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 
 
 
 
 
 
 
 
 
 
Additional copies of this guidance are available from the Office of Communication, Outreach 
and Development (OCOD), (HFM-40), 1401 Rockville Pike, Suite 200N, Rockville, MD 20852-
1448, or by calling 1-800-835-4709 or 301-827-1800, or e-mail ocod@fda.hhs.gov, or from the 
Internet at 
http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guida
nces/default.htm. 
 
For questions on the content of this guidance, contact OCOD at the phone numbers or e-mail 
address listed above. 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Biologics Evaluation and Research 
March 2014  Contains Nonbinding Recommendations 
 
Table of Contents 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 2 
III.  SCOPE OF THIS GUIDANCE ....................................................................................... 3 
IV.  SPONSORS AND INVESTIGATORS ........................................................................... 4 
V.  PREPARING INDS FOR CERTAIN HPC, CORD BLOOD UNITS ......................... 5 
VI.  ADDITIONAL INFORMATION .................................................................................. 11 
VII.  REFERENCE .................................................................................................................. 12 
i  Contains Nonbinding Recommendations 
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 
 
 
This guidance represents the Food and Drug Administrations (FDAs) current thinking on this 
topic.  It does not create or confer any rights for or on any person and does not operate to bind 
FDA or the public.  You can use an alternative approach if the approach satisfies the 
requirements of the applicable statutes and regulations.  If you want to discuss an alternative 
approach, contact the appropriate FDA staff.  If you cannot identify the appropriate FDA staff, 
call the appropriate number listed on the title page of this guidance. 
 
 
I.  INTRODUCTION 
 
We, the Center for Biologics Evaluation and Research (CBER), FDA, are providing advice to 
you, potential sponsors (e.g., cord blood banks, registries, transplant centers, or individual 
physicians serving as sponsor-investigators), to assist in the submission of an Investigational 
New Drug Application (IND) for certain hematopoietic progenitor cells from placental/umbilical 
cord blood (HPC, Cord Blood)1, when such HPC, Cord Blood units are not licensed in 
accordance with Title 21 of the Code of Federal Regulations Part 601 (21 CFR Part 601), and 
when a suitable human leukocyte antigen (HLA) matched cord blood transplant is needed for 
hematopoietic and immunologic reconstitution in patients with disorders affecting the 
hematopoietic system that are inherited, acquired, or result from myeloablative treatment and 
there is no satisfactory alternative treatment available.  If unlicensed HPC, Cord Blood units are 
made available for clinical use, they must be distributed under an IND meeting the applicable 
requirements in 21 CFR Part 312. 
 
This guidance finalizes the draft guidance of the same title dated June 2013, (78 FR 36194) and 
supersedes the guidance entitled Guidance for Industry and FDA Staff:  Investigational New 
Drug Applications (INDs) for Minimally Manipulated, Unrelated Allogeneic Placental/Umbilical 
Cord Blood Intended for Hematopoietic Reconstitution for Specified Indications dated June 
2011 (August 2, 2011, 76 FR 46303) (2011 IND guidance).  The changes from the 2011 IND 
guidance include replacing the term HPC-C with the term HPC, Cord Blood, which is the 
proper name for these products, expanding the clinical indication, and clarifying the applicability 
of the requirement for a table of contents in the IND submission.   
                                                 
1 For the purposes of this guidance, the term HPC, Cord Blood refers to the final drug product (cryopreserved or 
thawed) of minimally manipulated hematopoietic stem/progenitor cells from placental/umbilical cord blood, sourced 
from an unrelated allogeneic cord blood donor and intended for hematopoietic and immunologic reconstitution in 
patients with disorders affecting the hematopoietic system that are inherited, acquired, or result from myeloablative 
treatment. 
1  Contains Nonbinding Recommendations 
 
FDAs guidance documents, including this guidance, do not establish legally enforceable 
responsibilities.  Instead, guidances describe FDAs current thinking on a topic and should be 
viewed only as recommendations, unless specific regulatory or statutory requirements are cited.  
The use of the word should in FDAs guidances means that something is suggested or 
recommended, but not required. 
 
