Type: Article

OPENCORONA: Accelerating pandemic preparedness with DNA vaccine manufacturing 

NorthX Biologics delivers plasmid DNA for COVID-19 vaccine development 

In the early days of the COVID-19 pandemic, NorthX Biologics took a bold step by joining a pan-European, EU-funded scientific consortium, a move that carried significant risk for a small CDMO but underscored our deep commitment to scientific innovation and societal impact. The OPENCORONA project, funded under the Horizon 2020 program, set out to develop a DNA-based vaccine targeting SARS-CoV-2, bringing together academia and industry in a powerful alliance to accelerate innovation. 

With a total budget of only €3 million (approximately 30 mSEK), our consortium set out to do what global pharmaceutical giants were doing but with a fraction of the resources. For context, Pfizer invested over $2 billion of private capital in its mRNA vaccine, while BioNTech received around €475 million in public funding. Despite this disparity, our team advanced from concept to clinical trial in just two years, a remarkable timeline given the scale and complexity of the task. 

NorthX Biologics played a critical role by delivering high-quality plasmid DNA for both toxicology studies and GMP-grade material for Phase I clinical trials. Our lean and agile approach allowed us to learn from early vaccine frontrunners, adapt to emerging data, and refine our vaccine design. The result was a next-generation DNA-based booster – a smart cocktail informed by the scientific insights and challenges of the first pandemic wave. 

This project demonstrates that when academic excellence is matched with industrial agility and a shared mission, even modest funding can drive major breakthroughs. We are proud to have contributed to a model of collaboration where innovation thrives not just through scale, but through purpose. 

Overcoming challenges in DNA vaccine manufacturing

The OPENCORONA team faced several key challenges: 

  • Rapid viral mutations required late-stage redesigns of the vaccine construct. 
  • Compressed timelines demanded fast decision-making and agile execution. 
  • Scaling up production from research-grade to GMP-grade plasmid DNA while maintaining quality and regulatory compliance. 

NorthX Biologics: Agile plasmid DNA manufacturing partner 

NorthX Biologics was instrumental in overcoming these hurdles. The team produced HQ plasmid DNA for preclinical toxicology and later delivered GMP-grade plasmid DNA for clinical use. When the vaccine design was updated to include emerging variants such as Alpha and Beta, the company swiftly re-manufactured the HQ batch, ensuring the vaccine remained relevant and effective. 

Thanks to a flexible CMC (Chemistry, Manufacturing, and Controls) model and robust plasmid DNA platform, the consortium was able to adapt quickly without compromising timelines or quality. 

Collaborative innovation across Europe

The OPENCORONA consortium brought together seven expert partners: 

  • NorthX Biologics – plasmid DNA manufacturing 
  • Karolinska University Hospital – clinical trials 
  • Plus additional partners in delivery technology and immunological testing 

Despite pandemic-related restrictions, the consortium maintained momentum through clear communication, rapid decision-making, and mutual trust. 

Scientific innovation 

Unlike most COVID-19 vaccines that focused solely on the spike (S) protein, OPENCORONA’s DNA vaccine included: 

  • Receptor Binding Domains (RBDs) from Wuhan, Alpha, and Beta variants 
  • Membrane (M) and Nucleocapsid (N) proteins 

This multi-antigen design aimed to induce broad T cell immunity and offer protection against a wider range of SARS-CoV variants—making it especially suitable as a booster vaccine. 

Clinical impact and lessons learned 

The Phase I trial targeted individuals who had already received three doses of RNA vaccines. Early data showed strong T cell activation, suggesting potential benefits for immunocompromised patients. 

The project also underscored the value of public-private partnerships in early-phase research. Initiatives like OPENCORONA demonstrate how biotech companies can collaborate with academia to accelerate vaccine development and improve pandemic preparedness. 

Read more here: OPENCORONA | Karolinska Institutet 

Lessons learned from a pandemic vaccine consortium 

Published in Vaccine Insights (2023) (OPENCORONA: lessons learned from a pandemic vaccine consortium), this interview highlights the EU-funded OPENCORONA project, a pan-European consortium formed in early 2020 to develop a DNA-based COVID-19 vaccine. Led by Karolinska Institutet and supported by NorthX Biologics, the project successfully brought a vaccine candidate into Phase I clinical trials in under three years. 

Key highlights: 

  • NorthX Biologics produced both high-quality plasmid DNA for toxicology studies and GMP-grade plasmid for clinical trials. 
  • The vaccine design included multiple antigens: RBDs from Wuhan, Alpha, and Beta variants, plus membrane (M) and nucleocapsid (N) proteins, aiming for broad T cell immunity and cross-variant protection. 
  • The project adapted rapidly to emerging data, redesigning both the vaccine and clinical trial to serve as a booster for individuals previously vaccinated with RNA vaccines. 
  • The consortium emphasized fast decision-making, cross-sector collaboration, and clear communication – key factors in navigating pandemic constraints. 

Lessons learned: 

  • Agility and trust among partners enabled swift progress despite limited funding. 
  • DNA vaccines, while slower to market than RNA counterparts, offer unique advantages in immune response diversity and variant coverage. 
  • The experience underscored the value of private–academic partnerships in early-phase innovation and pandemic preparedness. 

Read the full article here. 

NorthX Biologics – A new kind of biologics company

NorthX Biologics is an established provider of process development and manufacturing services with expertise in the biologics used in vaccines, gene therapy and other advanced applications. Headquartered in Matfors in central Sweden, the company has been manufacturing biologics to GMP since 1992, with a proven track record of converting early-stage processes into manufacturing processes suitable for clinical applications and on into commercialization.

