Arvind Srivastava

Gene therapy has rapidly expanded conceptually and technically, now covering a wide array of tools and methods, including the advancement of viral vector delivery for gene therapies. Lentiviral vectors and adeno-associated virus (AAV) are two primary delivery mechanisms of gene therapies. While versatile and robust, there are some inherent weaknesses in the production of both AAV and lentivirus vectors, and, as a result, production is not well optimized. Over time, significant improvements have been developed to facilitate the manufacture of these viral vectors at each stage.

Addressing Developmental Challenges of Gene Therapy Viral Vectors

Pharmaceutical Technology’s Trends in Formulation eBook

Pharmaceutical Technology’s October 2022 Trends in Formulation

Ger Brophy, is the executive vice-president of Biopharma Production, Arvind Srivastava is a technical fellow, Bioprocessing, and Greg Swan is business development manager for Cell & Gene Therapy; all are at Avantor.

, October 2022
October 2022
Pages: 36–40

When referring to this article, please cite it as G. Brophy, A. Srivastava, and G.Swan, “Addressing Developmental Challenges of Gene Therapy Viral Vectors," 

Pharmaceutical Technology Trends in Formulation

Articles

Significant improvements have been developed to tackle the challenges in viral vector manufacturing at each stage.

Adeno-associated virus (AAV) has emerged as a leading platform for gene delivery for treating various diseases due to its excellent safety profile and efficient transduction to various target tissues. However, the large-scale production and long-term storage of viral vectors are not efficient, resulting in lower yields, moderate purity, and shorter shelf-life compared to recombinant protein therapeutics. The manufacturing of AAV includes several upstream, downstream, and fill/finish unit operations. Cell lysis is one of the key downstream unit operations, where the outer boundary or cell membrane is broken down or destroyed to release viral vector from the host cell. During cell lysis and separation of viral vector from cell debris, viral vectors are exposed to harsh shear stress that aggregates, unfolds, and precipitates virus. In this paper, the authors discuss a novel cell lysis solution that is efficient and generates low foam, making it easy to use. The novel solution also protects the viral vector from shear-induced damage during the manufacturing process, resulting in an improved viral vector titer. The solution is environmentally friendly and biodegradable.

Submitted: March 18, 2022
Accepted: March 31, 2022

Arvind Srivastava*, arvind.srivastava@avantorsciences.com, is technical fellow, research & development; Courtney O’Dell is senior scientist; Lori Fortin is senior research manager; Jonathan Fura is manager, research & development; William Connors is scientist, research-upstream processing; and Nandkumar Deorkar is vice-president, research & development; all are at Biopharma Production, Avantor. Michael Hill was formerly senior research scientist at Avantor.

*To whom all correspondence should be addressed.

When referring to this article, please cite it as A. Srivastava et al., “A Novel Cell Lysis Method to Improve the Viral Vector Manufacturing Process,” 

Researchers demonstrated a new cell lysis method using a novel solution to improve viral vector production.

A Novel Cell Lysis Method to Improve the Viral Vector Manufacturing Process

Subcutaneous (SC) injection is a method of administering medication as a bolus under the skin that is often used as an alternative delivery method for oral administration and now also for high-dose administration through intravenous (IV) infusion. SC injection provides flexibility in dosage form and options of self-administration outside of a health care setting. It may also help reduce drug cost and increase patient compliance. Biopharmaceuticals intended for delivery as SC injections are commonly formulated at an acidic pH with a variety of stabilizing agents and buffers, including histidine, phosphate, and citrate. In addition, SC injections are limited by a maximum injection volume of 2 mL or less per dose, making SC injection of monoclonal antibodies (mAbs) challenging. MAbs requires high dose; therefore, for SC injection it must be formulated at high concentration so the total injection volume remains within 2mL. An increase in protein concentration in the formulation increases the solution viscosity, which may cause increased injection-site pain in an SC dosage. The authors will discuss how formulations containing citrate compare to other buffers in reducing SC injection-site pain and discuss a formulation and excipients selection strategy that formulators can use to mitigate the risk of injection-site pain due to buffer, pH, and viscosity. 

	Submitted: Nov 18, 2019
	Accepted: Dec. 18, 2019

, arvind.srivastava@avantorsciences.com is technical fellow, and Ger Brophy, PhD, is executive vice-president, Biopharma Production; both are at Avantor. Meera Agarkhed was a senior manager, Technology & Innovation, at Avantor.

To whom all correspondence should be addressed.


	Vol. 44, No. 6
	June 2020
	Pages: 32–37

	When referring to this article, please cite it as A. Srivastava, et al., “Approaches to Alleviating Subcutaneous Injection-Site Pain for Citrate Formulations,” 

The authors compare formulations containing citrate with other buffers in reducing subcutaneous injection-site pain and discuss a formulation and excipients selection strategy.