December 6, 2019 PAP-Q4-19-NI-005
A: Many of the change agents I have seen in 2019 are derived from changes in regulatory law, commercial downscaling, and impact from patent expiry strategies. The largest external regulatory change came from the issuance of the long-awaited EMEA Annex I, clarifying which technologies are required and acceptable, when and why.
The change in operational focus, from clinical scale-up to commercial scale-down, is enabling use of smaller, modular, flexible fillers with self-contained isolators. In parallel with the approval of biosimilars and biobetters, there is strong industry focus on individualized micro-batches, for CAR-T solutions and gene therapy products. The use of process automation and robotics have increased in all fill-finish unit operations. Widespread implementation of ready-to-use/ready-to-sterilize components and single-use (SUT) in upstream and downstream (SUS) through final fill designs have changed how facilities are planned, reducing plant size and changing warehouse space to accommodate densely packaged plastics goods.
Filling modalities have also been changing; bags that can be mated to lock-luer fittings with pre-sterilized needles and blow-fill-seal/form-fill-seal are re-emerging as processes that offer potential unit cost reduction. Traditional vial and syringe container designs are also changing as suppliers improve standardize offerings while having options including clear plastics.
A: The challenges involved in biologic drug development differ greatly to those of small molecule drugs, and today’s innovators are more often focused on discovery, so they need to outsource other activities to progress programs.
At the same time, larger biopharma companies are seeking to forge more long-term relationships with fewer suppliers.
Following a year-long initiative and consultation exercise, Catalent Biologics launched OneBioSM Suite, an integrated biologics development solution designed specifically for those innovators looking for increased speed to the clinic and on to the market, while also reducing complexity and risks from projects.
OneBio offers innovators a single, integrated provider, reducing timelines and complexity associated with contract negotiation, site inspections and handoffs and poor communication between multiple vendors. The platform leverages Catalent’s advanced technologies and expertise to support programs from cell line development through to fill-finish, packaging, clinical supply and commercial launch under a single contract, program manager and harmonized quality systems.
The OneBio Suite draws upon Catalent’s proven track record of progressing biologic drugs to market, which includes over 120 global clinical trials and 12 commercially marketed biologics using the company’s proprietary GPEx® cell line development technology and 25 approved products through fill-finish and commercial supply to global markets.
A: The most exciting technological or scientific advancement that has influenced our business strategy in 2019 is our novel epigenetic regulator program. Unlike gene therapies, which target and modify DNA directly by inserting specific genes into patient’s cells, epigenetic regulators control or modify gene expression through processes that do not alter the sequence of DNA directly. Our lead asset DUR-928 is a small endogenous molecule that plays an important role in regulating cellular functions such as lipid homeostasis, inflammation and cell survival, crucial pathways involved in many acute and chronic diseases. DUR-928 has shown positive results in a phase IIa trial for the treatment of alcoholic hepatitis, a devastating acute condition with high mortality rates and limited therapeutic options. We are also advancing programs in other indications that could benefit from DUR-928, such as non-alcoholic steatohepatitis (NASH) or psoriasis. We believe that epigenetic regulation is a powerful and untapped treatment approach for many challenging diseases.
A: One breakthrough technology that has had a transformative effect on our research and development efforts this past year has been advances in next-generation sequencing (NGS) technologies, including single-cell RNA sequencing (scRNA-seq).
When combined with ongoing advances in bioinformatics, the complex data sets generated by scRNA-seq have great potential to identify previously unrecognized cell populations and relationships between genes that could help uncover new targets for researchers to focus on. We recently received a grant from the French National Research Agency to collaborate with academic researchers at premier cancer centers in France to use scRNA-seq and bioinformatics approaches to validate new targets linked to myeloid cells, an important type of suppressive immune cells. This grant and subsequent collaborations could have a positive impact on development of new therapies for immune-related diseases, such as cancers and autoimmune diseases. We're eagerly anticipating additional breakthroughs with NGS technologies that could provide researchers with novel targets to leverage innovative new treatment options for all patients in need.
A: Although continuous flow has been utilized in a variety of industries for over a century, the pharmaceutical industry has been slow to adopt this technology for historical and regulatory reasons. The advantages that continuous flow has for chemical synthesis include both safety and efficiency, and there are a number of examples of pharmaceutical companies looking to leverage the technology for process improvements in clinical phase development.
Cambrex identified a need for continuous process development capabilities within the CDMO industry and took the decision to establish a continuous flow Centre of Excellence at its site in High Point, NC. The site has installed a number of continuous flow reactor platforms and, as a result, now has several continuous flow projects underway with pharma customers of varying sizes. Customers have access to a dedicated engineering group and the process development work carried out in High Point can be seamlessly transferred to Cambrex’s drug substance manufacturing facilities in the U.S. and Europe,
A: In recent years, technological advances in the immuno-oncology field have been focused on the development of checkpoint therapies, bispecific antibodies and, most notably, cell therapies such as CAR-T or TCR-T approaches.
