July 1, 2020 PAP-Q2-20-CL-002
The advent of the COVID-19 pandemic has created an urgent need for new treatments and vaccines to combat infections by the novel SARS-CoV-2 coronavirus. Extensive drug discovery and development efforts are underway to get novel antibodies (and antibody-like treatments) that could lessen the effects of infection by SARS-CoV-2 into clinics as rapidly as possible. Simultaneously, many academic and industry groups are working to advance novel sub-unit and recombinant protein–based vaccines with the potential to illicit strong immune responses against this virus.
These companies need access to small quantities (milligrams to grams) of research-grade protein to investigate their performance in animal models and in vitro tests and are looking for outsourcing partners that can supply material very rapidly, typically from transient expression systems.
Selected pharma and biotech organizations already have encouraging preclinical data, with constructs promising enough to advance into clinical trials. These companies are relying on outsourcing partners with experience working with cell-based expression systems and sufficient bioreactor capacity to quickly develop suitable production processes. Of key importance — especially for a pandemic emergency response — is the ability to rapidly develop compliant production processes and transfer into GMP manufacturing to generate sufficient quantities of clinical trial materials.
Timelines for early-phase programs have already shrunk significantly in recent years, owing to the introduction of accelerated approval programs (i.e., Fast Track, Breakthrough Therapy, Priority Review). Biologics CDMOs leverage their process knowledge and have developed platform technologies and new techniques that enable rapid movement from cell line development to upstream and downstream processing. These approaches are highly applicable to COVID-19 projects.
On accelerated timelines, rapid generation of platform cell line systems combined with platform upstream and downstream processes or development paradigms ensure swift IND-enabling process development. With novel cell line expression systems and platform knowledge, process development can finish before clonal cell lines are generated. This saves several months of development work and takes development off the critical path.
However, it is still absolutely essential to follow appropriate quality and safety procedures to ensure that any therapies or vaccines that are developed are well characterized and safe for every clinical trial participant and potential patient. Quality and safety cannot be compromised, even in a scenario like the current COVID-19 pandemic.
Since the pharmaceutical industry is an essential business sector, development and manufacturing operations continue at Avid Bioservices. We are actively monitoring COVID-19 developments globally while following the guidelines of our local, state, and federal health authorities.
As a critical supply chain manufacturer for the pharmaceutical industry, we are taking measures to ensure the safety of our employees and to minimize any impact on the continuity of our operations. Hygiene and segregation policies have been revised, and nonessential personnel are working remotely. Personal protective equipment must now be worn by all employees, not just those in the lab and production area. Nonessential onsite visits have been postponed, and shift schedules have been devised to allow for maintenance, repair, and the continuation of research projects that must be conducted in the lab.
We are increasingly leveraging digital technologies for communication, not only among Avid personnel, but also with our suppliers and customers. For example, we used video conferencing to access remote support from an equipment vendor, enabling the successful installation and activation of a new bioreactor system.
For our existing and potential customers that find travel to our site difficult to arrange, Avid previously developed digital programs both for meetings and immersive tours of our site that, according to feedback we have received, make online visitors feel as if they are physically walking through the laboratory and the plant. Access to these technologies has been particularly valuable during the COVID-19 pandemic, and we will continue to build on these capabilities going forward.
From a supply chain perspective, we have not seen any supply challenges beyond what we typically face under normal conditions. Overall, we have not experienced significant impact to our day-to-day operations or our ability to provide process development and drug substance manufacturing services.
For accelerated projects, such as those involving process development and production of antibody and antibody-like constructs to combat SARS-CoV-2, an established and effective project management structure can make the difference between success and failure.
The structure should include a well-defined sequence of project management steps, from an initial kick-off meeting and regulatory strategy meetings to regular project and technical breakout meetings. A project management system should be sufficiently flexible to allow for the development of solutions tailored for each customer and each specific project.
A project timeline — with contracted deliverables and action/decision logs —should be established at the start and made visible to all internal and external team members. A well-defined escalation structure is also essential to ensure that issues that do arise are rapidly brought to the right organizational level — even up to the CEO if needed — and addressed.
Joint steering committee meetings provide the right level of executive oversight to review high-level milestone advancements, discuss updates on the program and potential changes to the scope, and highlight and establish consensuses on opportunities for improvement.
For all projects, but particularly for highly accelerated programs, creating phase-appropriate process development solutions is crucial. That can only be achieved by starting with a thorough client interview that enables the CDMO to fully understand the product and project and determine the target product profile (TPP).
Delving more deeply into the product itself comes next. Knowledge of which product quality attributes are essential will drive the design of the process development program. The right CDMO can help clients fully flesh out the relevant quality attributes to ensure development of the right product for their program. For many antibodies, there is a well-established number of quality attributes, where platform methods are readily available. For more complex antibody-like constructs and recombinant proteins, the level and type of glycosylation and less common posttranslational modifications make each product and process unique. This is where the experience of Avid matters the most — to deliver on programs in the shortest amount of time with the least level of risk.
Investing time up front to develop the TPP can help avoid later problems that can add significant costs or delays. Furthermore, it enables the development of a comprehensive analytical strategy for measuring relevant quality attributes early in the program during development, which accelerates timelines.
CDMOs with extensive experience in biopharmaceutical process development, such as Avid Bioservices, have worked with many different biomolecules and found solutions for a wide range of challenges. Many of the quality attributes are common among biologics, but the importance of each can vary immensely from one product to another, and some are unique. That is where long-term experience helps; it can be applied even to new biomolecules and structures not seen before.
Technology transfer has a direct impact on the level of success of a cGMP manufacturing campaign, particularly for accelerated projects. A well-established team that supports tech transfer is invaluable. The best approach is to have a cross-functional team — comprising process development, technical operations, MSAT, manufacturing, quality, and supply chain — involved right from the start.
