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Tips from the Bench: Ancillary Materials for Cell, Gene, and Tissue-Engineered Therapies

Commitment to Quality

Mirus has delivered comprehensive, high-performance transfection reagents to the life science research market since 1995. Our commitment to quality is integral to our brand and your success. With our VirusGEN® family of products for recombinant AAV and lentivirus production [TransIT-VirusGEN® Transfection Reagent (2017), TransIT-VirusGEN® SELECT Transfection Reagent (2019) and TransIT-VirusGEN® GMP Transfection Reagent, (anticipated Q1 2021), Mirus is dedicated to ensuring that customers developing gene and cell therapies can rely on us for transfection reagents of exceptional quality from early stages of research and development through clinical trials and commercial manufacturing.

What are Ancillary Materials?

Ancillary materials (AMs), also called raw materials in Europe, are components, reagents, and materials used for the manufacture of cell, gene, and tissue-engineered (CGT) therapies but that are not intended to be present in the final product formulation. AMs include, but are not limited to, cell culture reagents and additives (e.g. transfection reagents and antibiotics), cryopreservation agents, and disposables such as plasticware and bioprocessing bags. Although ancillary materials are not intended to be present in the final CGT product, their presence in the manufacturing process may affect its safety, efficacy, stability and consistency. Therefore, it is critical for CGT therapy manufacturers to carefully define the selection criteria and the subsequent qualification program for AMs.

Qualification Categories

The rapidly changing landscape of CGT therapeutics places a critical focus on the selection and quality of AMs used from development through commercialization. A significant challenge faced by CGT product manufacturers is a lack of global AM-specific regulations that explicitly define the regulatory and quality requirements for AMs. Additionally, the diversity of AMs, many of which have unique or complex characteristics, makes it difficult to have a universal qualification program that applies to all AMs. As a result, the burden falls on the CGT therapy manufacturer to develop a comprehensive qualification program.

Chapter <1043> of the United States Pharmacopeia (USP) provides guidance for AM selection and qualification by categorizing materials into four tiers from low to high risk (Figure 1). Depending on where an AM falls within these categories, different degrees of qualification may be required that involve the acquisition and evaluation of data demonstrating the source, identity, purity safety and suitability for use in the manufacture of CGT products. A comprehensive qualification program for AMs used in CGT product manufacturing should evaluate each of the following areas: (1) identification; (2) selection and suitability for use in manufacturing; (3) characterization; (4) vendor qualification and (5) quality assurance and control. For more information on developing a qualification program, consult USP <1043>. Additional guidance on ancillary material best practices can be found in ISO/TS 20399:2018, Parts 1-3.

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Ancillary Material Risk Tiers per USP <1043>

Figure 1. Ancillary Material Risk Tiers Outlined in USP <1043>: Ancillary Materials for Cell, Gene and Tissue-Engineered Products. Transfection reagents generally fall in Tiers 2-4 depending on whether they are cGMP or research grade material. 

Research vs. cGMP Grade Ancillary Materials

Although USP chapter <1043> and ISO 20399-1:2018(E) offer guidance for AMs used in CGT products, in the United States there is not a set of defined regulations that outlines the grade of AM that is required for development through manufacture of CGT therapies. Ultimately, the it is the responsibility of the CGT product manufacturer to select the quality of AM used from development through manufacture. CGT product manufactures may have the option of sourcing research grade, intermediate grade, and/or AMs manufactured under Current Good Manufacturing Practices (cGMP). In early phase discovery and development, it may be deemed acceptable to assume higher risk and use research grade AMs that have lower requirements for quality testing and documentation. As development progresses into preclinical and early phase clinical trials, a CGT manufacturer may select intermediate grade AMs that are produced using additional manufacturing and testing processes that are included on the product quality documentation. In late phase clinical trials and commercial manufacturing, cGMP grade AMs are preferred (when available) to reduce risk, by ensuring the that AMs are traceable, safe, pure and effective.

It is important to note that transitioning from research to cGMP grade materials requires optimization and validation to ensure processes and performance are equivalent. This testing can result in significant cost; therefore, a CGT product manufacturer may choose to use cGMP AMs from development through manufacture to reduce overall risk associated with therapeutic development and commercialization. Alternatively, consistent performance can also be ensured by utilizing AMs that are identical in formulation across multiple product grades, allowing the CGT manufacturer to choose the appropriate grade for the development phase.

Working with Mirus as Your Ancillary Material Supplier

The CGT product manufacturer is responsible for qualifying an AM to ensure it meets the requirements outlined by regulatory agencies regardless of AM labeling claims because a given AM’s label may or may not reflect is intended use in CGT product development. When you establish a close partnership with Mirus early in your development process, we can assist you in multiple ways throughout qualification, including quality documentation and exceptional technical support to streamline your workflow.

Quality Transfection Reagents from Mirus

Mirus provides high quality transfection reagents that enable high titer AAV and lentivirus production from discovery to clinic. The TransIT-VirusGEN® product family includes TransIT-VirusGEN® Transfection Reagent, TransIT-VirusGEN® SELECT Transfection Reagent and TransIT-VirusGEN® GMP Transfection Reagent (anticipated Q1 2021).

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VirusGEN Product Family with USP <1043> Risk Tiers

Figure 2. TransIT-VirusGEN® Product Family Characteristics.

References

  1. USP <1043> Ancillary Materials for Cell, Gene and Tissue Engineered Products; 2013.
  2. ISO/TS 20399-1:2018(E). Biotechnology – Ancillary materials present during the production of cellular therapeutic products – Part 1: General requirements.
  3. ISO/TS 20399-3:2018(E). Biotechnology – Ancillary materials present during the production of cellular therapeutic products – Part 3: Best practice guidance for ancillary material users.
  4. Solomon (2016) Current perspectives on the use of ancillary materials for the manufacture of cellular therapies. Cytotherapy. 41, 18. PMID: 26596503.

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