Safeguarding Biopharmaceutical Production

The Importance of Bioproduction

Bioproduction is pivotal due to its efficiency and sustainability in producing complex biological products that would be challenging or impossible to manufacture through chemical synthesis. By using the natural pathways found in cell lines and microorganisms, or modifying these pathways through genetic engineering, researchers can synthesize various biological products that are essential across the food, textile, agricultural, energy, and pharmaceutical industries. These biological products have played an important role in our everyday lives by enhancing the nutritional value and safety of food,^1,2 dyeing textiles,³ boosting crop growth,⁴ creating renewable energy sources,⁵ and addressing health issues by preventing infections⁶ and treating diseases.^7,8

The production of biopharmaceuticals in particular has significantly contributed to advancements in modern medicine by offering solutions that conventional small-molecule drugs cannot achieve.⁹ For instance, the production of cell and gene therapies has enabled personalized treatments for diseases like cancer and sickle cell disease.^7,8 Another prominent example is the production of recombinant human insulin using microorganisms like Escherichia coli or Saccharomyces cerevisiae.⁹ These microbial expression systems enable large-scale, cost-effective, and consistent manufacturing of recombinant human insulin, thereby improving production capacity and reducing the need for harvesting insulin from animals.⁹

Challenges in Biopharmaceutical Production

Despite the advantages of biopharmaceuticals, the production of these therapeutics is not without challenges. The use of living systems opens the possibility of microbial contamination or the presence of host cell impurities, which can affect the quality and safety of the final product.^10,11 Microbial contaminants, for instance, can be introduced throughout the production process from sources like equipment, raw materials, water, process gases, and personnel.¹² The presence of these contaminants can then result in issues like product variability, loss of potency, and increased endotoxin levels, among others, which in turn can result in manufacturing delays, revenue loss, and potential drug shortages.¹² More importantly, microbial contamination poses a serious threat to consumers as it can cause adverse reactions or potentially death.¹³

Host cell impurities, such as residual DNA, are another concern in bioproduction. Residual DNA from the host cells used in the production process can remain in the final product; these impurities may be tumorigenic or infectious for the recipient.¹⁴ In response to these concerns, regulatory bodies like the United States Food & Drug Administration, European Medicines Agency, and World Health Organization have set criteria regarding the maximum amount of residual host DNA allowed in products.^15-17

The Role of Authenticated Reference Materials in Quality and Safety Testing

Comprehensive quality and safety testing is important for detecting and measuring microbial contamination or host cell impurities in biopharmaceutical products. To ensure the accuracy of these analyses, it is paramount that authenticated, high-quality reference materials are used when validating or calibrating test methods. For cell lines, authentication involves rigorous procedures such as short tandem repeat (STR) profiling, mycoplasma testing, cytochrome oxidase 1 barcoding, karyotyping, and isoenzyme analysis. These processes verify the identity, purity, and genetic integrity of the cell lines to prevent contamination or misidentification. For microorganisms, authentication includes detailed phenotypic analyses, genomic sequencing, proteomics analysis, and functional testing. These materials serve as standards to validate and calibrate testing methods, providing a reliable benchmark for comparison that helps ensure consistent and trustworthy results. 

How ATCC Can Help

ATCC provides a variety of rigorously authenticated quality control strains and analytical reference materials that support quality and safety testing.

• Quality control testing – Our portfolio includes numerous high-quality microbial strains cited as test strains in United States Pharmacopeia (USP) general chapters. The latest addition to this collection includes our new precisely quantitated MicroQuant™ controls and panels, which support USP <51> and <61>. These innovative products were developed using a novel cryopreservation technology to provide our best-in-class microbial controls in the form of stable, rapidly rehydrating pellets that deliver consistent quantitation and accurate, reproducible results—addressing the key challenges faced by microbial testing laboratories.
• Mycoplasma testing – To simplify your testing needs, ATCC offers a Universal Mycoplasma Detection Kit that includes the components and protocols you need to detect over 60 species of mycoplasma. We also provide titered reference strains and quantitative DNA certified reference materials for you to build and validate your own assay in addition to the quality control strains cited in USP <63>.
• Residual host cell DNA testing – We have formed a strategic collaboration with USP to develop a comprehensive set of highly characterized and pure genomic DNA analytical reference materials for validating the performance of molecular assays designed to detect and measure residual host cell genomic DNA. These high-quality reference materials are derived from authenticated host cell lines commonly used in the production of vaccines and biologics, and they were manufactured, evaluated, and quantitated using robust processes.

In addition to these important materials, ATCC also provides a robust portfolio of resources that support various areas of bioproduction. For instance, we provide an expanding collection of commonly used bioproduction cell lines for the manufacture of viruses and proteins, including STAT 1 and BAX knockout cell lines for enhanced virus production. We also provide CAR-T target luciferase reporter cells to support cell therapy development as well as highly characterized viral reference materials for determining the dose and potency of gene therapy products. Furthermore, ATCC delivers a variety of microbial strains that support the production of antibiotics, organic acids, biofuels, and pigments. Complementing these offerings, ATCC delivers reference-quality omics data through the ATCC Genome Portal and ATCC Cell Line Land. The ATCC Genome Portal provides whole-genome sequencing data for authenticated ATCC microorganisms, while ATCC Cell Line Land offers RNA-seq and whole-exome sequencing data for human and mouse cell lines. These platforms support research, product development, and quality assurance workflows by providing scientists with access to high-quality, reference-grade data essential for advancing bioproduction applications.

Overall, bioproduction has undeniably revolutionized industries and modern medicine by offering innovative solutions for producing essential biological products. From enhancing everyday life to addressing health challenges, its impact is widespread and transformative. However, reliance on living systems demands vigilant safety and quality measures to mitigate risks like microbial contamination or host cell impurities. As bioproduction continues to evolve, the continual use of authenticated reference materials during quality and safety testing will remain essential for ensuring the production of high-quality, safe, and effective biological products.

Did you know?

ATCC Microquant™ controls are available in high-titer (10⁷ to 10⁸ CFU per pellet) and low-titer (100 to 1,000 CFU per pellet; 10 assays) formats to meet USP General Chapter requirements.

References

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8. US Food & Drug Administration. FDA Approves First Gene Therapies to Treat Patients with Sickle Cell Disease. FDA News Release: December 08, 2023. Available online: https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patients-sickle-cell-disease.
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