The Food and Drug Administration issued two final guidance documents (one for BLAs and one for INDs) for hematopoietic progenitor cells (HPC) sourced from umbilical/placental cord blood. These guidance documents finalize draft versions dated June 2013 of the same title, and supersede similarly titled final guidance documents published in 2009 and 2011, respectively.
Effective Oct. 20, 2011, minimally manipulated HPC, Cord Blood for unrelated allogeneic use requires a BLA prior to being marketed, or must be distributed under an IND. The FDA has published two guidance documents, "Minimally Manipulated, Unrelated Allogeneic Placental/Umbilical Cord Blood Intended for Hematopoietic Reconstitution for Specified Indications," October 2009; and, " Investigational New Drug Applications for Minimally Manipulated, Unrelated Allogeneic Placental/Umbilical Cord Blood Intended for Hematopoietic Reconstitution for Specified Indications," June 2011, to assist by providing recommendations to meet the regulatory requirements for BLAs and INDs, respectively.
In June 2013, FDA updated the aforementioned guidance documents and issued draft versions for public comment.
FDA published final versions of both the BLA and IND guidance documents in Mar. 2014. In large part, the revisions proposed in the 2013 BLA draft guidance of were incorporated into the final guidance for industry. The final Mar. 2014 guidance is titled "Biologics License Applications for Minimally Manipulated, Unrelated Allogeneic Placental/Umbilical Cord Blood Intended for Hematopoietic and Immunologic Reconstitution in Patients With Disorders Affecting the Hematopoietic System." The revisions include an expansion of the indications for use of HPC, Cord Blood which were previously limited to hematopoietic reconstitution for specific diseases in the 2009 BLA guidance. FDA's "reexamination of the legacy docket data" and "consideration of the proceedings of the 2011 meeting of the Cellular, Tissue and Gene Therapies Advisory Committee" led to the expansion of the list of included indications. Additionally, the guidance clarified the types of clinical information that should be submitted in the BLA, and includes applicable references to guidance documents on process and methods validation. The term HPC-C is also replaced with HPC, Cord Blood, which is the proper name and International Standard for Blood and Transplant 128-compliant term.
Similarly, FDA finalized a related guidance document titled "Investigational New Drug Applications for Minimally Manipulated, Unrelated Allogeneic Placental/Umbilical Cord Blood Intended for Hematopoietic and Immunologic Reconstitution in Patients With Disorders Affecting the Hematopoietic System." The guidance documents provide recommendations to assist establishments in obtaining submitting INDs when HPC, Cord Blood units do not meet the criteria to be distributed under an approved BLA.
Tabular summaries of significant changes from 2009 BLA guidance and 2011 IND guidance to their respective 2014 versions are provided below.
Category / Section (Section Number) | 2009 FINAL Guidance | |
Title | “Guidance for Industry - Minimally Manipulated, Unrelated Allogeneic Placental/Umbilical Cord Blood Intended for Hematopoietic Reconstitution for Specified Indications” | “Guidance for Industry: Biologics License Applications for Minimally Manipulated, Unrelated Allogeneic Placental/Umbilical Cord Blood Intended for Hematopoietic and Immunologic Reconstitution in Patients with Disorders Affecting the Hematopoietic System” |
Nomenclature
| Used the term “HPC-C” | Uses the term “HPC, Cord Blood” |
Indication (Section II.A) | “Intended for hematopoietic reconstitution in patients with any of the following diseases:
| “Intended for use in unrelated donor hematopoietic progenitor cell transplantation procedures in conjunction with an appropriate preparative regimen for hematopoietic and immunologic reconstitution in patients with disorders affecting the hematopoietic system that are inherited, acquired, or result from myeloablative treatment.” |
Clinical Outcome Data (Section VIII.A) | -- | Added the statement “Examples of product-related clinical outcomes include graft failure or delayed engraftment, infusion reactions, and transmission of infections.” |
Footnote in Validation Section (Section V.D.2)* | You may find additional information on comparability in the following publications:
| You may find additional information on process validation in the FDA guidance entitled, “Guidance for Industry: Process Validation: General Principles and Practices” dated January 2011 (January 25, 2011, 76 FR 4360) |
References
| -- | Added the following reference: |
* Web addresses provided in the guidance documents are not duplicated in the table.
Category / Section (Section Number) | 2011 FINAL Guidance | 2014 FINAL Guidance |
Title | “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” | “Guidance for Industry and FDA Staff: Investigational New Drug Applications for Minimally Manipulated, Unrelated Allogeneic Placental/Umbilical Cord Blood Intended for Hematopoietic and Immunologic Reconstitution in Patients with Disorders Affecting the Hematopoietic System” |
Nomenclature
| Used the term “HPC-C” | Uses the term “HPC, Cord Blood” |
Minimal Information to be Included in the IND (Table A.B and subsequent text) | “We intend to exercise enforcement discretion with respect to the requirement for a table of contents for a request for treatment of a single patient as such requests are expected to be brief. All other applications must include a table of contents” | “All applications must include a table of contents; we expect that a table of contents for requests for treatment of a single patient will be brief.” |
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