 
II.  BACKGROUND 
 
In the Federal Register notice dated January 17, 2007 (72 FR 1999), FDA announced the 
availability of the draft guidance for licensure of minimally manipulated cord blood entitled 
Guidance for Industry:  Minimally Manipulated, Unrelated, Allogeneic Placental/Umbilical 
Cord Blood Intended for Hematopoietic Reconstitution in Patients with Hematological 
Malignancies dated December 2006 (2006 draft licensure guidance).  FDA received comments 
on the 2006 draft licensure guidance, those comments were considered, and the guidance was 
finalized.   
 
In the Federal Register notice dated October 20, 2009 (74 FR 53753), FDA announced the 
availability of the finalized guidance entitled Guidance for Industry:  Minimally Manipulated, 
Unrelated Allogeneic Placental/Umbilical Cord Blood Intended for Hematopoietic 
Reconstitution for Specified Indications dated October 2009 (2009 licensure guidance).  The 
2009 licensure guidance provided recommendations to cord blood manufacturers applying for 
licensure of their HPC, Cord Blood units for specified indications.   
 
Some of the comments received by FDA on the 2006 draft licensure guidance expressed the 
importance of access and availability of HPC, Cord Blood units that do not meet standards for 
licensure and therefore cannot be licensed.  FDA acknowledged that there would be situations in 
which there will not be a licensed cord blood unit that provides an appropriate match for a 
patient and that an unlicensed cord blood unit may be the best match.  Because we recognized 
the importance of these products, we published the companion draft IND guidance in October 
2009 to address IND submissions for unlicensed HPC, Cord Blood.  FDA finalized the draft IND 
guidance in August 2011 (2011 IND guidance).   
 
In addition to issuing this guidance, which supersedes the 2011 IND guidance, we are also 
issuing a guidance which supersedes the 2009 licensure guidance, entitled 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 dated March 2014 (2014 licensure 
guidance).  As discussed therein, the 2014 licensure guidance expands the clinical indication that 
was in the 2009 licensure guidance and makes additional clarifying changes.  
 
The clinical indications contained in this guidance differ from the indications listed in the scope 
of the 2011 IND guidance and the 2009 licensure guidance.  This difference is a result of the 
Agencys re-examination of the legacy docket data and the Agencys consideration of the 
2  Contains Nonbinding Recommendations 
proceedings of the September 2011 meeting of the Cellular, Tissue, and Gene Therapies 
Advisory Committee (Ref. 1).   
 
 
III.  SCOPE OF THIS GUIDANCE 
 
This guidance document is applicable to certain unlicensed HPC, Cord Blood units that are made 
available for transplantation in cases when no satisfactory alternative treatments are available.  
Thus, this guidance applies to HPC, Cord Blood units that are: 
 
  Manipulated minimally; and 
  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.  
 
This guidance does not apply to the use of unlicensed HPC, Cord Blood for indications other 
than described above.  In addition, this guidance does not apply to any use of licensed HPC, 
Cord Blood.   
 
There are a variety of reasons why an HPC, Cord Blood unit may not be licensed.  For example, 
these reasons may include: 
 
  The HPC, Cord Blood unit does not meet the standards for licensure.  This could be 
the case for units that were placed in inventory either before or after the cord blood 
bank received a biologics license.  HPC, Cord Blood units that do not meet all 
licensure criteria may be banked or maintained to enhance diversity of HLA 
phenotypes of units in inventory to increase the likelihood that individuals with less 
common HLA types will be able to find suitably matched HPC, Cord Blood units for 
transplantation.  Examples of units that do not meet licensure criteria include: 
 