Read the article by clicking the link below.

A new kind of biologics company

Finding your match in the biotech world: The CDMO dating game

In the dynamic and complex world of pharmaceuticals and drug development, the quest to find the right Contract Development and Manufacturing Organization (CDMO) often feels akin to searching for a life partner. As a person often facing and meeting the companies scouting for a CDMO I have heard this analogy so many times.  This kind of partner hunt it’s a journey filled with careful considerations, weighing options, and seeking that perfect match that aligns with your unique innovation needs. It is a in a way a “do we have the chemistry” test without pointing to the real type of chemistry.  This intricate process, surprisingly like finding a soulmate, requires more than just a scientific approach – it’s about understanding, compatibility, and a shared vision.

The romanticized idea of finding “the one” in a world brimming with potential partners parallels the challenges in the CDMO landscape. Just as there’s no single destined soulmate for each individual, the notion of one perfect manufacturing partner amidst a plethora of providers is equally unrealistic. In both scenarios, numerous potential partners could foster healthy, productive relationships. However, the selection process in the biotech industry involves less emotion and more objective evaluation (hopefully!), focusing on specific criteria that align with a company’s strategic goals.

Embarking on this ‘dating’ journey with CDMOs means engaging in a series of ‘dates’ – site visits, audits, and meetings that are crucial for understanding each other’s capabilities, goals, and values. At NorthX, we have  learned that compatibility, trust, and shared objectives are paramount for a successful partnership. Just like in personal relationships, these factors heavily influence the selection process. It takes a lot and  is not  easy to be able to show the true side, the naked truth in this dating game, but this is where transparency really has its purpose. As a customer you can set quite high expectations and as a CDMO representant  it means that you need to know your whole organization and trust your organizations to its full potential. Therefore being big is not always better in the CDMO space.

In the world of CDMO selection, it’s not just about the allure of state-of-the-art facilities or advanced bioreactors (a shiny new thing might of course be an extra plus). The real connection lies in the less tangible yet critical aspects like shared vision, trust, and effective communication. These elements form the heart of a strong partnership. For instance, financial compatibility and transparency are as vital in this relationship as they are in personal life, ensuring that your project’s budget aligns with the CDMO’s pricing structure.

The team behind the CDMO plays a role comparable to meeting a partner’s family. Their collective expertise, dedication, and collaboration will significantly impact the success of your project. This is especially true in the unique nature of biologics manufacturing, where precision, understanding, and a collaborative spirit are essential. The recent consolidation in the CDMO market, resulting in fewer but more diverse providers, has introduced new dynamics in the selection process. This change has led to providers acquiring additional capabilities (horizontal integration) or adding upstream or downstream services (vertical integration). These integrations promise simplicity and speed, but as a actor open to meet your perfect match you should sometimes instead  look for added technical benefits. Adding on also challenge the internal work structure and communication. This internal communication is so important and the mutual respect that different departments must display is crucial for an efficient scale up, scale out and transfer. So when you are dating, please dare to test the culture and climate of your CDMO,  do not satisfy with “ most convenient”. Be mindful of potential red flags indicating incomplete integration or separate operation of teams within a CDMO, but do not judge without asking about it. Even though a meeting with a “convenient”   person can lead to a flourishing long lasting relationship, it is quite rarely. You should not choose your life partner because this person was just the easiest one to get hold of or the only one still standing at three o’clock when you are walking home. Referrals is so underestimated, it should be the core if possible.  By using your existing network you add a layer of security, someone has already done the screening, and when it comes to CDMOs I would really recommend dating your best friends friend rather than blind dates ( meeting a stranger).

When you meet  “the family “ for the first time, you need to embrace all the members of the family.  A family dinner is never pleasant when some persons in the family do not really get a long, and if the family is very big the possibilities for this  kind of stressful family gatherings increases. Such nuances can reveal much about the internal culture and operational effectiveness of a CDMO.

During my years I have also encountered a lot of smaller biotech companies telling me about how they were not satisfied with their CDMO, but despite lack of trust and a lot of water under the bridges they choose to come back, year after year. This kind of bouncing back to your ex might seem like a really easy thing to do, you know what to expect and what you get, and you just started to hope that the ex had changed and became this prince/princess that you at first thought he/she was.  But honestly, bouncing back seldom gives you the “happily ever after”.  From a statistical point of view this reunition with your ex/former CDMO might have a 50/50 success rate,but it might also end up in you judging and he/she not being pleased with the way you communicate? This bouncing back can sometimes delay projects ( material to start clinical trial etc) more than actually moving and changing partner even though you always add time doing a new Tech Transfer.

In conclusion, selecting the right CDMO is akin to finding a long-term, committed life partner in the personal realm. It’s a decision that extends beyond the immediate, tangible aspects to the core of shared values, goals, and mutual understanding. This choice not only impacts your immediate project needs but also sets the stage for long-term success in the evolving world of therapeutic biologics. As you navigate this ‘dating’ landscape, remember that the right match is out there – a CDMO that understands your vision, aligns with your goals, and stands ready to join you in advancing healthcare innovation. Lets find the one, Lets Journey Together!

