Guidance for Industry 
 
Implementing a Collection Program 
for Source Plasma Containing Disease-
Associated and Other Immunoglobulin 
G (IgG) Antibodies  
 
 
 
 
 
 
 
 
 
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 Office of Blood Research and Review 
at 301-827-3524. 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Biologics Evaluation and Research 
August 2006 Contains Nonbinding Recommendations 
 
Table of Contents 
 
I.  INTRODUCTION.............................................................................................................1 
II.  DISCUSSION....................................................................................................................1 
III.  RECOMMENDATIONS..................................................................................................2 
IV.  OTHER NATURALLY OCCURRING OR PRE-EXISTING IgG ANTIBODIES...3 
V.  EXCEPTIONS...................................................................................................................4 
 
i  Contains Nonbinding Recommendations 
 
Guidance for Industry 
 
Implementing a Collection Program for Source Plasma Containing 
Disease-Associated and Other Immunoglobulin G (IgG) Antibodies 
 
 
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 
 
Source Plasma manufacturers might want to implement a collection program to collect Source 
Plasma from donors who have detectable levels of disease-associated Immunoglobulin G (IgG) 
antibodies and other existing IgG antibodies (see section IV).  Such disease-associated IgG 
antibodies are antibodies that have occurred in response to exposure to disease agents or other 
antigens.  This guidance is intended to assist you, a Source Plasma manufacturer, in submitting 
the appropriate information to FDA when implementing an IgG antibody collection program or 
when adding a new IgG antibody collection to your existing program.  This guidance finalizes 
the draft guidance entitled Guidance for Industry:  Recommendations for Implementing a 
Collection Program for Source Plasma Containing Disease-Associated and Other 
Immunoglobulin (IgG) Antibodies dated October 2005 (70 FR 61135; October 20, 2005), and 
replaces the draft Reviewers Guide, Disease Associated Antibody Collection Program, issued 
October 1, 1995. 
 
FDAs guidance documents, in general, 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.  Insofar as this guidance adjusts reporting categories for manufacturing changes 
pursuant to section 506A of the Federal Food, Drug, and Cosmetic Act and 21 Code of Federal 
Regulations (CFR) 601.12, it does have binding effect.  If you have any questions about the 
effect of any portion of this guidance, contact the Office of Blood Research and Review, 
Division of Blood Applications, at 301-827-3524. 
 
 
II.  DISCUSSION 
 
Source Plasma donors participating in a disease-associated IgG antibody collection program 
must meet all donor suitability requirements under  640.63 (21 CFR 640.63).  Donors who have 
1  Contains Nonbinding Recommendations 
 
disease-associated IgG antibodies are individuals who are in good health at the time of donation 
and either have recovered from their illness or were exposed to the disease agent but remained 
asymptomatic.  Donors participating in a disease-associated IgG antibody collection program 
possess specific IgG antibodies as a result of their exposure to the disease agent. 
 
Source Plasma collected from donors participating in disease-associated IgG antibody collection 
programs and in other IgG antibody collection programs (see section IV) may be used in the 
manufacture of injectable products and for noninjectable products, such as controls for in vitro 
diagnostic assays. 
 
This guidance does not include recommendations for the implementation of Immunoglobulin M 
(IgM) antibody collection programs; nor does it include recommendations for donors who do not 
meet all donor suitability requirements under  640.63.  The review and approval of collection 
programs for plasma containing IgM antibodies and for plasma from donors who do not meet all 
donor suitability requirements under  640.63 will continue through the submission of a prior 
approval supplement (PAS) to the biologics license application (BLA) for Source Plasma. 
 
 
III.  RECOMMENDATIONS 
 
Donors of Source Plasma, including Source Plasma collected under a disease associated IgG 
antibody collection program, must meet donor suitability requirements under  640.63. 
 
