Thursday, 31 May 2018

Contamination Control in Pharmaceutical Cleanrooms

Cleanrooms have meticulous levels of contamination (ISO Class) specified by the number of particles per cubic meter at a specified particle size. Air entering a cleanroom from the outside must be filtered to exclude dust. The air inside a cleanroom must be constantly recirculated through high-efficiency particulate air (HEPA) filters to control contaminants that are generated inside the room. Particle levels are tested using a particle counter and microorganisms are detected and counted using environmental monitoring methods.

An overview of good cleanroom design is provided by Juan Miguel Cana Lopez and Kim Zurawski, Grifols, in Controlled Environments magazine.

Here is an extract: “Consideration must also be given to cleanroom features such as nonporous and smooth surfaces, including walls and ceilings that can withstand routine decontamination; proper pressure differentials between rooms, the most positive pressure being in the aseptic processing rooms or areas; use of unidirectional airflow in the immediate vicinity of exposed product or components; sufficient air change frequency; appropriate humidity and temperature environmental controls; and a documented sanitization program.”

To access the article, see: Controlled Environments

Posted by Dr. Tim Sandle

Thursday, 24 May 2018

Pyrogen Detection: Want to stop using animal based methods and get higher sensitivity?

Pyrogen Detection: Want to stop using animal based methods and get higher sensitivity? 

Ready-to-use PyroMAT™ in vitro system 

We are glad to inform you that our new in vitro solution for pyrogen detection is now available: our PyroMAT™ system is the only cell-line based Monocyte Activation Test (MAT) provided as a ready-to-use kit on the market.

The PyroMAT™ system is based on the use of the Mono-Mac-6 cell line: it is designed to provide a standardized reactivity. Once these human monocytes come into contact with pyrogens from a contaminated sample, they produce cytokines such as interleukin-6 (IL-6), which can be detected with enzyme-linked immunosorbent assay (ELISA).

With the PyroMAT™ System, we offer a new robust and sensitive solution for pyrogen detection supported by international regulations and guidelines to reduce animal consumption for pyrogen tests. Make the move to in vitro methods, and benefit from our expertise:

The advantages of monocyte activation test… 

  • Detection of the full range of pyrogens to ensure patient safety. Like the rabbit pyrogen test, MAT is effective in the detection of both endotoxins and Non-Endotoxin Pyrogens (NEP). 
  • Extended range of testable products: the most frequently applied methods are limited in the product types they are able to test. The MAT offers more flexibility regarding its applications. 
  • In vitro assay that mimics the human immune reaction: for a robust predictive model that reduces animal consumption. • Compliance with international regulations and guidelines in line with ethical trends of industry and regulatory authorities to decrease the use of animal based testing. ... Combined with the benefits of using a cell line • Standardized reactivity and high sensitivity (LOD 0.05 EU/mL) 
  • Convenience of a ready-to-use cell line to avoid laborious lab work to maintain the cell line and avoids the need of a culture cell laboratory. • Qualified cells: in addition to being cited in the international validation of MAT, MonoMac-6 cells are qualified for the detection of all types of pyrogens via testing of the expression of all surface Toll-Like Receptors (TLRs). 

Click here to learn more

Tuesday, 22 May 2018

Cleanroom Cleaning and Disinfection: Eight Steps for Success

The CDC Handbook: A Guide to Cleaning and Disinfecting Cleanrooms

Cleanrooms in healthcare and pharmaceutical facilities must be kept in a state of microbiological control. This article outlines eight key steps for keeping a cleanroom clean.

Cleanrooms in healthcare and pharmaceutical facilities must be kept in a state of microbiological control. This is achieved in a number of ways, including the physical operation of Heating, Ventilation, and Air Conditioning (HVAC) systems, control of materials, properly gowned and trained personnel, and through the use of defined cleaning techniques, together with the application of detergents and disinfectants.

The object of cleaning and disinfection is to achieve appropriate microbiological cleanliness levels for the class of cleanroom for an appropriate period of time. Thus the cleaning and disinfection of cleanrooms is an important part of contamination control.

