The biopharmaceutical industry is always under pressure to deliver cost-effective therapies to market in the shortest time frame possible, while adhering to the regulations that govern manufacturing practices. In recent years, however, biopharmaceutical organizations have experienced additional analytical challenges, with the trend towards increasingly complex and strict regulations that drive deeper product understanding. Vendors have responded with innovative analytical technologies that better support advanced bioprocesses and the rigorous analyses required for quality control. While new advances promise to accelerate biotherapeutics research and manufacturing, the adoption of new technology brings its own challenges—both tangible and perceived.

Faster progress can be achieved when biopharmaceutical companies, vendors, and regulatory bodies understand each other’s priorities and challenges. By better understanding the specific needs of biopharmaceutical companies, vendors, and regulatory bodies can be better positioned to deliver innovative technologies and appropriate guidelines that efficiently integrate into existing workflows. Biopharmaceutical leaders, however, must not only be receptive to change to achieve productivity gains from new technology, but they must also be able to demonstrate the potential benefits to others within their company if the changes are to be implemented. In this complex and changing landscape, how can parties work together to achieve joint goals of safety, quality, low-cost, and speed? 

Over the last decade, there has been an unprecedented explosion of knowledge and technological advances, enabling deeper biological insights and new possibilities for the development of novel therapies. New classes of biotherapeutics have emerged, such as antibody-drug conjugates and gene therapies, creating a need for new regulations to guide manufacturing. Regulatory agencies support the manufacture of new modalities by developing guidelines in line with the principles of Quality by Design (QbD)—a systematic, process-focused approach to development. For manufacturers, navigating this dynamic regulatory landscape can be difficult, as they must keep up with the constant changes and find ways to remain compliant.

Often, more sensitive technologies are needed to enable the detection of impurities at low concentrations. Therefore, biomanufacturing companies constantly have an array of cutting-edge technologies presented to them, and they must decipher whether the potential value of adoption is sufficient to warrant the change within their manufacturing processes. While these technologies often have desirable qualities, such as process simplification and more detailed analytics, the thought of change and its associated hurdles can make it less tempting to make the leap. Resistance to embracing new technology may occur for a number of possible reasons:

It can be difficult and time-consuming to identify which technologies truly offer the most value and are likely to help solve a company’s challenges without creating new ones.

When introducing a new instrument, companies must develop and validate a new workflow to remain compliant, which often requires a significant time investment.

There may be a reluctance to accept the financial cost required to invest in the new technology, which not only includes the capital cost but also the cost of potential short-term downtime and delays, plus the training of staff.

While manufacturers would want to be aware of impurities posing a potential safety risk, there may be concerns that the new powerful analytical technology may bring an awareness of previously unknown impurities. In other words, some may believe that it is easier not to risk adopting technology with a higher level of sensitivity in case the new analyses create a need for additional work.

Resistance to change is a natural component of human psychology that doesn’t always serve us when we are presented with new, better ways of working. Consequently, committing to new technology and workflows, individually and as a team, can be challenging—even when innovative, streamlined approaches may lead to productivity gains and increased operator confidence. Such resistance is compounded when there is less opportunity to engage in detailed communication between the parties. This is often also seen between biopharmaceutical companies and regulatory bodies. When this is the case, regulatory bodies may be viewed as barriers to development, and the potential for mutually beneficial discussions and developments is further limited.

Shifting perception to see knowledge as a competitive edge

Regardless of the challenges involved in their adoption, the reality is that analytical instruments are key tools that facilitate the manufacture of life-changing therapies. In the competitive biopharmaceutical space, with the increasing regulatory guidelines, compliance-friendly and streamlined instruments are needed more than ever. Sensitive, specific, reliable, and robust instruments can have a huge bearing on the cost-effectiveness and success at each stage of drug development and manufacture, including process development, improving ongoing quality control, and batch release testing.

Increased efficiency is amplified most successfully when an instrument not only has built-in compliance features, but also delivers multiple data types. Such capabilities are desirable in today’s environment, where the QbD concept is encouraged. QbD principles drive efforts to design and develop manufacturing processes during product development to consistently ensure a predefined quality at the end of the manufacturing process (ICH Guidance, 2009 [1]). The multi-attribute method (MAM) is one approach suited to QbD and has gained popularity in recent years, adding a more high-throughput dimension to molecular analyses (2). MAM has been developed with mass spectrometry-based techniques and, as the name implies, enables multiple critical quality attributes to be assessed. Originally developed to monitor and quantify multiple post-translational modifications in biotherapeutic molecules, MAM enables more information to be extracted from the results of a single analytical method—and has the potential to improve efficiency by replacing other conventional quality control methods (2).