Navigating the production of non-GMP proteins in a GMP-driven environment

As the pharmaceutical and biotechnological industries are obliged to align their operations with Good Manufacturing Practice (GMP) guidelines, a unique set of challenges emerges for facilities tasked with producing non-GMP proteins. GMP is widely recognized as the gold standard for ensuring that products are consistently produced and controlled according to quality standards. However, in some cases, the production of non-GMP proteins (or “technical proteins), often required for research, industrial applications, or other non-clinical purposes, becomes a necessity.  At NorthX we serve both the non-gmp and GMP protein communities and place a strong emphasis on utilizing a strong Quality Management System, while at the same time respecting the process for each product.

Producing these proteins efficiently within a predominantly GMP-driven environment poses several challenges:

Segregation

Both GMP and non-GMP processes have their distinct sets of protocols and standards. Applying spatial, procedural or time-based segregation between GMP and non GMP products is essential. In cases where GMP manufacturing is the prevailing standard this will also stipulate how and what is needed to be done so ensure this segregation. Normally is not allowed to produce more than one pharmaceutical product at a time in a multipurpose facility and thorough product change over routines need to be in place to ensure the risk for carry overs and mix ups are minimized also contributing to the integrity and high quality of the non GMP protein manufactured.

Documentation dilemmas

GMP operations thrive on meticulous documentation. Every step, change, or deviation is carefully recorded. While non-GMP production doesn’t demand the same level of rigorous record-keeping, facilities must strike a balance. Too little documentation for non-GMP processes can lead to inefficiencies or inconsistencies, while over-documenting can unnecessarily tie up resources.

Training and personnel challenges

Staff trained predominantly in GMP protocols might find it challenging to switch gears for non-GMP production. The mindset and attentiveness required for GMP can be deeply ingrained, making it difficult to adapt to the more flexible requirements of non-GMP production.

Resource allocation

In a facility primarily designed for GMP production, resources – be it equipment, personnel, or space – are typically allocated with GMP requirements in mind. Efficiently producing non-GMP proteins requires a rethinking of these allocations without compromising GMP production.

Cross-contamination concerns

Even with segregation in place, the risk of cross-contamination always looms. It is therefore important that the superior quality system stipulates what operations is needed to be in place and what measures to take between batches. Ensuring that non-GMP proteins don’t compromise the quality of GMP products is paramount.

Regulatory scrutiny

Regulatory bodies, aware of the potential risks, might subject such dual-purpose facilities to heightened scrutiny. This can lead to more frequent inspections and audits, creating additional pressure on the facility to demonstrate clear demarcation and control over its two types of production.

Efficiently navigating the dual landscape

  • While the challenges are significant, they’re not insurmountable. With strategic planning and a clear understanding of both GMP and non-GMP requirements, facilities can effectively navigate this dual Tailored Training Programs: Implement training modules specifically designed to address the nuances of working in a dual production environment.
  • Robust Quality Management Systems (QMS): Implement a QMS that can adapt to both the rigorous demands of GMP and the flexibility of non-GMP.
  • Regular Internal Audits: Periodically review and assess the efficacy of the separation strategies in place.

The expanding horizons of non-GMP technical proteins: A deep dive

In the biopharmaceutical arena, the importance of Good Manufacturing Practice (GMP) often takes center stage. However, beyond this GMP-centric world lies an equally essential category of proteins known as “industrial” or “technical proteins”. While they might not be used directly in therapeutic applications, they serve a myriad of functions that propel innovation and understanding in biotechnology. Let’s explore the expanding applications of these technical proteins.

1. Enzymes

Enzymes are the meticulous craftsmen of the biological world. They speed up chemical reactions, sculpt molecules, and construct or deconstruct various compounds. Their role in biotechnology is diverse:

  • Biocatalysis: Enzymes, with their ability to catalyze reactions under mild conditions, offer eco-friendly alternatives in chemical synthesis. They’re used in producing biofuels, fine chemicals, and even pharmaceutical intermediates.
  • Biomolecular Engineering: Restriction enzymes, ligases, and polymerases are the workhorses of genetic engineering, enabling DNA manipulation and amplification.
  • Industrial Applications: From the enzymes in your laundry detergent that break down stains, to those in the food industry aiding cheese production, these proteins have a multitude of commercial applications.

2. Ligands

Ligands are molecules that can bind to other specific molecules. In biotechnology, protein ligands have invaluable roles:

  • Affinity Chromatography: Protein ligands are used to purify other proteins or molecules. They bind to the target molecule, enabling its separation from a mixture.
  • Diagnostics: Ligands play a central role in many diagnostic tests. For instance, they can capture specific biomolecules, indicating the presence or absence of a disease marker.
  • Biosensors: Ligands are vital for the development of sensors that can detect specific molecules, from toxins in the environment to glucose in blood.

3. Analytical proteins

These proteins are indispensable for research, diagnostics, and quality control:

  • Reporter Proteins: Proteins like Green Fluorescent Protein (GFP) are used to track gene expression, protein localization, and even monitor cellular events in real-time.
  • Quality Control: Proteins employed in assays ensure that therapeutic products are consistent, potent, and free from contaminants.
  • Drug Development: Proteins used in assays can screen potential drug candidates, assess their efficacy, or gauge potential side effects.

4. Structural and functional probes

To understand the complex dance of life at the molecular level, proteins are used as probes:

  • Protein Crystallization: Some proteins can induce crystallization of other proteins or large complexes, aiding in their structural determination.
  • Functional Assays: Proteins can be used to test the function of other molecules, be they drugs, other proteins, or even whole cellular pathways.

Championing the value of technical proteins

While the biopharma industry and regulatory bodies necessarily emphasize GMP due to its direct implication on human health, the role of technical proteins cannot be understated. They serve as the unsung heroes, facilitating innovation, preliminary testing, and foundational research.