This article examines the eight key steps to be followed, in relation to cleaning and disinfection, in helping to keep cleanrooms “clean.”

See Tim Sandle’s article in Controlled Environments magazine here.

Posted by Dr. Tim Sandle

Wednesday, 16 May 2018

Infection prevention and control programs are essential to antibiotic stewardship efforts

Infection prevention and control (IPC) and antibiotic stewardship (AS) programs are inextricably linked, according to a joint position paper published today by the Association for Professionals in Infection Control and Epidemiology (APIC), the Society for Healthcare Epidemiology of America (SHEA), and the Society of Infectious Disease Pharmacists (SIDP) in APIC and SHEA’s peer-review journals, the American Journal of Infection Control and Infection Control and Hospital Epidemiology.

This paper is an important update to a 2012 paper that affirmed the key roles of infection preventionists (IPs) and healthcare epidemiologists (HEs) in promoting effective use of antimicrobials in collaboration with other healthcare professionals. The new paper highlights the synergy of IPC and AS programs, including the importance of a well-functioning IPC program as a central component to a successful AS strategy.

“The issues surrounding the prevention and control of infections are intrinsically linked with the issues associated with the use of antimicrobial agents and the proliferation and spread of multidrug-resistant organisms,” said Mary Lou Manning, PhD, CRNP, CIC, FSHEA, FAPIC, lead author of the new paper. “The vital work of IPC and AS programs cannot be performed independently. They require interdependent and coordinated action across multiple and overlapping disciplines and clinical settings to achieve the larger purpose of keeping patients safe from infection and ensuring that effective antibiotic therapy is available for future generations.”

Antimicrobial stewardship programs encourage the appropriate use of antimicrobials (including antibiotics) to minimize overuse, improve patient outcomes, reduce microbial resistance, decrease the spread of infections and preserve the efficacy of antibiotics. Multidrug-resistant organisms cause a significant proportion of serious healthcare-associated infections (HAIs) and are more difficult to treat because there are fewer and, in some cases, no antibiotics that will cure the infection. The Centers for Disease Control and Prevention (CDC) states that each year in the United States at least 2 million people become infected with bacteria that are resistant to antibiotics and at least 23,000 people die as a result.

According to the paper, when AS programs are implemented alongside IPC programs, they are more effective than AS measures alone, verifying that a well-functioning IPC program is fundamental to the success of an AS strategy.

“It is important that all clinicians depend on evidence-based IPC interventions to reduce demand for antimicrobial agents by preventing infections from occurring in the first place, and making every effort to prevent transmission when they do,” said 2018 APIC President Janet Haas, PhD, RN, CIC, FSHEA, FAPIC . “IPC and AS programs are intrinsically linked, making effective collaboration essential to ensure patient safety.”

The three societies present their position against a backdrop of increased awareness of antimicrobial resistance among healthcare providers, policy makers, and the public, and national action plans and forums designed to address the issue, which emphasize the important role of IPC programs in advancing successful AS interventions across the continuum of patient care.

“IP and HE leaders are IPC subject matter experts who are also trained with social and behavioral skills that allow them to effectively engage with different professional disciplines within healthcare to promote, implement, evaluate, support and sustain IPC strategies across practice settings. These are similar skills as those exhibited by leaders of successful AS programs,” said Keith Kaye, MD, MPH, FSHEA, president of SHEA.

APIC, SHEA, and SIDP support the CDC Core Elements of AS framework and identify the synergy of IPC and AS within each element of the CDC recommendations. In addition, the three societies believe that microbiology laboratory staff members and clinical microbiologists play an essential role in successful IPC and AS programs.

“IPs and HEs engage a diverse range of clinical disciplines across practice settings in HAI prevention. The work of physician and pharmacist AS program leaders is greatly enhanced by the support of other key groups, including IPC programs,” said Elizabeth Dodds Ashley, PharmD, MHS, BCPS, Duke University Department of Medicine and president of SIDP.