Not just the different analytical techniques, but the multiple data formats generated by MAM and other technology combinations can be difficult to manage and can cause issues when creating a robust audit trail. Whereas the use of multiple data formats creates more room for error and inefficiencies, a streamlined, built-for-purpose data software system decreases the burden on technicians and auditors alike. Central data systems are increasingly being designed to calibrate instruments, manage workflows, and provide real-time reporting across multiple technologies. Today, chromatography data services exist where combinations of gas, liquid and ion chromatography, and mass spectrometry can be managed through one system.

In order to continue the development of biotherapeutics alongside tightening regulations, there is a need to not only embrace innovative technologies, but also foster cross-industry collaborations. For biopharmaceutical companies, forming a long-term partnership with a trusted vendor who reliably delivers on their commitment can bring about wide-reaching benefits that extend beyond customer support. With the right cross-section of experts, vendors can offer a high level of technical and practical knowledge to complement the expertise found within biopharmaceutical companies.

As vendors are constantly designing systems to work within the highly regulated biopharmaceutical industry, they are well positioned to help companies develop workflows that ensure compliance and speed up the progression of the product to market. Therefore, leveraging a vendor’s comprehensive, up-to-date regulatory understanding can be invaluable for biopharmaceutical companies. Often, intricate knowledge is an indication of a well-connected vendor; when vendors help regulatory bodies understand the technology available to support compliance, in turn they also benefit from the partnership, which ultimately strengthens industry alignment.

Strengthening the industry through training initiatives

In recognition of the importance of experiential learning and shared perspectives, training laboratories have emerged to equip scientists and other industry professionals with the knowledge and skills required for the future, such as those related to document keeping, data integrity, and good manufacturing practices (GMP) inspection. At the Biopharmaceutical Analysis Training Laboratory (BATL) of Northeastern University, there are ongoing efforts to train regulators, students, and various decision-makers and industry leaders in the areas of biotherapeutic manufacturing, with special emphasis on surrounding regulatory issues. Providing professionals with the opportunity to obtain a deeper understanding of the analytical capabilities and realities of the laboratory helps give them the background knowledge they need to update guidelines and be open to new technology.

One of the key aims of BATL’s training courses, as well as providing access to skill-based credentials, is to reduce the fear around innovating in the analytical space. Such an approach is welcome for vendors who witness the hesitation around the adoption of new innovations first-hand—a frustrating experience when they believe the technology can help get a product to market faster and ensure better quality. Trainers at BATL have been encouraged to see increasing openness by regulatory authorities to industry conversations and innovation, as well as showing an eagerness to learn more about the changing biomanufacturing space.

When navigating the analytical and regulatory challenges within the biopharma space, it helps to remember that biopharmaceutical companies, vendors, and regulatory bodies are ultimately all working towards the same goal: to bring innovative, high-quality drugs to patients using the safest, fastest, and most economical approaches. Each party contributes to the space differently and can strengthen their own capabilities by forming strong partnerships.

Driving biotherapeutic development through open communication

By working closely with regulators, vendors can anticipate trends and stay one step ahead of biotherapeutic development. Bioprocesses can be optimized sooner when vendors clearly communicate the value, scope, and limitations of their technology, which is made easier when regulatory bodies are open to conversations around new technology and product innovations. In summary, open communication channels across all parties is critical to maintaining alignment across the sector and helps avoid unnecessary delays in implementing new ideas.

The biopharmaceutical industry of today is complex, dynamic, and increasingly driven by quality. It is an evolving landscape that holds exciting possibilities for the development of cutting-edge biotherapeutics and also prevents challenges for all parties involved. In order to move forward in this tightly controlled space, vendors, regulatory bodies, and biopharmaceutical companies need to communicate openly in order to anticipate opportunities and understand each other’s challenges. Collaborative and networking opportunities can be found in training initiatives, such as those provided by BATL, where each party can decipher how best to navigate obstacles and implement the innovations at hand.

Guidance for Industry, Q8(R2) Pharmaceutical Development

 (CDER, CBER, November 2009).
2. R.S. Rogers, et al., 

, j.auclair@northeastern.edu, is associate dean, Professional Programs and Graduate Affairs, and director, Biopharmaceutical Analysis Training Lab, Northeastern University, and Lori Stansberry is marketing manager, Pharma & BioPharma, Thermo Fisher Scientific.