As the industry continues to evolve, so will the applications of these non-GMP proteins. By understanding and championing their value, we can ensure that both the R&D and GMP spheres of biotechnology and pharmaceuticals continue to thrive and innovate hand in hand. The future is bright, and technical proteins will undoubtedly play a significant role in illuminating the path forward.

Have a technical protein in mind?  We would love to discuss with you how to move your project forward.  Please email us at contact@nxbio.com to learn more!

Check out the new conference insight on what’s cooking in the ATMP space

Current trends in ATMPs

This article is written by Helena Strigård and Jonathan Royce.

Having returned from a series of conferences staged in the spring of 2023, when barely any event missed the opportunity to highlight ATMPs through presentations and panel discussions, we felt that there is a general desire to grasp what this toolbox really means for those of us operating in life sciences.

Consequently, we put together this overview of what’s cooking in the space. The text that follows is based specifically on the talks and panel sessions held at the BIO International Convention 2023, with a ‘sneak peek’ forward to the upcoming Nordic Life Science Days, where ATMPs will again be at the top of the agenda.

Link to Article

What exactly is isolator technology?

The primary purpose of isolator technology is to prevent the transfer of undesirable elements such as vibration, noise, heat, electromagnetic interference (EMI), or contamination between isolated components or systems.

A wide range of techniques and devices are used to achieve isolation. These can involve the use of specialized materials, physical barriers, damping mechanisms, or complex engineering designs to achieve the desired level of isolation between components or systems. Isolator validation ensures that all components of the isolator meet pre-determined specifications for cleanliness, air quality, and other factors. 

In addition, product contact surfaces must be thoroughly cleaned and disinfected before use to prevent any potential contamination issues. Isolators are commonly used in various fields, including engineering, electronics, telecommunications, and science, where isolation is crucial for optimal performance or protection.

Here are a few examples of isolator technologies:

  • Vibration isolators: These devices are designed to reduce or eliminate the transmission of mechanical vibrations between two objects. They are often used in applications where sensitive equipment, such as scientific instruments or electronic devices, needs protection from external vibrations.
  • Noise isolators: Noise isolators, also known as soundproofing or acoustic isolators, are used to prevent the transmission of sound or noise between different spaces. They are commonly employed in buildings, recording studios, or industrial environments to minimize the impact of noise on occupants or to create soundproof environments.
  • Thermal isolators: Thermal isolators are used to control heat transfer between two components or systems. They are often employed in electronic devices or systems to prevent thermal coupling and protect sensitive components from excessive heat. Thermal isolators can include materials with low thermal conductivity or specialized designs to minimize heat transfer.
  • EMI isolators: Electromagnetic interference (EMI) isolators are utilized to reduce the transmission of electromagnetic waves or interference between components or systems. They are crucial in electronic equipment to prevent electromagnetic interference that can disrupt the normal functioning of sensitive devices or systems.
  • Contamination isolators: Contamination isolators are specifically designed to maintain a controlled environment by isolating a particular space or process from the external environment. They are widely used in industries such as pharmaceuticals, biotechnology, or semiconductor manufacturing, where sterility testing in a clean environment is an essential procedure.

The Importance of Contamination Prevention

Preventing contamination is crucial in industries that require high levels of hygiene and safety, as even the smallest impurities can cause significant damage to products and people. Thereby, isolators are widely used in pharmaceuticals, biotechnology, and medical device manufacturing.

Isolators are essentially enclosed systems designed to isolate a process or product from its environment, thereby minimizing any risk of contamination. Their use ensures that no contaminants enter or exit the system during processing or packaging stages, helping maintain quality control and regulatory compliance. Isolation technology has become increasingly important in recent years due to rising standards for cleanliness and hygiene in pharmaceutical production environments.

By making sure isolation technology is properly implemented during pharmaceutical development, companies can confidently produce high-quality pharmaceutical products that meet stringent quality standards without worrying about potential contamination issues throughout their production processes.

The Role of Glove Boxes in Isolator Technology

Glove boxes play a critical role in maintaining a sterile environment and minimizing the risk of contamination during pharmaceutical production. They serve as containment isolators or aseptic isolators to ensure product quality and sterile manufacturing. Moreover, they provide microbiological control by preventing any outside contaminants from entering the isolated area.

Glovebox technology ensures product quality and operator safety during pharmaceutical production. They provide effective microbiological control by isolating hazardous materials from operators’ immediate surroundings while also allowing them to perform necessary tasks safely.

The effectiveness of this piece of equipment must be maintained with proper cleaning. Glove boxes must undergo a decontamination process to ensure they remain sterile between operations. This involves cleaning the entire system, including all surfaces inside and outside of the glove box and using appropriate cleaning agents. Regular cleaning validation ensures that all areas have been appropriately cleaned and disinfected before reuse.

Operator safety is another crucial aspect when it comes to glove boxes. Glove boxes isolate hazardous substances from operators’ immediate surroundings, protecting personnel from exposure to potentially dangerous chemicals or biological agents. Additionally, regular cleaning validation ensures that all areas have been adequately cleaned and disinfected before reuse.

Cleanrooms and Their Applications

Cleanrooms provide a controlled environment free from contaminants for sterile testing and manufacturing practices. The use of these advanced technologies allows for more stringent control measures to be implemented while maintaining regulatory requirements in check. Similarly to airtight bubbles, cleanrooms are filtered out to create an airtight barrier that is free of contamination. 

