Leaders in Pharmaceutical Business Intelligence (LPBI) Group

FDA Cellular & Gene Therapy Guidances: Implications for CRSPR/Cas9 Trials

Reporter: Stephen J. Williams, PhD

The recent announcement by Editas CEO Katrine Bosley to pursue a CRSPR/Cas9 gene therapy trial to correct defects in an yet to be disclosed gene to treat one form of a rare eye disease called Leber congenital amaurosis (multiple mutant genes have been linked to the disease) have put an interesting emphasis on the need for a regulatory framework to initiate these trials. Indeed at the 2015 EmTechMIT Conference Editas CEO Katrine Bosley had mentioned this particular issue: the need for discourse with FDA and regulatory bodies to establish guidelines for design of clinical trials using the CRSPR gene editing tool.

See the LIVE NOTES from Editas CEO Katrine Bosley on using CRSPR as a gene therapy from the 2015 EmTechMIT Conference at http://pharmaceuticalintelligence.com/2015/11/03/live-1132015-130pm-the-15th-annual-emtech-mit-mit-media-lab-top-10-breakthrough-technologies-2015-innovators-under-35/

To this effect, I have listed below, the multiple FDA Guidance Documents surrounding gene therapy to show that, in the past year, the FDA has shown great commitment to devise a regulatory framework for this therapeutic area.

Cellular & Gene Therapy Guidance Documents

• Homologous Use of Human Cells, Tissue, and Cellular and Tissue-Based Products; Draft guidance for Industry and FDA Staff (PDF – 120KB)
  10/2015
• Recommendations for Microbial Vectors Used for Gene Therapy; Draft Guidance for Industry (PDF – 447KB)
  10/2015
• Design and Analysis of Shedding Studies for Virus or Bacteria-Based Gene Therapy and Oncolytic Products; Guidance for Industry (PDF – 120KB)
  8/2015
• Considerations for the Design of Early-Phase Clinical Trials of Cellular and Gene Therapy Products; Guidance for Industry (PDF – 313KB)
  6/2015
• Determining the Need for and Content of Environmental Assessments for Gene Therapies, Vectored Vaccines, and Related Recombinant Viral or Microbial Products; Guidance for Industry
  3/2015
• Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) from Adipose Tissue: Regulatory Considerations; Draft Guidance for Industry
  12/2014. For more information, please refer to footnote 1 in the 2015 GUIDANCE AGENDA under RESOURCES FOR YOU.
• Minimal Manipulation of Human Cells, Tissues, and Cellular and Tissue-Based Products: Draft Guidance for Industry and Food and Drug Administration Staff
  12/2014. When finalized, this guidance will supersede the FDA guidance entitled, “Minimal Manipulation of Structural Tissue Jurisdictional Update,” September 2006. Please refer to footnote 1 in the 2015 GUIDANCE AGENDA under RESOURCES FOR YOU.
• Draft Guidance for Industry: Same Surgical Procedure Exception under 21 CFR 1271.15(b): Questions and Answers Regarding the Scope of the Exception
  10/2014. For more information, please refer to footnote 1 in the 2015 GUIDANCE AGENDA under RESOURCES FOR YOU.
• Guidance for Industry: BLA for Minimally Manipulated, Unrelated Allogeneic Placental/Umbilical Cord Blood Intended for Hematopoietic and Immunologic Reconstitution in Patients with Disorders Affecting the Hematopoietic System (PDF – 385KB)
  3/2014. (This guidance finalizes the draft guidance of the same title dated June 2013.)
• Guidance for Industry and FDA Staff: IND Applications for Minimally Manipulated, Unrelated Allogeneic Placental/Umbilical Cord Blood Intended for Hematopoietic and Immunologic Reconstitution in Patients with Disorders Affecting the Hematopoietic System
  3/2014. (This guidance finalizes the draft guidance of the same title dated June 2013.)
• Guidance for Industry: Preclinical Assessment of Investigational Cellular and Gene Therapy Products
  November 2013. (This guidance finalizes the draft guidance entitled “Guidance for Industry: Preclinical Assessment of Investigational Cellular and Gene Therapy Products” dated November 2012)
• Guidance for Industry: Preparation of IDEs and INDs for Products Intended to Repair or Replace Knee Cartilage (PDF – 157KB)
  12/2011. (This guidance finalizes the draft guidance of the same title dated July 2007.)
• Guidance for Industry: Clinical Considerations for Therapeutic Cancer Vaccines (PDF – 75KB)
  10/2011. (This guidance finalizes the draft guidance of the same title dated September 2009.)
• Guidance for Industry and FDA Staff: Investigational New Drug Applications for Minimally Manipulated, Unrelated Allogeneic Placental/Umbilical Cord Blood Intended for Hematopoietic Reconstitution for Specified Indications. (PDF – 104KB)
  6/2011
• Guidance for Industry: Potency Tests for Cellular and Gene Therapy Products (PDF – 311KB)
  1/2011. (This guidance finalizes the draft document of the same name, dated October 2008.)
• Guidance for Industry: Cellular Therapy for Cardiac Disease
  10/2010. (This guidance finalizes the draft guidance entitled “Guidance for Industry: Somatic Cell Therapy for Cardiac Disease” dated March 2009 (April 2, 2009, 74 FR 14992).
• Draft Guidance for Industry: Assay Development for Immunogenicity Testing of Therapeutic Proteins (PDF – 161KB)
  12/2009
• Guidance for Industry – Minimally Manipulated, Unrelated Allogeneic Placental/Umbilical Cord Blood Intended for Hematopoietic Reconstitution for Specified Indications (PDF – 462KB)
  10/2009
• Guidance for Industry: Considerations for Allogeneic Pancreatic Islet Cell Products
  9/2009
• Guidance for FDA Reviewers and Sponsors: Content and Review of Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs)
  4/2008
• Guidance for FDA Reviewers and Sponsors: Content and Review of Chemistry, Manufacturing, and Control (CMC) Information for Human Somatic Cell Therapy Investigational New Drug Applications (INDs)
  4/2008
• Guidance for Industry: Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products
  8/2007
• Guidance for Industry: Gene Therapy Clinical Trials – Observing Subjects for Delayed Adverse Events
  11/2006
• Guidance for Industry: Supplemental Guidance on Testing for Replication Competent Retrovirus in Retroviral Vector Based Gene Therapy Products and During Follow-up of Patients in Clinical Trials Using Retroviral Vectors
  11/2006
• Guidance for Industry: Guidance for Human Somatic Cell Therapy and Gene Therapy
  3/1998

Withdrawn Guidance Documents

• Withdrawn – Draft Guidance for Industry: Validation of Growth-Based Rapid Microbiological Methods for Sterility Testing of Cellular and Gene Therapy Products
  May 2015

Three other posts on this site goes into detail into three of the above-mentioned Guidance Documents

FDA Guidance on Use of Xenotransplanted Products in Human: Implications in 3D Printing

New FDA Draft Guidance On Homologous Use of Human Cells, Tissues, and Cellular and Tissue-Based Products – Implications for 3D BioPrinting of Regenerative Tissue

FDA Guidance Documents Update Nov. 2015 on Devices, Animal Studies, Gene Therapy, Liposomes