December 6, 2019 PAP-Q4-19-CL-010
While small molecules still account for the largest percentage of drugs on the market, demand for biologics is growing at a rapid pace. A significant portion of the pharmaceutical industry pipeline consists of recombinant proteins and antibodies, as well as next-generation biopharmaceuticals, such as gene and cell therapies.
Estimates for the value of the global biopharmaceuticals market vary somewhat, but they are all in the several hundred billion dollar range. One research firm predicts the market will expand at a compound annual growth rate (CAGR) of 8.59% from $237 billion in 2018 to nearly $390 billion in 2024.1
Biosimilars are an emerging segment of the biopharmaceutical market. According to research company Bioplan Associates, in March 2019 there were over 1,500 follow-on biologics under development, including over 1000 biosimilars and over 550 biobetters.2 The growth in biosimilars is having an impact on biologics drug manufacturing, leading to an overall increase in outsourcing of approximately 15%.2
Today, BioPlan reports that contract development and manufacturing organizations (CDMOs) manufacture ≤33% of biopharmaceutical products.2 Since 2000, more than 115 new contract manufacturing organizations (CMOs)/CDMOs have been established to provide biologics development and manufacturing services.3 The value of the global contract biopharmaceutical manufacturing market is estimated to be expanding at a CAGR of 7.5%.4
Unlike most new CDMOs that begin with smaller, early-stage projects and eventually move into commercial biologics manufacturing, Avid Bioservices’ first two clients had phase III and commercial projects. As a result, our quality systems were designed at a very high level from the start.
In fact, Avid Bioservices, which is based in Tustin, California, began as a subsidiary of the drug maker Peregrine Pharmaceuticals, offering contract manufacturing services to fill excess capacity. As an embedded CDMO, we brought all of the expertise we had accumulated in biologics development and manufacturing for Peregrine products to the limited number of projects we accepted.
Since then, Avid Bioservices has transitioned into a fully dedicated CDMO focused completely on meeting the needs of our customers. We are committed to the continuous improvement of our facilities, equipment and systems. We bring over 26 years of development and manufacturing experience and are personally invested in the success of our clients, from beginning to end.
Avid provides fully integrated biomanufacturing services for our clients and can support projects from concept to commercial supply, including cell line optimization, protein characterization, upstream (batch, fed-batch and perfusion) and downstream process development using a wide range of expression systems, optimization, scale-up and validation, and cGMP clinical and commercial manufacturing.
All of these services are provided from one location that also includes laboratories and experts in analytical method development, qualification and validation, QC release and stability testing, and regulatory strategy development and implementation.
Our project management program ensures that each client project is viewed from technical/scientific, operational, quality and business perspectives, as well as continuity and seamless transfers as projects progress.
The strong information transfer program at Avid for onboarding client projects, which includes facility fit evaluations and gap analyses, accelerates the launch of new projects. Regardless of whether a project is early or late stage, we always develop processes with commercialization in mind, further reducing timelines and leading to robust processes from a CMC/manufacturing point of view. In addition, our process development, manufacturing and quality teams partner seamlessly to ensure that operations result in safe, high-quality products.
Avid Bioservices is committed to each client’s success at every level and every step of the way. We recognize that each client and project is unique. We have thus focused on establishing flexible manufacturing capabilities to meet those very diverse needs. An expansion in 2016 included a new state-of-the-art late-stage clinical and commercial facility located adjacent to Avid’s headquarters.
In our GMP manufacturing building, we have both stainless steel and single-use bioreactors ranging from 100 to 2000 liters. Clients have the option of fully disposable biomanufacturing for late phase III clinical and commercial production. In addition, the new suite includes monolithic modular cleanroom walls and dedicated support utilities for each key processing area. Unidirectional process flows, separating personnel and materials, provide assurance that the design meets the most stringent regulatory requirements for commercial biologics API manufacturing.
Over the past 26 years, Avid Bioservices has developed expertise in the manufacture of a wide range of protein biotherapeutics using different CHO cell lines and other system (NS0).
In addition to more conventional biotherapeutics like monoclonal mAbs, we have experience developing processes for the production of unique molecules, such as Fc fusions and other fusion molecules, enzymes, vaccine subunits and other recombinant proteins.
Our manufacturing flexibility — in both upstream and downstream unit operations — allows us to accommodate these specialty biologic drug substances, which require processes that cannot be implemented using established platforms.
Advances in bioprocessing are occurring at a rapid pace. Within just the last decade, cell densities have increased dramatically. Titers as high as 10 g/L are now possible.
The increased yields and productivity have been a boon for upstream production, but create challenges for downstream processing. A process on a 2,000-L scale with a titer of 10 g/L will afford 20 kg of protein that must be purified. In addition, in many cases, these high-producing cell lines take time to achieve their high production rates, which can extend development and production timelines.