  HPC, Cord Blood unit with a cell dose smaller than the value of the licensed 
o
product; however, the smaller cell dose unit may be appropriate for use in 
some pediatric patients. 
  HPC, Cord Blood unit from an ineligible donor or from a donor who did not 
o
undergo complete screening and testing.  For example, in donors with a 
complete donor eligibility determination, an ineligible donor is one who has 
an identified risk factor or a reactive/positive test result.  In the event that the 
HPC, Cord Blood unit is from an ineligible donor, the HPC, Cord Blood unit 
may only be used if there is a documented urgent medical need as defined in 
21 CFR 1271.3(u) and the requirements described in 21 CFR 1271.65 are met.  
Similarly, an HPC, Cord Blood unit from a donor for whom the donor 
eligibility determination is not complete may only be used, if there is a 
documented urgent medical need as defined in 21 CFR 1271.3(u) and the 
requirements in 21 CFR 1271.60 are met.  
3  Contains Nonbinding Recommendations 
  HPC, Cord Blood units that are not comparable to licensed inventory.  For 
o
example, HPC, Cord Blood release criteria are different from those in the 
product license and insufficient information is available to demonstrate their 
comparability, e.g., lower total nucleated cell count (TNC), or the CD34+ cell 
count was not performed. 
  HPC, Cord Blood units that were manufactured prior to licensure that do not 
o
conform to current good manufacturing practices (CGMPs). 
 
  The HPC, Cord Blood unit was manufactured in a cord blood establishment that does 
not hold an approved Biologics License Application (BLA) for manufacturing HPC, 
Cord Blood units. 
 
  The HPC, Cord Blood unit is in a bank where a license application has not yet 
o
been submitted or is pending. 
  The HPC, Cord Blood unit is in a non-United States bank without a license 
o
and is listed in an international cord blood registry. 
 
 
IV.  SPONSORS AND INVESTIGATORS 
 
The HPC, Cord Blood units described in section III of this guidance, may be made available for 
clinical use when an IND is submitted to FDA and the IND goes into effect under  
21 CFR 312.40(b).  The individual or entity that submits an IND is considered a sponsor  
(21 CFR 312.3(b)).  The sponsor of the IND may be the manufacturer (generally a cord blood 
bank), a transplant center, or a national or international cord blood registry involved in 
coordinating the distribution of HPC, Cord Blood units from participating cord blood banks.   
 
A physician seeking to transplant an unlicensed HPC, Cord Blood unit may serve as an 
investigator under the IND, but a physician also can be a sponsor-investigator  
(21 CFR 312.3(b)).  A licensed physician under whose immediate direction an investigational 
drug is administered or dispensed is considered an investigator.  A licensed physician under 
whose immediate direction an investigational drug is administered or dispensed, and who also 
submits an IND as described in this guidance, is considered a sponsor-investigator, and must 
comply with the requirements applicable to a sponsor and investigator set forth in  
21 CFR Part 312 Subpart D to the extent they are applicable to the IND (21 CFR 312.3(b)).   
 
Sponsors are responsible for: 
 
  Submitting IND safety reports and annual reports (when the IND or protocol 
continues for one year or longer) to FDA as required by 21 CFR 312.32 and  
21 CFR 312.33.  
  Obtaining a curriculum vitae or other statement of qualifications of the licensed 
physician(s) in order to ensure that the physician is qualified to administer the 
investigational drug (21 CFR 312.53(c)(2)).  
  Providing licensed physicians who will be administering the investigational drug with 
an investigator brochure, as well as information about new observations, particularly 
4  Contains Nonbinding Recommendations 
with respect to adverse effects (21 CFR 312.55) in order to minimize the risk and 
maximize the potential benefits of the investigational drug.  (Note:  A sponsor-
investigator is not required to prepare an investigator brochure.) (21 CFR 312.55). 
  Maintaining an effective IND with respect to the investigations (as set forth in the 
IND regulations in 21 CFR 312.50). 
  Maintaining adequate drug disposition records, and other required records in a 
manner consistent with the requirements of 21 CFR 312.57. 
 
Investigators are responsible for: 
  
  Reporting adverse drug events to the sponsor (21 CFR 312.64(b)).  
  Ensuring that the informed consent requirements of 21 CFR Part 50 are met.  
  Ensuring that Institutional Review Board (IRB) review of the use of the HPC, Cord 
Blood units under the IND is obtained in a manner consistent with the requirements 
of 21 CFR Part 56.  
  Maintaining accurate case histories and drug disposition records and retaining records 
in a manner consistent with the requirements of 21 CFR 312.62. 
 