While initial progress is encouraging, these treatment options present challenges that pertain to specificity, safety and durability of response, as well as manufacturing challenges in the case of cell therapy approaches. A primary driver of our motivation at Cue Biopharma was to develop an alternative therapeutic approach that could mitigate the challenges discussed above and hence provide a differentiated and superior path for the future of immunotherapy that would significantly improve upon what current therapies can accomplish, with broad applications within and beyond immuno-oncology. To that end, we have been engineering a class of injectable biologics to selectively engage and modulate targeted T cells within the patient’s body to transform the treatment of cancer and autoimmune diseases. Our breakthrough technology, the Immuno-STAT™ (Selective Targeting and Alteration of T cells) platform, represents a fundamentally different mechanism for leveraging T cells to treat diseases with the potential to be more targeted, more powerful and safer, while at the same time far less costly and cumbersome than cell therapies.
A: Improving our execution of extractable and leachable science and the increasing regulatory support for rapid methods presents interesting opportunities, although the transformative impact hasn’t yet been fully realized.
The collaboration, support and encouragement from both the regulatory agencies and industry will make the next few years exciting as we start to see shifts in how we align our services.
A: Katalyst D2D is a web-based software application from ACD/Labs that offers a single interface for high-throughput experimentation from design to decide.
Katalyst is purpose-built to automate and analyze an entire high-throughput experiment workflow in one interface. It helps scientists design, plan and execute array-based experiments by integrating with lab automation (informatics systems and laboratory hardware). The user interface (UI) is key for users — with various possible interface layouts, sets of visible application components within dashboard(s), settings and any notifications. The browser code handles how to respond to various user actions and inputs. Those are converted to service requests, and the appropriate responses and results are provided back quickly to the user. Applications that can perform synchronous or asynchronous requests without having to (re)load pages present a user with a less disrupted experience. A configurable, extensible, sufficiently fast, efficient, robust, secure and scalable architecture is desired to satisfy users and the IT personnel that support innovative web services–based technologies.
A: For oral solid dosage forms, we’ve recently developed a new proprietary manufacturing process known as AEMP®. In our first success with AEMP, we combined the respective benefits of two existing, monographed polymers to create a new combination polymer called EUDRAGIT® FL 30 D-55. This advanced polymer for enteric coatings is highly flexible and easy to process, making it ideal for a range of APIs and dosage forms including multiparticulates.
We are also developing advanced polymers and 3D printing processes that can be leveraged by pharmaceutical companies to create personalized medicines in an oral solid dosage form. Similar activities are also underway to support the development of bioresorbable implantable medical devices with patient-specific parts that can match the patient’s natural healing process. Other core technology areas being pursued include the production of advanced foods and biofabricated materials utilizing microbial fermentation processes, the use of lipid nanoparticle technologies for the delivery of nucleic acids such as mRNA and tissue engineering for wound healing and organ repair.
A: For our industry, the development of abuse-deterrent technology and nanotechnology for cannabinoid-derived therapeutics is evolving to be transformative in treating high unmet medical needs.
These technologies are not only instrumental in enhancing the solubility of THC and CBC products that have been shown to relieve symptoms of pain and inflammation, but are of critical importance given the widespread opioid crisis. For example, the potential of cannabinoid-based medicines as an alternative to opioids for pain management is significant and of particular concern worldwide, as chronic pain is associated with more than $900B USD in healthcare costs per year. The use of deterrence technologies, particularly non-opioid alternatives, allows us to formulate and harness multiple delivery systems for cannabinoid-derived therapeutics in a safe manner while optimizing patient care. As more companies from Big Pharma begin to explore cannabinoid-based therapies, the industry will depend on abuse deterrent technology and nanotechnology to identify prescription-strength alternatives for healthcare providers and patients.
A: In 2019 at Charles River, we announced a strategic partnership with Atomwise, bringing their unique, structure-based artificial intelligence (AI) technology, based on convolutional neural networks for hit identification and optimization, to our partner projects.
The power of this technology is an exciting step forward for Charles River into the AI arena, as it opens up the opportunity to predict binding to protein targets for vast numbers of compounds, including synthesis-on-demand libraries, within a matter of days. Access to such large regions of chemical space becomes very important for those protein targets that are traditionally considered challenging for hit finding and highly competitive “hot targets” where access to novel chemical space is highly desired.
Thom is a biotechnology industry specialist with a key focus on filling technology designs for drug product and aseptic manufacturing. Through his leadership and technical expertise, he advances product pipelines by designing scalable solutions that reduce time and complexity in technology transfers and new product introductions. Thom has a strong working knowledge of the regulatory aspects of the FDA’s aseptic guidelines and EMEA Annex1-2 requirements.
Many of the change agents I have seen in 2019 are derived from changes in regulatory law, commercial downscaling, and impact from patent expiry strategies. The largest external regulatory change came from the issuance of the long-awaited EMEA Annex I, clarifying which technologies are required and acceptable, when and why.
The change in operational focus, from clinical scale-up to commercial scale-down, is enabling use of smaller, modular, flexible fillers with self-contained isolators. In parallel with the approval of biosimilars and biobetters, there is strong industry focus on individualized micro-batches, for CAR-T solutions and gene therapy products. The use of process automation and robotics have increased in all fill-finish unit operations. Widespread implementation of ready-to-use/ready-to-sterilize components and single-use (SUT) in upstream and downstream (SUS) through final fill designs have changed how facilities are planned, reducing plant size and changing warehouse space to accommodate densely packaged plastics goods.
Filling modalities have also been changing; bags that can be mated to lock-luer fittings with pre-sterilized needles and blow-fill-seal/form-fill-seal are re-emerging as processes that offer potential unit cost reduction. Traditional vial and syringe container designs are also changing as suppliers improve standardize offerings while having options including clear plastics.
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