1. Business Domain

Cardiac Rhythm Management

The business domain mainly dealing with implantable devices to treat arrhythmias.

EP/Ablation

The business domain dealing with catheters (thin tubes that are inserted into the body) with disposable electrodes for examination and treatment of arrhythmias.

Cardiovascular Surgery

The business domain dealing with devices used to replace blood vessels lacking their original function with artificial vessels for treatment by surgical procedures.

Transvascular Intervention

The business domain dealing with devices to treat myocardial infection, etc. by catheters (thin tubes that are inserted into the body) inserted into blood vessels through the skin.

2. Disease/Product

Pacemaker

An implantable medical device.

It keeps the heart rhythm by artificially providing electrical stimulation for arrhythmia (bradycardia), a condition in which the heart beats slower than normal.

ICD (Implantable Cardioverter Defibrillator)

An implantable medical device.

It detects the occurrence of a fatal arrhythmia, ventricular fibrillation, which is one of the types of arrhythmia (tachycardia) where a heart rate is abnormally fast, and restores a normal heartbeat by delivering an electric shock.

CRT‐P (Cardiac Resynchronization Therapy Pacemaker)

An implantable medical device.

For a serious heart failure, this device provides electrical stimulation to both the left and right ventricles of the heart to correct cardiac dyssynchrony and improve pumping function.

S‐ICD(Subcutaneous Implantable Cardioverter Defibrillator)

An implantable medical device.

With a conventional ICD, the lead is implanted into a heart via a vein, while with the S-ICD, the entire system is implanted subcutaneously, so no foreign objects are implanted into the blood vessels or the heart.

CRT‐D (Cardiac Resynchronization Therapy Defibrillator)

An implantable medical device.

In addition to the function of a biventricular pacemaker, it also has the defibrillation function. In case of a fatal arrhythmias, the device delivers electrical stimulation to the heart to treat it.

Ablation Catheter

A catheter (a thin tube that is inserted into the body) used to cauterize the channel of irregular electrical signals in the heart that cause tachycardia.

Electrophysiological (EP) Catheter

A catheter (a thin tube that is inserted into the body) used for examinations to diagnose arrhythmias and determine the indications for treatment methods.

It identifies the cause of the arrhythmia by measuring the potential inside the heart and inducing arrhythmias.

Internal Atrial Cardioversion Catheter

A catheter (a thin tube that is inserted into the body) that enables by intracardiac defibrillation minimally invasive termination of atrial fibrillation that occurs during ablation procedures.

It also has a diagnostic function as an EP catheter.

Endoscopic Laser Ablation Catheter

A balloon-shaped ablation catheter (a thin tube that is inserted into the body) used to cauterize the area causing tachycardia by irradiating with a laser from inside the balloon.

An endoscope inside the catheter enables precise placement and cauterization.

Radio‐frequency Transseptal Needle

A mechanical needle that is designed to make a hole in the wall between the left and right atria (atrial septum) using radiofrequency to insert a catheter during ablation procedures, etc.

Vascular Graft

An artificial device that is used to replace diseased blood vessels, such as an aneurysm or stenosis.

It is made of fibers such as polyester and fluororesin.

Open Stent Graft

A medical device to treat thoracic aortic diseases such as aortic aneurysm and aortic dissection.

Compared to procedures using conventional vascular prosthesis, this device enables minimally invasive and short-time treatment.

Stent Graft

A vascular prosthesis made of artificial fabric sewn on a metal mesh tube called a stent, that is used for the treatment of aneurysm etc.

The stent is put in a catheter (a thin tube that is inserted into the body), which is then inserted into the diseased area and expanded inside the artery to reinforce the aorta.

Balloon Catheter

A catheter (a thin tube that is inserted into the body) that is used for the treatment of myocardial infarction or angina pectoris, which is caused by a narrowing of the blood vessel (coronary artery) that supplies oxygen and nutrients to the heart muscle.

