Sunday, November 28, 2010
This just in from the UK-based newspaper, The Guardian. People will soon be able to tell if they have an STD by urinating on a small computer chip and inserting it into a mobile phone or computer, doctors and scientists in Britain claim. The small devices, similar to pregnancy testing kits, will reportedly be able to give people a home diagnosis within minutes. Millions of pounds have been poured into the project to combat an STD epidemic in Britain, where infections reached a record 482,696 last year. The research has been given the thumbs up by Professor Noel Gill, the head of HIV and STIs at the British government's Health Protection Agency, who said he hoped the application of new technology would reduce infections among young people. The HPA would coordinate large-scale evaluations of the technology within a network of collaborating STI clinics.
"Your mobile phone can be your mobile doctor. It diagnoses whether you've got one of a range of STIs, such as chlamydia or gonorrhea and tells you where to go next to get treatment," Dr Tariq Sadiq, the sexual health expert from the University of London who is leading the project. The developers of the rapid testing devices - which include experts in microbiology and phone operators like O2 - expected them to be sold for a pound each in vending machines in nightclubs, pharmacies and supermarkets.
I am aware of at least one RMM company that is able to control their technology via a mobile device, so this type of communication platform is certainly a viable opportunity for the industry.
Tuesday, November 23, 2010
When government and industry were looking for a way to identify more rapidly the presence of the pathogenicClostridium perfringens bacterium in food and water, Daniel Fung of Kansas State University realized he had a potential solution on his shelf. He applied what’s known as the Fung Double Tube method that he developed decades earlier and determined that the detection time can be reduced from about a day or two down to four hours.
“In the meat industry and related food industries, the faster one can detect and enumerate live major pathogens such asC. perfringens, the faster corrective actions can be implemented or the food can be destroyed before reaching the consumers,” said Fung, a food science professor who researched the issue as a Food Safety Consortium-supported project. “The benefit of a rapid method to detect and enumerate live C. perfringens in foods in four hours is obvious.”
According to a paper in the November Journal of Clinical Microbiology, a new, fully automated system based on nanoparticle probes has been developed for the detection of influenza A and B, and respiratory syncytial virus (RSV) A and B. The new technology promises faster and more appropriate treatment of patients. The full reference is as follows: P. J. Jannetto, B.W. Buchan, K. A. Vaughan, J. S. Ledford, D. K. Anderson, D. C. Henley, N. B. Quigley, N. A. Ledeboer. 2010. Real-Time Detection of Influenza A, Influenza B, and Respiratory Syncytial Virus A and B in Respiratory Specimens by Use of Nanoparticle Probes. Journal of Clinical Microbiology; 48.11: 3997-4002.
"Instead of relying on insensitive but rapid influenza tests for diagnosis in the clinic, or waiting 24 hours or more for molecular results to come back, we can now provide molecular level sensitivity in less than three hours," says principal investigator Nathan A. Ledeboer of the Medical College of Wisconsin, and Dynacare Laboratories, Milwaukee.
"This will mean that hospitalized patients with influenza and RSV infections will be isolated faster, which will decrease the risk of transmission to other patients in the hospital," says Ledeboer. The faster turnaround also means that "fewer patients will be placed on empiric therapy, which will decrease costs and decrease the risk of an adverse event caused by medication." In the study, the assay, a microarray, was tested on 720 patient samples collected throughout the US.
The new technology, called Respiratory Virus Nucleic Acid Test SP" (RVNATsp), is 98 percent sensitive (meaning that 98 percent of positive results are accurate) and 96 percent specific, meaning that 96 percent of negative results are accurate). By comparison, the conventional alternative, culture, is nearly 100 percent specific, but only 70 percent sensitive.
Influenza virus infects millions annually. It is typically associated with infections of the upper respiratory tract and can cause mild to severe illness. RSV can cause severe symptoms in infants, young children, and immunocompromised individuals, and is the leading cause of hospitalization of children under five years of age. In the most vulnerable individuals, children less than six months old, people with chronic lung disease, and immunocompromised individuals, RSV can migrate from the initial site of infection in the upper airway to the smaller bronchioles of the lower airway, where it can cause life-threatening bronchiolitis or pneumonia.
Monday, November 15, 2010
I came across a very interesting article on gene sequencing. Biophysicist Stuart Lindsay, of the Biodesign Institute at Arizona State University, has demonstrated a technique that may lead to rapid, low cost reading of whole genomes, through recognition of the basic chemical units, the nucleotide bases that make up the DNA double helix. His group's research appears in the current issue of the journal Nature Nanotechnology.