The authors acknowledge that successful AS programs require a significant investment on the part of the healthcare facility. “Changing practices and prescribing patterns and learned behaviors of physicians, nurses, pharmacists, and other healthcare providers will take time and investment, but it is critical to affect a long-term solution to the rise of AMR and CDI infections,” they state in the paper.

The authors urge healthcare leaders to prioritize IPC and AS as part of wider patient safety initiatives and recommend that IPC and AS leaders collaborate in communications to the C-suite. “Given the synergy between AS and IPC programs, IPC and AS program leaders should seize every opportunity to benefit from each other’s expertise and organizational influence and partner when making the case for program support and necessary resource allocation to clinical and administrative leadership.”

Posted by Dr. Tim Sandle

Monday, 14 May 2018

Practical Approaches to Risk Assessment and Management Problem Solving

The PDA has published a new e-book series on risk assessment and risk management. Tim Sandle has authored the fourth volume is the series.

The reference is:

Sandle, T. (2018) Risk Management Library Volume 4: Practical Approaches to Risk Assessment and Management Problem Solving: Tips and Case Studies, PDA/DHI, River Grove, Il, USA

Receive expert guidance on major topics, such as regulatory perspectives on risk and five insightful case studies to help develop the best approaches to problem solving based upon the "what if" and "five whys" method.

For details see: PDA

Posted by Dr. Tim Sandle

Friday, 11 May 2018

Continuously killing bacteria on coated stainless steel

Bacteria can grow on stainless steel surfaces, contaminating food. Current coatings available on the market are pricey and potentially harmful, so scientists have now developed an affordable specialized polymer coating for such surfaces that they can recharge with bleach treatments.
The researchers are presenting their results at the 255th National Meeting & Exposition of the American Chemical Society (ACS). Current efforts to avoid such bacterial growth incorporate silver or copper ions, which can be pricey. "In addition, silver and copper are usually alloyed in the metal, and they have been tucked away so they are not very effective," Demir notes. "There is also a health concern with using silver." Silver could leach from the stainless steel and into foods that are later consumed, she says.
Scientists have previously added molecules called N-halamines to textiles for their antimicrobial properties because it is easy to attach these substances to cotton. N-halamines are a group of compounds that have one or more nitrogen-halogen covalent bonds. These compounds are affordable, chemically stable and nontoxic to humans. Demir, a postdoctoral researcher in the lab of Dave Worley, Ph.D., at Auburn University, wants to expand the use of N-halamines into the medical and food industries.

Other groups have linked N-halamine polymers to stainless steel surfaces with the aid of a binder, but Worley's team has now shown, for the first time, that N-halamine can be attached to stainless steel directly. To do this, the researchers first roughed up the surface with hydrogen peroxide and sulfuric acid. This creates negatively charged oxygen groups on the surface to which the N-halamine polymer can attach through a chemical reaction. When the researchers put bacteria on the coated surface, the microbes did not grow. Demir tested many types of bacteria, including E. coli and Staphylococcus aureus, which are common culprits implicated in many foodborne bacteria outbreaks at food processing facilities. All of the bacteria tested were killed within 15 minutes of coming into contact with the treated surface.
Early testing showed that the N-halamine polymer coating was effective for five rounds of killing bacteria before it lost some of that activity. Further, Demir says, "we could regenerate the antibacterial activity of the coated surface by simply wiping it down with a diluted bleach solution."
Bleach contains chlorine, a halogen, which by itself is extremely unstable; however, when attached to the N-halamine polymer, it becomes stable. When bacteria come into contact with the treated surface, the chlorine is released, killing the bacteria."
Future plans include manipulating the surface of stainless steel in a more user-friendly way. "The greatest challenge is roughing the surface of the stainless steel. Although this is easily done in the laboratory, it would not be easily done in a manufacturing plant," Worley states. "We need a better way of attaching N-halamines to the surface, and we have some ideas as to how we can do that." The researchers also need to perform toxicity testing on samples to investigate the safety of the coated surfaces and examine any biofilms that may develop. "An antimicrobial surface in a food processing plant is badly needed, and it could revolutionize the industry," Worley says.