As the project progresses, these team members can keep a close eye on facility fit, supply chain lead times, and other challenges that may require additional attention, such as onboarding of new equipment and qualification of unique raw materials. Experts from technical operations and manufacturing quality also provide feedback to the process development design to help select manufacturing-friendly solutions. Having established technology transfer policies in place that clearly outline individual responsibilities helps to ensure that each individual has the appropriate training on documentation, knows their role in the tech transfer process, and understands the scope of the information required for a successful tech transfer.
Technology transfer can be even more successful — and efficient — if the transition from early preclinical work to GMP production for early- and late-stage clinical trials and, ultimately, commercial production, is performed seamlessly at one location, as it is at Avid Bioservices. As a result, all phases of development and production proceed within the same quality and project-management systems.
The teams involved are in close proximity and can readily communicate with one another. Process development scientists can interact directly with operators and plant engineers to understand how a process may actually be performed at production scale. This feedback helps process development efforts stay focused on aspects of the process that will have the greatest impact on practical implementation. The result is a lean and cost-effective manufacturing process that is optimally fit for the production facility. Often, one or more key team members follow the project through all of the phases, ensuring continuity of knowledge and operational success.
With this approach, clients can immediately transition to commercial supply with the same company at the same site and avoid the need for technology transfer, either between different outsourcing partners or internally within a CDMO that operates from multiple sites. Any time a process or method is transferred from one site or facility to another, more time and resources must be invested, costs are often greater, and risk is always increased. Taking a project from the beginning to commercial production at the same site is the fastest and most efficient approach.
Avid Bioservices is a fully dedicated CDMO with experience developing processes for conventional biotherapeutics, like monoclonal antibodies, and unique molecules, such as Fc fusions and other fusion molecules, enzymes, vaccine subunits, and complex recombinant proteins.
Avid provides fully integrated cGMP biomanufacturing services for both clinical and commercial supply. We support projects from concept to commercial supply, including clone selection, protein characterization, upstream (batch, fed-batch, and perfusion), and downstream process development, using a wide range of mammalian expression systems.
All of these services are provided from one location in Southern California that also includes development laboratories and experts in analytical method development, qualification and validation, QC release and stability testing, and CMC regulatory support.
Our project management program en-sures that each client project is viewed from technical/scientific, operational, quality, and business perspectives and provides continuity and seamless transfers as projects progress. When onboarding projects, we conduct facility-fit evaluations and gap analyses to achieve first-time-right success for new projects.
Regardless of whether a project is early or late stage, we always develop processes with commercialization in mind, further reducing timelines as projects progress and leading to robust processes from a CMC/manufacturing point of view. Our process development, manufacturing, and quality teams partner seamlessly to ensure that operations result in safe, high-quality products.
For intensified projects, similar to potential COVID-19 therapeutics, Avid Bioservices is actively working with its clients to develop robust processes and high-performance systems that offer predictable performance and rapidly reach peak production levels. Our goal is to achieve high cellular productivity and readily scalable upstream and downstream processes for more rapid production while still maintaining an exceptionally high performance.
With a state-of-the-art process development laboratory, pilot plant, and production suites all located at one site, Avid can de-risk scale-up, developing suitable processes from nonclonal stable pooled cell lines even before the optimum clonal cell line has been established, which helps to move process development off of the critical path and dramatically accelerate timelines. This work is supported by our experienced analytical team, which has a wide range of established platform methods and can also develop custom methods, including plate- and cell-based potency assays, for each project. Avid continues to expand in development and manufacturing to maintain a bench of scientists and capacity to immediately on-board new programs.
In March, Avid Bioservices was honored to receive 2020 Contract Manufacturing Organization (CMO) Leadership Awards for Capabilities, Expertise, Reliability, Compatibility, and Service based on market research and surveys conducted by Industry Standard Research (ISR) and presented by industry publication Life Science Leader. We were also named a 2020 CMO Leadership Award Champion in the categories of Expertise and Service.
These awards are truly gratifying, because Avid’s entire business philosophy is built upon the concept of doing whatever it takes to deliver for our customers. We work to an incredibly high standard, with our teams taking real ownership of client programs and treating them as if they were internal projects.
They also underscore the key attributes of Avid as a CDMO well-positioned to help companies responding to the COVID-19 pandemic. We can support the process development and manufacture of traditional and novel potential therapies. We can rapidly advance candidates all the way to commercialization from a single site, eliminating complex and time-consuming site transfers.
Avid Bioservices is a dedicated contract development and manufacturing organization (CDMO) focused on development and cGMP manufacturing of biopharmaceutical products derived from mammalian cell culture. The company provides a comprehensive range of process development and high-quality cGMP clinical and commercial manufacturing services for the biotechnology and biopharmaceutical industries. With over 25 years of experience producing monoclonal antibodies and recombinant proteins in batch, fed-batch and perfusion modes, Avid’s services include cGMP clinical and commercial product manufacturing, purification, bulk packaging, stability testing and regulatory strategy, submission, and support. The company also provides a variety of process development activities, including cell line development and optimization, cell culture and feed optimization, analytical methods development, and product characterization.
Dr. Schroeder joined Avid as the VP of Process Development in May 2018. He most recently served as a director at AGC Biologics a global CDMO organization, where he successfully supported client projects towards first-in-human clinical trials, commercial product launch and ongoing commercial supply. Dr. Schroeder earned his Ph.D. in biochemical engineering and his M.S. in molecular biotechnology from Bielefeld University in Germany. He has previously served as a visiting scientist at Rensselaer Polytechnic Institute and at the University of Minnesota.
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