To whom all correspondence should be addressed

Articles

Features

Vendors are finding ways to address the increasingly complex analytical challenges in the biopharmaceutical industry to further biotherapeutic development.

Is Collaboration the Key to Accelerating Biotherapeutic Development?

Taking the time to comply with lab data integrity practices during the COVID-19 pandemic in a resourceful and operative manner is crucial for pharmaceutical laboratories. 

spoke with Bob Voelkner, vice president of Sales and Marketing at LabVantage Solutions; Charles Fracchia, CEO of BioBright and vice president of Data, Dotmatics; John Maier, director of labs data management at PPD Laboratories; and Kimberly Remillard, senior manager of Regulatory Affairs for Digital Science at Thermo Fisher Scientific about the best practices for lab data integrity during the COVID-19 pandemic.

 Are there any new regulations regarding lab data integrity? How do current and/or new regulations apply to research going on for COVID-19 therapies?

 The most recent regulations or standards for data integrity came in 2018, when FDA published updated guidance for industry on ensuring data integrity and compliance with CGMP [current good manufacturing practice] (1). At the same time, the World Health Organization and [the United Kingdom’s] MHRA issued guidance on data integrity, which is largely in line with FDA’s (2, 3). Today, the need for organizations dealing with COVID-19 to comply and adhere to the FDA guidance is no different than any other organization developing and manufacturing new drug products. The goal of data integrity is to assure the safety of, and therefore increase the confidence in, all pharma products being created and produced. Data integrity takes on heightened importance, as new COVID therapies and vaccines are on the fast track to market and prospective patients want assurances of the integrity of the drugs being offered to them. Operating a compliant lab in this environment, with data integrity at its foundation, is vital.

 (1), defines data integrity as ‘the completeness, consistency, and accuracy of data.’ While there haven’t been any new regulations regarding lab data integrity, the good clinical practice (GCP) principle that requires data to be attributable, legible, contemporaneous, original, accurate, and complete (ALCOAC) applies to all clinical trials including ongoing research for COVID-19 therapies. In order to meet the accelerated timelines of COVID-19 trials, study setup timelines have been minimized while maintaining data integrity by employing innovative technologies and processes such as:

A single global lab database to eliminate the need to merge and harmonize data

Simplified protocol definitions to improve study database quality and shorten startup timelines

Interactive web-based portals for investigators with electronic lab requisitions to significantly improve the completeness and accuracy of the data on entry

Interactive web-based portals and dashboards to enable study sponsors and project teams to monitor study wide data in real time

Powerful interfaces that combine lab data with the clinical development database in real time and continuously cleanse the data to streamline study closeout.

 In response to COVID-19, researchers and regulators have found it necessary to adjust priorities and protocols to meet new restrictions and practices for researchers, patients, and healthcare workers. Several guidance documents have been published to provide direction on how to adjust to the new conditions while maintaining data integrity and patient safety. The guidance documents make it clear that the same ALCOA+ data integrity principles apply in addition to ensuring patient safety, protection of personal data, and data validity for any trial interruptions or protocol changes. With interruptions in protocols and new remote methods of monitoring being utilized, data integrity is becoming even more critical to ensure research data maintains its validity.

Specific documentation is required to detail why protocol changes, deviations, or alternative processes are implemented, including why protocol-specified data may be missing. All alternative approaches must maintain trial participant safety and trial data quality and integrity, while minimizing missing data.

In addition to changes needed in the clinical trial and research space, fast track Emergency Use Authorizations allow for exemptions from certain GMP controls in the manufacturing area. Data integrity is critical to help reduce risk with the use of these GMP exemptions. For example, data integrity to show traceability and adequate control of source materials, data around batch records, and testing must be in place. Validation to support the consistency of the manufacturing process, including computerized systems validation, is also critical to ensure data integrity can be maintained.

Applying data integrity principles during the research and development of COVID-19 therapies to ensure the data complete, accurate, consistent, trustworthy, and reliable will support regulatory submission efforts and contribute to patient safety. Digitalization of the laboratory with integrated technologies such as a laboratory information management system (LIMS) to manage the workflow of data can add efficiency and traceability and help to ensure data integrity principles are met.

How challenging or difficult is it to comply with lab data integrity regulations during the COVID-19 pandemic?

Accelerated startup and overall timelines of COVID-19 trials have presented a significant challenge to ensuring compliance with lab data integrity regulations. We have been able to significantly reduce our setup timelines by utilizing specialized global rapid implementation teams along with the innovative technologies and processes previously mentioned.

