Guidance for Industry 

Implementing a Collection Program 

for Source Plasma Containing DiseaseAssociated 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

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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 Administration’s (FDA’s) 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. 

FDA’s guidance documents, in general, do not establish legally enforceable responsibilities. 

Instead, guidances describe FDA’s 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 FDA’s 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 

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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 

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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. 

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V. EXCEPTIONS 

Source Plasma may only be collected and shipped following FDA’s 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. 

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