Revision of USP Chapter <1047> on Gene Therapy Medicinal Products

The USP Chapter <1047> on gene therapy medicinal products has been valid in its current version since November 2020. With the further development of other guidance documents and pharmacopoeia chapters, it appears that a revision of these chapters, at least in part, has also become necessary.

Objectives of the Chapter

Gene therapy products enable the targeted modification of the genetic material of cells through the application of nucleic acids. They are divided into three main categories based on the delivery method: viral vectors, which carry genes but do not self-replicate; naked DNA; and nucleic acids combined with agents such as liposomes to improve cell penetration. When the nucleic acid is introduced into cells ex vivo, the treated cell population forms the gene therapy product. Specific guidelines for the production and processing of these cell-based products can be found in "Cell-based advanced therapies and tissue-based products".

The choice of a suitable gene vector is often complex and requires careful consideration. Commonly used viruses are murine retroviruses, human adenoviruses and adeno-associated viruses (AAVs). In this context, gene therapy is defined by the transduction of nucleic acids, which leads to the expression of RNA and subsequently proteins. Examples of different gene therapy strategies include gene replacement, direct cell elimination and immunotherapy.

This chapter covers the clinical applications, manufacturing processes and analytical methods of gene therapy products, which are constantly evolving. Both commercial products and materials for clinical trials are discussed. Reference is made to applicable guidelines such as the International Council for Harmonization (ICH) quality guidelines. The chapter is comprehensive and takes into account the different requirements and processes involved in the manufacture of gene therapy products. It is divided into two main parts: general aspects of manufacturing and process development and specific topics such as vector design. The handling and application of the products in the clinic requires specialized facilities and knowledge. Additional sections deal with analytical methods, stability, storage, shipping and labeling. A glossary explains the terms and abbreviations used.

Points included in amendment proposal

The current amendment proposals include, for example, the following points:

• Delete the reference to "Safety Tests-Biologicals" in "Biological Reactivity Tests, in vivo" from the chapter
• Delete the Safety Tests-Biologicals section from Chapter <88>, as the corresponding FDA Code of Federal Regulations, 21 CFR §610.11, was revoked on August 3, 2015.
• In addition, some formal and editorial changes.

A detailed description of the Chapter and the current amendment proposals can be found on the USP website after prior registration.