A balloon is inflated at the blocked artery, and restores blood flow.

Guidewire

A hair-thin wire used to guide a balloon catheter into a blocked area of a blood vessel.

A wire is passed through to the end of the blocked area of the blood vessel, and the balloon catheter is inserted along with the wire.

DES (Drug-Eluting Stent)

A stent (metal tube) with the surface coated with a special drug.

After being placed in a coronary artery, the drug gradually releases into the blood vessels, preventing restenosis, in which the blood vessels become narrowed again.

Atrial Septal Defect Closure

An implantable medical device that can close a congenital defect in which there is a hole in the wall that divides the left and right atria of the heart (atrial septal defect) without surgical operation.

The disk-shaped device closes the hole and treats the defect.

ASD (Atrial Septal Defect)

A congenital defect in which there is a hole in the wall that divides the left and right atria of the heart.

Angina Pectoris

Temporary chest pain caused by insufficient oxygen supply to the heart.

It is caused by smoking, lower oxygen levels in the blood due to a respiratory disease, restricted coronary blood flow due to coronary artery insufficiency, or when the heart works harder than normal. In most cases, angina pectoris is a chronic disease caused by ischemia of the myocardium due to sclerosis or stenosis of the coronary arteries which supply blood to the myocardium.

Sinus Rhythm

A normal condition without irregularity, tachycardia and bradycardia on the electrocardiogram.

Ischemia

A condition in which the blood flow to the heart is insufficient.

It appears as chest pain or other symptoms when the coronary arteries, which supply oxygen and nutrients to the heart muscle, become narrowed due to arterial sclerosis etc., or when the blood flow is restricted due to spasm of the blood vessels.

Ischemic Heart Disease

A heart disease, also called coronary artery disease, caused by insufficient blood supply to the myocardium due to narrowing of the coronary arteries.

CAG (Coronary Angiography)

A cardiac examination procedure that uses a catheter to contrast the coronary arteries to look for stenosis and other problems.

Usually, a left ventriculography is also performed simultaneously.

AMI (Acute Myocardial Infarction)

Necrosis of the myocardium in the area controlled by the coronary arteries due to interruption or reduction of blood supply caused by obstruction or spasm of the vessels due to arteriosclerosis.

Bradycardia

A general term for diseases of abnormally slow heart rate. Symptoms include a sudden feeling of darkness, dizziness, shortness of breath, fatigue, etc. Depending on the condition and symptoms, a permanent pacemaker is implanted.

Tachycardia

A general term for diseases of an abnormally fast heart rate.

A general term for diseases in which a heart rate is faster than normal. Symptoms include a pounding heart, dizziness, lightheadedness, fainting, and convulsions, and some cases can lead to death.

Treatments may involve drug or non-drug procedures (implantable cardioverter defibrillator (ICD) implantation or ablation).

AF (Atrial Fibrillation), A-fib

A heart disease (a type of tachyarrhythmias) that causes quivering and spasms in the chambers of the heart called atria and prevents them from working properly.

Arrhythmia Catheter Ablation

A treatment to stop the irregular electrical signals that cause tachyarrhythmias.

There are two main types of treatment procedures: "catheter ablation," in which a catheter (a thin tube that enters the body) is used to heat the myocardium one point at a time, and "balloon ablation," in which a catheter with a balloon-shaped device attached to its tip is used to treat the myocardium with the inflated balloon in close contact with it.

Brockenbrough Procedure

Brockenbrough procedure: Transseptal puncture procedure

A procedure performed when inserting and placing a catheter into the left atrium, using a needle (RF needle) from the right atrium to puncture the wall between the right and left atria (atrial septum) to make a hole to allow access to the left atrium.

This Brockenbrough is mainly used during ablation of AF (atrial fibrillation) to cauterize the pulmonary veins in the left atrium.

Aortic Dissection

Dissecting aortic aneurysm.

