That’s a good question. Here’s another, “Is my media sterile”? Most people would answer the sterility question with an enthusiastic, “YES, of course it is, given the fact that my autoclave print out has revealed time and temperature were adequate and the biological indicator is negative.” But is your autoclave printout really telling you the truth? How about that biological indicator? Some say, “spores don’t lie.” I have personally witnessed several biological indicators placed in a liquid load, the autoclave performed a flawless sterilization cycle, BIs were incubated at 55-60˚C for 48 hours, and when inspected, were negative, but the load was not sterile. Further, the autoclave printout indicated that time, temperature and pressure were within range. So why are my autoclave and biological indicator lying to me? “I have a bad batch of biological indicators,” is probably the first thing out of your mouth. Well … more than likely it was “dog-gone it … ” and after you apologized to you co-workers for your unprofessional outburst, you immediately dialed your supplier of biological indicators and politely told them their BIs are “C_ _ P!”

So, before I inflict my wrath upon my co-workers and that nice Biological Indicator person on the other end of the phone, I should ask myself some questions:

1.                 Is the air in the autoclave chamber being replaced by steam? “Yep … when I close the door and turn or press a couple buttons, a buzzer eventually goes off, and when I open the door, everything is really hot!”

During a liquid load cycle, the steam supply enters the autoclave chamber usually from an inlet located in the upper rear of the chamber. The steam pushes the air from the top of the chamber down the drain usually located at the bottom front of the chamber. If your autoclave repair person has recently visited and ensured you that the autoclave steam traps and solenoid valves are functioning properly, then you should check to see if the load, itself, is trapping air. If a media flask is placed into a container to catch boil off from the flask, air can be trapped in the container and insulate the lower portion of the flask from heat energy transfer. Also, is the autoclave periodically calling for steam? If the autoclave is in its sterilization cycle and is not making any noise (i.e., clicking noise from activating solenoid valves or an intermittent whooshing sound of steam entering the chamber), the autoclave could be experiencing a “superheated” condition. When the chamber atmosphere is not steam-saturated, the flasks will be experiencing the same conditions as exposure to hot air and will not be sterile. 

2.                 Is this load validated? “Yep … same number of flasks and same amounts of liquid … well, maybe I did add a little extra of this and a pinch of that to the recipe.” If someone has not placed mechanical devices (i.e., thermocouples) into a load like the one you are running and determined where the hot and cold locations are for that load, you will not know where to place the BI, which flask to test for growth promotion and pH range, or how long to run the sterilization cycle. During load validations, “come-up” time and the “exhaust cycle” are considered in determining how long a sterilization cycle should be. When all of these factors are considered, risk of overcooking of media is greatly reduced, and sterility is greatly assured.

3.                 Did I place my Biological Indicator in the right place? “Yep … I followed the validation protocol map, and I know exactly where to place the BI.”

Logically, you placed the BI in the flask at the “cold” location specified by the validation study. But did you use the correct BI and did you locate it in the flask in the proper location? There are several BI manufacturers. For example, SGM Biotech manufactures a biological indicator called MagnaAmp™. Because this BI is for steam sterilization of solutions (contains the spore Geobacillus stearothermophilus) and is designed to sink. If your BI is simply floating on the surface of the liquid you are trying to sterilize, the BI will not be monitoring the cold location of the liquid (typically middle and toward the bottom of the flask), but will be subjected to, and accumulating lethality from chamber temperature.

In thermal sterilization processes, “time at temperature” is critical to achieve required product sterility.

According to the U.S. FDA, process validation is defined as: Establishing by objective evidence that a process consistently produces a result or product meeting its predetermined specifications.

Scott D. Ferraro

Quality Control Manager

The history of clinical research has followed a very similar path in the industrialized countries of the world: Initiation, Acceleration, Rationalization and Harmonization.  The understanding that controlled clinical research would need to be conducted to evaluate the safety and efficacy of therapies prior to public use was eventually reached by all of the industrialized countries. During the 1960’s and 1970’s many laws were passed regarding the evaluation and reporting of drug safety, quality and efficacy. During this time the drug industry was becoming more international and seeking to market their products globally, but the process was slowed by the requirement to register each product nationally. Therefore, the same fundamental research was being required by each regulatory system to show product safety and efficacy. This requirement stemmed from technical requirements within each regulatory system that caused expensive and time consuming research to be duplicated on drugs that had previously been proven safe and effective. Concerns regarding the cost of duplicating research and increasing health costs while slowing the availability of therapies that are safe and efficacious to patients who needed them could be reduced through regulatory harmonization.

Harmonization of regulatory requirements between countries was pioneered in Europe in the 1980s and proved that it was possible. Discussions between Europe, the US and Japan progressed to plans of action in 1989 and the International Conference on Harmonization became a reality in 1990.