During study execution, the sheer volume of subject and sample data collected within the condensed timelines has made real-time data monitoring and reconciliation critically important to the success of COVID-19 trials. To facilitate this, we have implemented innovative analytical tools that proactively monitor study data integrity and notify lab and clinical teams of investigator and procedural non-compliance before it impacts timelines.

During the COVID-19 pandemic, new protocols and methods for monitoring are often necessary and need to be implemented quickly. More remote data collection and management activities are occurring in the effort to minimize risk of COVID-19 for researchers, trial participants, and manufacturers alike. Due to this, it is critical that data integrity is maintained to ensure the validity of the study data as well as the protection of the patient information. Digitalization of the laboratory workflow using validated systems can reduce the risk of data integrity issues. Permission controlled systems with controlled workflows, integration to reduce potential points of human error, access across sites, and enhanced security features can all work together to support the data integrity and validity of research data. Use of secure cloud-based LIMS systems can help to connect not only the instrument data within your lab, but also allow for connectivity between sites.

I would argue it’s really only challenging or difficult for those labs that aren’t equipped with the right tools and solutions. Lab-dedicated software, like an LIMS, is designed to ensure the integrity of all the data gathered by the system. This includes dynamic auditing, so even data in temporary memory is audited prior to being committed to permanent/durable memory. These automated, connected LIMS eliminate manual data entry and risks of transcription errors or purposeful manipulation of data.

Largely speaking, because the regulations haven’t changed, the compliance hasn’t changed either. There are COVID-19 specific challenges that have arisen, largely due to the fact that fewer people are working on site, personnel density restrictions, access to certain facilities (in particular manufacturing) has been heterogeneous from company to company, and even between sites of the same company. Challenges of this kind have affected our industry particularly hard due to the acute need for the work itself. It is certain that the importance of having a safe and efficacious vaccine, alongside the politicization of the vaccine availability, have negative effects on the environment surrounding the development. Even before the pandemic hit, there have been reports of data integrity bypasses and fraud. Pressure due to the pandemic has only increased existing trends in this environment and combined with a generalized lowering of the public’s trust in any vaccine, this makes data integrity and compliance a crucial aspect of the response.

How do you suggest other organizations improve/enhance their lab data integrity activities (specifically, workflow, day-to-day operations, etc.), and how can this particularly help companies that are trying to develop a COVID-19 therapeutic?

 Data integrity relies on a combination of people, technology, and processes. Robust processes are necessary to ensure consistency and quality assurance. A good culture of quality will help to ensure the human resources involved in the laboratory will execute the processes in the correct way. And the right technology to meet the needs of the laboratory and regulations such as 21 

] Part 11 can help to reduce the risk of human error and process deviations.

Whenever possible, integrating the laboratory with validated digital systems to meet your workflow needs will help to reduce the risk of data integrity issues. The same principles will apply whether digitalized or not; however, more checks and monitoring may be required for systems which are not digitally controlled. Ensuring all data specific and attributable, including clearly and specifically documenting any changes or missing data, is key to be able to show the integrity and validity of your data.

 In order to improve lab data integrity activities, companies must review their existing practices and replace wherever possible error-prone, manual steps in the reporting of results and tracing of individual steps. With a robust, automated, informatics system taking care of recording and tracking vital laboratory or manufacturing information, a company can reduce the chances of having data integrity issues. Crucially, companies must also assess their systems’ cybersecurity posture, because with increased automation and informatics also comes a potential for external manipulation. Unfortunately, the vast majority of bioinformatics or laboratory informatics tools have very poor cybersecurity practices and hygiene and create a large opportunity for third parties to steal and modify data in said systems, and understanding the weaknesses and avenues that could cause deviations or data manipulations are absolutely key for companies. This is particularly true if —as the FBI has warned (4)—the company has publicly announced efforts in search of a COVID-19 therapeutic. Finally, we strongly recommend that companies set up a process to review new data and results that are being put into the record. This practice, common in clinical environments, needs to be performed by a person who is not familiar with the specific experiment, ideally even a disinterested third party. This will create human oversight and catch errors such as missing data, ambiguous results, unsupported conclusions, and more. Enacting this practice will ultimately give the executives, the company’s team, and even the public a level of safety in trust in the result that is sorely needed in this moment.

 Organizations can improve lab data integrity by implementing systems and processes that reduce the level of effort to set up and validate the lab database by utilizing a single global database; limit the amount of data captured to only those elements required for analysis; employ robust quality controls that QC [quality control] data on entry, when modification are made and prior to reporting; and provide innovative web-based tools that facilitate electronic data capture (electronic lab requisitions) and real-time data access to investigators and clinical team members for continuous data review and reconciliation.

