Friday, 27 January 2023

The chase: viruses vs bacteria


 

We are all aware of the presence of microbes, such as bacteria, fungi, and viruses, which wreak havoc on our well-being in our daily lives when we come into contact with the bad ones. Many people are unaware that the raging war does not spare the microscopic world. Humans have used the enmity of microbes for hundreds of years to treat infectious diseases. Among the scenarios that revealed the imperceptible microscopic wars were Alexander Fleming's discovery of penicillin and Twort and D'Herelle's discovery of bacteriophages. A virus is the smallest entity known to humans; it is capable of colonizing both the macroscopic and microscopic worlds without concern. They are well suited to infiltrate host cells and trigger a series of events that favor either their survival in the cell or their multiplication in order to infect other cells. Bacteriophages are among the most well-known bacterial killers; in recent years, they have gained popularity as the last resort when antibiotics have failed.

By Raphael Hans

What are bacteriophages?

 Bacteriophages  possesses viral proteins capable of disrupting the host cell. It attaches itself to a susceptible bacterial cell and injects its genetic material into it. The viral genome takes over the host cell's machinery and uses bacterial components to release viral proteins. Bacteriophage attacks are natural, but scientists have attempted to manipulate them to fit the needs of experiments or applications. These particles, like other viruses, are specific to the host they infect, so phages that affect one strain of bacteria may or may not be able to infect another. Furthermore, bacteriophages do not infect human cells at all. Phages, like bacteria, are found everywhere; in fact, they exist whenever bacteria do because they rely on the host cells to multiply. Places rich in bacteria, such as sewage, dumps, fertile soil, and many others, will also have a variety of viral particles that prey on the available bacteria.

The natural effect of bacteriophage on the environment

Bacteriophages maintain the ecosystem's balance by acting as bacteria predators. Because organic matter derived from lysed host cells is immediately consumed by heterotrophic bacteria, lytic bacteriophages are recognized as important regulators of nutrient cycles. Bacteriophages, as a natural enemy of bacteria, including pathogenic bacteria, have also been studied as biological control agents. Phage aids in the balance of microflora in the human gut, among other places. Despite their susceptibility to UV light from the sun, phages can survive in the environment for extended periods of time.

Phage resistant bacteria

Bacteria, as usual, are not helpless in the face of phages; instead, bacteria have developed a number of mechanisms to neutralize or resist phage actions. The most well-known is a CRISPR region that protects bacteria by releasing CAS9 enzymes against bacteriophages, though phages have reversed the action by developing anti-CRISPR mechanisms. Another method of phage infection resistance is a suicidal mission involving bacterial abortive infection (programmed cell death), which involves cell death once the cell is infected by the phage so that the infection does not spread to the entire population.

Application of bacteriophages

Bacteriophages have got numerous applications in this world we are living in, starting from the production of phage-based vaccines, Disinfecting equipment, Diagnosis of bacterial diseases, cleaning fresh food products, phage display, and clinical phage applications like phage therapy. As much as phage technology is considered naive to the world, everyday discoveries are lining up so that the world can appreciate the potential of these particles.

Bacteriophage therapy

Because of their uniqueness and effectiveness in eradicating superbugs, scientists all over the world have been on the lookout for these natural bacterial predators in recent years (multidrug-resistant strains of bacteria). Phages are capable of auto-dosing once applied; they are also capable of mutating in the event that bacteria mutate to gain resistance against them; they have no adverse effects on humans; they are easily removed by the immune system; and they have no effect on other microflora. It has already been reported that these particles have successfully treated multidrug-resistant bugs. When antibiotics failed, phages became the last line of defense.

Despite their colorful properties that apprehend their usefulness, phages have got a negative side too. Among them are; they are capable of causing horizontal antibiotic resistance genes between a bacterium and a bacterium to occur, can be easily removed by the immunity hence act only for short time in case of systemic application, they have a narrow host range and lastly but not least they take a long duration to prepare. To counteract the negative side effects of phage application, scientists have proposed several solutions such as using micelle-like structures to increase phage persistence in the circulation system, creating bacteriophage cocktails to broaden the host range, and having a phage bank that can be used in an emergency. Some people have expressed concern about using the entire virus for treatment, so the solution has been to extract the enzyme lysins and use them against bacteria.

 

Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Thursday, 26 January 2023

eBook: Proven Applications Using Variable Pathlength Spectroscopy



Image: CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=2974242

This eBook provides details and insight into using Slope Spectroscopy and the CTech™ SoloVPE® variable pathlength spectroscopy system. The SoloVPE® system provides a rapid, robust, and repeatable, non-disruptive concentration measurement method for proteins, plasmid DNA, and nucleic acid modalities. 

