For those close to the cell and gene therapy world, the term 'ancillary material' may be as familiar as 'DNA.' However, if you are navigating the regulatory landscape of cell and gene therapy manufacturing for the first time, understanding this terminology and its importance may be more of a challenge.
In this TransMission Transfection 101 we will cover:
- What Are Ancillary Materials (AMs)?
- Qualification Categories for AMs and Their Importance
- Working with Mirus as Your Ancillary Material Supplier
- Related References
What Are Ancillary Materials (AMs)?
Ancillary materials (AMs), also called 'raw materials' in Europe, are components that are used in manufacturing but not intended to be present in the final product formulation. In cell, gene and tissue-engineered (CGT) therapies, example AMs are tissue culture media and additives, disposables such as plasticware, cryopreservation agents and, notably, transfection reagents. Although AMs are not supposed to be present in the final CGT product, they can still affect critical quality attributes of the final CGT product. Therefore, it is important for CGT therapy manufacturers to carefully define the selection criteria and the subsequent qualification program for AMs.
Qualification Categories for AMs and Their Importance
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 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 best practices for AMs can be found in ISO/TS 20399:2018, Parts 1-3.
Although USP chapter <1043> and ISO 20399:2018(E) offer guidance for AMs used in CGT products, it is ultimately the responsibility of the CGT product manufacturer to select the appropriate source and vet the quality of AM used from R&D through clinical trials and commercial manufacturing. In early phase discovery and development, it may be deemed acceptable to assume higher risk and use AMs that have lower requirements for quality testing and documentation. As development progresses into the clinic and commercial manufacturing, a CGT product manufacturer may select AMs that are produced using more controlled manufacturing and testing processes to ensure traceability, safety, purity and efficacy. To further reduce risk, sourcing AMs that are produced under current Good Manufacturing Practice (cGMP) may be preferred.
It is important to note that switching AMs 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 AMs manufactured under cGMP throughout all phases of developing and manufacturing the therapeutic. 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. 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.
Contact Mirus Bio to learn how the TransIT-VirusGEN® product family can enable your CGT therapy program from bench to bedside.