The aorta is made up of three layers: adventitia, media, and intima. Aortic dissection is a condition in which a tear occurs in the intima, the inner layer of aorta, for some reason, and blood enters into the media, the middle layer, causing the aorta to split in the long axis direction.

There are several types depending on the part of the tear and the area of dissection, but Type A dissection is by far the most common, which is more urgent.

Various factors such as arterial sclerosis, high blood pressure, smoking, stress, hyperlipidemia, diabetes, sleep apnea syndrome, and heredity are considered to be related to the disease.

Aortic Aneurysm

True aortic aneurysm.

A condition in which the aorta partially bulges like a " hump".

Those that occur in the thoracic aorta (ascending, arch, or descending aorta) are called thoracic aortic aneurysm, and those that occur in the abdominal aorta are called abdominal aortic aneurysm.

Once a "bump" develops, the blood vessels in that area become weak and gradually widen, leading to rupture.

Various factors such as arteriosclerosis, high blood pressure, smoking, stress, hyperlipidemia, diabetes, sleep apnea syndrome, and heredity are considered to be related to the condition.

Arrhythmia

The heart muscles contract and relax regularly by electrical signals to pump blood. However, if the electrical signals are disturbed for some reasons, the rhythm of the heartbeat becomes temporarily irregular.

This results in an irregular heartbeat, arrhythmia.

There are three major types of arrhythmia: Bradycardia (slow heart rate), Tachycardia (fast heart rate), and extrasystole, which is perceived as the skipped heartbeat.

3. Helthcare Industry

Special Treatment Material

Medical devices that are priced separately from medical service fees (procedure fees, drug fees, etc.).

Most of the products JLL handles are included in this category.

Exception: The liver cancer needle "arfa" is included in procedure fees.

Medical Device Classification

Medical devices are classified according to the level of risk to the human body.

Class IV Specially Controlled Medical Device

Risk : High ~

May have serious effects on human life and health in case of adverse reactions or malfunction.

Application : Notification to PMDA

Manufacture and sale : Class I Medical Device Marketing Authorization

Examples : Pacemakers, vascular prosthesis

Class III Specially Controlled Medical Device

Risk : Moderate ~ high

May have serious effects on human life and health in case of adverse reactions ormalfunction.

Application : For designated controlled medical devices, Certification of a third-party body (ARCB)

Manufacture and sale : Class I Medical Device Marketing Authorization

Example : Dialysis device

Class II Controlled medical device

Risk : Low ~ moderate

May have effects on human life and health in case of adverse reactions or malfunction.

Application : Approval of PMDA

Manufacture and sale : Class II Medical Device Marketing Authorization

Example : Injection needle

Class I General medical device

Risk : Low

Little risk of affecting human life and health even in case of adverse reactions or malfunction.

Application : Approval of PMDA

Manufacture and sale : Class III Medical Device Marketing Authorization

Example : Non-woven fabric for surgery

NHI (National Health Insurance)

Insurance Reimbursement Price.

The government sets the price for medical devices covered by health insurance benefits, and the price is called insurance reimbursement price. This price is also called the official price.

PMDA (Pharmaceuticals and Medical Devices Agency)

The organization aims to contribute to the improvement of public health by providing prompt remedies for health hazards caused by adverse drug reactions and infection via biological products (health hazard remedies), providing guidance and examinations of the quality, efficacy and safety of drugs and medical devices before clinical trials through approval (approval examinations), and collecting, analyzing and providing safety information after release to the market (safety measures).

FDA (Food and Drug Administration)

U.S. Food and Drug Administration.

Public agency which is equivalent to Japan's Ministry of Health, Labour and Welfare.

When a medical device is to be exported to the U.S. market, it must be registered, notified, or approved by FDA.

NB (Notified Body)

A private organization appointed by the appropriate competent authority to verify whether a medical device complies with the mandatory applicable regulatory requirements as stipulated in European Medical Devices Directive.

