Guidance for Industry 
 
Informed Consent Recommendations 
for Source Plasma Donors 
Participating in Plasmapheresis and 
Immunization Programs  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Additional copies of this guidance are available from the Office of Communication, Training and 
Manufacturers Assistance (HFM-40), 1401 Rockville Pike, Suite 200N, Rockville, MD 20852-
1448, or by calling 1-800-835-4709 or 301-827-1800, or from the Internet at 
http://www.fda.gov/cber/guidelines.htm. 
 
For questions on the content of this guidance, contact the Division of Blood Applications, Office 
of Blood Research and Review (OBRR), Center for Biologics Evaluation and Research (CBER), 
at 301-827-3543.  
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Biologics Evaluation and Research 
June 2007
        Contains Nonbinding Recommendations 
 
 
Table of Contents 
 
 
I.  INTRODUCTION.............................................................................................................1 
II.  DISCUSSION....................................................................................................................1 
A.  Informed Consent for All Source Plasma Donors.............................................1 
B.  Additional Informed Consent Considerations for Immunization Programs..4 
C.  Special Recommendations for Female Participants..........................................5 
III.  REFERENCES..................................................................................................................7 
 
  i    Contains Nonbinding Recommendations 
 
 
Guidance for Industry 
 
Informed Consent Recommendations for Source Plasma Donors 
Participating in Plasmapheresis and Immunization Programs  
 
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 
 
This guidance provides recommendations to you, a blood establishment, for obtaining written 
informed consent from a prospective Source Plasma donor participating in a plasmapheresis 
program or an immunization program.  In this guidance, we, FDA, provide recommendations on 
how to satisfy the requirements for informed consent under 21 Code of Federal Regulations 
(CFR) 640.61Informed consent, as they relate to plasmapheresis and immunization programs.  
This guidance is intended to assist you in planning and applying for your original Biologics 
License Application (BLA) or in supplementing your existing BLA regarding your informed 
consent procedures and documents.  This guidance finalizes the draft guidance of the same title 
issued April 2006, and replaces the document entitled, Draft Reviewers Guide:  Informed 
Consent for Plasmapheresis/ Immunization, issued October 1995. 
 
FDAs guidance documents, including this guidance, do not establish legally enforceable 
responsibilities.  Instead, guidances describe the 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.  DISCUSSION 
 
You must follow all requirements for informed consent under 21 CFR 640.61.  In this section, 
we discuss the relevant regulatory requirements and provide recommendations concerning 
informed consent. 
 
A.  Informed Consent for All Source Plasma Donors 
 
1.  Prior to donation, a prospective donor must provide written informed consent  
(21 CFR 640.61). 
 
  1    Contains Nonbinding Recommendations 
 
 
2.  You must maintain the donors written informed consent in the donors record 
(21 CFR 606.160(b)(1)(i)). 
 
3.  Before the donor consents, a qualified licensed physician1 must explain to the 
prospective donor the hazards of the procedure (21 CFR 640.61). 
 
  The hazards of the procedure include the following: 
 
a.  blood loss from the inability to return red blood cells during automated 
plasmapheresis, which may result in: 
  the procedure being terminated, and 
  deferral from donation for 8 weeks (21 CFR 640.63(e)). 
 
b.  hemolytic transfusion reaction if the donor is given the red blood cells of 
another donor (e.g., when manual plasmapheresis is performed). 
 
c.  complications such as a hematoma or localized infection at the 
venipuncture site; 
 
d.  tingling of lips or fingers or muscle cramping due to the citrate 
anticoagulant used in an automated plasmapheresis procedure; 
 
e.  allergic reactions such as flushing, itching, hives, abdominal cramps, 
difficulty breathing, chest pain, or bronchospasm, which may vary in 
severity from mild to life-threatening;  
 
f.  nausea, vomiting, light-headedness, fainting, or seizures; and  
 
g.  any other adverse reaction specified by the manufacturer of the automated 
collection device in its operators manual or instructions for use. 
 
