PFSB/ELD/OMDE (Yakushokuki) Notification 1207 No.1
December 7, 2011

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 cell sheets used in the regeneration of periodontal tissue, orthopedic customized
artificial hip joint prostheses and computer-aided diagnostic devices, and the advice for
evaluation. We would like your cooperation in promulgating this guidance among the relevant
vendors and service providers under your jurisdiction for use as a reference when filing anapplication 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 otherkinds 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 for
approval 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 2)
Guidance on Evaluation of Orthopedic Customized Artificial Hip Joint Prosthesis
1. Introduction
In the field of orthopedics, implants (classified as “medical devices” by the Pharmaceutical
Affairs Law) have been used widely as ready-made implants due to their proven mechanicaland biological safety and efficacy, and have contributed to the improvement in the quality of
medical care and the lives of people in Japan. However, in clinical practice, bone structureand geometry vary among individual patients, and there are reports of cases where readymade implants cannot be used effectively. Therefore, there is a compelling need for implants
with greater compatibility for individual patients, so-called customized implants, as a solution
to the problem of biological incompatibility.
Because customized implants are compatible with individual patients, they are expected toplay a major role in the introduction of bone preservation therapies, ensuring compatibility
and stability, implementation of less invasive surgical procedures, successful functional
reconstruction, improvement of implant service life, early rehabilitation and reentry into
society, and reduction in the need for revision surgery. In other words, it will be beneficial not
only for patients and medical workers but also in terms of medical economics to have theneeds of patients and medical workers satisfied and to secure excellent clinical results throughthe clinical adoption of customized implants that meet the requirements of individual patients.
As technological innovation has made marked advances and made it possible to produce
customized implants that meet such clinical needs, it is now feasible to produce safer implants
with better biocompatibility.
Customized implants are expected to be used for applications such as joint prostheses anddevices for osteosynthesis. In clinical practice, joint prostheses (e.g., artificial hip joint, knee
joint, shoulder joint, and elbow joint) are typical examples of applications that require
customized implants optimally shaped to fit various bone geometries and accommodate
serious bone defects and/or deformations. This guidance is designed to specify therequirements for customized artificial hip joint prostheses for which there is a high demand inclinical practice.

2. ScopeAmong orthopedic implants, the scope of this guidance is artificial hip joint prostheses(including femoral head prosthesis). In this guidance, a customized artificial hip joint
prosthesis is defined as an artificial hip joint prosthesis with improved biocompatibility andstability achieved through minimal modification to the shape of a ready-made prosthesis inorder to match the bone geometry of an individual patient for whom a ready-made prosthesis
is not suitable.
3. Role of This Guidance
In consideration of the fact that the scope is orthopedic artificial hip joint prostheses(including femoral head prosthesis) that are being developed based on the remarkabletechnological advances occurring in this area, this guidance is designed to indicate current
issues instead of providing a comprehensive list of problems and points to consider.
Therefore, it will be revised as technological innovation progresses and knowledge
accumulates, and it does not mandate what information must be included in application
documents for approval.
For the evaluation of customized artificial hip joint prostheses, it is necessary to have athorough understanding of the characteristics of individual products and to handle the data ina flexible and scientifically 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 Artificial Hip Joint
Prosthesis(1) Form, Structure and Mechanism
In the section “Form, Structure and Mechanism,” specify the dimensional ranges in which thecustomized artificial hip joint prosthesis can be produced, separately from the ready-madeprosthesis upon which the production of customized prosthesis is based.

(2) Purpose of Use, Indications or Efficacy
In the section “Purpose of Use, Indications or Efficacy,” specify that the customized artificial
hip joint prosthesis is to be used in the following cases:
1) When a physician judges that a sufficient therapeutic effect cannot be obtained with aready-made prosthesis.
2) When a physician judges that a more significant therapeutic effect can be obtainedwith a customized artificial hip joint prosthesis than with a ready-made prosthesis.
(3) Product Specifications
In terms of production and structure, specify the technological reference data showing that theperformance of the customized artificial hip joint prosthesis is equivalent to or higher thanthat of the corresponding ready-made prosthesis.
(4) Other1) Specify the data of the ready-made prosthesis used as the basis for producing thecustomized artificial hip joint prosthesis.
2) Attach the draft specification form prepared by a physician.
5. Evaluation of Customized Artificial Hip Joint Prosthesis(1) Evaluation of Production Technology
Specify that the production technology is equivalent to that of the corresponding ready-madeprosthesis, or equivalent or superior to that of other ready-made prostheses made or suppliedby your own company and which have already been approved.
(2) Evaluation of Safety
Specify that the basic safety profile (e.g., biological safety) of the materials needed to produce
the customized artificial hip joint prosthesis is equivalent or superior to that of thecorresponding ready-made prosthesis. Submission of safety data on customized prostheses
can be omitted if its safety can be proven using the data and scientific evidence for readymade prostheses. When it is determined that high functionality and durability are needed inclinical practice, submit the data and the scientific basis for similar biomaterials approved foruse in artificial hip joint prostheses.

