PFSB/ELD/OMDE (Yakushokuki) Notification 1215 No.1
December 15, 2010
Attn: Directors of Prefectural Public Health Departments/Bureaux
Director, Office of Medical Devices Evaluation
Evaluation and Licensing Division, Pharmaceutical and Food Safety Bureau
Ministry of Health, Labour and Welfare
Re: Publication of the Guidance for the Evaluation of Emerging Technology Medical Devices
The Ministry of Health, Labour and Welfare of Japan intends to establish a guidance for theevaluation of emerging technology medical devices, for which there is a high demand inclinical practice, by selecting the target areas to be studied in order to facilitate efficient
product development and speed up the approval process through the advance preparation andpublication of documents, such as a guidance for technical evaluation, to be used for thereview.
Here, we present the guidance comprising the documents that may be required for theevaluation of the regeneration of articular cartilage, neurological function restoration devices
and customized orthopedic devices for osteosynthesis, and the advice for evaluation. We
would like your cooperation in promulgating this guidance among the relevant vendors andservice providers under your jurisdiction for use as a reference when filing an application for
manufacturing/marketing approval. Attention should be paid to the following points.
(For your reference, copies of this notification will also be sent to the Chief Executive of thePharmaceutical and Medical Devices Agency, Chairman of the Japan Federation of Medical
Devices Associations, Chairman of the American Medical Devices and Diagnostics
Manufacturers’ Association, and the Chairman of the Medical Equipment Committee of theCouncil of the European Business Community in Japan.)1.

The guidance makes recommendations regarding points that should be considered in
product evaluation (evaluation items) from the viewpoints of collecting application
documents for approval and accelerating the review process. The guidance is not
positioned as a legal standard but is designed simply to suggest currently recognizedevaluation items for emerging technology medical devices. It has to be noted that otherkinds of evaluation may be needed, or there may be some exceptions to this guidance
depending on the product characteristics.
2.

When collecting documents and data required for submission of an application forapproval of individual products, it is recommended that the issues presented in theguidance be discussed in advance, and to use the consultation service of thePharmaceutical and Medical Devices Agency at the earliest possible opportunity.

(Attachment 3)

Guidance on Evaluation of Customized Orthopedic Devices for Osteosynthesis

1. Introduction
In the orthopedic field, implantable devices are widely used and contribute to theimprovement of medical care and the quality of life of the Japanese people. These devices areready-made products with defined width, length and thickness, and their mechanical andbiological safety as medical devices has to be established in accordance with the JapanesePharmaceutical Affairs Law. However, each patient has his/her own skeleton and bonegeometry, and ready-made devices may not fit their skeletal structure. In such cases, the useof a customized device that can be fully adapted to individual skeletal structure is required.
The use of customized devices enables excellent fixation and restoration of function, leading
to better surgical outcomes, the implementation of minimally invasive surgery, earlyrehabilitation, early reentry into society after surgery and a decrease in the risk of revision
surgery, thereby bringing benefits to both patients and medical professionals.
The background to the need for customized devices for osteosynthesis is as follows: thepurposes of these devices are becoming increasingly diverse; design concepts of these devices
are becoming increasingly complex; and the highly developed technology for productstructure and surface treatment have enabled the development of highly biocompatible
devices. Accordingly, the introduction of devices with better adaptability to the human bodyhas been sought in the orthopedic field. In other words, the adoption of devices that meet theneeds of individual patients, namely, customized devices that can be readily adapted to meetthe requirements of individual patients, bring not only benefits to patients and medical
professionals but also benefits in terms of medical economics by securing better long-termclinical results.
Although customized devices are expected to be used for applications such as devices forosteosynthesis and joint prostheses, the scope of this guidance is limited to devices forosteosynthesis for which the clinical need is particularly pronounced. This guidance isdesigned to specify the basic requirements for customized devices for osteosynthesis.
Customized devices with proper articular bone geometry and optimal shape toaccommodate significant bone loss, bone deformity and other defects are also required forjoint prostheses (e.g., total hip, bipolar, total knee, total shoulder, and total elbow). Therefore,

it was considered necessary to further investigate the remaining issues including the range ofapplication, structural and mechanical properties and the three-dimensional structure of thesedevices.