4.  The explanation of hazards must consist of such disclosure and be made in 
such a manner that intelligent and informed consent is given and that a clear 
opportunity to refuse is presented (21 CFR 640.61).  We believe that the use 
of exculpatory language in a written consent form through which the donor is 
made to waive, or appear to waive, any of his/her legal rights, or to release the 
blood establishment or its agents from liability for negligence, interferes with 
intelligent and informed consent.  We recommend the following additional 
elements to assist in obtaining intelligent and informed consent by the donor: 
 
a.  an opportunity for the donor to ask questions; 
 
                                                 
1 Note that FDA has approved under 21 CFR 601.12 and 640.120 alternative procedures under which a trained 
physician substitute working under the supervision of a licensed physician may perform the duties of a qualified 
licensed physician, described in 21 CFR 640.61 (Refs. 1 and 2). 
  2    Contains Nonbinding Recommendations 
 
 
b.  an explanation of the plasmapheresis procedure, including how long the 
procedure takes and the limitations on the frequency of donations; 
 
c.  information that a sample for total plasma or serum protein, including 
immunoglobulin levels, will be collected and testing performed at least 
every 4 months (as required in 21 CFR 640.65(b)(1)(i)), and that if the 
results are low or not within normal limits, the donor must be removed 
from the program until the values return to normal (21 CFR 
640.65(b)(2)(i)); 
 
d.  information regarding potential consequences if the results of tests for 
communicable disease agents are reactive, positive, or outside of normal 
limits.  These consequences could include: 
  detection of infectious agents such as Human Immunodeficiency Virus 
(HIV), or hepatitis, 
  donor notification, as required under 21 CFR 630.6, 
  temporary or permanent deferral from donation, as required under 21 
CFR 610.41, and the entry of the donors identification information in 
a deferral registry, and 
  reporting of results to public health officials, if applicable (for 
example, if required under the laws of your state) and any subsequent 
public health investigation which may occur. 
 
e.  information that blood establishment records, including donor records, are 
subject to inspection by FDA and, if applicable, other regulatory agencies; 
 
f.  information about the window period for infection (the time interval 
early in infection during which tests for diseases such as HIV or hepatitis 
may be negative although infection may still be transmitted); 
 
g.  a cautionary disclosure that the donor should participate in only one 
plasmapheresis program at a time, and that the donation of Whole Blood 
or Red Blood Cells while participating in the plasmapheresis program may 
serve as a basis for an 8-week deferral (21 CFR 640.63(e)), or a 16 week 
deferral for a double Red Blood Cell donation; and 
 
h.  additional information about HIV transmission, in accordance with the 
April 23, 1992 memo entitled, Revised Recommendation for the 
Prevention of Human Immunodeficiency Virus (HIV) Transmission by 
Blood and Blood Products.  Such information may be included in the 
donor consent document or in a separate informed consent document (as 
described in the April 23, 1992 memo).  In either event, we recommend 
that the document include a statement, to be signed by the donor, that the 
donor has read and understood the information on high risk groups/AIDS 
and believes he/she is not at risk for transmitting HIV infection to others 
through this donation. 
  3    Contains Nonbinding Recommendations 
 
 
5.   We recommend that all informed consent documents be signed and dated by 
both the Source Plasma donor and the physician overseeing the consent 
process. 
 
B.  Additional Informed Consent Considerations for Immunization Programs 
 
1.  A donors participation in a program to elicit an immune response2 through 
the administration of a vaccine or other antigen such as red blood cells before 
collecting Source Plasma exposes the donor to additional risks.  Accordingly, 
the explanation of hazards provided to the donor must include the risks of a 
hemolytic transfusion reaction if the donor is given the cells of another donor, 
and the hazards involved if the donor is hyperimmunized (21 CFR 640.61).  In 
addition, the donor should be advised that the following adverse reactions may 
occur: 
 
a.  local reactions at the site of injection which may include redness, 
induration (hardening), tenderness, pain, swelling, itching and nodule 
formation; 
   
