Reinventing the wheel

With all the concerns over the high cost of prescription drugs, and with the threat of terrorists exposing the public to releases of chemicals from manufacturing plants, let us step into the shoes of a pharmaceutical plant safety engineer needing to upgrade his plant. Everyone wants our pharmaceuticals to be safe, reliable, and reasonably priced. But an antiquated approach to regulating process improvements is harming our ability to satisfy these goals.

This is a regulated world. Some might say an over—regulated world. But the true downside of over—regulation is not just the cost of compliance, it is the hidden cost of bureaucratic inertia. The bureaucratically safe decision is to keep things exactly the same. The technology of pharmaceutical manufacturing is improving all the time, but the FDA does not have a system to allow manufacturers to test and certify new products and get them easily adapted to existing validated processes. To get along with the FDA, the easiest course is to turn your manufacturing plant into a technology museum on the day it is built. Do not try to upgrade it to include the newer technology with better process control, sanitation or other improved quality controls America's ceaseless technological progress makes available. Make your drug exactly the same way you did on the day you got your process validated, despite the improvements in the available technology.

But let us assume you are committed to serving the public, and want to produce better products more inexpensively. And you want to make your plant safer from terrorists. Do you solicit help from the Department of Homeland Security? Don't expect much help there. Accepting personal responsibility you check the available resources. You already have an extensively documented process under FDA Process Validation.   Since you use steam to sterilize the vessel, it has a code stamp from the American Society of Mechanical Engineers, governed by the ASME Pressure Code. You are charged with ensuring the process meets all pertinent regulations. Since the AMSE has recently issued a revised, tougher code on rupture discs, a type of pressure relief device used to relieve overpressures, you've got to do something. The old installation no longer meets the tougher code requirements. Inactivity is not an option. And you want to do something and do it now. If a terrorist attacks, you need to have already taken steps to mitigate the potential for uncontrolled explosion of the pressure vessel.

First, you take the latest continuing education course on preventing explosions  hen you consult your existing rupture disc manufacturer for advice. He has gotten the required certifications to meet the revised ASME Code as well as those covering quality (ISO), pressure relief (National Board), sanitation (3A) and others. And he has a beautiful new design that has better longer service life, better relief capacity and improved sanitation with zero impact on the process. The new design does everything the old did, just better. And the increased capacity yields a greater margin of safety for destructive overpressure events. Boy, you're in hog heaven!

Not so fast! We are talking about a validated process. So you've got to get past the FDA cops. Now you're between a rock and a hard place. The state fire marshal and your insurance carrier want you to come into compliance with the latest pressure codes from the ASME, and you have every reason to upgrade to the new technology to protect your own employees and equipment from danger. But the manufacturer must differentiate between the designs so their customers can tell whether the disc meets the new code. It cannot be exactly what is in the detailed validation specification already on file. So you must re—validate.

The FDA does allow re—validation, but the procedure that will take hours (I've had estimates of 12 engineering hours per installation). Even that is not so bad if you could make it a new manufacturing standard design, so the next time it is a matter of building on past experience. And every other pharmaceutical manufacturer has exactly the same problem at the same time.

The problem is the FDA cops don't work with a global perspective. They consider each process a separate issue, so they make you waste 12 hours on every process. You must 're—invent the wheel' every time you use the new standard design. There is no institutional memory to learn from past experience and apply it broadly. If you've got 100 fermenters in your plant, instead of 12 hours up front and one more hour per fermenter for a total of 111 hours to install the new technology, you will spend 1200 hours. And your competitor across the street is dealing with exactly the same problem. He'll spend 1200 more hours on repetitive paper work.

Wouldn't it make sense for the FDA to devise an expedited re—validation system to save everyone some time?  After all, it would take over six months of continuous effort on just this one issue to make your plant more terrorist resistant by preventing explosions in pressurized vessels containing exotic chemicals. Isn't there a way to get the FDA to acknowledge the efforts of all those other watchdog parties such as the ASME, ISO and 3A to ensure quality and safety? Reinventing the wheel every time you manufacture a car does nothing to improve vehicle safety.

There are a lot of retired people who want to spend less money on drugs and have lived to see multiple technological revolutions during their life spans. Could they be willing to accept a move to the best available control technology (BACT). That's exactly what the EPA demands on their pollution control permits. The public doesn't want bureaucracy, they want improved healthcare at lower cost. Let's turn our plants into showcases, not museums.