CE marking

A mark that certifies that a product meets safety standard requirements (requirements to protect the health and safety of users/consumers and ensure the common good) when exported to EU member countries.

In order to have CE Mark on a product, it needs to be certified by an authorized body (NB (Notified Body)) to determine whether it complies with the requirements of the MDD (Medical Devices Directive).

Effective May 26, 2020, the MDD will be replaced by the MDR (Medical Device Regulation), with a three-year transition period.

CRO (Contract Research Organization)

A company that undertakes clinical trials (clinical development) for product development on behalf of another company.

CDR (Cardiac Device Representatives)

A person who provides information of specialized medical devices and medical technology about cardiac pacemakers and ICDs (Implantable Cardioverter Defibrillators).

QA (Quality Assurance)

Assurance that there will be no problems in the use of the goods or services provided, at the time they are delivered to the customer or afterwards.

It is distinguished from "quality control" (QC), which controls whether there are any problems in the production, manufacturing, and operation processes of the goods and services provided.

IFU (Instructions for Use)

Documents attached to drugs and medical devices that describe precautions for use, dosage and administration, efficacy when taken, adverse reactions, and other information.

It is intended for users of the product, including physicians and other medical professionals.

They are important official documents that are the basis for the correct and appropriate use of pharmaceuticals and medical devices for the safety of patients.

Recall

An action by a manufacturer, distributor, etc. to take back pharmaceuticals, medical devices, or other products that they manufactured, distributed, and/or obtained approval.

Includes "refurbishment" and "patient monitoring," and excludes "inventory disposal" and "replacement of the original product."

It is classified into classes I-III according to the level of risks to health posed by the product recalled.

In the general description of recalls, it is distinguished between "refurbishment" in which the medical device is repaired or adjusted without being moved, and "patient monitoring" in which the progress of the patient is observed without removing the medical device from the patient.

PMS (Post Marketing Surveillance)

A generic term for research conducted to confirm the efficacy and safety of a product that has been released on the market and to gather information on new effects and adverse reactions that were not gained in the clinical trials before release on the market.

Study

Investigation of actual conditions to collect objective data, such as product performance evaluation, from physicians who use the product.

This information is used as a sales promotion tool and as reference information for product improvement and development.

KOL (Key Opinion Leader)

A physician or other professional influential in sales promotion.

Since KOLs have a great influence on physicians working in the field by providing appropriate treatment plans, KOLs are expected to play the role of promoters in disseminating the latest information to other physicians.

GPO (Group Purchasing Organization)

An entity that coordinates the purchase of medical equipment needed by hospitals at favorable prices through group purchasing vendors.

NHA (Nihon Hospital Alliance)

One of the largest organizations in Japan for the group purchasing of medical equipment.

VHJ (Voluntary Hospitals of Japan)

NPO VHJ Organization (Voluntary Hospital of Japan)

An entity engaged in the group purchasing of medical equipment.

It also conducts quality evaluation of medical materials and pharmaceuticals, and clinical research.

Sterilization Validations

Validation: To verify the validity of a method or process.

Sterilization validation is the process of verifying the adequacy of a manufacturing facility's structural equipment, procedures and processes, and other manufacturing and quality control methods for sterilization to assure permanent sterility of products with documentation.

The verification includes the sterilization action (exposure) time, temperature and humidity conditions, gas concentration, degassing time, possible number of times for sterilization, and the loading pattern inside the sterilizer.

It also examines whether the product performance can be guaranteed even under the maximum load of sterilization, and whether the product can be sterilized reliably even in areas or conditions where it is difficult to be sterilized.

EOG (Ethylene Oxide Gas) Sterilization

Sterilization methods for medical devices include high-pressure steam sterilization, radiation sterilization, and EOG sterilization, and the sterilization method is determined according to each characteristic.