 One critical way to ensure product quality is to prevent data integrity lapses at the outset, so proper lab automation is key. For companies that have abandoned traditional, paper-based record-keeping practices or deficient legacy IT systems, in favor of preconfigured and prevalidated LIMS built specifically for today’s regulated labs, they’re already on the right track. Such a LIMS enables automated connection to lab instruments so that results can be directly recorded into the LIMS, not only speeding the process, but increasing data integrity.

It’s worth noting that modern LIMS, which should be 100% browser-based, can help lab directors and managers to physically distance laboratorians who can work with tablets or other mobile devices.

 What trends are driving the need for data integrity in the laboratory setting?

 Besides the politicization and fraught recent history of data integrity that was discussed above, the next most important trend affecting data integrity is the deluge of data that is now commonplace in our industry. In processes where thousands of data points per day was the norm, we now routinely see workflows that generate millions of data points per day, both qualitative ones (such as images) and quantitative ones (e.g., assays). This dramatic uptick in data volume is a blessing for data-driven research, but it is also an unprecedented challenge to verify, validate, and commit [these] data to record. The need for automated tools is now clear, and such tools must be aware of automation capabilities and be hardened against cyber manipulations or we risk the robustness and trust of the whole system in this transition.

 The continuous push to bring therapeutics to market quicker and more cost effectively will continue to drive innovation and system integration throughout all phases of the clinical trial life cycle and in the laboratory setting, to ensure data integrity is maintained. We will continue to develop improved analytical tools and are beginning to explore artificial intelligence predictive models to improve subject, site, sponsor, and lab compliance, which in turn will help enhance data integrity, reduce study timelines, and ultimately drive down costs.

Data Integrity and Compliance with Drug CGMP

, www.fda.gov, accessed Nov. 9, 2020.
2. MHRA, 

‘GXP’ Data Integrity Guidance and Definitions

, www.gov.uk, accessed Nov. 9, 2020.
3. WHO, 

, www.who.int, accessed Nov. 9, 2020.
4. CISA, “FBI and CISA Warn Against Chinese Targeting of Covid-19 Research Organizations,” Press Release, May 13, 2020.

Lauren Lavelle is the assistant editor for 


Vol. 44, No. 12
December 2020
Pages: 36-40

When referring to this article, please cite it as L. Lavelle, “Complying with Lab Data Integrity Practices During COVID-19,” 

Pharmaceutical laboratories must keep lab data integrity practices in mind in order to properly handle the effects of the COVID-19 pandemic.

Cooperating with Lab Data Integrity Practices During COVID-19

On Dec. 14, 2020, FDA announced that it approved a first-of-its-kind intentional genomic alteration (IGA) in GalSafe pigs, a line of domestic pigs, that may be used for human therapeutics as well as food applications. The agency reported in a press release that this approval is the first IGA in an animal that it has approved for both human food consumption and as a source for potential therapeutic uses. The approval was granted to Revivicor, a US-based regenerative medicine company.

The IGA in the pigs is intended to eliminate alpha-gal sugar on the surface of the animals’ cells. Alpha-gal syndrome (AGS) occurs in people, who exhibit mild to severe allergic reactions to alpha-gal sugar found in red meat (e.g., beef, pork, and lamb). The altered GalSafe pigs may potentially provide a source of porcine-based materials for producing human medical products that are free of detectable alpha-gal sugar. For example, GalSafe pigs could potentially be used as a source of heparin, a blood thinner, allowing heparin to be produced free of detectable alpha-gal sugar. In addition, tissues and organs from GalSafe pigs could potentially address the issue of immune rejection in patients receiving xenotransplants, as alpha-gal sugar is believed to be a cause of rejection in patients.

As part of its review, the agency evaluated the safety of the IGA for the animals and people eating meat from them as well as the product developer’s intention to market the IGA for its ability to eliminate alpha-gal sugar on pigs’ cells. FDA determined that food from GalSafe pigs is safe for the general consumption. FDA’s review also focused on ensuring the effectiveness of the IGA through the evaluation of data demonstrating that there is no detectable level of alpha-gal sugar across multiple generations of GalSafe pigs.

The agency also assessed the risk of the IGA to promote the emergence or selection of antimicrobial-resistant bacteria in or on GalSafe pigs and concluded that the microbial food safety risk is low, mitigated by the low number of GalSafe pigs entering the food supply and the ongoing surveillance for antimicrobial resistance, among other factors.