Avid Bioservices is actively working to develop proprietary technologies for these intensified projects to establish high-performance systems that are robust, offer predictable performance and rapidly reach peak production levels. The goal is to achieve high cellular productivity and readily scalable downstream processes for more rapid production while still maintaining exceptionally high performance.
Projects at Avid Bioservices fall into one of three categories: transfer in of well-established processes; transfer of existing processes that require optimization; or de novo upstream and downstream process development.
Each type of project involves a slightly different approach to process development. The key to success is having a conversation with the client at the earliest possible point to understand the specific needs and establish a target product profile. In addition to process knowledge, it is essential to have the right process engineering data at hand so that process development efforts can be fit to address the crucial issues for each different system.
Avid’s process development group collaborates closely with our analytical team, which enables us to establish the relevant process design space with a minimal number of experiments, and a minimal quantity of material. We also partner with equipment suppliers offering industry-leading systems and platforms, including GE, Thermo Fisher Scientific, Waters, Repligen, MilliporeSigma and Sartorius Stedim Biotech to ensure that the processes we develop are both efficient and cost-effective.
Our team of experts has years of product development and manufacturing experience that enable us to smoothly transition molecules onto the next phase, on time, and within budget. Our cell line, upstream, and downstream development processes combine to ensure our clients receive a well-characterized biologic with consistent product quality.
Recent projects have included rapid CHO cell culture optimization for a phase I clinical project resulting in >6 g/L titer and high capacity downstream process; cell culture optimization, downstream processing improvement and scale-up to 1000 L for a complex non-IgG immunoglobulin with a complex glycoprofile; and phase-appropriate optimization of a process throughout clinical development (change in cell line, switch from a stainless-steel to a disposable bioreactor, media and feed optimization, scale-up to 1000 L and downstream process optimization) resulting in an overall 10-fold increase in comparable product yield.
To support the growing number of clients with projects advancing through late-phase clinical trials towards commercial launch, we recently invested in an integrated pilot facility and process development lab to enable de-risking of the scale-up process for a seamless transition from the lab to commercial production.
The new PD lab, launched in early October 2019, has 30 identical state-of-the-art single-use and glass bioreactor systems ranging from 3 L to 15 L, which allows Avid to perform statistically significant process development, characterization and validation work in shortened timelines. The new equipment significantly accelerates our ability to develop and deliver cost-effective, robust, scalable and compliant processes and to drive efficient and rapid onboarding of new client programs progressing to manufacturing.
Avid Bioservices strives to be a strategic partner with our clients, helping them to successfully deliver their products to the patients that need them. We aim to pave the way for the commercial launch of client products and take pride in our ability to think creatively and respond rapidly to any challenges that arise. Within the constraints of quality, cost and time, our goal is always to provide the best service offering — development of optimized product and provision of high-quality product.
Indeed, quality is our passion and the paramount measure of our success. We deliver on our commitments to provide uncompromised compliance, deliver high-quality products to patients and achieve the key time-sensitive milestones that drive our clients’ successes. Our robust quality systems are compliant with U.S. FDA, EU and ROW regulations, and we have an excellent 14-year regulatory inspection history. Avid’s Quality Control group serves as our internal oversight team, ensuring that each product receives the utmost attention to detail needed to achieve compliance.
Our focus on quality goes hand in hand with our excellent inspection and compliance history, providing you with peace of mind in your choice of a CDMO partner. We take your projects to the next level with our commitment to your commercial success.
Biopharmaceuticals Market — Growth, Trends, and Forecast (2019-2024). Research and Markets. Aug. 2019. Web.
Rader, Ronald A. and Eric S. Langer. “Biosimilars Set to Further Expand the Biopharmaceutical Market.” American Pharmaceutical Review. 22 Mar. 2019. Web.
Biopharmaceutical Contract Manufacturing Market (3rd Edition), 2019–2030. ReportLinker. 18 Jun. 2019. Web.
Biopharmaceuticals Contract Manufacturing Market Analysis Report By Source, By Service (Process Development, Analytical & QC Studies), By Product (Biologics, Biosimilars), And Segment Forecasts, 2018 – 2025. Rep. Grand View Research. Sep. 2018. Web.
Richard Richieri joined Avid as Chief Operations Officer in October 2019, overseeing Process Development, Clinical and Commercial Manufacturing, Technical Support, and Facilities. Mr. Richieri previously spent 15 years with Avid Bioservices and its former parent company, Peregrine Pharmaceuticals, including the role of Senior Vice President of Manufacturing. He earned a bachelor’s degree in chemical engineering from the University of California, Los Angeles and a master’s degree in chemical engineering from the University of California, San Diego.