These controlled environments are perfect for sterile testing and manufacturing in various industries. Operators must enter through material transfer chambers to avoid direct contact with the entire cleanroom environment. Glove interventions are necessary when handling materials within the cleanroom, further reducing potential contamination risk.

Cleanroom technology is an attractive solution in various industries that require high levels of cleanliness, such as pharmaceutical development, biotechnology, and semiconductor manufacturing. Cleanroom design and operation must follow strict regulatory requirements to reduce contamination risk and ascertain consistent product quality. Maintaining the entire cleanroom’s integrity requires regular decontamination cycles using specialized equipment and techniques.

Isolator Technology in the Pharmaceutical Industry

The basic principles of the pharmaceutical industry demand that product requirements are stringent. Isolator systems play an integral role in achieving high-quality products while also complying with strict regulatory requirements to maintain product sterility assurance.

There are different types of isolators used for various applications within the pharmaceutical industry. One common type of isolator is a containment isolator, which protects operators from hazardous materials during handling and processing. Another type is an aseptic processing or sterile filling isolator used to maintain an aseptic environment during manufacturing processes.

Pharmaceutical isolators must comply with specific requirements such as ISO 5 classification for cleanrooms or grade A air quality levels, essential for sterility assurance. The isolation provided by these devices enables efficient production while maintaining product integrity, making them indispensable tools for pharmaceutical manufacturers.

Biotech Applications of Isolator Technology

Isolator technology has revolutionized the way sensitive materials are handled. In the biotech industry, isolators have enabled manufacturers to create high-quality products with precise specifications while protecting against contamination throughout the entire process – from development to distribution. Biotech applications of isolator technology include restricted access barrier systems (RABS) and aseptic manufacturing.

The biotech industry has greatly benefited from the advancements in isolator technology, as it provides a clean environment for processing critical substances. With this level of control, companies can create unique products with specific properties that traditional manufacturing techniques cannot achieve. This means that biotechnology companies can produce higher quality products than ever before, which is great news for consumers who rely on these products for their health and well-being.

Food Production and Isolator Technology

In the food production industry, isolators ensure that products meet strict quality standards. One of the main benefits of using isolator technology in food production is preventing cross-contamination, which can occur when different types of food come into contact with each other during processing or packaging. Isolators provide a barrier between different stages of production by ensuring that each stage remains isolated from one another.

Isolator gloves are also an important part of this technology as they allow workers to handle food products without coming into contact with them directly. This helps to prevent any potential contamination from human contact while working inside the isolator environment. Additionally, flexible wall isolators can be customized to fit specific needs, making them ideal for use in various areas within a facility.

Bio-decontamination is also essential, as it ensures that any bacteria or viruses present on surfaces are eliminated before work begins inside the enclosure. This involves using chemical agents or radiation sources such as UV-C light for the sterilization of surfaces within the isolator environment. By eliminating harmful microorganisms, companies can produce safe and high-quality products for their customers.

Isolator Technology in Nuclear Power Plants

Isolator technology is used in nuclear power plants to maintain a clean, controlled environment that prevents radioactive products from escaping into the atmosphere. Its ability to create a controlled environment with minimal intervention helps reduce human error and ensures maximum protection for both workers and the surrounding ecosystem

Isolator technology works by controlling the internal air pressure within a sealed chamber, which creates a positive pressure differential that prevents contaminants from entering. In addition, isolators can be equipped with various interventions such as gloves or robotic arms that allow workers to manipulate equipment and materials while maintaining isolation. This allows workers to perform tasks inside the chamber without being exposed to radiation or other harmful substances.

Isolation technology capabilities are strictly regulated by limit values for radioactive exposure set by national and international organizations. If any breach of isolator integrity and contamination were to happen, decontamination agents must be applied to neutralize any hazardous substances before they escape into the environment.

Advancements in Isolator Technology

Isolator technology has come a long way from traditional cleanrooms, providing more efficient solutions for contamination control in pharmaceutical manufacturing. The capabilities of isolation technology add an extra layer of protection against environmental factors, humidity control, and oxygen control. Additionally, modern ergonomic designs help reduce worker fatigue and increase productivity during extended periods of use.

Advancements in this technology rely on aseptic practices that minimize human intervention during production processes. This reduces the likelihood of microbial contamination and ensures that products meet strict quality standards. Risk analysis is also important and designs must take into account all potential risks associated with the process to minimize any negative impacts on performance or safety. As industries continue to push for higher standards in manufacturing practices, we can expect further improvements in isolator technologies to contribute towards achieving these goals.

The Future of Isolator Technology in Various Industries

One of the most promising areas for isolation technology is the pharmaceutical manufacturing environment, where contamination risk is high due to microbial bodies. Isolation technology not only leads to a reduction of contamination risk but also allows for a more controlled production process.

Another area where isolation technology shows great promise is in the aseptic filling processes. These involve filling sterile products into containers without exposing them to external contaminants. Isolators provide an ideal environment for this type of process because they can maintain a sterile environment while still allowing workers access to the product through glove interventions or other openings.

Overall, the future of isolator technology looks bright as it continues to evolve alongside advances in industry needs and standards. From the reduction of contamination risk in pharmaceutical manufacturing environments to facilitating safer aseptic filling processes, isolators offer numerous benefits that make them an essential component in many industries’ workflows today and well into tomorrow’s world.ç

Pharmaceutical development services

In today’s rapidly evolving world, the need for precision, safety, and controlled environments has become increasingly important across a multitude of industries. From pharmaceuticals to biotechnology, advanced research laboratories, and even high-tech manufacturing processes, the demand for technologies that protect sensitive materials and personnel is paramount.