We, FDA, believe that, for establishments licensed to collect Source Plasma, the implementation 
or expansion, consistent with the recommendations in this section, of a program involving 
collection from eligible donors of Source Plasma containing the disease-associated IgG 
antibodies to the following disease agents or antigens, represents a change in the product that has 
a minimal potential to have an adverse effect on the identity, strength, quality, purity, or potency 
of the product as it relates to the safety or effectiveness of the product: 
 
1.  C-Reactive Protein 
2.  Mononucleosis (Epstein Barr) 
3.  Cytomegalovirus (CMV) 
4.  Herpes Type I 
5.  Herpes Type II 
6.  Varicella Zoster 
7.  Coccidioidomycosis 
8.  Histoplasmosis 
9.  Pseudomonas 
10. Rubella 
11. Mumps 
12. Hepatitis A (Anti-HAV) 
13. Hepatitis B surface (Anti-HBs) 
14. Hepatitis B core (Anti-HBc)* 
*Anti-HBc reactive donations, otherwise nonreactive when tested for HBsAg, 
have a low risk of infectivity for Hepatitis B virus (HBV) and must not be shipped or 
2  Contains Nonbinding Recommendations 
 
used under 21 CFR 610.40(h)(1).  However, 21 CFR 610.40(h)(2)(v) permits the use 
of these donations for further manufacturing into plasma derivatives (e.g., hepatitis B 
immune globulin), since the derivative manufacturing process will inactivate the 
HBV.  In addition, when labeled under 21 CFR 610.42(a), these donations may be 
used for reagents in in vitro diagnostic products (e.g., positive controls for Anti-HBc 
test kits). 
15. Toxoplasmosis 
16. Rubeola 
17. Respiratory Syncytial Virus (RSV) 
18. Chlamydia 
19. Hemophilus influenza 
20. Parvovirus B19 
 
Upon implementing or expanding such a program at your establishment, you must document this 
change in an annual report to the approved BLA and submit the report to FDA under  601.12(d) 
(21 CFR 601.12(d)).  Your annual report notification should confirm that donors meet all required 
donor suitability criteria for Source Plasma under  640.63, and that the plasma is collected from 
donors who have been exposed to the disease agent but are in good health at the time of 
collection. 
 
Changes to the labeling to describe the products must be submitted as a Supplement  Changes 
Being Effected (21 CFR 601.12(f)(2)(i)(E)). 
 
 
IV.  OTHER NATURALLY OCCURRING OR PRE-EXISTING IgG ANTIBODIES 
 
For establishments licensed to collect Source Plasma, the implementation or expansion of a 
program involving collection of other naturally occurring IgG antibodies from donors meeting all 
donor suitability requirements under  640.63, represents a change in the product that has a 
minimal potential to have an adverse effect on the identity, strength, quality, purity, or potency 
of the product as it relates to the safety or effectiveness of the product.  As described in Section 
III, report the manufacturing change in an annual report (21 CFR 601.12(d)) and changes to the 
labeling as a Supplement  Changes Being Effected (21 CFR 601.12(f)(2)(i)(E)). 
 
In addition, for collections of Source Plasma containing pre-existing red blood cell antibodies, 
we recommend that at the time of donation, donors not be in any immunization program, and not 
have been immunized, either deliberately or by transfusion, within the past twelve months.  Your 
annual report should describe the procedures you have implemented to address this issue. 
 
3  Contains Nonbinding Recommendations 
 
V.  EXCEPTIONS 
 
Source Plasma may only be collected and shipped following FDAs review and approval of a 
BLA for the product.  If you make manufacturing changes to an existing Source Plasma BLA to 
collect Source Plasma containing IgG antibodies as described below, we believe that, because of 
the substantial potential for adverse effect of the change on the identity, strength, quality, purity, 
or potency of the product, changes involving the following collections require supplement 
submission and approval (PAS) prior to distribution of the products made using the change 
(major change) (21 CFR 601.12(b)).  In some circumstances, such collections may be made only 
if FDA grants a variance under 21 CFR 640.120 to permit the collections.  This paragraph 
applies to the following collections: 
 
  Plasma collected from donors tested and found to be positive for evidence of 
infection due to communicable diseases as required under 21 CFR 610.40; 
  Plasma collected as a by-product of therapeutic procedures; 
  Plasma collected from donors participating in an immunization program (e.g., 
smallpox, anthrax); and 
Plasma collected from donors who do not meet all required donor suitability criteria for 
Source Plasma under  640.63.  
4