Posted by Dr. Tim Sandle

Wednesday, 9 May 2018

USP 1116 Microbiological Control Of Aseptic Processing Environments And Its Implications

Chapter <1116> is arguably one of the most comprehensive informational chapters from the USP, and it is particularly challenging due to its proposal regarding measurement of microbial contamination based on Contamination Recovery Rates (CRR) rather than the conventional enumeration of colony forming units (cfu).

Claudio Denoya, PhD, and Gilberto Dalmaso, PhD, Particle Measuring Systems have written a useful overview of USP <1116> “Microbiological Control Of Aseptic Processing Environments”, for Pharmaceutical Online.

Here is an extract:

“The chapter emphasizes that even with a good total particulate monitoring program in place, “It is not possible to clearly distinguish between background particulate contamination generated…by mechanical operations and the total particulates contributed by personnel.” Therefore, it is standard routine to implement both total particulate and microbiological monitoring programs. The chapter also discusses the differences between operating in conventional cleanrooms and open RABS, and more controlled environments where personnel interventions have significantly less impact on microbial contamination, such as in closed RABS and isolators. It is clear that the relative risk of microbial quality depends on the different types of aseptic barrier systems; the greater the barrier, then the lower the expected contamination risk.”

To view, see Pharmaceutical Online

Posted by Dr. Tim Sandle

Tuesday, 8 May 2018

Contract Pharma Trends 2018

Outsourcing to contract manufacturers can be a valuable, even critical, option allowing companies to focus their resources and talents on their primary objectives. In many cases, having others do operations that otherwise could not be done efficiently, or at all, in-house is a rational manufacturing strategy.

A new ebook explores:

The methodologies, technologies, and strategies essential for multi-product environment success
BioPlan survey findings on the contract manufacturing industry’s role in biopharma R&D and manufacturing
How contract packagers accelerate pharma packaging innovation

See: Contracting out  

Posted by Dr. Tim Sandle

Sunday, 6 May 2018

Using light to turn yeast into biochemical factories

Researchers have used a combination of light and genetic engineering to controlling the metabolism, or basic chemical process, of a living cell. Building on techniques that already have transformed the field of neuroscience, the researchers used light to control genetically-modified yeast and increase its output of commercially valuable chemicals.

Yeast has been used for centuries to make bread, wine and beer. Through fermentation, yeast cells transform sugar into chemicals that make bread rise and turn grape juice into wine. Using their new technique, the Princeton researchers have now used fermentation and genetically-engineered yeast to produce other chemicals including lactic acid, used in food production and bioplastics, and isobutanol, a commodity chemical and an advanced biofuel.

Light played a key role in the experiment because it allowed the researchers to switch on genes that they had added to the yeast cells. These particular genes are sensitive to light, which can trigger or suppress their activity. In one case, turning on and off a blue light caused the special yeast to alternate between producing ethanol, a product of normal fermentation, and isobutanol, a chemical that normally would kill yeast at sufficiently high concentration.

The achievement of producing these chemicals was significant, but the researchers were intrigued by the development of light's broader role in metabolic research.The researchers started by putting a modified gene from a marine bacterium that is controllable by blue light into yeast's DNA. They then used light to turn on a chemical process that activates enzymes that naturally allow yeast to grow and multiply by eating glucose and secreting ethanol. But while those enzymes are active, ones that influence the production of isobutanol can't work. So the team turned to darkness to switch off the ethanol-producing enzymes to make room for the expression of their competitors.

READ MORE: Yeast helps hunt for new medicines

Scientists have developed a new way to predict potentially useful drugs from a pool of undefined chemicals. They were able to more quickly identify leads that could be used to treat a range of diseases, from infections, to cancer to Alzheimer's. The finding will also help better match drugs to a disease to maximize the benefit and reduce side-effects. See: Yeast news

Using light to control yeast's chemical production offers several advantages over techniques involving pure genetic engineering or chemical additives. For one, light is much faster and cheaper than most alternatives. It's also adjustable, meaning that turning it on and off can toggle the function of live cells on the spot at any point in the fermentation process (as opposed to chemicals, which generally can't be turned off once they are added.) Also, unlike chemical manipulators that diffuse throughout a cell, light can be applied to specific genes without affecting other parts of the cell.