At NxBio, we possess the technology and expertise to successfully handle the pharmaceutical product manufacturing process. We specialize in all aspects of developing early-stage processes into manufacturing processes, including making use of the best isolator systems and making sure isolator validation is properly leveraged. Together, we can create a potent product for patients that makes the best out of the advantages of isolation technology.

How are DNA Plasmids made?

What are DNA Plasmids?

DNA plasmids are small, circular DNA molecules that exist naturally in bacteria. They play a crucial role in gene transfer between cells and can carry additional genes that enhance the survival of the bacterium.

Why are DNA Plasmids important?

DNA plasmids play a crucial role in molecular cloning and genetic engineering. The purpose of these recombinant DNA molecules is to carry genetic information, making them indispensable for a wide range of biochemical techniques.

Here are five key aspects that make DNA plasmids essential tools in the field:

  1. Carriers of Genetic Material: Plasmids serve as vehicles for transferring specific genes or pieces of DNA between organisms. They can carry a broad range of genetic material, including genes responsible for antibiotic resistance or other desirable traits.
  2. Replication: Plasmid DNA can replicate independently from the host organism’s chromosomal DNA. This allows for easy amplification and propagation of the desired genes.
  3. Restriction Sites: Plasmids contain specific recognition sites for restriction enzymes, which enable precise manipulation and modification of the inserted DNA sequences.
  4. Expression Vectors: Certain plasmids function as expression vectors, allowing scientists to control the production of proteins encoded by inserted genes. This enables the study or production of specific proteins in different host organisms.
  5. Antibiotic Resistance Genes: Many plasmids possess antibiotic resistance genes, which provide a selectable marker for identifying bacteria that have successfully taken up the plasmid during transformation experiments.

History of DNA Plasmids

The discovery of plasmids dates back to the 1950s when it was observed that certain bacterial strains contained extra-chromosomal genetic material. This led scientists to investigate further and discover these small, autonomous DNA molecules. Initially, plasmids were seen as selfish elements because they could replicate independently from the host cell’s genome. As research progressed, scientists recognized the potential applications of plasmids in molecular biology.

Researchers discovered how to isolate specific fragments of DNA sequences using restriction enzymes and manipulate them by adding or removing genes of interest. These modified plasmids, known as recombinant plasmids, became invaluable tools for cloning genes and producing proteins on a large scale. Today, DNA plasmid production involves sophisticated techniques that allow for rapid amplification of specific DNA sequences.

What Exactly Is DNA Sequencing?

Components required for DNA Plasmid construction

To construct a DNA plasmid, scientists use a DNA fragment containing the desired gene or sequence of interest. To obtain this fragment, various methods such as polymerase chain reaction (PCR) or gene synthesis technologies are used. This fragment is inserted into the plasmid using specialized enzymes called restriction enzymes.

The plasmid itself consists of multiple key elements. These include:

  • An origin of replication that allows for autonomous replication within the bacterial host cell;
  • Antibiotic resistance markers that enable selection for cells carrying the plasmid;
  • A promoter region to enable the expression of the inserted gene.

Steps Involved in DNA Plasmid preparation

  • DNA plasmid preparation starts by isolating a bacterial host cell and obtaining a DNA fragment containing the desired gene or sequence of interest.
  • The raw material must be inserted into a suitable vector, which is usually a circular plasmid. This vector will serve as the carrier for the gene of interest.
  • Certain components must be incorporated into the plasmid to ensure successful cloning and expression of the desired gene. For instance, a selectable marker will allow for easy identification and selection of cells that have taken up the plasmid. Additionally, the origin of replication is necessary for efficient replication inside bacterial cells.
  • After constructing the expression plasmid, various cloning techniques can be used to introduce it into the bacterial host cell. One commonly used method is transformation, where the plasmid is introduced into competent bacteria that can take up foreign genes.
  • Once successfully transformed, recombinant proteins can be produced in large quantities within the host cells. To confirm successful insertion and evaluate the purity, gel electrophoresis can be performed on samples extracted from transformed cells. Further purification steps may also be required to obtain highly pure recombinant proteins suitable for downstream applications.

Choosing the Right DNA Plasmid backbone

When selecting a DNA plasmid backbone, it’s essential to consider several factors:

  • The size of the plasmid vector: Plasmids come in various sizes, ranging from small vectors that can accommodate up to 2 kilobases (kb) of DNA to larger ones capable of carrying more than 20 kb. The choice depends on the size of the insert being introduced into the plasmid.
  • Copy number: This refers to the number of copies of a particular plasmid present within a host bacterium. Different strains of bacteria have varying copy numbers for specific plasmids. It’s essential to select a plasmid with an adequate copy number that will ensure sufficient production of the desired protein or gene product.
  • Compatibility with the desired expression system:  Some expression systems require specific features such as promoters or regulatory elements that are not present in all available plasmids. Ensuring compatibility between the chosen backbone and expression system is vital for efficient protein production.
  • The availability of restriction enzymes: These are important for restriction digests and should also be considered when selecting a DNA plasmid backbone. Restriction enzymes are used in molecular biology laboratories to cut and manipulate DNA fragments during cloning procedures.

