Most of us in the pharmaceutical industry have heard the phrase “targeted therapy”. Targeted therapies are drugs or other substances specifically designed to prevent cancer cells from dividing or destroying them directly, and are intended to target only cancer cells. While standard chemotherapy may affect all cells in the body (including healthy, non-cancerous tissue), targeted therapy uses drugs or other specially created substances (e.g., custom designed proteins) to specifically target cancer cells alleviating the side effects often accompanying standard chemotherapy. The FDA has approved several targeted therapies for use in cancer treatment, including hormone therapies, immunotherapies, angiogenesis inhibitors, and toxin delivery complexes.
A new addition to the targeted therapy arsenal has gained much attention recently. CRISPR (Clustered Regularly Interspaced Palindromic Repeats) is a molecular tool that is essentially a DNA code reader. Scientists can customize and engineer a CRISPR complex to find a target DNA sequence of interest (i.e., causing disease, or resulting in a protein structural malfunction). Once introduced into a cell and the offending DNA target is located, an enzyme associated with CRISPR complex precisely removes the unwanted DNA. The CRISPR complex can carry and incorporate a corrected segment of the excised “bad” DNA, then normal cell division machinery begins to produce cells that are no longer defective.
Using CRISPR, the possibilities to develop products to treat varied health conditions outside of cancer are numerous, exciting, and within technical reach. For the FDA and the healthcare industry, there are complicated considerations, including the ethical, and social implications of the CRISPR “gene editing” technologies.
Currently, there are no FDA approved human health products using CRISPR based technology. However, the US National Institutes of Health (NIH) have recently approved a proposal to use CRISPR in a cancer therapy regime (Dent, S. (2016). CRISPR gene-editing approved for first human trials.). For the FDA, the regulating entity would be the FDA’s Center for Biologics Evaluation and Research (CBER). Immunology and virology concepts are the key knowledge prerequisites required to help answer the questions associated with the development of a safe and efficacious manufacturing process. One critical requirement will be to recognize and eliminate any off-target effects that may accompany inaccurate editing of the gene. Consistent with the current regulations, the manufacturer will need to prove that they can produce the product in a safe manner with the intended effect. The FDA will be predictably cautious in its approval for this class of compounds. For the manufacturer, early and frequent communication should lead to the path of common understanding and potential acceptance. For the patients, this is potentially a paradigm shift in available treatment options and has been a long time coming, since the publication of the NIH Guidelines governing experiments using recombinant DNA.