2. Scope
The orthopedic devices evaluated using this guidance include metallic implantabledevices for osteosynthesis such as bone plates, epiphyseal plates, intramedullary nails,
compression hip screws (CHS), short femoral nails, and bone nails.
The customized devices evaluated using this guidance include devices created by partly
modifying the shape of a ready-made product. These are altered in order to fit the bonegeometry of an individual patient, and the specifications for customized devices are requiredto be stated in the certificate of approval. Therefore, the devices evaluated using this guidance
are different from the custom-made prostheses and artificial bones used in the treatment ofmalignant tumors or for re-implantation as special treatment materials.
This guidance should not be applied to devices which are produced by manufacturing
processes that are different from those used for ready-made products.

3. Role of This Guidance
In consideration of the fact that the scope is customized devices that are being developed
based on the remarkable technological advances occurring in this area, this guidance isdesigned to indicate current issues instead of providing a comprehensive list of problems andpoints to consider. Therefore, it will be revised as technological innovation progresses andknowledge accumulates, and it does not mandate what information must be included inapplication documents for approval.
For the evaluation of customized devices, it is necessary to have a thorough understandingof the characteristics of individual products and to handle the data in a flexible andscientifically rational manner.
It is also recommended that other relevant guidelines from both Japan and overseas
should be consulted in addition to this guidance.

4. Contents of Written Application for Approval of Customized Devices(1) Form, Structure and MechanismIn the section “Form, Structure and Mechanism,” specify the dimensional ranges in which
the customized device can be produced, separately from the ready-made product uponwhich the production of customized device is based.
(2) Purpose of Use, Indications or Efficacy
In the section “Purpose of Use, Indications or Efficacy,” specify that the customized device
can be used in the following cases:i) When a physician judges that a sufficient therapeutic effect cannot be obtained withready-made products.
ii) When a physician judges that a more significant therapeutic effect can be obtained witha customized device than with ready-made products.
(3) OtherWrite “including customized device” in the remarks field.

5. Evaluation of Customized Devices(1) Evaluation of Production Technology
Specify that the customized device can be manufactured using the production technology
equivalent to that of the corresponding ready-made product.
(2) Evaluation of SafetySpecify the basic safety profile (e.g., biological safety) of the materials needed to produce
the customized device. When the data is omitted by submitting the safety information froma previously approved product, explain the reason for the omission.
(3) Evaluation of Mechanical Safety
Specify that the mechanical safety of the device is not inferior to that of the ready-madeproduct.

Examples of such methods are as follows:i) Specify the mechanical safety by performing a mechanical test or finite element analysis(FEA) in accordance with the guidelines for the product.
ii) The mechanical safety information can be omitted if data are presented to show that thedimensions of the customized device are within the acceptable range of thecorresponding ready-made product.
iii) If it is obvious that the changes make the customized device mechanically safer than theready-made product, documents on mechanical safety can be omitted by describing thesafety of the ready-made product with reference to following examples:a) Bone plate

A. Increase in width
B. Increase in thickness
C. Change in length
D. Decrease in number of holes
E. Change in position of holes (The change of the interval between screw holes in thelong axis shall be applied to the direction of both ends. The change in the shortaxis shall be measured to the center, but the distance between the holes cannot bechanged.)b) Epiphyseal plate
A. Increase in width
B. Increase in thickness
C. Change in length
D. Decrease in number of holes
E. Change in position of holes (The change of the interval between screw holes in thelong axis shall be applied to the direction of both ends. The change in the shortaxis shall be measured to the center, but the distance between the holes cannot bechanged.)c) Intramedullary nailA. Decrease in length
B. Increase in diameter
C. Decrease in curvature of inflection
D. Decrease in the number of holes for side-locking screws to prevent rotationd) CHS
A. Increase in width
B. Increase in thickness
C. Change in length
D. Decrease in number of holes
E. Change in position of holes (The change of the interval between screw holes in thelong axis shall be applied to the direction of both ends. The change in the shortaxis shall be measured to the center, but the distance between the holes cannot bechanged.)e) Short femoral nailA. Decrease in length
B. Increase in diameterC. Decrease in curvature at nail part (maximum fitting)
D. Decrease in the number of holes for side-locking screws to prevent rotation