Inserting desired genes into a DNA Plasmid

Inserting the desired genes into the plasmid allows scientists to introduce foreign genes such as those encoding human proteins or therapeutic genes into a gene-containing plasmid. This process is as follows:

  • Selection of competent cells: These cells are usually bacteria capable of taking up foreign DNA.
  • Transformation: This process involves mixing the competent cells with gene-containing plasmid and subjecting them to specific conditions that promote DNA uptake. It can be achieved through heat shock or electroporation techniques.
  • Selection of suitable cells: It is crucial to select cells that have successfully taken up the gene-containing plasmid. This selection is typically done by growing transformed bacteria on selective media containing antibiotics that only permit the growth of bacteria harboring the target protein.
  • Isolation of individual colonies: Researchers isolate individual bacterial colonies and screen them for the presence of their desired gene. Plasmid samples containing the correct gene sequence are used for further experiments.

Verification and characterization of DNA Plasmids

Gel electrophoresis is often used to verify and characterize transformed genes. This procedure separates DNA fragments based on size using an electric field, allowing researchers to determine the optimal DNA plasmid concentration required for efficient cloning and transformation.

Characterization of the gene-containing plasmids can be done by sequencing the inserted DNA region or by analyzing the amino acid sequence predicted from its coding sequence. These methods provide valuable information about the fidelity of actual cloning and can help confirm whether the correct gene has been inserted.

What To Ask When Searching For a Biologics Company?

Applications and future directions of DNA Plasmids

The use of recombinant plasmids holds great promise and has already shown success in preclinical and clinical trials. DNA plasmids are useful in a wide range of industries, from medicine to agriculture:

Research and development procedures enabled by DNA plasmids include:

  • Gene therapy: DNA plasmids can be used as a delivery system for therapeutic genes, allowing them to be introduced into target cells and potentially cure genetic disorders.
  • Protein production: Plasmids are also used to produce proteins of interest, such as antibodies or enzymes, on a large scale. This involves introducing the plasmid into random bacteria which then act as “factories” to farm proteins.
  • Antibiotic resistance studies: Plasmids play a crucial role in understanding antimicrobial resistance by carrying genes that confer resistance to antibiotics. Studying these plasmids helps researchers understand how antibiotic resistance spreads among bacterial populations.

One potential future application for DNA plasmids is the development of gene therapies to treat genetic disorders. DNA plasmids can be engineered to carry specific genes that can be targeted to correct mutations or provide missing functions in patients with genetic diseases. Additionally, linear fragments of DNA can be transformed into bacteria using electroporation or other techniques, which increases the potential applications of DNA plasmids.

High-quality grade DNA Plasmid manufacturing

DNA plasmids are incredibly useful in modern pharmaceutical settings. Not only are they a critical starting point for gene therapy, but they also play a key role in preclinical applications. At NxBio, we specialize in DNA Plasmid manufacturing techniques, empowering researchers and aspiring entrepreneurs to effectively assess the quality, purity, and consistency of recombinant plasmids. Thanks to our high-quality standards, you are guaranteed an efficient development process, complete regulatory compliance, and fast turnaround times.

Recombinant DNA Plasmid Manufacturing

What are the phases of cell therapy production?

Phase 1: research and development

The initial phase in the production of cell-based therapies is where innovative ideas are explored and potential therapies are identified. In the dynamic and rapidly evolving field of cell therapy, thorough research and development play a vital role in bringing safe and effective treatments to patients.

During this phase, extensive laboratory work is conducted to understand the underlying mechanisms of action and optimize the manufacturing process. Scientists investigate various cell types, their behavior in different conditions, and their potential therapeutic applications. They also evaluate different techniques for cell isolation, expansion, and characterization.

The goal of Phase 1 of the cell therapy manufacturing process is to establish proof-of-concept and gather sufficient data to support future clinical development. Process controls are put in place to ensure consistency and reproducibility of the manufacturing process. In addition, quality control measures are implemented to meet the strict standards set by regulatory authorities.

Phase 2: preclinical testing

Phase 2 oversees the effectiveness and safety of cell therapy through the use of animal models. This allows researchers to gather valuable data before proceeding to human trials. During Phase 2, extensive characterization studies are conducted on cell products, including functional assays and downstream processing optimization. All these activities adhere to strict guidelines set by organizations like the International Organization for Standardization (ISO).

Here is what you need to know about Phase 2:

  • Preclinical animal models: In this phase, various animal species are used to mimic human diseases and evaluate the therapeutic potential of cell-based treatments.
  • Release assays: These tests assess the quality and potency of the cells manufactured for therapy. They ensure that only safe and effective products move forward in the development process.
  • Process development challenges: Developing robust manufacturing process controls for cell therapies can be complex due to factors like scalability, reproducibility, and regulatory compliance.

Phase 3: clinical trials – phase I

Phase 3 is where the safety and efficacy of the cell therapy will be evaluated in humans. This phase is commonly known as Phase I of clinical trials, which are a crucial step in cell therapy production. In phase I of clinical trials, small groups of individuals receive the experimental treatment for the first time. These trials help researchers determine how cells behave within the human body and evaluate any potential risks associated with their administration. 

Researchers must closely monitor participants for any adverse effects or unexpected responses. The scale of Phase I clinical trials may vary depending on factors such as available funding, study design, and regulatory requirements. Furthermore, meticulous documentation and analysis are essential to gather valuable data regarding dose optimization and patient response.

Phase 4: clinical trials – phase II

Phase II focuses on a larger group of participants, typically ranging from several dozen to a few hundred individuals. During this phase, researchers closely monitor critical process parameters such as cell expansion, ensuring that batches of cell therapy products are manufactured consistently using pluripotent stem cells as raw materials.