 
V.  PREPARING INDs FOR CERTAIN HPC, CORD BLOOD UNITS 
 
This guidance document outlines the minimum information that should be included in an IND 
for the HPC, Cord Blood units described in this guidance.  Sponsors who follow this guidance 
may choose to either submit one IND to cover the use of multiple cord blood units, or submit a 
separate IND for each single-patient use.  The general content and format of information to be 
included in the submission of an IND can be found in 21 CFR 312.23.  The minimal information 
that should be included in the IND for the HPC, Cord Blood units for which this guidance is 
applicable is summarized in Table A.  Note that the requirements listed in Table A are not meant 
to be an exhaustive list.  Additional regulatory requirements in 21 CFR Part 312 may be 
applicable.   
5  Contains Nonbinding Recommendations 
 
TABLE A:  MINIMAL INFORMATION TO BE INCLUDED IN THE IND2 
 
A. Cover Sheet 
Form FDA-1571 
(21 CFR 312.23(a)(1)) 
All applications must include a table of contents; 
B. Table of Contents 
we expect that a table of contents for requests for 
(21 CFR 312.23(a)(2)) 
treatment of a single patient will be brief. 
C. Introductory Statement  Description of intended use and reason(s) why 
(21 CFR 312.23(a)(3))  HPC, Cord Blood units cannot be licensed. 
D. Investigators Brochure 
Product description and instructions for use. 
(21 CFR 312.23(a)(5)) 
E. Protocol  Include treatment plan, safety monitoring, 
(21 CFR 312.23(a)(6))  outcomes assessment, safety reporting plan, and 
model consent form.  
F. Donor Eligibility  Include description of donor eligibility 
(21 CFR Part 1271 Subpart C)  determination. 
G. Manufacturing, Release Testing and  Summary of manufacturing information. 
Specifications 
Summary of product testing: 
(21 CFR 312.23(a)(7)) 
  Sterility (no evidence of contamination) 
  Total Nucleated Cell (TNC) count 
  Cell viability 
  HLA 
  ABO/Rh 
  Hemoglobin testing 
                                                 
2 The information in the right column reflects certain regulatory requirements and/or what FDA considers current 
best practices. 
6  Contains Nonbinding Recommendations 
H. Labeling  Container label and English language 
(21 CFR 312.23(a)(7), 21 CFR 1271.55,  supplemental labeling (if applicable) as described 
21 CFR 1271.60(d)(2), 21 CFR  in the regulations, including: 
1271.65(b)(2)) 
  Donor eligibility summary of records (for 
HPC, Cord Blood units manufactured on 
or after May 25, 2005) 
  Directions for use 
  Caution statement for IND use 
  Warning of communicable disease risk 
I. Pharmacology/Toxicology  It is unlikely that this requirement would be 
(21 CFR 312.23(a)(8))  applicable. 
J. Prior Human Experience  It is unlikely that this requirement would be 
(21 CFR 312.23(a)(9))  applicable. 
K. Charging for Investigational Drugs 
A request to charge, in accordance with the 
under an IND 
regulation, may be included. 
(21 CFR 312.8) 
 
A. Cover Sheet  The cover sheet must include:  the sponsors name, address, and telephone 
number; date of the application; commitment that an IRB will be responsible for review and 
approval of the study; name and title of the person responsible for monitoring the clinical 
investigation; and signature of the sponsor.  A Form FDA-1571 is used to convey this 
information, available at 
http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083533.pdf.  
 
B. Table of Contents  As indicated above, 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.   
 
C. Introductory Statement  The cover letter should plainly indicate that the IND is being 
submitted in accordance with this guidance.  The cover letter should also indicate the reason(s) 
why the HPC, Cord Blood unit(s) to be used cannot be licensed (see section III of this guidance 
for applicable indications).   
 