With all the concerns over the high cost of prescription drugs, and with the threat of terrorists exposing the public to releases of chemicals from manufacturing plants, let us step into the shoes of a pharmaceutical plant safety engineer needing to upgrade his plant. Everyone wants our pharmaceuticals to be safe, reliable, and reasonably priced. But an antiquated approach to regulating process improvements is harming our ability to satisfy these goals.

This is a regulated world. Some might say an over—regulated world. But the true downside of over—regulation is not just the cost of compliance, it is the hidden cost of bureaucratic inertia. The bureaucratically safe decision is to keep things exactly the same. The technology of pharmaceutical manufacturing is improving all the time, but the FDA does not have a system to allow manufacturers to test and certify new products and get them easily adapted to existing validated processes. To get along with the FDA, the easiest course is to turn your manufacturing plant into a technology museum on the day it is built. Do not try to upgrade it to include the newer technology with better process control, sanitation or other improved quality controls America's ceaseless technological progress makes available. Make your drug exactly the same way you did on the day you got your process validated, despite the improvements in the available technology.

But let us assume you are committed to serving the public, and want to produce better products more inexpensively. And you want to make your plant safer from terrorists. Do you solicit help from the Department of Homeland Security? Don't expect much help there. Accepting personal responsibility you check the available resources. You already have an extensively documented process under FDA Process Validation.   Since you use steam to sterilize the vessel, it has a code stamp from the American Society of Mechanical Engineers, governed by the ASME Pressure Code. You are charged with ensuring the process meets all pertinent regulations. Since the AMSE has recently issued a revised, tougher code on rupture discs, a type of pressure relief device used to relieve overpressures, you've got to do something. The old installation no longer meets the tougher code requirements. Inactivity is not an option. And you want to do something and do it now. If a terrorist attacks, you need to have already taken steps to mitigate the potential for uncontrolled explosion of the pressure vessel.

First, you take the latest continuing education course on preventing explosions  hen you consult your existing rupture disc manufacturer for advice. He has gotten the required certifications to meet the revised ASME Code as well as those covering quality (ISO), pressure relief (National Board), sanitation (3A) and others. And he has a beautiful new design that has better longer service life, better relief capacity and improved sanitation with zero impact on the process. The new design does everything the old did, just better. And the increased capacity yields a greater margin of safety for destructive overpressure events. Boy, you're in hog heaven!

Not so fast! We are talking about a validated process. So you've got to get past the FDA cops. Now you're between a rock and a hard place. The state fire marshal and your insurance carrier want you to come into compliance with the latest pressure codes from the ASME, and you have every reason to upgrade to the new technology to protect your own employees and equipment from danger. But the manufacturer must differentiate between the designs so their customers can tell whether the disc meets the new code. It cannot be exactly what is in the detailed validation specification already on file. So you must re—validate.

The FDA does allow re—validation, but the procedure that will take hours (I've had estimates of 12 engineering hours per installation). Even that is not so bad if you could make it a new manufacturing standard design, so the next time it is a matter of building on past experience. And every other pharmaceutical manufacturer has exactly the same problem at the same time.

The problem is the FDA cops don't work with a global perspective. They consider each process a separate issue, so they make you waste 12 hours on every process. You must 're—invent the wheel' every time you use the new standard design. There is no institutional memory to learn from past experience and apply it broadly. If you've got 100 fermenters in your plant, instead of 12 hours up front and one more hour per fermenter for a total of 111 hours to install the new technology, you will spend 1200 hours. And your competitor across the street is dealing with exactly the same problem. He'll spend 1200 more hours on repetitive paper work.

Wouldn't it make sense for the FDA to devise an expedited re—validation system to save everyone some time?  After all, it would take over six months of continuous effort on just this one issue to make your plant more terrorist resistant by preventing explosions in pressurized vessels containing exotic chemicals. Isn't there a way to get the FDA to acknowledge the efforts of all those other watchdog parties such as the ASME, ISO and 3A to ensure quality and safety? Reinventing the wheel every time you manufacture a car does nothing to improve vehicle safety.

There are a lot of retired people who want to spend less money on drugs and have lived to see multiple technological revolutions during their life spans. Could they be willing to accept a move to the best available control technology (BACT). That's exactly what the EPA demands on their pollution control permits. The public doesn't want bureaucracy, they want improved healthcare at lower cost. Let's turn our plants into showcases, not museums.