Articles in this eBook cover a variety of topics including viral filtration integrity, polysorbate UV-Vis spectral and slope analysis, how to measure Co-Oximetry parameters in bovine hemoglobin, accurately calculating the plasmid DNA purity ratio in human gene therapy products, techniques for real-time biomanufacturing process monitoring, and the application of in-line variable pathlength chromatography for high-concentration oligonucleotide solutions.

 

 

To access, see: eBook


Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)



Wednesday, 25 January 2023

How to Avoid Biospecimen Procurement Mistakes

 

Image byAzaToth - self made based on PDB entry, Public Domain, https://commons.wikimedia.org/w/index.php?curid=68596

Biospecimen procurement can be challenging, but technology, planning and new procurement strategies can make it easy and efficient. Many companies run into issues when trying to procure samples, from difficulties finding enough to documentation challenges and everything in between. How can mistakes and delays in biospecimen procurement be avoided?

 

By Emily Newton 

 

Prioritize Biospecimen Procurement Planning

Many of the most common mistakes in biospecimen procurement are simply due to a need for adequate planning. This may be because the R&D team is unfamiliar with biospecimen procurement or because a project started hastily. Whatever the reason, poor planning can cripple the procurement process and potentially jeopardize the entire project.

 

To minimize the likelihood of any procurement issues, plan out as many factors as possible as far in advance as possible. R&D teams should have a detailed kit and training process for sample collection, especially if the samples require special care, such as a temperature-controlled environment or rapid delivery to the lab. A clear kit and advanced training for collection personnel will streamline the acquisition process and minimize the risk of improperly collected samples disrupting research processes.

 

Similarly, R&D teams need to take a critical look at the timeline they have in mind for their procurement process and project as a whole. Project timelines are more likely to be overly optimistic, setting unrealistic expectations about how quickly a certain quantity of samples can be collected. Bioprocessing 4.0 innovations — such as smart analytics programs and remote sample monitoring — can help make the R&D process as a whole more efficient.

 

Unfortunately, there are countless possible delays research teams can face when trying to acquire biospecimens. They might need patients with particular traits or an exceptionally large quantity of a certain biospecimen. Even collecting plasma and blood samples takes time when more than a handful of samples are necessary. Planning for delays and a lengthy procurement process allows everyone to use their time and funding efficiently.

Consider Direct-to-Patient Procurement

A lack of adequate information on the origin of samples can pose a particular risk of R&D mistakes. This is especially true if certain patient information is necessary for accurate results, such as info on a patient’s race, ethnicity or any environmental factors they might have.

 

Unfortunately, brokers may be reluctant to share this information, creating issues for researchers. Rather than go through a broker, companies and researchers should consider forming direct relationships with hospitals and biobanks. Some industry leaders are even building directories for biobanks and research companies to connect directly with one another. This saves time and money and ensures R&D teams have all the necessary information concerning sample origins.

 

Direct-to-patient biospecimen procurement is also another option. Patients are the ones providing biospecimens, so why not go directly to them? This method requires highly detailed planning, but it can be far more efficient than conventional procurement methods.

 

Direct-to-patient biospecimen procurement proved highly effective early in the COVID-19 pandemic when labs worldwide worked to develop vaccines as quickly as possible. Platforms like the popular LabCorp Patient Direct network connected labs directly to patients willing to provide samples and participate in clinical trials. Since then, more broad platforms like iSpecimen Marketplace have launched to help companies connect directly with specimen providers, indicating the high potential for this procurement method.

 

Direct-to-patient biospecimen procurement helped make the COVID-19 mRNA vaccines the fastest developed in history. It is important to note that part of why direct-to-patient procurement methods worked so well for COVID-19 vaccine development was patient awareness.

 

When large numbers of samples were necessary, everyone was aware of the COVID-19 pandemic and the urgent need for a vaccine. This awareness likely played a role in the number of patients who volunteered for sample collection campaigns and clinical trials.

 

Any company or research group can employ direct-to-patient biospecimen procurement, but it requires comprehensive planning and marketing efforts to raise awareness of the project’s goal. Patients will need highly detailed kits instructing them how to collect and handle samples properly. Companies will also need an efficient process to obtain samples from patients.

Digitize Procurement Processes

Digitalization is becoming increasingly popular in the biotechnology and pharmaceutical industries. IRB approval and documentation are among the most common procurement issues companies and research groups face. It isn’t always possible to speed up IRB approval, but organizations can streamline document collection and processing.

 

Moving documents to digital platforms makes them easier to deliver to patients and collect once signed. This streamlines documentation and compliance audits. However, companies and research groups need to ensure they follow IRB electronic documentation guidelines. Electronic signatures are legally binding, but the way electronic signatures and documents are obtained and collected is vital for patient privacy.