D. Investigators Brochure (IB)  An IB is required when the sponsor is distributing an HPC, 
Cord Blood unit to an investigator.  A sponsor-investigator is not required to prepare an IB.  The 
recommended format for an IB is outlined in Chapter 7 of the ICH E6 document Good Clinical 
Practice:  Consolidated Guidance dated April 1996, available at 
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
CM073122.pdf.  At a minimum, the IB must describe the product and its formulation (cell 
content and additives), and contain a description of possible risks.  Instructions for HPC, Cord 
7  Contains Nonbinding Recommendations 
Blood handling, thawing and administration, and instructions for reporting a serious adverse 
event related to the product should also be included. 
 
E. Protocol  A request to treat a single patient should include in the cover letter, or an 
additional separate document, the patients diagnosis, treatment history and relevant 
comorbidities, the treatment plan (including minimum HPC, Cord Blood cell dose), safety 
monitoring schedule, safety reporting plan, and consent form.  For a request to treat multiple 
patients, the protocol should include the subject eligibility requirements, treatment plan, safety 
monitoring, outcomes assessment, safety reporting plan, and model consent form  
(21 CFR 312.23(a)(6)(iii)).  The details in the protocol may be limited to use of the HPC, Cord 
Blood units alone.  The outcome assessment should include a plan for data review to determine 
whether any adverse experience (e.g., seroconversion or other evidence of relevant 
communicable disease agent or disease transmission, failure to engraft) or other serious or 
unexpected outcomes identified may be due to problems with product manufacture.  
Alternatively, a conventional protocol with scientific objectives may be submitted.  In all cases, 
the diagnoses for eligibility are limited to those listed in section III of this guidance.   
 
F. Donor Eligibility  For HPC, Cord Blood units manufactured on or after May 25, 2005, you 
must follow 21 CFR Part 1271 Subpart C (Donor Eligibility Regulations) including the 
requirement that a donor eligibility determination must be made for each allogeneic HPC, Cord 
Blood donor.  For a request to treat a single patient, the IND should include the results of the 
donor eligibility determination (See 21 CFR 1271.55(b) Summary of records).  For a multiple 
patient protocol, the IND should describe procedures used for making a donor eligibility 
determination.  Additional information about the donor eligibility determination is available in 
the FDA guidance entitled Guidance for Industry:  Eligibility Determination for Donors of 
Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) dated August 2007, 
available at 
http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guida
nces/CellularandGeneTherapy/ucm072929.htm.  For HPC, Cord Blood units manufactured 
before May 25, 2005, describe the donor screening and testing performed to prevent the spread 
of communicable disease.  In the event that the HPC, Cord Blood is from an ineligible donor, the 
HPC, Cord Blood unit may only be used if there is a documented urgent medical need as defined 
in 21 CFR 1271.3(u) and the requirements described in 21 CFR 1271.65 are met.  Similarly, an 
HPC, Cord Blood unit from a donor for whom the donor eligibility determination is not complete 
may only be used, if there is a documented urgent medical need as defined in 21 CFR 1271.3(u) 
and the requirements in 21 CFR 1271.60 are met.  See Section H of this guidance, for additional 
labeling requirements for HPC, Cord Blood units from ineligible or incompletely screened and 
tested donors.   
 
G. Manufacturing, Release Testing and Specifications  In this section of the IND, you 
should provide a summary of the manufacturing of the HPC, Cord Blood, which includes a 
description of the processing, testing performed on the unit, test methods used, and the 
acceptance criteria for test results that should be obtained before the unit is released for use in 
patients.  The description of processing should include information on volume reduction such as 
plasma reduction, red cell depletion, or other nucleated cell concentrating methods that were 
8  Contains Nonbinding Recommendations 
used.  The manufacturing information should also include the description of the cryopreservation 
procedure and storage.  
 