The meat from these GalSafe pigs will be supplied by mail order, rather than in supermarkets, the agency stated in its press release.

“Today’s first ever approval of an animal biotechnology product for both food and as a potential source for biomedical use represents a tremendous milestone for scientific innovation,” said FDA Commissioner Stephen M. Hahn, MD, in the agency’s press release. “As part of our public health mission, [FDA] strongly supports advancing innovative animal biotechnology products that are safe for animals, safe for people, and achieve their intended results. Today’s action underscores the success of the FDA in modernizing our scientific processes to optimize a risk-based approach that advances cutting-edge innovations in which consumers can have confidence.”

“[FDA] is committed to continuing its close work with developers to facilitate safe advancements of animal biotechnology. Our Veterinary Innovation Program focuses on providing greater certainty in the regulatory process, encouraging development and research of innovative public health products, as well as supporting an efficient and predictable pathway to the approval of IGAs in animals,” said Steven M. Solomon, director of FDA’s Center for Veterinary Medicine. “The developer of GalSafe pigs participated in this program, proving the impact of this important FDA initiative. We look forward to continued work with other developers to evaluate the safety and effectiveness of additional innovative animal biotechnology products.”

News

The product represents a first-of-its-kind intentional genomic alteration in a line of domestic pigs that may be used for human therapeutics.

FDA Approves Genomically Altered Line of Pigs for Potential Therapeutic Uses

On Dec. 1, 2020, PlantForm, a privately held Canadian biopharmaceutical company, announced that the Natural Sciences and Engineering Council of Canada (NSERC) awarded it and its research partner, University of Alberta (UAlberta) scientist Dr. Warren Wakarchuk, an Alliance Grant to conduct research that will enable the commercial-scale production of effective, low-cost, plant-made protein therapeutics, including an antidote to chemical nerve agents.

The Wakarchuk lab pioneered the use of enzymes to make or remodel glycans, which play a key role in regulating immune cell signaling and function, and PlantForm’s plant-based manufacturing system for large-molecule protein drugs (biologics) requires glycan remodeling. Glycan remodeling on proteins effectively mimics human glycan structures, which reduces the risk of rejection and improves the circulation lifetime of the protein, according to PlantForm in a company press release.

The two-year project, which will be supported by $184,000 from NSERC plus a $92,000 cash and in-kind investment by PlantForm, will focus on using 

 glycan remodeling to improve the efficacy and serum half-life of butyrylcholinesterase (BuChE), a countermeasure for chemical nerve agents, such as soman and sarin. The BuChE is produced using PlantForm’s proprietary plant-based vivoXPRESS platform. The researchers will use enzymes engineered by the Wakarchuk team to remodel glycans on target proteins for improved stability and drug efficacy, with a focus on commercial-scale production.

“This Alliance Grant expands and strengthens our research collaboration with Dr. Wakarchuk and his team to continue to advance our novel glycosylation technology for our pipeline of innovative protein-based drugs,” said Dr. Don Stewart, PlantForm’s president and CEO, in the press release.

“Plants are an excellent alternative to mammalian cell cultures for the low-cost production of protein-based drugs. But the production of the authentic human glycan structures is difficult to control in both mammalian- and plant-based expression systems,” said Wakarchuk, a professor in the Department of Biological Sciences at the Faculty of Science as well as scientific director of GlycoNet, a pan-Canadian Network of Centers of Excellence consisting of more than 140 researchers centered in UAlberta, in the press release.

The grant will support the advancement of glycoengineering technology for plant-derived proteins developed by a University of Alberta scientist partnered with PlantForm.

NSERC Honors PlantForm with Alliance Grant to Enable Commercial-Scale Production of Protein Therapeutics

According to a Dec. 8, 2020 press release, the International Society for Pharmaceutical Engineering (ISPE) and Gilead Sciences have partnered up for the establishment of an internship program.

The ISPE Foundation Diversity Internship Program is a 12-week course, which will take place in the summer months, offering graduate students and undergraduate students the opportunity of working on high-priority, impactful engineering and facilities projects and workstreams in Gilead’s Corporate Operations organization. Currently, two internship opportunities are available at Gilead: Mechanical engineering with a focus on energy/sustainability; and electrical engineering with a focus on process control/automation.

“It is a privilege to partner with Gilead on the launch of a program that will be truly life changing to the careers of a diverse pool of talented students and future leaders in the pharmaceutical field,” said Antonio Moreira, PhD, ISPE Foundation Board chair, vice provost, Academic Affairs, University of Maryland Baltimore County, in the press release. “The ISPE Foundation Diversity Internship Program interns will be immersed in creative and innovative projects, they will be connected with role models and senior leaders at Gilead, and they will be encouraged to let their imagination go to places they had not thought possible. I can't think of a more inspiring and energizing way to start my role as the ISPE Foundation Chair.”

