As of the conclusion of our semiannual meeting last week, our Subcommittee has 96 members and is responsible for 45 approved methods, plus another 13 currently in the process of development.  In the interest of brevity, I will describe only two examples of the latter.

The first of special note is a modification of E 1174, the ASTM version of the FDA method specified for testing of handwash products intended for use in healthcare. The modification involves the procedure for contaminating the hands with Serratia marcescens, the indicator bacterium used to challenge product antimicrobial efficacy, and is particularly important in that the new method will be much more appropriate for testing leave-on (non-water-aided) hand sanitizers.

Another method-in-the-making is one for testing liquid microbicides versus bacterial biofilms, organized assemblages that are considerably more resistant to antibiotics, topical antimicrobials, and disinfectants than are planktonic (free-floating) bacteria.  Only in the last decade, or so, has the important role that biofilms play in disease causation and environmental fouling been understood, and colleagues from the Center for Biofilm Engineering at Montana State University here in Bozeman have been in the forefront of methods development in E 35.15.

Although I have selected for comment only these from among our many methods, I would welcome any questions you may have about testing of antimicrobial formulations and how the testing methods are created collaboratively by volunteers from industry, regulatory agencies, and CROs such as BioScience Laboratories.

– John Mitchell, Director of Quality Assurance and Chief Medical Officer

The mechanisms of transmission are:

1. Exposure to large respiratory droplets
2. Exposure to small-particle aerosols in the immediate vicinity
3. Direct contact transfer from contaminated hands to the nose and eyes

There is no proven evidence that shows one mechanism is more effectiven than the other.  Droplet transmission requires close contact and is generated by the infected person sneezing, coughing or talking.  Localized airborne transmission of influenza via small particles may occur in short distances (as much as 6 feet).   Influenza is not known to spread in airborne transmission of distances any longer than this, thus special air handling systems are not necessary to prevent the spread of influenza in healthcare settings.  Direct contact transmission of influenza has been suggested as a contributing factor in several studies.  It is therefore important to practice thorough and frequent handwashing as well as masks, gloves and gowns in a healthcare environment.

Are you practicing good techniques in your work place, in your home and in any place you come in contact with others to prevent transmission of the H1N1 A virus?  Does your employer have an H1N1 A virus prevention or response program should an outbreak occur in your company?

 – Jim Verzuh, Director of Marketing, BioScience Laboratories

What you must do:  Take the time to think through all the parts and pieces that make up your overall cleaning program to ensure the program is effective, practical for every day activities.

Product Selection:  

Alcohols:  Broad-spectrum efficacy against vegetative bacteria.  Typical concentration of 70% used.  Not effective against molds or spores. 

Aldehydes: Powerful and aggressive disinfectants.  However, are highly toxic to personnel and require long contact times for sporicidal claims.  

Sodium hypochlorite (NaOCl) and other chlorine compounds:  Broad-spectrum biocidal activity.  Chlorine solutions are corrosive, unstable over time, and rapidly lose activity.  Typically concentrations for sodium hypochlorite are 500 to 50,000ppm.  A low ppm will be effective against most vegetative bacteria within 10 minutes.  Unfortunately, to kill spores/molds the concentration must be greater.  Good disinfectant – Poor cleaner.  Will not remove soil load.   

Hydrogen peroxide: A potent biocide and environmentally friendly.  Peroxides are deactivated in the presence of soil loads, so pre-cleaning is required to achieve the desired reduction in the microbial population.  Typical concentrations as low as 0.5 percent.  Hydrogen peroxide can be combined with other ingredients to dramatically increase its germicidal potency and cleaning performance.

Phenolics: Broad range of disinfectants that are used on environmental surfaces. Typical concentrations are 2 to 5 percent with contact times of 5 to 10 minutes.  Added detergents are effective in removal of soil loads. 

Quaternary ammonium compounds: Non-irritating and non-corrosive to surfaces.  Typical concentrations of 0.1 to 2 percent and require 10 minutes of contact time to kill microorganisms.  However most are not effective in removing biofilms and leave surfaces with a residue that must be removed after disinfection.

Application Procedure:

A spray procedure is a quick way to effectively treat a surface.  However, with many of the disinfectants a pre-clean may be required to remove any soil load.  A wipe procedure is also very effective in mechanically removing microorganisms and is a great addition to any disinfectant cleaning program.

How can BioScience help?