6. Preparation and Actions by Marketing Authorization Holder
The marketing authorization holder shall prepare the documents stipulated in the Ordinanceon Standards for Manufacturing Control and Quality Control of Medical Devices and in vitro
Diagnostic Drugs (MHLW Ministerial Ordinance No.169, 2004, “QMS Ordinance”),
Ordinance on Standards for Quality Assurance for Drugs, Quasi-drugs, Cosmetics andMedical Devices (MHLW Ministerial Ordinance No.136, 2004, “GQP Ordinance”),
Ordinance on Standards for Post-marketing Safety Management for Drugs, Quasi-drugs,Cosmetics and Medical Devices (MHLW Ministerial Ordinance No.135, 2004, “GVPOrdinance”), or the Ordinance on Standards for Post-marketing Survey and Examination ofMedical Devices (MHLW Ministerial Ordinance No.38, 2005, “GPSP Ordinance”), andspecify in the documents the following information in order to comply with theserequirements.
(1) Design of Customized Device
The marketing authorization holder shall design a customized device within the rangethat has been approved in accordance with the written specifications prepared by aphysician.
(2) Documents to be Retained by Marketing Authorization Holder
The marketing authorization holder shall keep the following documents related to theproduction of a customized device and selling/offering it to the physician who prepared
the written specifications.
i) Name of the physician who prepared the written specificationsii) Written specifications prepared by the physician (including data on the patient’s bonegeometry)iii) Documents to verify that the design is compatible with the data on bone geometryiv) Documents to show that the physician confirmed that the product shape conforms to

the written specifications at the design stage or after the final product was made.
(3) Evaluation of Efficacy
The marketing authorization holder shall evaluate the clinical efficacy of the customized
device by comparing it with the patient’s bone geometry before and after implantation, incollaboration with the physician.
(4) Post-marketing SurveyAfter implantation of the customized device, the marketing authorization holder shallassess the suitability of the customized device and collect information on adverse eventsin cooperation with the physician. If necessary, a partial change application or safetymeasures should be taken.

7.

Precautions for Use
The marketing authorization holder shall specify the following information in the section“Precautions for Use” or other sections.
i)

The customized device can be used only when the physician judges that the patient
will not gain a sufficient therapeutic effect with ready-made products, or that thepatient will have a significantly better therapeutic effect compared to ready-madeproducts.

ii)

The attending physician shall prepare the written specifications before using acustomized device.

iii) When preparing the specifications, physicians shall ensure that the customized device

does not interfere with soft tissues (including nerves, vessels, muscles) or the range ofjoint movement is not limited, by fitting the bone geometry within the approved range.
iv) Physicians shall submit the written specifications to the marketing authorization holderv)

Before using the customized device, the physician shall verify whether the customized
device meets the written specifications at the design stage or after the final productwas made.

vi) The physician shall take precautions by, for example, preparing a surgical plan thattakes into consideration the option of using ready-made products in situations where
the customized device cannot be used due to a product defect or clinical problem thatarises during surgery.
vii) Because the customized device is designed to fit an individual patient, unused

products must not be used for other patients.
viii) Physicians shall evaluate the clinical efficacy of the designed customized device bycomparing the bone geometry of the patient before and after surgery.
ix) When the customized device is used, the physicians shall evaluate the suitability of thecustomized device or collect information on adverse events and then promptly report
the information to the marketing authorization holder.
x)

The physician shall ensure that the written specifications are appropriately retainedwith the patient’s medical records.