1. INTRODUCTION
Plasmids are double-stranded, circular DNA biological molecules that can be used as starting materials during the manufacture of cell and gene therapy (CGT) products, including linearization and subsequent translation for mRNA drug production. The goal of this general chapter is to describe considerations for the manufacture and release of plasmids for use as starting materials in the production of CGT products.
These considerations include:
Manufacturing considerations
Quality and risk management
DNA plasmid starting material quality
Plasmid material intended for use as a starting material in the manufacture of CGT products may be described as manufactured in compliance with good manufacturing practices (GMPs) or other statements such as clinical grade, pharmaceutical grade, etc. These terms imply that the plasmid material is appropriate for use in the manufacture of CGT products intended for humans or veterinary medicinal products. Such statements are not applied consistently among plasmid manufacturers since established quality standards for plasmids used in CGT products do not exist. Because these materials are used to introduce a recombinant nucleic acid sequence into a CGT product (or may be present as a residual in CGT products), it is essential that these plasmids have robust quality control. Therefore, it is incumbent upon the end user, who is using the plasmid to manufacture a CGT product, to conduct a quality audit of the supplier of the plasmid to document the level of compliance with quality standards and in conjunction with other objective evidence, such as test results, to establish whether the plasmid supplier meets the quality systems requirements of a CGT manufacturer.
2. SCOPE
Given the diverse uses of plasmid DNA in CGT drug development, the scope of this chapter is to discuss plasmids that are used as starting materials. Table 1 lists terminologies often used to describe plasmids used in CGT products and describes which uses are considered in or out of scope for this chapter. In general, plasmids used as a starting material for the manufacture of gene therapies, including genetically modified cells, are in scope. Plasmids that are used as a drug substance or drug product, or plasmids used in protein production are out of scope as these uses of plasmid are described elsewhere in other guidance or best practice documents, for example, the FDA guidance for industry, Considerations for Plasmid DNA Vaccines for Infectious Disease Indications (1), ICH Q5B (2), Gene Therapy Products 〈1047〉, Quality of Biotechnological Products: Analysis of the Expression Construct in Cells Used for Production of r-DNA Derived Protein Products 〈1048〉, and European Pharmacopeia (Ph. Eur.) 5.14 (3).
Source from USP and Please refer to USP for details:
Polymer Vial for cell and gene therapies
Copyright © Shijiazhuang Xinfuda Medical Packaging Co., Ltd. All Rights
MAKE AN ENQUIRY