“Gilead is committed to investing in the next generation of engineers and are pleased to partner with the ISPE Foundation on this program,” added Joydeep Ganguly, senior vice-president of Corporate Operations at Gilead, in the press release. “We believe that diverse teams are inherently strong teams and look forward to the ways these interns will contribute to our highest priority projects.”

ISPE and Gilead Sciences have partnered up for the establishment of an internship program.

ISPE Foundation and Gilead Sciences Launch Internship Program

According to a Dec. 2, 2020 press release, the Cell and Gene Therapy Catapult (CGT Catapult) has launched the Advanced Therapies Skills Training Network (ATSTN), designed to open career opportunities and upskill staff in advanced therapy and vaccine manufacturing in the United Kingdom.

The nationwide initiative, driven by industry and coordinated by the CGT Catapult, comprises dedicated online resources and national centers to upskill, and provides an opportunity for people to identify how they can enter the industry. ATSTN is funded by an award of £4.7 million (US $6.3 million) from the Department for Business, Energy & Industrial Strategy (BEIS) through UK Research and Innovation (UKRI).

“It is vital that we upskill our workforce to develop and manufacture vaccines and treatments at scale, ensuring the advanced therapy and vaccine manufacturing sectors are stronger and more resilient in the future,” said UK Business Secretary Alok Sharma, in the press release. “Backed with almost £5 million government investment, this first-of-its-kind skills network will equip people at all stages of their careers to pursue opportunities in advanced medicines and vaccine manufacturing. This will help to create highly skilled jobs across the country while putting the UK in the strongest position to respond to future pandemics.”

“One of the tasks of the government’s Vaccines Taskforce is to ensure the UK has the capabilities to respond to future health crises, and this includes scaling up our ability to manufacture safe and effective vaccines and treatments,” added Kate Bingham, chair of the Vaccines Taskforce, in the press release. “By upskilling and expanding the UK’s vaccine manufacturing industry, this new skills network will help to ensure the UK has the capacity to produce successful vaccines at scale, including for coronavirus, helping to protect the UK population for generations to come.”

“The ATSTN initiative reiterates our commitment to upskill new and existing members of the advanced therapy workforce, building on the success and impact of the ATAC apprenticeship program,” commented Matthew Durdy, CEO of CGT Catapult, in the press release. “Not only is it rewarding to work so closely with industry to deliver on this need, but it is also extremely motivating for all involved to think that this initiative is going to be the start of so many promising careers and additional job opportunities. We look forward to seeing the success stories from users of this ground-breaking platform.”

CGT Catapult has launched the Advanced Therapies Skills Training Network, designed to open career opportunities and upskill staff in advanced therapy and vaccine manufacturing in the UK.

Nationwide Skills Development Program for Advanced Therapies Begins in UK

On Dec. 1, 2020, BioSkryb, a developer of genomic amplification technologies, reported the release of foundational data demonstrating that primary template-directed amplification (PTA) has a superior ability to accurately and uniformly amplify the genomes of single cells. The data was released on bioRxiv, the preprint server, prior to publication.

Whole genome amplification (WGA) is required for low-input DNA and single-cell analysis, and single-cell approaches are critical for tackling difficult biological questions involving genomic heterogeneity. Current WGA technologies and methods for single-cell or low-input DNA analysis, however, only cover a fraction of the genome, have a limited capacity to detect genetic variation in each cell, and suffer from significant biases, experimental artifacts, and poor reproducibility. The new data show that PTA can overcome these limitations as well as provide high-quality, scalable analysis of single-cell genomic heterogeneity. Having access to this analysis can enable new insights into human disease at the cellular level and empower high-resolution diagnostics for cancer, gene-editing, and other applications, BioSkryb stated in a company press release.

Furthermore, the PTA technology accurately calls genomic variants within tissues, one cell at a time, and reproducibly captures more than 95% of the genomes of those cells in a more controlled and accurate manner than existing approaches. According to the data released, PTA can be reliably used to call copy number variation in primary cancer cells and genome-wide variant detection in gene-edited cells. The technology can enable the feasibility of performing single-cell evaluations of biopsies from cancer and gene-edited tissues.

