First to make and fill glass syringes in-house, Taiyo's success recognized with Facility of the Year Award
Major Process Equipment Suppliers
Primary Works
Plastic Forming LineDaiichi Jitsugyou K.K.
Preparation SystemItochu Foodec K.K./Clean Mechanical K.K.
Isolator DeviceK.K Airex
Syringe Sterilization MachineSakura Seiki K.K.
Syringe Washing/Filling LineWinckler & Co., Ltd./Groninger
SCADA SystemK.K. Systech Ushijima
AccumulatorMurata Seiko K.K.
Syringe Inspection MachineHitachi Information & Control Solutions, Ltd.
Syringe Handling Inspection MachineMurata Seiko K.K.
Assembly Machine for inserting plunger rods and labelingWinckler & Co., Ltd./Groninger
Pillow Packing MachineWinckler & Co., Ltd./SIG
Cartoning MachineWinckler & Co., Ltd./IWK
VHP Sterilization MachineMurata Seiko K.K./K.K. Airex

Secondary Works
Glass Syringe Pipes Washing MachineDaiichi Jitsugyou K.K./K.K. Haginoya Machinery
Glass Syringe Forming LineWinckler & Co., Ltd./SPAMI
Water, Pure Steam GeneratorItochu Foodec K.K./Clean Mechanical K.K.
Preparation SystemItochu Foodec K.K./Clean Mechanical K.K.
Isolator DeviceK.K. Airex
Rubber stopper and Luer lock Dosing DeviceK.K. Kit
Syringe Washing/Filling LineWinckler & Co., Ltd./Groninger
AccumulatorMurata Seiko K.K.
SCADA SystemK.K. Systech Ushijima
Glass SyringeHitachi Information & Control Solutions, Ltd.
Glass Syringe Handling Inspection MachineMurata Seiko K.K.
Assembly Machine for inserting plunger rods and labelingWinckler & Co., Ltd./Groninger
Pillow Packing MachineWinckler & Co., Ltd./SIG
Cartoning MachineWinckler & Co., Ltd./IWK
The combination of the time-honored Japanese operating philosophy of kaizen (constant improvement) with value engineering (VE) and value analysis (VA) principles has proven to be a potent formula for success at Taiyo Yakuhin, a privately-held company located in Takayama City, Gifu, in central Japan, where it has been producing generics and OEM products for some four decades now.

Taiyo's unit factory building, which incorporates its pre-filled syringe manufacturing line - believed to be the first in the industry currently capable of producing and filling glass syringes in-house - was awarded one of the five prestigious annual Facility of the Year Awards sponsored by ISPE, INTERPHEX, and Pharmaceutical Processing magazine - in the equipment innovation category for 2007.

Asked what might have swayed the judges in Taiyo's direction, Hiroaki Mizuno, Project Manager says, "This is the first time in the industry that a pharmaceutical company is producing glass syringes and filling them also in-house. Every other pharmaceutical company purchases syringes from an outside manufacturer. Taiyo is doing both in-house - this is one of the unique features of this project."

"Doing all of this in-house is not easy because on the one hand you are required to make the syringe on the facility and do the complete filling and packaging in an isolator in-house," he says. The main product in the pre-filled syringes will be influenza vaccines, though the company has identified about 10 other products so far for this line. The glass syringes for the line will be in two sizes 1 ml and 2.25 ml. Reflecting an extremely high degree of automation, the two shifts on the fully automated 128-meter-line, are manned by just four to five operators per shift.

A tremendous amount of inspection, testing and checking is involved in the whole line to ensure or guarantee the quality of the syringes, according to Mizuno.

He explains that this entails the combination of the generally tough, rugged manufacturing functions required to produce an extremely high quality syringe with the very precise and clean filling of the product. This is being done much more routinely with the far simpler plastic syringes both in Japan and elsewhere in the world.

