Installment 5
ISPE management deserve special praise for inviting a high-ranking engineer from a generic pharmaceutical manufacturing company---in this case, the rapidly growing Teva, to speak at this meeting.
As ISPE vice chair Bruce Davis affirmed, generics manufacturers are not "the enemy," but an increasingly important part of the global healthcare system. They also face margin and profit pressures that present a possible future scenario for pharma innovators---pressures that demand that they embrace new ways of doing things.
So far, Ajaz Hussain has been fairly quiet about development and manufacturing challenges at Sandoz, so it was interesting to hear from Uri Boneh, director of global engineering at Teva Global Generic Resources, about how the company has applied GMP principles and some Toyota-esque principles to the building of a new oral solid dosage manufacturing plant in Jerusalem.
As Mr. Boneh said, "Tomorrow ---and at least half of the next decade---is already here. We have to think about what we'll do after that point.:
The facility has been designed to facilitate expansion, he said. I wished that he'd focused a bit more on "how" but assume that would have been considered giving away trade secrets.
Mr. Bonet devoted a great deal of his presentation to affirming the fact that oral solid dosage manufacturing is still fairly low tech and labor-intensive, and has been operated the same way---using mixing, drying, milling, sieving, blending, tablet compression, filling.... for decades. "The market is growing, people are living longer and need more medications...someone has to make OSDs...
"I was sitting last week with leading tablet press manufacturers who showed how equipment had improved"¦.when I asked him how process had changed in last 150 years he had to admit, "not very much," Boneh said. "I hear that Novartis is working with MIT on long term 10-year project to change the way we make drugs"¦.I am curious"¦.this should be very interesting"¦.maybe in 10 years everything will be different"¦.for the moment, it's pretty much all the same"¦."
Mr. Boneh outlined the main functions critical to the process: Warehousing, transport and staging, washing, in process control, tooling and size parts, and noted that conventional production concepts needed detailed planning and control and aimed for high utilization of equipment and other resources.
The result, he said, has been long cycle time and low flexibility. "Like a commander on the battlefield, each department manager would issue work orders but [didn't] know what's going on in other departments"¦.
To eliminate waste, the new plant was designed with a "pull" focus for production planning and manufacturing. Cycle time is now 1.5 days, where, for some of the company's older plants, it's typically three weeks.
Design for the new plant began late in 2002, by 2005 it was ready for inspection and FDA inspected it in 2006.
"Online quality assurance equipment is there but it is labor intensive," Boneh said, "and results depend on the quality of your staff. You need comprehensive quality systems in place, to prove to yourself and inspectors that you are really in control of what you're doing.
The new facility uses a newer, crossfunctional approach to operations, he suggested. "We don't need chief of staff to tell everyone what to do."
Since packaging has to work all the time, it determines requirements for other departments.
Teva has also created virtual production lines or "lean production" lines extending from weighing, granulation, fluid bed drying. At this point, he says, only packaging is 80-100% utilized.
To use gravity fully, the company needed to build a high facility (several floors), but tall buildings are more expensive, and require more local permitting issues, so Teva eventually decided on a four-floor concept.
To enhance GMP, a critical part of the facility design was the concept of closed material transfer between process steps, Boneh said. Manufacturing is carried on in production suites, each of which is separated from the others by corridors with airlocks. Each suite produces one specific product. Everything is washed inside each suite so that nothing dirty comes out.
Airlocks, meanwhile, enhance separation and ensure that no air is recirculated into the HVAC system. Only cleaned containers, parts and equipment leave the suites.
Production people didn't like airlocks at first, Boneh said, but they improved overall hygiene. Once staff pass airlocks they must wear extra protective gear. Environmental and ergonomic considerations also drove design. Special focus was given to exhaust air filtration, solvents and thermal oxidation, wastewater treatment and noise reduction.
Teva used simulation extensively to design the facility, which uses a multilevel concept model. The plant is based in North Jerusalem, where the government offers investment incentives. Teva manufactures globally in 36 plants, Bohen says, and plans to double production by 2012.
It will be interesting to learn more of the specifics of this facility and its design. In the meantime, it was important to see representation from generics at this conference.
