USP 1047

Gene Therapy Products: Targeted treatment at the source

The United States Pharmacopeia (USP) information chapter USP <1047> defines a gene therapy product as one involving the administration of nucleic acids to modify the genetic material of cells. Delivery of nucleic acids to cells can be accomplished in a few different ways:

  • Through the use of viral vectors
  • By administering nucleic acid in simple form (naked DNA)
  • By administering nucleic acids formulated with agents that increase their ability to penetrate the cell

Whichever method is used, the nucleic acid material introduced into cells can, depending on the specific therapy, either encourage expression of new genes or inhibit expression of already expressed genes and products. Examples of nucleic-acid-based gene therapy products include, among many others:

  • Growth factor vector used to treat cardiovascular disease
  • Factor VIII and IX vectors for hemophilia patients
  • Recombinant oncolytic virus therapy for killing of cancer cells
  • Gene-modified autologous lymphocytes for arthritis treatment

USP <1047> provides comprehensive discussion of how gene therapy products should be developed, manufactured and safety tested, along with recommended analytical methods for evaluating product quality. This document includes detailed guidance on:

  • Vector selection (backbone, promoter, therapeutic gene, polyadenylation signal)
  • Targeting considerations (viral host range, cell-surface receptors, immune-response barriers to cell transduction)
  • Preventing the use of recombination-capable cell lines and plasmids
  • Product contamination detection, either from outside sources or through unwanted nucleic acid variants
  • Use of well-defined decision-making criteria during manufacturing
  • Establishment of clear specifications for gene therapy products to ensure safety and efficacy of the product before use

Particularly key within the broad scope of USP <1047> are the document’s guidelines on analytical testing procedures for a final product. Table 1 below summarizes specific methods for determining accurate identity, dose, potency, purity and safety information that must be known before a gene therapy product can be made available for patient administration.

USP <1047> addresses the need for stability testing as well, to ensure that the potency and purity of the gene therapy product are maintained throughout packaging, shipping and storage.


Reference 

Potts, Ph.D., Rebecca. “Standards and Best Practices for Cell, Gene and Tissue-Based Therapies.” CASSS Sharing Science Solutions, https://www.casss.org/resource/resmgr/cmc_no_am_jul_spkr_slds/2017_CMCS_PottsRebecca.pdf.