Harmonization objectives are divided into three topics: Quality, Safety and Efficacy and represent the basis of therapy approval. Expert Working Groups (EWGs) were formed to discuss the scientific and technical issues regarding each of these topics. The initial objective of the ICH was to remove duplication and redundancy in the development and review process by defining data sets that would demonstrate quality, safety and efficacy of investigational therapies. Over time the ICH has developed the Common Technical Document (CTD), this document provides the harmonized format and correct content for international product applications. 

Today the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) attempts to gain consensus between the regulatory authorities of Europe, Japan and the United States by involving experts from each region to discuss scientific and technical issues regarding product registration.  The purpose is to make recommendations on ways to achieve greater harmonization regarding the interpretation and application of technical guidelines and requirements for product registration to reduce the need for duplicate testing during the research and development of new therapies. The result of effective harmonization is the more economical use of human, animal and material resources, and the reduction of unnecessary delays in the global development and availability of new therapies and maintaining quality, safety and efficacy. This approach represents the proverbial three legged stool and will simply not work without all three topics (Quality, Safety, and Efficacy) addressed correctly.  This approach has provided the ICH with success because it harmonization was/is developed on the foundation of scientific consensus from both the industry and the regulatory associations from each of the three regions.                                 

John Dyba
Senior Account Executive

A recent survey conducted by Green Seal and EnviroMedia Social Marketing reveals that “Four out of five people say they are still buying green products and services today–which sometimes cost more–even in the midst of a U.S. recession”.  However, the survey results also noted that “about one in three consumers say they don’t know how to tell if green product claims are true”.  With consumers become more savvy about green products and continuing to educate themselves — “Consumers are verifying green claims by reading the packaging (24%) and turning to research (going online, reading studies; 17%)”—manufactures and marketers are now, more than ever being held accountable for correctly portraying their products, and having the data to backup their claims.

As a consumer what means are you taking to validate the greenness of the products you purchase?  As a manufacturer or marketer how are you making sure this information is available to your customers? 

With website such as www.greenwashingindex.com, consumers can rate various green advertising from “authentic” to “bogus”, and share their thoughts with others.  Green product advertising has been increasing exponentially over the past few years, and now consumers are willing to look beyond the advertising to the product itself.  Will this shift in consumer self-education be the next big swing in product marketing?

Sabrina Bakich
Manager of Marketing Execution

Recently our organization went through an investigation to determine our level of ISO compliance and the value of ISO compliance in the market place.  After much research and discussion with customers, industry consultants and compliance registration firms, we found that the ISO/IEC 17025 Standard was the most generally applicable standard to our core business as a contract testing laboratory and clinical trials services provider.

As our quality assurance staff looked through this standard, we found that our current GLP and GCP compliant programs met or exceeded nearly all of the required components listed.  This self-assessment was confirmed in late December of 2008 when one of our clients audited our quality program against ISO/IEC 17025.  In his final evaluation, the independent auditor hired by our client stated that our quality program was the best amongst those seen during his audits of the laboratories on the client’s short list.  He also stated that, even though we do not claim ISO/IEC 17025 compliance, our quality program matches up very well with this standard.  He provided a list of recommendations to consider if we wanted to upgrade our quality program to this level, and our quality assurance department is working on those.

In parallel with assessing our quality program’s ISO/IEC 17025 compliance, our sales and marketing staff has been talking with customers to determine the value of such compliance in the market place.  To date, our research has shown that ISO/IEC 17025 certification is not required by our North American client base, but rather, GLP and GCP compliance is the standard.  In Europe, we are seeing a trend toward such compliance amongst testing laboratories.  The trend is fueled by the universal acceptance in European Union of ISO/IEC 17025 for testing laboratories.  We have not found, though, that this universal acceptance is based on government regulation; rather, it is a cooperative agreement amongst the countries of the European Union.

So what is the true value of being ISO/IEC 17025 compliant?  It seems that being GLP and GCP compliant provides a high enough level of quality for North America manufacturers and government agencies.  Will our clients see added value if we are ISO compliant or certified?  Would they being willing to pay a higher price for services performed under a quality system compliant with ISO/IEC 17025?  Our research says “no” to these questions, as regards the North American market.  In Europe, although it seems being ISO/IEC 17025 may be a competitive necessity for participation in the market, it still does not seem that it would add value to our clients there.  Better answers to these questions, though, would come from more information than we have been able to accrue so far.  I invite you, then, to respond to these questions.  Does your organization value or require ISO/IEC 17025 compliance from its testing and clinical trials service provider and does your answer depend on the geographic area in which you intend to sell your product?  

Jim Verzuh
Director of Marketing and Special Projects