(3) Evaluation of Mechanical Safety
Submission of mechanical safety data can be omitted if data are presented to show that thedimensions of the customized artificial hip joint prosthesis are within the range of thecorresponding ready-made prosthesis, or that the mechanical safety is not inferior to that of
the corresponding ready-made prosthesis.
It is possible to show that the mechanical safety is not inferior to that of ready-madeprosthesis by the following methods:
1) When the customized artificial hip joint prosthesis is modified to make it mechanicallysafer than the corresponding ready-made prosthesis, mechanical safety testing can beomitted by specifying it using the Appendix listing items to be customized as areference (test data on approved products made or supplied by your own company canalso be used).
2) When it is necessary to modify sites subjected to a structural load, specify thatmechanical safety can be guaranteed based on a mechanical test performed inaccordance with some other guideline (test data on approved products made or
supplied by your own company can also be used).
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, “GVP
Ordinance”), or the Ordinance on Standards for Post-marketing Survey and Examination of
Medical 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 Artificial Hip Joint Prosthesis
The marketing authorization holder shall design a customized artificial hip joint prosthesis
within the range that has been approved in accordance with the written specifications preparedby a physician.
(2) Documents to be Retained by Marketing Authorization Holder
The marketing authorization holder shall keep the following documents related to the
production of a customized artificial hip joint prosthesis and selling/offering it to thephysician who prepared the written specifications.
1) Name of the physician who prepared the written specifications
2) Written specifications prepared by the physician (including data on the patient’s bonegeometry)3) Documents to verify that the design is compatible with the data on bone geometry4) 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
artificial hip joint prosthesis by comparing it with the patient’s bone geometry before and after
implantation, in collaboration with the physician.
(4) Post-marketing Survey
After implantation of the customized artificial hip joint prosthesis, the marketing
authorization holder shall collect information on clinical outcomes and adverse events incooperation with the physician.

If necessary, a partial change application or safety measures

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.
1) The customized artificial hip joint prosthesis can be used only when the physician
judges that the patient will not gain a sufficient therapeutic effect with a ready-madeprosthesis, or that the patient will have a significantly better therapeutic effectcompared to a ready-made prosthesis.
2) The patient shall be provided with the information on the need for and clinical efficacy
of a customized artificial hip joint prosthesis and give informed consent.
3) The attending physician shall prepare the written specifications before using acustomized artificial hip joint prosthesis.
4) The physician shall submit the written specifications to the marketing authorization
holder in order to clarify the items to be customized.
5) Before using the customized artificial hip joint prosthesis, the physician shall verify
whether the customized artificial hip joint prosthesis meets the written specifications
at the design stage or after the final product was made.
6) The physician shall take precautions by, for example, preparing a surgical plan thattakes into consideration the option of using a ready-made prosthesis in situations
where the customized artificial hip joint prosthesis cannot be used due to a productdefect or clinical problem that arises during surgery.
7) The physician shall evaluate the clinical efficacy and collect information on adverse
events in order to provide the information promptly to the marketing authorization
holder.
8) Because the customized artificial hip joint prosthesis is designed to fit an individual
patient, unused products must not be used for other patients.
9) The physician shall ensure that the written specifications are retained with the patient’s
medical records.

Appendix. Items to be Customized
1. Acetabular Components(1) Acetabular Shell (Socket)•

Shaping (partial increase in volume aiming to achieve compatibility with bone geometry,improved support of marginal area, increased thickness, optimized diameter, optimized
curvature of bone-contacting surface, and optimized area of surface treatment)•

Optimized position, number and shape of screw holes•

Optimized position and number of spikes, pegs, and fins(2) Cementless Polyethylene Liner•

Shaping of polyethylene material (optimized shape of marginal area and polyethylenematerial)(3) Cemented Polyethylene Socket•

Shaping of polyethylene material (optimized shape of marginal area, etc.)

2. Femoral Stem
(1) Proximal Area
Cementless stem•

Shaping (optimized shape of parts in the superolateral, superomedial, superoanterior andsuperoposterior areas and collar shape to achieve compatibility with bone geometry)•

Optimized area of surface treatment to achieve compatibility with bone geometry•

Optimized neck length, neck-shaft angle, and anteversion angle
Cemented stem•

Shaping (optimized shape of parts in the superolateral, superomedial, superoanterior andsuperoposterior areas and collar shape to achieve compatibility with bone geometry)•

Added surface treatment (optimized area needed to achieve cement fixation)•

Optimized neck length, neck-shaft angle, and anteversion angle(2) Distal Area
Cementless stem•

Shaping (optimized length, diameter and curvature of the distal area to achieve

compatibility with bone geometry)•

Added surface treatment (optimized area needed to achieve bone induction/conduction)•

Optimized position and size of locking screw holes on the stem side and screw holes for
greater trochanter fixation
Cemented stem•

Shaping (optimized length, volume and curvature of the distal area to achieve
compatibility with bone geometry)(3) Optimized biocompatibility and durability required for sites on which structural load isapplied•Mechanical safety shall be guaranteed (safety to the level approved for ready-madeprostheses shall be guaranteed)