b.  mild, generalized reactions which may include fever, malaise, fatigue, 
headache, nausea, vomiting, dizziness, myalgia (muscular pain), arthralgia 
(neuralgic pain in a joint) and lymphadenopathy (enlarged, sometimes 
tender lymph glands); 
 
c.  severe, generalized reactions, including specific reactions related to 
administration of the vaccine or antigen that may be administered, and the 
complications that may result, including severe disability and/or 
permanent neurologic sequelae (damage).  (For licensed products that you 
use in accordance with the package insert, information on adverse 
reactions is found in the manufacturers package inserts; if another product 
is approved under 21 CFR 640.66 for this purpose by the Director, CBER, 
additional information on adverse reactions may be identified by CBER); 
 
d.  information on possible severe allergic reactions (anaphylactoid) and/or 
life-threatening reactions for which immediate medical care should be 
provided; and 
 
e.  any other appropriate information about potential problems associated 
with the specific vaccine or antigen to be used. 
 
2.  In addition to the informed consent provisions described in section II.A of this 
document, we believe that information concerning the following additional 
elements will further support intelligent and informed consent by Source 
Plasma donors (21 CFR 640.61) who participate in an immunization program: 
                                                 
2 21 CFR 640.66, Immunization of donors. 
  4    Contains Nonbinding Recommendations 
 
 
 
a.  the expected rate of success of the immunization procedure, the volume 
and the route of administration of the injection, the interval between the 
initial injection and subsequent boosters, and the criteria for 
discontinuation of the donors participation in the program, e.g., 
unacceptable level of antibody; 
 
b.  a warning that the donor should participate in only one immunization 
program at a time; that participation in the immunization program may 
make the donor ineligible to participate in other donation programs, 
including plasmapheresis or Whole Blood donation; and that participation 
in multiple collection programs will likely result in donor deferral due to 
the additional risks to donor safety; and 
 
c.  for red blood cell immunization: 
  
  although the donor of the red blood cells is tested for infectious 
disease initially and again 12 months later prior to the use of the 
red blood cells for immunization, there remains the possibility of 
infectious disease transmission by these immunizing cells (Ref. 3); 
and 
 
  red blood cell immunization may stimulate production of 
antibodies other than the specific antibody that is the subject of the 
immunization.  The development of additional antibodies in the 
donors blood may cause an establishment to determine that the 
donors plasma is undesirable in blood products and unsuitable for 
future use.  In addition, the presence of additional antibodies in the 
donors blood may make it more difficult to locate compatible 
blood for transfusion or an organ for transplant in the event that the 
donor needs a transfusion or transplant in the future. 
 
C.  Special Recommendations for Female Participants 
 
Unless studies have established that a vaccine will not have harmful effects on the fetus 
or on a nursing infant exposed to the vaccine through human milk, we recommend that 
female donors should be advised that they should not participate in an immunization 
program if they are currently pregnant or nursing, or if they may become pregnant while 
participating in the immunization program. 
 
For red blood cell immunization programs, we further recommend that a female donor 
not participate unless she is permanently incapable of bearing children.  Immunization 
with red blood cells may lead to the development of unexpected antibodies which may 
cause hemolytic disease of the newborn, and may affect the donors childbearing 
potential in the future.  We recommend that you document in the donor record the basis 
  5    Contains Nonbinding Recommendations 
 
 
for a conclusion that a female donor is permanently incapable of bearing children (e.g., 
the donors statement that she has undergone a hysterectomy, or is post-menopausal). 
  6    Contains Nonbinding Recommendations 
 
 
III.  REFERENCES 
 
1.  FDA Memorandum to All Licensed Manufacturers of Source Plasma on Physician 
Substitutes, dated August 15, 1988. 
 
2.  Guidance for Industry:  Changes to an Approved Application:  Biological Products:  Human 
Blood and Blood Components Intended for Transfusion or for Further Manufacture.   
(http://www.fda.gov/cber/guidelines.htm) 
 
3.  FDA Memorandum, Revised Recommendations for Red Blood Cell Immunization Programs 
for Source Plasma Donors, dated March 14, 1995. 
 
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