How can biopharmaceutical production be optimized for rare diseases?

Rare diseases are often neglected by the mainstream pharmaceutical industry, as they affect a small number of patients and require specialized and costly treatments. Biopharmaceuticals, which are drugs derived from living organisms or their components, offer a promising alternative for developing therapies for rare diseases, as they can target specific molecular mechanisms and modulate the immune system. However, biopharmaceutical production also faces many challenges, such as low yield, high variability, and complex quality control. In this article, you will learn how biopharmaceutical production can be optimized for rare diseases, using some of the latest technologies and strategies.

1 Cell line engineering

One of the key factors that determines the quality and quantity of biopharmaceuticals is the choice and engineering of the cell line that produces them. Cell lines are cultures of cells that can be grown in the laboratory and manipulated to express the desired protein or antibody. For rare diseases, cell line engineering can help to improve the stability, productivity, and specificity of the biopharmaceuticals, as well as to reduce the risk of contamination and immunogenicity. Some of the techniques that can be used for cell line engineering are gene editing, such as CRISPR-Cas9, which can introduce precise modifications in the genome; and synthetic biology, which can create novel genetic circuits and pathways to enhance the functionality of the cells.

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2 Process optimization

Another important aspect of biopharmaceutical production is the optimization of the process parameters that affect the growth and expression of the cells. Process optimization involves finding the optimal conditions for the culture medium, temperature, pH, oxygen, nutrients, and other factors that influence the cell viability and productivity. For rare diseases, process optimization can help to increase the yield and quality of the biopharmaceuticals, as well as to reduce the cost and time of production. Some of the methods that can be used for process optimization are design of experiments, which can test multiple variables and interactions in a systematic way; and process analytical technology, which can monitor and control the process in real time using sensors and feedback loops.

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3 Product characterization

A crucial step in biopharmaceutical production is the characterization of the product, which involves analyzing its structure, function, purity, and safety. Product characterization is essential for ensuring the efficacy and safety of the biopharmaceuticals, as well as for complying with the regulatory standards and requirements. For rare diseases, product characterization can help to demonstrate the specificity and potency of the biopharmaceuticals, as well as to identify and quantify any impurities or contaminants that may affect their performance. Some of the techniques that can be used for product characterization are mass spectrometry, which can measure the molecular weight and composition of the product; and bioassays, which can evaluate the biological activity and immunogenicity of the product.

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Abyson Joseph, Ph.D.

Senior Scientist || Experienced Lead & Protein Chemist Specialized in Downstream Process Development || Vaccines || Biosimilars || Monoclonal Antibodies || Early stage development || Scale-Up || Tech-transfer | IISER-TVM
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In the landscape of biologic drug development, the meticulous management of in-process quality attributes (IPQAs) and critical process parameters (CPPs) play a pivotal role in ensuring the production of safe/efficacious therapeutic agents. IPQAs encompases characteristics that are monitored and controlled throughout various stages of bioprocessing. The monitoring of these attributes enables real-time assessment of the production process,allowing timely adjustments to optimize product quality. Concurrently, CPPs represent the variables that have a direct impact on the critical quality attributes (CQAs) of the final biologic product. These parameters must be precisely controlled to ensure consistency and reproducibility in bioproduction.

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4 Quality by design

A holistic approach to biopharmaceutical production is the quality by design (QbD) concept, which aims to integrate quality into every stage of the development and manufacturing process, rather than relying on end-product testing. QbD involves identifying the critical quality attributes (CQAs) of the product, which are the properties that affect its safety and efficacy; and the critical process parameters (CPPs) of the process, which are the variables that influence the CQAs. For rare diseases, QbD can help to optimize the biopharmaceutical production by establishing a clear link between the product and the process, and by applying risk management and statistical tools to ensure the robustness and reliability of the outcomes. Some of the benefits of QbD are improved product quality, reduced variability, enhanced regulatory compliance, and increased efficiency and flexibility.

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5 Continuous manufacturing

A novel paradigm for biopharmaceutical production is the continuous manufacturing (CM) model, which involves running the process in a continuous or semi-continuous mode, rather than in discrete batches. CM can offer several advantages over batch manufacturing, such as higher productivity, lower cost, smaller footprint, and better quality. For rare diseases, CM can help to meet the demand and supply of biopharmaceuticals, as well as to enable faster and more responsive development and delivery. Some of the challenges of CM are the integration of the unit operations, the automation and control of the process, and the regulatory acceptance and validation of the system.

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6 Collaborative networks

A final element that can facilitate the optimization of biopharmaceutical production for rare diseases is the formation of collaborative networks among the various stakeholders involved in the field, such as researchers, developers, manufacturers, regulators, patients, and advocacy groups. Collaborative networks can help to share knowledge, resources, and best practices; to accelerate innovation and technology transfer; to harmonize standards and regulations; and to enhance patient access and engagement. Some of the platforms that can support collaborative networks are consortia, such as the International Rare Diseases Research Consortium (IRDiRC), which coordinates global research efforts on rare diseases; and public-private partnerships, such as the Innovative Medicines Initiative (IMI), which fosters collaboration between the European Union and the pharmaceutical industry.

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Manikanta K, M.Pharm.

Senior Manager | Regulatory Expert with 14+ Years' Experience | Driving Successful Approvals & Market Access for Pharmaceuticals | Lectiophile 📚
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In optimizing biopharmaceutical production for rare diseases, collaborative networks emerge as catalysts for innovation and efficiency. A prime illustration is the synergy between Shire Pharmaceuticals and Sangamo Therapeutics, jointly propelling gene therapy advancements for rare conditions. Similarly, the Critical Path Institute's Consortium spearheads collaborative efforts, transcending organizational boundaries to streamline regulatory pathways and foster breakthroughs. These networks, akin to symphonies of expertise, not only accelerate research but redefine treatment landscapes.

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7 Here’s what else to consider

This is a space to share examples, stories, or insights that don’t fit into any of the previous sections. What else would you like to add?

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Avishek Basu

Global Manager (Pharma) | "Views are my own"
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Modern drug development of rare biologicals are targeted therapeutics with very specific indication profile. This reduces the size of the patient population subset, and in turn shrinks the market potential. The industry needs more small/ mid sized CMOs, who are specialised to cater to that kind of batch size demand. Big Pharma usually drop such projects due to small revenue opportunity and the unmet need persists.

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How can biopharmaceutical production be optimized for rare diseases?

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1 Cell line engineering

2 Process optimization

3 Product characterization

4 Quality by design

5 Continuous manufacturing

6 Collaborative networks

7 Here’s what else to consider

Biotechnology

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