Implementing a Collection Program for Source Plasma Containing Disease-Associated and Other Immunoglobulin (IgG) Antibodies: Guidance for Industry

Administrative guidance, not enacted legislation. This captured publisher edition preserves the listed document and attachments; later developments are not independently consolidated.

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
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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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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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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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