We can perform the following testing (1) use-dilution tests (screening disinfectants for their efficacy at various concentrations and contact times against a wide range of standard test organisms and environmental isolates); and (2) surface challenge tests (using standard test microorganisms and microorganisms that are typical environmental isolates, applying disinfectants according to your cleaning procedures. 

– Liv Graving, Microbiologist and In-Vitro Study Director 

Amy L. Juhnke, Manager of Quality Assurance/Document Control

For those wondering about the responsibilities of a principal investigator, here is the result of my research on this topic.

The Principal Investigator receives no direct supervision and has complete authority and responsibility for the clinical trials they perform. Personal initiative is imperative. He or she must have a firm understanding of the principles of planning, organizing and management. The Principal Investigator must promote Good Clinical Practices thought the clinical research process by ensuring strict adherence to the protocol, protection of the patient’s health and welfare, integrity of the data generated, and compliance with all federal and state regulations The person who holds this position must have a current physician’s licensure to practice with five to eight years of experience in clinical research. They must have an above average ability to interface with patients, staff, sponsor, and IRB. The Principal Investigator is responsible for maintaining a cohesive team that consistently completes clinical trials on time and at budget.

Provides investigator qualifications and agreements to sponsors by maintaining current curriculum vitae, demonstrates the proper education, training and experience to conduct the clinical investigations Principal Investigator is responsible for signing Form FDA 1572, the protocol, and all sponsor contract(s), and complete disclose of any conflicts of interest

Ensures protocol compliance by possesses a thorough understanding of the protocol, determines if the inclusion/exclusion criteria are compatible with the intended study population, establishes recruitment goals and gains approval of both the IRB and the sponsor prior to any amendments or protocol deviations

Ensures continuous oversight of the clinical trial by the IRB, by providing the protocol, investigator’s brochure, informed consent, recruitment materials, protocol amendments or deviations, adverse events and any other materials regarding the study to the IRB for review

Ensures adequate facility and number of staff to conduct the study and makes adequate time to supervise and conduct the study.

Manages medical care and ensures that all medical decisions related to the clinical trial are made by a qualified physician. The Principal Investigator evaluates subject compliance and response to therapy, is responsible for adverse events, proper medical attention in the occurrence of an adverse event, and notification of primary care physician

Protects the rights and welfare of subjects ensuring the informed consent is in accordance with CFG 56 and 45 and that the subjects are aware of all aspects of the clinical trial

Oversees the quality of the trial by ensuring all case report forms are legible, complete, and accurately reflect the source documents. Reviews, understands, and approves corrections made to case report forms and ensures the proper quarantine and use of the investigational materials

Communicates effectively with subjects, the research team, the sponsor, and the IRB and is responsible for the clarity of the protocol and purpose of therapies by the research staff. The Principal Investigator will participate in study monitoring conducted by the sponsor and regulatory administrations

The Principal Investigator maintains professional knowledge and technical expertise by reviewing medical research publications and participating in professional organizations

John Dyba, Senior Account Executive

Nowadays it is much easier thanks to the YouTube and the makers of video cameras.  With a camera costing around $500, an external microphone and good lighting, anyone can make a video of their product or service.  The simplest approach is to limit editing by shooting a demonstration of your product or conversation about your service.  As long as the content is meaningful, your customer will not care if you make a mistake or two in delivery.

Once the video is complete and digitally saved, simply upload it to YouTube.  Their site accepts many formats of video files and converts it to their FLV format, so don’t worry too much about the file type until a problem arises.  YouTube has many features including indexing the video (i.e. separating it in chapters) to make it easier for the viewers.  Within YouTube, it is important to add a title and description that includes keywords that will online searchers find the video.  A link from your company’s website can also be added to the video on YouTube.  Since it is becoming quite common for companies to make use of YouTube to host video content, online viewers of your website will be quite used to be redirected to YouTube.

I followed the above steps and was able to post multiple videos in the same day.  Already clients have responded that is much easier to understand how we conduct testing after watching our testing demonstrations posted on YouTube.  It also has increased our visibility on line for search engines.  What have your experiences been like with online video?

Jim Verzuh, Director of Marketing

Additionally, other testing methods have also been developed using the EpiDerm tissue model.  These other testing methods are conducted in ways very similar to the dermal irritation method and are also performed at BioScience Laboratories:

Dermal corrosion testing measures the production of scarring usually as a result of corrosive tissue destruction (necrosis) following the application of a substance (irreversible).  The potential for chemically-induced dermal corrosion is an important consideration in establishing procedures for the safe handling, packing, and transport of chemicals.