The PTA technology has been made a part of BioSkryb’s ResolveDNA kits, which contain all the enzymes and reagents needed for whole genome amplification from single cells or ultra-low DNA inputs. The kits employ a unique set of nucleotides to prevent recopying of the amplification products, which results in less errors and higher, more uniform coverage of the genome. The PTA technology also enables the attachment of cell barcodes to the resultant products for pooling and downstream analysis.

“We developed PTA to accurately and efficiently decipher genetic diversity at the cellular level so that we can better detect, understand, and treat disease,” said Charles Gawad, MD, PhD, inventor of the PTA technology, cofounder of BioSkryb, and associate professor at Stanford University, in the press release. “These data show that PTA amplifies the genomes of single cells with high coverage breadth and uniformity in a reproducible manner to significantly improve variant calling of all types. The ability of PTA to enable highly accurate genetic information at single-cell resolution could uncover new drug targets for cancer and neurological diseases as well as identify CRISPR off-target activity to monitor the safety and fidelity of gene editing.”

“Chuck and I cofounded BioSkryb to ensure researchers had access to the most advanced DNA analysis technologies, so it’s especially exciting to see the superior performance of PTA over current methods and to be able to make it commercially available through our ResolveDNA kits,” said Jay West, PhD, CEO, and cofounder of BioSkryb, in the press release. “Existing whole genome amplification methods uncover a fraction of the genomic information, but now with ResolveDNA, researchers can explore new places in the genome and be confident in the quality of the sequencing data at those sites.”

A novel PTA technology captures more than 95% of the genomes of single cells, providing more uniform, accurate, and reproducible single-cell analysis data.

BioSkryb Examines First Data Demonstrating Improved Accuracy in Single Cell Analyses

rBIO, a US-based early-stage synthetic biology company, achieved its first in-lab milestone in December 2020 when it was able to synthetically produce human insulin using its recombinant DNA (rDNA) model and process. The company can achieve upscale production of insulin, potentially lowering the cost of the drug by 30%, as well as identify other prescription drugs that can be manufactured by manipulating microorganisms to express peptide hormones.

rBIO’s approach applies recent breakthroughs in genetics and rDNA science to design new synthetic life that is capable of expressing a wide variety of peptide hormones. The company is using 

 bacteria as the host for rDNA synthesis of insulin, it stated in a Dec. 17, 2020 press release.

“We targeted insulin for our initial model because it checks two boxes: first, it’s a specialty drug that is priced too high for many people who depend on it and, second, its supply chain is vulnerable,” said Cameron Owen, founder and CEO of rBIO, in the company press release. “Our goal is to reshore insulin manufacturing to the United States and make this crucial hormone available at a lower cost for the millions of Americans suffering from diabetes.”

Having achieved lab-scale production of human insulin, the company’s next step is to increase insulin yields prior to seeking FDA approval. rBIO has also developed a shortlist of eight drugs that can be synthesized with this unique coding approach. “Our results with insulin clearly demonstrate that our technique works, so we’re also looking at epinephrine and erythropoietin, among others,” added Owen.

“There are a wide array of biological products that can be synthesized with this rDNA approach,” said Dr. Debanjan Dhar, professor of medicine at University of California, San Diego, in the press release. “Single-celled organisms like yeast, bacteria, and algae can be harnessed to drive the next manufacturing boom of biological products needed to meet patient demand for crucial drugs."

Using rDNA technology to synthesize production of proteins and peptide hormones, the biotech startup has achieved synthetic production of insulin, potentially lowering insulin cost by 30%. 

rBIO Hits Key Lab Milestone with Synthetic Production of Insulin

Computrac Vapor Pro XL Autosampler from AMETEK Brookfield, part of AMETEK's Instrumentation and Specialty Controls Division, aims to increase the efficiency of the Vapor Pro’s moisture-specific analysis technology by analyzing up to 16 samples automatically with individual test profiles.

The compact device is suited for applications that require test automation and increased throughput and provides a chemical-free substitute for Karl Fischer titration. Additionally, it provides testing for applications in the pharmaceuticals industry as well as in other industries (food, lubricants, paints and coatings, plastics, and batteries).

"Busy quality managers will enjoy peace-of-mind and boosted productivity with an automated moisture analysis of up to 16 product samples," said Kai Johnstad, AMETEK Brookfield's global product manager, in a Nov. 25, 2020 press release. "Product stakeholders will also benefit from time and cost savings by ensuring the perfect moisture content without using Karl Fischer titration."

New Technology

The compact device is suited for applications that require test automation and increased throughput and provides a chemical-free substitute for Karl Fischer titration.

Pharmaceutical Technology's In the Lab eNewsletter 01-06-2021