 

Similarly, HIPAA compliance regulations apply when using digital documentation. The platform used to deliver, obtain and collect electronic documents from patients needs to follow specific security and privacy regulations. While verifying compliance may take some time, electronic documentation ultimately saves time.

 

With a digital documentation platform, the startup could email patients a link to a patient portal where they can type in their e-signature and submit the forms, a process that takes a matter of minutes from start to finish. This method is especially useful when paired with an at-home collection method where the patient can complete the entire collection process without needing to visit a physical collection facility.

Simplifying Biospecimen Procurement

Effective planning, technology and patient and biobank outreach can help companies avoid the most common biospecimen procurement mistakes. By simplifying the procurement process with a few key strategies, samples are less likely to be damaged, lost, improperly collected or processed without crucial information. The procurement process can be frustrating at times, but a little innovation can go a long way toward making it easy and efficient.

 

Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Tuesday, 24 January 2023

Types of errors with pharmaceutical labeling and packaging

Image: Ralf Roletschek CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=20717356

Labeling errors arising from the manufacturer of the medicine are a product of poor packing practices. Bad packaging is itself the result of deficiencies in the quality assurance system. Errors with packaging and labeling can have serious consequences, and packaging defects can create problems that may result in drug recalls. Such defects may include breakage, and problems relating to printing or inks, or errors on labels and package inserts (patient information leaflets). The use of GMP and quality control will prevent the release of a defective medicinal product.

By Tim Sandle

Errors with labels can occur from several sources, such as human error, technical errors, errors pertaining to source information and so on. Common errors with labels include labeling the wrong product, spelling or grammatical mistakes, labeling on the wrong side of the package, similar labels on two different products, wrong expiry dates and translation errors. Other errors include incorrect or nonexistent barcodes on packages, and the wrong packaging of products in different packages.

Beyond this, the types of errors that can arise due to labeling issues are varied. Some examples are:

  • Gross Errors – These occur when necessary information is missing from label artwork. This type of error most often occurs when regulatory requirements change but the manufacturer fails to change the package artwork in response to the new guidelines.
  • Context and Meaning Errors – These types of errors occur when information on the label artwork is presented in an unclear or ambiguous way. A context or meaning error could occur if incorrect punctuation is used on the label. 
  •  Content Errors – These occur when there are significant errors in the detailed content of the artwork. The error could be due to the incorrect usage of a symbol on the package label.
  •  Technical Errors – These errors are in functional components of the artwork, including the product barcode.

Furthermore, errors noted by regulators include:

  • Key information, such as the product name, strength, and dosage form, is missing; is expressed in a confusing manner; or is not prominently located and displayed.  A product’s strength or concentration is critically important information for the end user.  If the product strength is not clearly displayed on the container label or is expressed in units of measure that are incongruent with those used in the dosing instructions, the wrong strength can be selected, or the wrong dose administered. Typically, the dose or expression of strength should appear in metric units of measure such as mL, mg, and mcg, rather than apothecary or household measurements (e.g., tsp for teaspoon).
  •     Key information does not appear in the same field of vision (i.e., the information is not readable without having to turn or rotate the container).
  •     Container labels and carton labeling look similar across multiple strengths of the same product or across multiple products within a company’s product line.
  •  Container labels and carton labeling look similar among multiple products from different manufacturers.
  • Container labels and carton labeling are visually cluttered by extraneous text or 107 distracting images and graphics.
  •  Error-prone abbreviations or symbols are used.
  • Text is difficult to read because of font size or style, insufficient color contrast, or other design elements.
  •  Overlapping text is printed on both sides of a clear, transparent, or translucent container label such as those that might be found on syringes, ampules, vials, intravenous bags or low-density polyethylene (LDPE) vials.

Many errors occur due to complexity and it is worthwhile undertaking an exercise that seeks to simply documentation.  Errors can be addressed through reviewing the artwork and label process as an aspect of data integrity. Key to this is developing and creating a data integrity focused culture.

It is important that each producer of medicinal products has written procedures describing in sufficient detail the receipt, identification, storage, handling, sampling, examination, and/or testing of labeling and packaging materials. It is also of importance that these written procedures are followed. There should also be regular checks in place with labeling and packaging materials being representatively sampled and examined or tested upon receipt and before use in packaging or labeling of a drug product.

It is not only of importance that such information is accurate and legible, it also needs to be understood. It remains that some instructions and precautions remain unnecessarily complex and are seldom tested for comprehension among consumers to include their feedback in the development process. This is a point that pharmaceutical and healthcare manufacturers should consider.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

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