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The PYRAMID News
November 2009 - Vol 1, Issue 2
In This Issue
How To Spot a Dirty Clean Room
Consultant's Corner
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MedhatWelcome to the second installment of the PYRAMID News. I mentioned in the first issue that we do not intend to make this newsletter into a commercial for PYRAMID Laboratories. Rather, we'd like to offer a quick read containing an item or two you'll find useful. In keeping with that, this issue has two articles that we hope you'll enjoy. In the first article, we present hallmarks of a suspect cleanroom....don't laugh, these things really happen. The second article gives a Consultant's perspective on healthcare reform. True, the articles aren't related, but we didn't promise to be cohesive. We'd just like to be useful.
 
Read on, and do let us know if you'd like us to explore a particular topic. 
 
Medhat Gorgy
President/CEO
How To Spot a Dirty Cleanroom
Did you know that nearly all recalls of parenteral drug products produced by aseptic processing alone were due to non sterility or lack of sterility assurance? Of the products recalled for lack of sterility assurance, both cGMP violations and concerns over container/closure integrity were sited as reasons. Since aseptic fill/finish had its beginnings in the 1920's, you'd think, as an industry, we should have the hang of it by now. And in fact, we do, for the most part. It's just that this critical piece of the manufacturing process is highly technique dependent, requires repetitive reinforcing training and presents management challenges to maintain the required high performance levels. But the consequences of failure, product recall or even patient morbidity or mortality, demand the investment of time and money.
 
Let's start with a few visible signs of a not-so-clean cleanroom operation:
 
  • Poor personnel and materiel flow design.
  • Personnel reaching over the fill line.
  • Lack of sufficient differential positive pressure between rooms.
  • Leaking HEPA filters with damaged media.
  • Surfaces that obviously trap particulate matter, e.g., window sills, crevices.
  • Flaky paint or damages in walls.
  • The use of non-cleanroom utensils and tools that are not easily cleanable.
  • Placing tools on the counter surfaces instead of immersion in IPA. 
  • Rust on carts and/or racks.  
  • Exposed human skin to the aseptic cleanroom environment.
  • Use of non-aseptic techniques by personnel during the filling operation.
  • Cleanroom crowded with personnel or equipment.
  • Non-continuous floor-wall-ceiling unions.
  • Loose ceiling tiles.
  • Fast movements by personnel.
  • Lack of barriers in equipment design.
 
Now, here are just a few must-have cGMP documentation items.
 
Documented...


  • Personnel training and retraining.
  • Personnel monitoring data.
  • Trending of monitoring data.
  • Environmental monitoring data.
  • Sampling procedures.
  • Air flow velocity studies.
  • Validation of aseptic filling process with defined parameters.
  • Performance of smoke studies for static and dynamic operations.
  • Continuous cGMP training.
  • Sterilization validation reports
  • Standard Operating Procedures
  • HEPA filter certifications
  • Equipment calibration reports
  • Internal audits.
 
The repetitive nature of the activities surrounding aseptic manufacturing adds to the overall challenge. Humans tend to perform at less than 100% when faced with repetitive tasks. The intent of this article is not to review every sign of a substandard cleanroom but to provide a refresher list of things of which to be aware. You can surely add to both lists.
  
Commercial vialingWe invite you to visit and tour our facilities at PYRAMID Laboratories in Southern California.
 
Charges of Price Gouging Raise Their Head
The column in this issue has been contributed by Dr. Steven Kuwahara. Originally from Hawaii, Dr. Kuwahara holds degrees in Biochemistry from Cornell and the University of Wisconsin. He has held positions in Quality in the biologics, device, gene and cell therapy segments of the pharmaceutical industry and is currently the Principal at GXP BioTehnology LLC.
Dr. Kuwahara has written several papers and book chapters and serves on the editorial advisory boards of BioPharm, BioQuality, and the Journal of GXP Compliance. He and a colleague have recently published translations of the Chinese GMPs and the Inspection Checklist for the Chinese GMP Certificates.

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The issue of prices for pharmaceuticals appears, once again, to be on its way to becoming an issue. Every few years the news media raise the issue of the price of therapeutic drugs and cite it as a major cause of the rising cost of healthcare. The issue eventually dies down after it becomes clear to everyone that the cost of therapeutic drugs is actually only a small percentage of the cost of healthcare. In the meantime there is a lot of finger pointing and accusations of price gouging. The issue will not go away because, like gun control, it is a convenient target for those who seek quick and easy answers to complex questions. In addition the current discussions on healthcare bring the subject into everyone's minds.

In part the industry itself must bear some of the blame. Stories about lavish dinners and expense paid vacations for clinicians who participate in clinical trials are widespread. Some of them are even true and are the result of poor public relations on the part of pharmaceutical companies. There have been many reports of limousines whisking physicians away to private dinners and to late night entertainment during national conventions. That this happens in clear view of others, may be a sign of openness, but at a time of public concern about the cost of healthcare, it is not wise.

The problem of course, is that there is a certain segment of the population that strongly believes that they should receive cradle to grave healthcare at absolutely no cost to themselves. In fact many of these people believe that they should receive all types of care from cradle to grave at no cost to themselves. The idea that the cost must then be borne by other members of society does not occur to them because they have a curiously distorted view of economics that says that the government can solve the whole problem by simply printing all the money that is needed without any consequences. The fact that many politicians pander to these people is a sad testimony to the sorry state of affairs with our secondary education system that should be giving the average citizen a basic grounding in economics.

This is not to say that there are no people who are in need of help. The media are very good at finding people who really do need help in paying for necessities. The pathetic stories are developed in a manner to elicit maximum sympathy. The stories are often presented in a manner to suggest that the majority of people are in this sad situation. Actually, these people really represent a small minority, and everyone, including the pharmaceutical industry hopes that the current interest in healthcare reform will produce solutions that will help these people in an effective and sensible manner. Of course this situation is found all through our society. There are desperate people who, through no fault of their own, need help in paying for other basic needs such as food, housing, and clothing. Their problems are being exploited by those who seek to manipulate public opinion for their advantage with no regard to the damage that they create.

Thus we can expect to go through another round of newspaper and TV news stories about how the evil pharmaceutical industry is over charging the defenseless public for their drugs. There will be no realistic stories of the true cost of developing and manufacturing drugs, nor will the costs of all of the safety and efficacy testing be discussed. Those of us who have been around a while have seen this before and after this round dies down, we will probably see more in the future. 

Dr.Steven Kuwahara 
Principal
GXP BioTehnology LLC
kuwahara@gxpbiotech.org
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PYRAMID Laboratories, Inc. (PYRAMID) is a Contract, Parenteral Drug Product Manufacturer and Analytical Service provider for the pharmaceutical and biotechnology industries. PYRAMID was established in 1988, is located in Southern California, USA, and is housed in three (3) buildings covering over 50,000 sq. ft.
 
PYRAMID offers a wide array of services for all phases of drug development. To read more about our services, please visit our website.