Ger Brophy

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

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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

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

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.