High-pressure steam sterilization: Sterilization method using steam. Since steam remains on the sterilized product, a drying process is required. It cannot be used for materials that are not heat resistant.

Radiation sterilization: Sterilization by gamma or electron beam. It leaves no residue on the sterilized product. Discoloration or deterioration may occur depending on the material.

EOG sterilization: A method of the sterilization of microorganisms using exposure (sterilization action) of ethylene oxide gas directly to the product. A degassing process is required since ethylene oxide gas remains in the product.

Clean Room Classification

A clean room is designed to eliminate suspended particulates and microorganisms, and to prevent them from being brought in, and is maintained and controlled at a specified level.

The level of cleanliness of the air is called a cleanliness classification, and is generally quantified by the number of particles in a unit volume.

The cleanliness of air in clean rooms is classified as Class 1 to 9 according to the ISO standard, which is an internationally unified standard.

DR (Design Review)

A process to have the deliverables of a development project checked by multiple people, as defined in the JIS (Japanese Industrial Standards) and ISO (International Organization for Standardization) 9000 series.

HRS (Heart Rhythm Society)

HRS is an international non-profit organization founded in 1979, specializing in arrhythmias, including cardiac pacing and electrophysiology.

JHRS (Japanese Heart Rhythm Society)

APHRS (Asia Pacific Heart Rhythm Society)

Arrhythmia and Electrocardiology Annual Meeting

A conference specialized in EP/ablation organized by JHRS. It is held once a year in the third quarter.

CPAP (Continuous Positive Airway Pressure)

A medical device used to treat patients with obstructive sleep apnea syndrome (OSAS).

It helps keep air passages open by the pressure of air delivered through a mask worn over the nose.

4. Law/Regulation

Guidelines on Transparency

Guidelines issued by the Japan Federation of Medical Devices Industries (JFMDA) for the purpose of ensuring transparency and credibility of relationships with medical and other organizations, and thereby to guarantee a high level of ethics in business activities.

Member companies shall set their own " policies for transparency" as standards for behavior in reference to this guideline.

Pharmaceutical Affairs Law

Act on quality, efficacy and safety assurance of pharmaceuticals and medical devices, etc.

QMS (Quality Management System)

Standards for manufacturing and quality control of medical devices or pharmaceuticals for in-vitro diagnostics.

GVP (Good Vigilance Practice)

Standards for post-marketing safety management of medical devices, etc.

GMP (Good Manufacturing Practice)

Manufacturing and quality control standards for pharmaceuticals and quasi-drugs.

ISO13485

International standard for quality management systems specific to the medical device industry.

It has been adopted as the basis for quality management methods in regulations related to medical devices in countries around the world, including Japan.

MDD (Medical Devices Directive)

Directives that must be complied with in order to distribute medical devices in Europe.

MDD has been replaced by MDR (Medical Device Regulation) from May 26, 2020.

MDR (Medical Device Regulation)

It replaces the MDD, a regulation on medical devices distributed in Europe, which was issued on May 5, 2017 and became effective on May 25, 2017.

The MDR has been applied since May 26, 2020, with a three-year transition period from the MDD.

The MDR regulates conformity assessment, post-market surveillance, etc. by NBs and the authorities more in order to protect human health and safety at a higher level.

MAH (Marketing Authorization Holder)

A representative that handles application procedures such as "approval review" and "certification review" of medical devices.

Since they are the regulatory applicant for the product and responsible for safety and quality control, they play the most important role in the manufacture of medical devices.

DMAH (Designated Marketing Authorization Holder)

If a foreign manufacturer does not have a facility in Japan when distributing a product in the country, it can become an applicant for a marketing authorization and hold the authorization itself under the special approval system for foreign countries, but in this case, it is necessary to designate a domestic marketing authorization holder.

DMAH is obliged to implement quality control based on QMS and post-marketing safety control operations based on GVP in Japan, as well as various other operations including product applications.