"This will be the first instance of this anywhere in the world - the production of glass syringes is complicated and involves melting and molding glass followed by fine and precise calibration, among other complicated processes," says Mizuno.

Acknowledging that the company was pleased with the Facility of the Year award, Mizuno stressed Taiyo's belief in the Japanese guiding principle of kaizen or constant improvement - which is most readily associated with the Toyota Motor Company's stellar achievements in the global auto industry.

"Kaizen for Taiyo is a very important factor, and this award will push Taiyo to do even more kaizen, more improvement," says Mizuno.

"Constant kaizen is one of the company's key goals along with value engineering and value analysis. When a project is finished, it is already outdated and old in the eyes of Taiyo, so constant improvements are necessary, and one should never be happy with what one has finished because there is always room for kaizen - to get better," says Mizuno.
Facility and Products

View of the Syringe Filling Line
The US$40 million pre-filled syringe line was designed and constructed within an existing six-floor factory. This expenditure covers the complete line, which starts with the production of the glass syringe from glass tubing all the way to the complete finished product that is packed into cartons for shipment.

The production line covering plastic and glass syringes was designed by Horiuchi Architecture Research, while production equipment design was done by the Taiyo team, headed by Hiroaki Mizuno. The construction management was done by Kashima Construction.

Design work started in November 2002, with some secondary work in February 2005. Construction was initiated in April 2003, and the plant was completed in May 2005, with secondary work completed in March 2006. Finishing validation took place in March 2005 for the primary work area and August of 2005 for the secondary work area. Manufacturing was initiated in August 2005 in the primary work area, with manufacturing in the secondary work area beginning in December 2006.

The engineering of the facility was executed in its entirety by Taiyo. The installation was done by the equipment suppliers working together with Taiyo staff. Most of the suppliers are based in Japan, but German and Swiss equipment suppliers participated as well.

"For the whole installation period, up to the final product testing, technicians and engineers from the equipment suppliers were in the factory working along with Taiyo," says Mizuno. "The installation of the pre-filled syringe line took approximately two months, and during this time technical staffs from the manufacturers were based in the factory," he adds.

Before the equipment was delivered from Europe, or even from the manufacturers in Japan, they were put through factory acceptance tests (FAT), where Taiyo staff engineers went to the individual suppliers, conducted a test run at their sites, and only after that was successful, that the equipment was shipped to Japan and installed and tested again by the technicians representing the machinery manufacturers.

"Currently, the commissioning work has been completed and all approvals from authorities have been received. The first vaccines will be filled in September 2007, when the factory will begin running at full capacity. It will produce 900,000 syringes per week, at the moment for the Japanese market only," says Mizuno.

"Taiyo considers this building, in which the new facility is located, a unit factory. There are four floors that can be divided into individual production areas.

"For example, this line was planned and purchased and built for influenza vaccines. So part of one floor was used to install the equipment," says Mizuno.

Glass Syringes/Barrel Molding Machine
In the entire building, it is possible to build 16 different production units, each of which could accommodate a different production facility, in accordance with customers' requirements. While each unit is approximately 400 square meters, the size can be adjusted to meet production requirements. Each story of the building has a floor but is otherwise empty. This means that everything from the air conditioning requirements to the internal layout could be negotiated and settled with a consigner to meet production flows and other requirements.

The technical facilities at the factory site include an isolator, a sterile room, dust prevention equipment and an area with a rigorous closed air conditioning system. The flexible layout makes it possible to change the configuration of this area to include new technical facilities and equipment, which may need to be brought onto the site based on the needs of consigners.

In its entirety, the Taiyo factory in Yakahama City has a total size of more than 110,000 square meters, and is operated by a staff of more than 500, including part-time, temporary and contract workers. The manufacturing department is the largest with 438 employees, followed by quality assurance with 58, technological development with 34 and plant engineering with three.