FDA acknowledges that there will be circumstances in which the IND sponsor may not be able 
to obtain all of the information on processing and testing of the various HPC, Cord Blood units.  
In particular, this may be true if the HPC, Cord Blood units that are used under the IND are from 
a wide range of manufacturers where different procedures, test methods, and acceptance criteria 
are used.  In such cases, an IND sponsor should describe the criteria they will use to select an 
HPC, Cord Blood unit and what, if any, additional testing will be performed prior to 
transplantation (e.g., confirmation of HLA).  This description should include how you will 
review accompanying manufacturing records and testing results, donor records, labels and 
labeling, and what criteria you will use to make decisions on the acceptability of the HPC, Cord 
Blood.  You should obtain as much information as possible from the manufacturer and submit 
that information to the IND.  We also recommend that you provide in each annual report a 
cumulative list of the manufacturers that provided the HPC, Cord Blood units and the 
information on how the HPC, Cord Blood was manipulated before cryopreservation (e.g., 
volume reduction).  
 
We suggest that the minimum acceptance criteria for an HPC, Cord Blood unit meet the release 
criteria recommended in the 2014 licensure guidance.  For pre-cryopreservation testing, this 
would include:  
 
  Sterility testing:  No evidence of microbial contamination. 
  TNC count:   5.0 x 108 TNC/unit HPC, Cord Blood (based on 20 kg recipient, a target 
dose of  2.5 x 107 nucleated cells/kg and  70% post-thaw recovery = 1.7 x 107 
nucleated cells/kg). 
  Viable CD34+ cell number:  1.25 x 106 viable CD34+ cells/unit HPC, Cord Blood (based 
on CD34+ cells  0.25% of TNC prior to freezing). 
  Cell viability:   85% viable nucleated cells. 
  Identity (HLA, ABO/Rh):  Report. 
  Hemoglobin testing:  Report. 
 
We understand that failure to meet these criteria may be one of the reasons that a unit will need 
to be used under IND.  Therefore, alternative specifications and the conditions where the 
alternative would be justified should be clearly defined and supported in the IND submission.   
Results of other tests used to evaluate the HPC, Cord Blood should be reported.  For example, 
results of such testing may include nucleated red blood cell content, colony forming unit assay 
(CFU), and other phenotyping analysis.  
 
If the IND sponsor is also the manufacturer, the IND should include instructions for the 
transplant center or end user regarding how the HPC, Cord Blood should be prepared for 
administration.  Such instructions may include procedures for:  thawing; washing to remove 
cryoprotectant; dilution; and reformulating for administration.  If the IND sponsor is not the 
manufacturer, we recommend that the instructions from the manufacturer be followed for 
thawing and preparation of the unit. 
 
9  Contains Nonbinding Recommendations 
Manufacturing information may be incorporated by reference from another regulatory file, such 
as another IND or a drug master file.  This allows FDA to use information in that referenced 
regulatory file to support the review of your IND.  To reference another regulatory file, you must 
obtain and include in your IND application a signed letter of cross reference stating that FDA has 
permission to access this information (21 CFR 312.420(b)).  This authorization letter must 
specify the information to be referenced and where the information is located in the referenced 
file (21 CFR 312.420(b)).  See 21 CFR 314.420 for information on drug master files.   
 
H. Labeling  Labeling includes the container label and all documents that accompany the HPC, 
Cord Blood.  A representative copy of all container labels and English language supplemental 
labeling (if applicable), as described in the regulations, should be submitted in the IND.  In 
addition, a description of how the immediate package label will be attached to the HPC, Cord 
Blood unit should be submitted in the IND.  For example, the sponsor may propose and justify 
the use of tie-tags, a second overwrap, or other means at the time of distribution. 
 
The immediate package label must include the statements, Caution:  New Drug - Limited by 
Federal (or United States) law to investigational use (21 CFR 312.6(a)).   
 
The donor eligibility summary of records must accompany the HPC, Cord Blood at all times (for 
HPC, Cord Blood units manufactured on or after May 25, 2005 (21 CFR 1271.55).  You should 
also provide instructions for preparation and administration of the HPC, Cord Blood with the 
HPC, Cord Blood unit. 
 
Additional labeling requirements may also be applicable.  If the requirements in  
21 CFR 1271.75, 21 CFR 1271.80 and 21 CFR 1271.85 have not been fully satisfied, the HPC, 
Cord Blood unit must be labeled according to the requirements in 21 CFR 1271.65(b)(2) or  
21 CFR 1271.60(d)(2), whichever applies.  
 