Here’s what can be expected during this phase:

  • Increased sample size: Phase II trials involve a larger number of participants to gather more data on how the treatment affects different individuals.
  • Dose determination: Researchers refine the dosing parameters established in Phase I by testing various doses or schedules to determine the optimal therapeutic effect.
  • Control groups: Some participants may receive a placebo or standard treatment as a control group for comparison purposes.
  • Efficacy assessment: The primary goal is to assess whether the treatment is effective in treating the specific condition or disease being targeted.

Phase 5: clinical trials – phase III

Phase III clinical trials are the final evaluation of the treatment’s safety and effectiveness. The goal is to ensure that the therapy can be produced consistently and reliably, meeting strict quality standards.

To achieve this, various factors need to be considered:

  • Cell sources must be carefully selected to ensure their suitability for therapeutic use. This involves assessing characteristics such as differentiation potential and immune compatibility.
  • Optimizing cell densities is crucial to achieving optimal therapeutic outcomes. Researchers aim to determine the ideal number of cells per dose to maximize efficacy while minimizing any potential adverse effects.
  • Cell viability is another critical parameter assessed during Phase III clinical trials. It refers to the percentage of viable cells within a given sample and serves as an indicator of product quality. High cell viability is essential for ensuring that patients receive a potent and effective therapy.
  • Disposable bioreactors are often used due to their ease of use and scalability. These systems allow for the efficient expansion of cells while maintaining strict control over environmental conditions.

Phase 6: regulatory approval

Regulatory approval ensures that the treatment meets all necessary standards for widespread use. This phase involves obtaining the necessary approvals from regulatory agencies to bring a cell therapy product to market.

Regulatory agencies carefully evaluate the data generated during clinical trials to assess whether the benefits of the treatment outweigh any potential risks. To obtain regulatory approval, several key processes must be followed to demonstrate the safety, efficacy, and quality of the cell therapy product.

The challenges of cell therapy regulatory approval are multifaceted:

  • Regulatory agencies require evidence-based documentation on various aspects of cell therapy including manufacturing processes, dosing regimens, adverse event monitoring, and follow-up protocols.
  • Ensuring product quality throughout manufacturing and distribution is essential for regulatory compliance.
  • Logistical challenges such as cold chain management and timely delivery also need to be addressed.

Phase 7: manufacturing and scale-up

The manufacturing and scale-up phase involves increasing production capacity to meet the demand for cell therapy products. During this phase, the focus is on efficiently producing large quantities of cell therapy materials while maintaining their quality and safety. The first step in this process is selecting the appropriate cell type for the therapy. In autologous cell therapy, the cells are derived from the patient themselves. When cells are sourced from a donor, the process is known as allogeneic cell therapy.

Cell isolation techniques are employed to separate desired cell populations from other components. Process decisions such as media formulation and culture conditions are considered to ensure optimal growth and functionality of the cells. These decisions need to comply with regulations specific to regenerative medicines. Scaling up production involves increasing batch sizes and implementing scalable production methods that can reliably produce a consistent drug product. It is crucial to continually monitor and control critical parameters such as temperature, pH levels, and nutrient supply.

Phase 8: quality control and assurance

During this phase, the quality of the medicine is assessed to meet the required standards for safety and efficacy. Quality control and assurance are crucial in the production of cell therapies to ensure that they are effective and safe for patients.

Here are three important aspects to consider during this phase:

  • Quality Control Assays: To verify the identity, purity, potency, and safety of the cell therapies, various assays are performed. These assays include testing for microbial contamination, measuring cell viability and functionality, and confirming genetic stability.
  • Chain of Custody: Maintaining a clear chain of custody is essential in ensuring traceability and accountability throughout the production process. This involves proper documentation at each step, from sourcing cells to final product distribution.
  • Contract Manufacturing Organization (CMO): Collaborating with cell therapy manufacturers streamlines quality control processes. CMOs have well-established quality systems in place to meet regulatory requirements.

Phase 9: distribution and patient access

A reliable distribution system ensures that patients have access to cell therapy products. A robust supply chain is essential for the large-scale production and distribution of these therapies. The distribution process begins after the cellular product manufacturing is completed and quality control has been performed. Allogeneic products, such as CAR-T cell therapy, require careful handling and storage to maintain their efficacy. 

The downstream process involves packaging, labeling, and shipping the products in accordance with regulatory guidelines. As part of this phase, proper cell collection and counting techniques are employed to ensure that each patient receives the appropriate dose of cells. Quality assurance protocols are implemented throughout the distribution process to guarantee consistent product quality at every step.

Key takeaways

  • The phases of cell therapy production include research and development, preclinical testing, and clinical trials in multiple phases.
  • Cell characteristics and selection are important factors in the production of cell therapies, including the selection of cell sources and optimizing cell densities.
  • Manufacturing processes and scale-up are crucial steps in cell therapy production, including regulatory approval and ensuring manufacturing and scale-up processes are in place.
  • Quality control and assurance are essential in cell therapy production, including maintaining product quality, implementing a distribution system, and employing accurate cell collection and counting techniques.

Cell therapy manufacturing services

Collaboration between academic institutions, biotech companies, and cell therapy manufacturers is crucial in the production of life-saving medicines. It promotes knowledge sharing and accelerates advancements in the cell therapy industry.

At NorthX Biologics, we specialize in providing a full suite of services to transform the way cell therapies are developed, produced, and delivered. Thanks to our state-of-the-art technological systems and expertise, you can rest assured knowing that your cell therapy products will be efficient, consistent, and of the highest quality.