Optogenetics, as the use of light to control genes is called, is already used in neuroscience and other fields, but this the first application of the technology to control cellular metabolism for chemical production. Gregory Stephanopoulos, an MIT chemical engineering professor who was not involved with Princeton's research, called it a turning point in the field of metabolic engineering.


Evan M. Zhao, Yanfei Zhang, Justin Mehl, Helen Park, Makoto A. Lalwani, Jared E. Toettcher, José L. Avalos. Optogenetic regulation of engineered cellular metabolism for microbial chemical production. Nature, 2018; DOI: 10.1038/nature26141

Posted by Dr. Tim Sandle

Saturday, 5 May 2018

Diagnostic innovation for childhood tuberculosis

Ahead of World TB Day 2018, the Foundation for Innovative New Diagnostics (FIND) has made two announcements:

Jointly with the South African Medical Research Council (SAMRC), FIND announced a new agreement to support diagnostic innovation for childhood tuberculosis (TB) in South Africa. The project is part of a global effort to improve childhood TB diagnosis, guide paediatric treatment, and reduce suffering, disease transmission and deaths from TB in babies and children.

Full release

FIND also announced that it has supported the World Health Organization (WHO) through the generation of critical evidence that has informed updated laboratory guidance for drug-resistant TB. The updated list of critical concentrations for drug susceptibility testing of medicines used in the treatment of drug-resistant TB is the result of a long collaboration between WHO and FIND on TB diagnostics and laboratory strengthening.

Friday, 4 May 2018

Detection of bacterial growth and Biofilm formation in pipelines

Bacteria embedded in the biofilm are more difficult and expensive to eliminate, than free-floating planktonic bacteria. Their presence in manufacturing pipelines can be responsible for a wide range of water quality and operational problems. By measuring bacteria bio-electrochemical activity (a phenomenon known as “ennoblement” or “cathodic depolarization”), the ALVIM technology detects biofilm formation since its first phases, online and in real time.

The system allows the user to decide when to apply CIP, and check in real time if biofilm was actually removed. .… Read More

Thursday, 3 May 2018

EU GMP Annex 1 presentation

A recording of Pharmig's response to draft EU GMP Annex 1, hosted by Tim Sandle

See: Annex 1 overview

Posted by Dr. Tim Sandle

Polyvinylidene Fluoride (PVDF)

PVDF (PVF2 or Polyvinylidene fluoride or polyvinylidene difluoride) is a semi-crystalline, high purity thermoplastic fluoropolymer.

News from Omnexus.

With service temperatures up to 150°C, PVDF displays good combination of properties such as:
  • Exceptional chemical resistance
  • High mechanical strength
  • Piezoelectric and pyroelectric properties
  • As well as good processability
Its highly desirable insolubility and electrical properties result from the polarity of alternating CH2 and CF2 groups on the polymer chain.

PVDF is readily melt-processible and can be fabricated into parts by injection and compression molding. As a result, it is commonly employed in chemical processing equipment such as pumps, valves, pipes, tubes and fittings; sensors and actuators etc.

It has many electronic applications, especially as jacketing materials for plenum-rated cable used in voice and video devices and alarm systems. The low flame spread and smoke generation of PVDF is a prime asset in these applications.

PVDF is gaining acceptance as a binder for cathodes and anodes in lithium-ion batteries, and as a battery separator in lithium-ion polymer systems.

Emerging applications of PVDF include fuel cell membranes, and components for aircraft interiors and office automation equipment.

PVDF (homopolymers and copolymers) is generally synthesized by the free radical polymerization of 1,1-difluoroethylene (CH2=CF2). The polymerization takes place in the suspension or emulsion from 10-150°C and pressure of 10-300 atm. The material obtained is then processed into film or sheets.

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