differences in this Article?
A6
The differences are the retention period of the records prescribed in paragraph 3 and
the date from which the storage period is calculated. In ISO 13485 it is required to have
a retention period of the lifetime of the medical device determined by the organization
(however, that period must not be shorter than 2 years from the organization‟s shipment
date or the period prescribed in related regulatory requirements). However, in the QMS

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Ministerial Ordinance the retention period (however, records pertaining to training is 5
years) set forth as follows from the date of the preparation is required.
(1) Products pertaining to specified maintenance control medical devices: 15 years
(however, in respect to relevant products on which the notation of the validity period
is required, when the period to which 1 year is added to that validity date is longer
than 15 years, the period to which 1 year is added to the relevant validity period)
(2) Products pertaining to medical devices other than specified maintenance control
medical devices: 5 years (however, in respect to relevant products on which the
notation of the validity period is required, when the period to which 1 year is added
to that validity date is longer than 5 years, the period to which 1 year is added to the
relevant validity period)

(In relation to Article 10 (Management commitment))

Q7
In the enforcement notice it is stated that “this Article corresponds to part of ISO 13485
“5.1 Management commitment,” but is it correct to think that the difference with this
Article is that with respect to the “customer requirements” in the ISO 13485, because
under the Pharmaceutical Affairs Law system, the customer of the manufacturer is the
marketing authorization holder and other persons who receive the product and so,
therefore, it is set forth in the QMS Ministerial Ordinance that the requirements of the
customer of the manufacturer are those of the marketing authorization holder and
other persons who receive the product?
A7
This is acceptable. Even in the enforcement notice it is noted that the “product
recipient” means “the person indicated by marketing authorization holder, etc.
pertaining to the relevant product.”

(In relation to Article 11 (Focus on the Product Recipient))

Q8
In the enforcement notice it is stated that “this Article corresponds to part of the ISO
13485 “5.2 Customer focus,” but is it correct to think that the difference with this
Article is that with respect to the “customer requirements” in the ISO 13485, because
under the Pharmaceutical Affairs Law system, the customer of the manufacturer is the
marketing authorization holder and other persons who receive the product and so,
therefore, it is set forth in the QMS Ministerial Ordinance that the requirements of the
customer of the manufacturer are those of the marketing authorization holder and

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other persons who receive the product?
Additionally, in a manufacturer, is it acceptable to operate without limiting the product
recipient to the marketing authorization holder and other persons who receive the
product?
A8
Both are acceptable.

(In relation to Article 16 (Responsible Engineering Manager))

Q9
In the enforcement notice it is stated that “this Article corresponds to part of the ISO
13485 “5.5.2 Management representative,” but is it correct to think that the difference
is that the responsibilities of the management representative required in ISO 13485 is
defined in the QMS Ministerial Ordinance as the responsibilities of the Responsible
Engineering Manager prescribed in Article 17, Paragraph 5 of the Pharmaceutical
Affairs Law? Additionally, in the event that multiple manufacturing facilities, etc. are
integrated and one quality management system is established, is it required to appoint
the management representative noted in ISO 13485 for each manufacturing facility?
A9
It is correct to think that the difference in this Article is that the requirements in the
QMS Ministerial Ordinance have as the subject the Engineering Manager (in the case of
a foreign manufacturer, the responsible person of the manufacturing facility which has
received accreditation or the person designated in advance by the relevant foreign
manufacturer) of the manufacturing facility prescribed in Article 17, Paragraph 5 of the
Pharmaceutical Affairs Law and that the implementation of operations pertaining to
the actual supervision regarding quality management systems in that manufacturing
facility are required. In the event that multiple manufacturing facilities, etc. are
integrated and one quality management system is established, it is not required to
appoint the so-called management representative of ISO 13485 for each manufacturing
facility regardless of the provisions of ISO 13485 and it is acceptable to appoint in
advance engineering managers in domestic manufacturing facilities or a staff who is
able to fulfill the duties as the management representative for each manufacturing
facility in foreign manufacturing facilities. Although the duties of the management
representative required in ISO 13485 and the Engineering Manager required in the
QMS Ministerial Ordinance are the same, it should be kept in mind that, as it is not
necessarily the case that the same person will be appointed, each manufacturer shall
make clear those roles and ensure that the duties of the Engineering Manager do not

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become a mere formality.

(In relation to Article 23 (Training, etc.))

Q10
In the enforcement notice it is stated that “this Article corresponds to the ISO 13485
“6.2.2 Competence, awareness and training,” but in Item 2 it is stated “To establish the
documented procedure for identifying the training needs” On the one hand, in the ISO
13485 this is not a requirement and, as a note it is stated that “National or regional
regulations might require the organization to establish documented procedures for
identifying training needs.” Is this an additional requirement?
A10
This is an additional requirement.

(In relation to Article 24 (Infrastructure))

Q11
In the enforcement notice it is stated that “Article 24, Paragraph 1, Paragraph 3 and
Paragraph 4 correspond to the ISO 13485 “6.3 Infrastructure,‟” but is Article 24,
Paragraph 2 an additional requirement?
A11
Paragraph 2 is an added requirement with respect to buildings and facilities being in
accordance with product characteristics. There is no difference as regards Paragraph 1,
Paragraph 3 and Paragraph 4.