The Takayama factory manufactures some 491 Taiyo brand items along with 194 consigners' branded items. These products include drugs for internal use such as tablets, capsules, fine or coarse granules, powders, acids, dry syrups, liquids and syrups. Its injectable drug line includes ampoules, vials, bags, syringes and kits. Among the drugs for external use produced at the facility are ointments and creams, suppositories, liquid medicines, medicated nasal drops, drug syringes for ophthalmologic use and lozenges. The entire site is 100% Taiyo-owned.
Cost Conscious

The Lure Part Molding Process
In all its services, Taiyo strives for high quality, complete information and a stable supply of products. "In addition, our products are low in price, easy for nurses to use, and importantly create little burden on the patients," according to company literature.

Taiyo has established a low cost structure using efficient information systems, high yields and operational rates of return from manufacturing equipment, keeping manufacturing costs down via the use of automation and a refined research and development force. "Through these measures, we were able to produce goods that are high quality, value added pharmaceutical supplies while still maintaining low prices," according to Taiyo literature.

Its syringe in-house strategy is a case in point. "By doing the syringe manufacturing and filling in-house, tremendous costs can be saved," says Mizuno.

"One of the first reasons for the establishment of this new facility was to lower the cost of producing pre-filled syringes, making them cheaper overall. Taiyo is producing the syringes, from the glass barrel all the way to the end packaging in-house. This has the effect of bringing down the cost," says Mizuno.

"At the same time, Taiyo has chosen to automate as much as possible to avoid human errors and to decrease manpower. The basic objective is to lower the cost and have a perfect product," says Mizuno.

"Normally, a syringe is purchased from an outside manufacturer and shipped from the producer's factory to the pharmaceutical company where it is unpacked, sterilized, filled and processed," says Mizuno, reiterating that Taiyo does all of these operations in-house.

"Basically, Taiyo receives glass tubing from Germany. From this, the syringe barrel is formed, and then it is brought to the floor where the cleaning, siliconizing, filling, stoppering and other operations leading up to labeling and final packaging into cartons is done."

"By executing all these processes in-house, we have managed to lower the cost per syringe to a fifth of what it would cost in the past. This cost reduction is a major factor, which is only possible because of the complete in-house production of the syringe," says Mizuno.

This is already having an effect on the market. "The news that Taiyo can lower the cost of pre-filled syringes so drastically has brought in a large intake of OEM orders from pharmaceutical manufacturers within Japan to fill syringes for them," says Mizuno.

Several technical measures add to the overall efficiency of this process, which in turn also help to keep overall costs down. One innovation involves packing the syringes in Tyvec pillows then putting them through a hydrogen peroxide decontamination process while they are on the line.

Furthermore, a number of individual checks have been built into the line. The strength of the lure of each syringe is individually checked - so there is 100% security that no lure has a crack.

"A big problem with purchasing syringe barrels from outside is that the quality of the silicone used to make the plungers run smoothly is not uniform. So Taiyo has installed a unique silicone spray system, with a sensor that controls exactly how much silicone is applied to the inside of the syringe barrel," says Mizuno.

Other key technical measures ensure that all the rubber stoppers, tip caps and lure locks are automatically set into the syringe structure so that there is no human contact or no possibility of contamination of the parts - it is all automated, according to Mizuno.

The facility has also taken steps to ensure that its effect on the environment is minimal and that it uses energy with the greatest efficiency.

At the center of its energy saving strategy, is the collection and storage of cheaper energy for use at times when the cost of power is much higher. "Basically at nights, cheap energy is collected and used during the day via electricity storage batteries," says Mizuno.

"The normal method to fill syringes these days is that the syringes are purchased from a plastic or glass supplier and taken to the pharmaceutical factory, where they are cleaned, sterilized, and treated with silicone, and put through other required processes.

"Taiyo has gone a different way by doing everything in-house. The environmental considerations: no transportation from suppliers' factories, no packaging material required, no manpower required - basically, the syringes are produced on the ground floor and sent up to the filling facilities. This has big environmental benefits," says Mizuno.