If, upon completion of all required donor screening and testing, the donor is determined to be 
ineligible, the HPC, Cord Blood unit must be labeled with the Biohazard legend and with the 
statement WARNING:  Advise patient of communicable disease risks.  
(21 CFR 1271.65(b)(2)); and the risk factor must be listed in the summary of records  
(21 CFR 1271.55(b)(4)).  If, on completion of all required donor screening and testing, the donor 
is determined to be ineligible because the donor has a positive test result, the HPC, Cord Blood 
unit must additionally be labeled with the statement WARNING:  Reactive test results for 
(name of disease agent or disease). (21 CFR 1271.65(b)(2)).   
 
The labeling requirements for HPC, Cord Blood units from donors who have not been 
completely screened and tested and that are to be used under conditions of urgent medical need 
(21 CFR 1271.60(d)(1)) are different from the labeling requirements described above.  If the 
donor eligibility determination has not been completed, the HPC, Cord Blood unit must be 
labeled, NOT EVALUATED FOR INFECTIOUS SUBSTANCES and WARNING:  Advise 
patient of communicable disease risks.  The results of any required donor screening and testing 
that have been completed, as well as a list of any required screening or testing that have not yet 
been completed, must accompany the HPC, Cord Blood unit (21 CFR 1271.60(d)(2)).  
 
10  Contains Nonbinding Recommendations 
In situations where the HPC, Cord Blood units are obtained from various manufacturers that do 
not use similar labeling procedures, the IND should describe your proposed approach to 
complying with the applicable regulations. 
 
I. Pharmacology/Toxicology  No pharmacology or toxicology information is required for 
INDs submitted in accordance with this guidance.  If the product is such that additional 
information is needed to demonstrate that the product is safe to use in humans in the dose and 
route planned, then it is likely this guidance does not apply.  
 
J. Prior Human Experience  No summary of prior human experience is required for the INDs 
submitted in accordance with this guidance.  A description of the prior human experience is 
available at www.regulations.gov under Docket numbers FDA-1997-N-0010 (Legacy Docket 
number 1997N-0497) and FDA-2006-D-0157 (Legacy Docket number 2006D-0514), which 
contain the data used to develop this guidance and the 2013 draft licensure guidance.  If 
additional information about prior human experience is needed to support the proposed protocol, 
then it is likely this guidance does not apply.  
 
K. Charging for Investigational Drugs under an IND  You must obtain prior written 
authorization from FDA to charge for an investigational drug used under an IND  
(21 CFR 312.8(a)(3)).  For INDs submitted in accordance with this guidance, a request to charge 
may be included.  The request must comply with the requirements set forth by 21 CFR 312.8, 
and include the amount to be charged and the documentation for the calculation of that amount. 
 
 
VI.  ADDITIONAL INFORMATION 
 
Although an IND sponsor may not be the manufacturer of an HPC, Cord Blood unit, the sponsor 
is responsible for the chemistry, manufacturing and control (CMC) information as well as the 
labeling information as described in this guidance, in addition to the clinical protocol.  You may 
request a pre-IND meeting with FDA during which you can pose specific questions to the FDA 
review team.  For information on requesting pre-IND meetings, please see the following 
Guidance for Industry:  Formal Meetings With Sponsors and Applicants for PDUFA Products 
dated February 2000, available at:  http://www.fda.gov/downloads/Drugs/GuidanceCompliance 
RegulatoryInformation/Guidances/UCM079744.pdf, which addresses how to request a pre-IND 
meeting.   
11  Contains Nonbinding Recommendations 
VII.  REFERENCE  
 
1.  Cellular, Tissue and Gene Therapies Advisory Committee (CTGTAC) Meeting #53 
September 22-23, 2011.  Transcripts available at 
http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandO
therBiologics/CellularTissueandGeneTherapiesAdvisoryCommittee/ucm280554.htm. 
 
12