Lindsay's technique for reading the DNA code relies on a fundamental property of matter known as quantum tunneling, which operates at the subatomic scale. According to quantum theory, elementary particles like electrons can do some very strange and counter-intuitive things, in defiance of classical laws of physics. Such sub-atomic, quantum entities possess both a particle and a wave-like nature. Part of the consequence of this is that an electron has some probability of moving from one side of a barrier to the other, regardless of the height or width of such a barrier. Remarkably, an electron can accomplish this feat, even when the potential energy of the barrier exceeds the kinetic energy of the particle. Such behavior is known as quantum tunneling, and the flow of electrons is a tunneling current. Tunneling is confined to small distances, so small that a tunnel junction should be able to read one DNA base at a time without interference from flanking bases. But the same sensitivity to distance means that vibrations of the DNA, or intervening water molecules, ruin the tunneling signal. So the Lindsay group has developed "recognition molecules" that "grab hold" of each base in turn, clutching the base against the electrodes that read out the signal. They call this new method "recognition tunneling."
To read longer lengths of DNA, Lindsay's group is working to couple the tunneling readout to a nanopore -- a tiny hole through which DNA is dragged, one base at a time, by an electric field. Sequencing through recognition tunneling, if proven successful for whole genome reading, could represent a substantial savings in cost and hopefully, in time as well. Existing methods of DNA sequencing typically rely on cutting the full molecule into thousands of component bits, snipping apart the ladder of complementary bases and reading these fragments. Later, the pieces must be meticulously re-assembled, with the aid of massive computing power.
Lindsay stresses much work remains to be done before the application of sequencing by recognition can become a clinical reality. "Right now, we can only read two or three bases as the tunneling probe drifts over them, and some bases are more accurately identified than others," he says. However, the group expects this to improve as future generations of recognition molecules are synthesized.
Wednesday, November 10, 2010
We have a number of compendial (USP and Ph. Eur.) and technical (PDA TR#33) documents at our disposal for the validation of rapid microbiological methods. However, specific guidance is lacking at the regulatory level, as there are no comprehensive written policies from the FDA, EMA, TGA or the Japanese PMDA. During the PDA 5th Annual Global Conference on Pharmaceutical Microbiology, a question was asked to FDA panelists when the Agency would develop a clear guidance document on RMMs. Dr. David Hussong, Director, Microbiology, CDER, responded that In the next few years there will be an internal document that the agency will follow.
Friday, November 5, 2010
Over the last few months, Steve Delity, President and CEO of Rapid Micro Biosystems, has provided his insights into the benefits of automation in the pharmaceutical microbiology lab. In my fourth and final blog on this subject, I asked Steve to briefly comment on the impact automation may have on validation.
Michael - Anyone who has attempted to validate a rapid solution knows the hurdles that must be overcome. Should companies be concerned that automation adds another level of complexity to the validation?
Steve – Not necessarily. In actuality, this could just be the opposite. A rapid method solution like ours or others in the market can greatly simplify the validation process, as automation could remove a number of validation performance requirements that other alternative methods might require. Additionally, automated methods that are based on compendial testing may also simplify this process. For most compendial microbiology methods, we utilize a certain sample size, media, incubation time and temperature and acceptance limits. Using a rapid method that has similar (or the same) testing elements will be straightforward to validate, since the difference is the automation. Methods that deviate and require different or additional steps may introduce variables and risk factors that will need to be addressed in the validation program.
Thursday, November 4, 2010
In this month's American Pharmaceutical Review, Jennifer Gray and her team from Novartis describe the steps they took to select, validate, and gain regulatory acceptance for a rapid sterility test as an alternative to the pharmacopoeial method. The full paper may be viewed and downloaded in PDF format from our References Page (http://rapidmicromethods.com/files/references.html) under the Applications section. An excerpt from their introduction is reprinted below:
There are many reasons why the traditional sterility test, with its lengthy 14 days incubation time, should be replaced with a Rapid Sterility Test. As a consequence to the 14 days incubation time, possible product-contaminations and the respective corrective actions are delayed resulting potentially in an enlarged amount of affected product batches. Another important advantage of shorter incubation time is for example reduction in the release time for sterile products, therefore reduction of stock keeping costs and earlier market delivery. Furthermore, the use of RMMs (rapid microbiological methods) is highly supported by regulatory guidance documents, which request pharmaceutical microbiologists to use these methods.
After the decision had been made at Novartis that a rapid microbiological method for the replacement of the traditional pharmacopoeial sterility test should be validated, the appropriate method for replacement had to be chosen. From many available systems and methods on the market, an appropriate choice for a Rapid Sterility Test based on ATP- Bioluminescence of micro-colonies was made.