AMS
Installment 5
ISPE management deserve special praise for inviting a high-ranking engineer from a generic pharmaceutical manufacturing company---in this case, the rapidly growing Teva, to speak at this meeting.
As ISPE vice chair Bruce Davis affirmed, generics manufacturers are not "the enemy," but an increasingly important part of the global healthcare system. They also face margin and profit pressures that present a possible future scenario for pharma innovators---pressures that demand that they embrace new ways of doing things.
So far, Ajaz Hussain has been fairly quiet about development and manufacturing challenges at Sandoz, so it was interesting to hear from Uri Boneh, director of global engineering at Teva Global Generic Resources, about how the company has applied GMP principles and some Toyota-esque principles to the building of a new oral solid dosage manufacturing plant in Jerusalem.
As Mr. Boneh said, "Tomorrow ---and at least half of the next decade---is already here. We have to think about what we'll do after that point.:
The facility has been designed to facilitate expansion, he said. I wished that he'd focused a bit more on "how" but assume that would have been considered giving away trade secrets.
Mr. Bonet devoted a great deal of his presentation to affirming the fact that oral solid dosage manufacturing is still fairly low tech and labor-intensive, and has been operated the same way---using mixing, drying, milling, sieving, blending, tablet compression, filling.... for decades. "The market is growing, people are living longer and need more medications...someone has to make OSDs...
"I was sitting last week with leading tablet press manufacturers who showed how equipment had improved"¦.when I asked him how process had changed in last 150 years he had to admit, "not very much," Boneh said. "I hear that Novartis is working with MIT on long term 10-year project to change the way we make drugs"¦.I am curious"¦.this should be very interesting"¦.maybe in 10 years everything will be different"¦.for the moment, it's pretty much all the same"¦."
Mr. Boneh outlined the main functions critical to the process: Warehousing, transport and staging, washing, in process control, tooling and size parts, and noted that conventional production concepts needed detailed planning and control and aimed for high utilization of equipment and other resources.
The result, he said, has been long cycle time and low flexibility. "Like a commander on the battlefield, each department manager would issue work orders but [didn't] know what's going on in other departments"¦.
To eliminate waste, the new plant was designed with a "pull" focus for production planning and manufacturing. Cycle time is now 1.5 days, where, for some of the company's older plants, it's typically three weeks.
Design for the new plant began late in 2002, by 2005 it was ready for inspection and FDA inspected it in 2006.
"Online quality assurance equipment is there but it is labor intensive," Boneh said, "and results depend on the quality of your staff. You need comprehensive quality systems in place, to prove to yourself and inspectors that you are really in control of what you're doing.
The new facility uses a newer, crossfunctional approach to operations, he suggested. "We don't need chief of staff to tell everyone what to do."
Since packaging has to work all the time, it determines requirements for other departments.
Teva has also created virtual production lines or "lean production" lines extending from weighing, granulation, fluid bed drying. At this point, he says, only packaging is 80-100% utilized.
To use gravity fully, the company needed to build a high facility (several floors), but tall buildings are more expensive, and require more local permitting issues, so Teva eventually decided on a four-floor concept.
To enhance GMP, a critical part of the facility design was the concept of closed material transfer between process steps, Boneh said. Manufacturing is carried on in production suites, each of which is separated from the others by corridors with airlocks. Each suite produces one specific product. Everything is washed inside each suite so that nothing dirty comes out.
Airlocks, meanwhile, enhance separation and ensure that no air is recirculated into the HVAC system. Only cleaned containers, parts and equipment leave the suites.
Production people didn't like airlocks at first, Boneh said, but they improved overall hygiene. Once staff pass airlocks they must wear extra protective gear. Environmental and ergonomic considerations also drove design. Special focus was given to exhaust air filtration, solvents and thermal oxidation, wastewater treatment and noise reduction.
Teva used simulation extensively to design the facility, which uses a multilevel concept model. The plant is based in North Jerusalem, where the government offers investment incentives. Teva manufactures globally in 36 plants, Bohen says, and plans to double production by 2012.
It will be interesting to learn more of the specifics of this facility and its design. In the meantime, it was important to see representation from generics at this conference.
AMS