Dermal phototoxicity testing identifies the existence or absence of possible hazards likely to arise from a test substance in association with exposure to UV and visible light.  A typical application is testing the phototoxicity of new sunscreen product formulations while in development to identify chemicals that might induce adverse skin reactions.

Percutaneous absorption testing uses various EpiDerm kits to calculate the permeability coefficient of a test article.  Also, this is the underlying technology used in transdermal drug delivery studies.

Looking towards the future, BioScience Laboratories is developing test methods to make use of the other tissue models available from the manufacturer of the EpiOcular and EpiDerm models. 

MelanoDerm is the model of choice in tissue testing procedures useful as an in-vitro means to evaluate cosmetic and pharmaceutical agents designed to modulate skin pigmentation and usually involves topical application of skin lighteners or self-tanning agents.

EpiAirway is the model of choice in tissue testing procedures for gas phase exposure of volatile articles for airway inflammation and irritancy studies.  These methods also allow the measurement of transepithelial permeability for inhaled drug delivery studies.

EpiOral is the model of choice in tissue testing procedures which enable the in-vitro study of irritation, oral pathologies, and basic oral cavity phenomena.  Some companies have also used this model to grow commensal and pathogenic bacteria in order to study their effects on the oral tissues.

Dendritic/Langerhans cells can be used to develop in-vitro assays for contact sensitization and other immunological reactions of the body.

As you look to develop new products and differentiate them within the marketplace, which of these tissue models are most attractive to your company to use in product testing?  How important is it to your customers that products are tested without harming animals?

Jessica McDonnell-Philipp, In-Vitro Laboratory Study Director

“Finally, it has arrived! The super duper doohickey with the detachable thingamajig. Hmmmm … nice box … kind of hard to get open … argh … ahhh … there … box cutter got’er done … oops … directions on the outside of the box say don’t use box cutter …oh well, it’s only a little scratch right there. Hey … it’s not assembled … dang! Guess I gotta get the instructions …  (pause while looking at instructions) … these instructions are too complicated … I can put it together without those silly things.”

And it is very possible that you are mechanically inclined enough to put this piece of equipment together. But what about that scratch that has been unintentionally placed? Unless you read and understand the instructions, you are unaware of the cautions/warnings and other pertinent information that could help avoid damage to yourself, others or the equipment.

User manual’s, technical manuals, work instructions, work documents, protocols, process instructions, policies … whew and wow! So many ways to provide information, but my personal favorite is the Standard Operating Procedure (SOP).

The standard operating procedure is a wonderful tool for controlling work. It defines those subtle details that make the difference between success and failure of the work you are performing. WIKIPEDIA (the on-line encyclopedia) defines the SOP as follows:

A standard operating procedure is a set of instructions having the force of a directive, covering those features of operations that lend themselves to a definite or standardized procedure without loss of effectiveness. Standard Operating Policies and Procedures can be effective catalysts to drive performance improvement and improving organizational results.

An Engineer reads aloud from the “Master” SOP, “Turn the nut clockwise, one revolution using the encapsulated nut rotating apparatus.” A worker crouched down over a very expensive and shiny piece of equipment makes eye contact with the engineer and repeats “Turn the nut clockwise one revolution using the encapsulated nut rotating apparatus.” The worker using the encapsulated nut rotating apparatus then turns the nut clockwise one revolution. He makes eye contact with the engineer and states, “The nut has been turned clockwise one revolution using the encapsulated nut rotating apparatus, check.” An Inspector standing next to the worker monitoring his every movement then states, “The nut has been turned clockwise one revolution using the encapsulated nut rotating apparatus, check.” The Engineer then states, “The nut has been turned clockwise, one revolution using the encapsulated nut rotating apparatus.” A second Inspector that has been standing next to the engineer and monitoring every movement in the building states, “The nut has been turned clockwise one revolution using the encapsulated nut rotating apparatus.” The Engineer and second Inspector then sign that the step has been performed.

Granted, you probably are not going to go to this length in ensuring that the written word is followed verbatim. But, hopefully, prior to starting that very important task you eventually will perform countless times, you read through the SOP relating to the task. Actually, if the work environment allows it, have an authorized copy of the SOP right at your side and follow it word-for-word. And if for some reason the SOP isn’t working for you, stop and revise it to describe clearly the correct procedure to be used in the future.

Scott D. Ferraro, Quality Control Manager