(In relation to Article 42 (Installation Activities))

Q12
Although it is noted in the enforcement notice that “this Article corresponds in part to
ISO 13483 “7.5.1.2.2 Installation activities,‟” what is the difference?
A12
This set forth what the manufacturer, etc. has to implement and is in line with the
requirements of Pharmaceutical Affairs Law Enforcement Regulations (Ministry of
Health and Welfare Ministerial Ordinance No. 1, 1961) Article 93 and Article 179 and is
not an additional requirement.

(In relation to Article 44 (Manufacturing Controls of Sterile Products))

Q13
In the enforcement notice it is stated that “this corresponds to the „7.5.1.3 Particular

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requirements for sterile medical devices‟ of ISO 13485,” but is paragraph 3 an
additional requirement in respect to ISO 13485?
A13
It is an additional requirement. In respect to sterile medical devices manufactures, etc.,
it added a building and facilities requirement being in accordance with product
characteristics.

(In relation to Article 49 (Traceability of Products pertaining to Specified Medical

Devices))
Q14
In the enforcement notice it is stated that “this Article corresponds to part of the
„7.5.3.2.2 Particular requirements for active implantable medical devices and
implantable medical devices‟ of ISO 13845,” but what is the difference with this Article?
A14
In ISO 13485 there is a requirement in respect to active implantable medical devices
and implantable medical devices, but in the QMS Ministerial Ordinance the subject is
restricted to the specified medical devises prescribed in Article 77-5 of the
Pharmaceutical Affairs Law and the changed requirement is in accordance with this.

(In relation to Article 56 (Internal Audit))

Q15
As the enforcement order notes that “this Article corresponds to the ISO 13485 „8.2.2
Internal audit,‟” is it appropriate to judge that if an internal audit with the ISO 13485
standards is implemented that this will be in conformity with this Article?
A15
As this Article prescribes that an internal audit be undertaken in order to make clear
whether “the provisions of this ministerial ordinance and the requirements pertaining
to the relevant quality management systems” are being conformed to, it cannot be
judged that this Article is being conformed to with the results of the internal audit
having the audit standards of ISO 13485 alone.
On the basis of the conformity report based on an internal audit pursuant to ISO 13485,
it is acceptable to judge that this Article is being conformed to base on an internal audit
made with the addition of the differences with the QMS Ministerial Ordinance.

(In relation to Article 58 (Monitoring and Measurement of Products))

Q16

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Although it is stated in the enforcement order that “this Article corresponds to the „8.2.4
Monitoring and measurement of product‟ of ISO 13485,” it is stated in paragraph 5 that
“manufacturers, etc. must not permit the advancement to the following stage of the
process, determine whether or not to ship the product from the manufacturing facility
or provide services until the completion without any problems of the monitoring and
measurement pursuant to the implementation guidelines prescribed in the product
realization plan.” In ISO 13485 it is required that “the shipment of products and the
provision of services will not be undertaken until the completion without problems of
the matters decided in the planning (refer to 7.1) of product realization.” Is “permit the
advancement to the following stage of the process” an additional requirement?
A16
It is not an additional requirement. It is acceptable to reason that this is the same as
the requirement in ISO 13485 because, with respect to “permit the advancement to the
following stage of the process,” a firm will make a determination as to what stage
confirmation should be made on the basis of information such as design development
and risk management, etc., and will confirm before advancing to the following stage
that monitoring and measurement pursuant to the implementation guidelines
prescribed in the product realization plan has been completed without any problems.

(In relation to Article 60 (Control of Nonconforming Products))

Q17
Although in the enforcement notice it is stated that “this Article corresponds to „8.3
Control of nonconforming product‟ of ISO 13485,” the “new work instructions must be
prepared” in paragraph 9 can be read as though there is a requirement to redraft the
work instructions each time. Is this an additional requirement in respect to the
documentation of the rework process of “shall document the rework process in a work
instruction” of ISO 13485?
A17
It is not an additional requirement. The “new work instructions must be prepared” in
paragraph 9 is not a requirement to redo the work instructions each time. As this
required the redrafting of the work instructions based on similar procedures when in
the original work instructions there are aspects which cannot address processes in the
event manufacturing is revised with respect to that product, it is acceptable not to
redraft if the work instructions to begin with considered the impact of revising
manufacturing and, furthermore, if manufacturing is revised within that scope.
The record of the revised manufacturing and the judgment as to whether it is within the

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scope of the work instructions when the work instructions are not redrafted is secured
in paragraph 3 and paragraph 6.

(In relation to Article 62 (Improvements))

Q18
Although it is stated in the enforcement notice that “this Article corresponds to „8.5.1
Improvement –General‟ of ISO 13485,” is the “this provision shall not apply in case
where the customer issues and implements the advisory notices, and the manufacturer,
etc. shall provide the customer with the information necessary for issuing the advisory
notices” prescribed in Article 62, Paragraph 2 an additional requirement in relation to
the requirements of ISO 13485? Additionally, in what way can the manufacturer
demonstrate this to the auditor?
A18
It is not an additional requirement. It was noted in order to harmonize the operations of
the marketing authorization holder required in the Pharmaceutical Affairs Law.
As a method of demonstrating to the auditor that “the product recipient proactively
issues and implements the advisory notices,” one can think of providing a documented
procedure, etc. for “providing the product recipient required information in the issuance
of advisory notices” which have been approved by the product recipient or letters of
agreement / memorandums of understanding, etc. with the product recipient and the
manufacturer, etc. in which those details are set forth. It is desirable the documented
procedure, etc. for “providing the product recipient required information in the issuance
of advisory notices” be prepared taking into consideration the importance of advisory
notices and the requirements of this paragraph.

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