Requirements for Blood and Blood

Components Intended for Transfusion

or for Further Manufacturing Use

Office of Blood Research and Review

CBER, FDA

Ask the FDA Session – AABB Annual Meeting

October 26, 2015
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 Outline
• Overview
– Historical Background
– Intent of the Rule
– Organization of the Rule
• Selected Provisions
– Relevant Transfusion-Transmitted Infection
– Control of Bacterial Contamination of Platelets
– Medical Supervision
– Donor Acknowledgement
– Alternative Procedures
– Donor Eligibility
• Implementation

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 GAO Oversight and FDA Concerns
• Publish in the form of regulations the guidelines that
FDA deems essential to ensure the safety of the blood
supply
• Concern about the delay in requiring testing for
emerging infectious agents, e.g. HTLV
• Concern about blood safety and the regulations being
out-of-date
• Concerns about donor safety

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Intent of the Final Rule
• To better assure the safety of the blood supply and to
help protect donor health
• To make donor eligibility and testing requirements
more consistent with current practices and to provide
flexibility with regard to emerging infectious diseases
• To accommodate technological advances
• To establish requirements for donor education, donor
history, and donor testing

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Organization of the Final Rule - 1
• A. General
• B. Definitions (§§ 606.3, 610.39, 630.3, 640.125)
• C. Standard Operating Procedures (§ 606.100)
• D. Control of Bacterial Contamination of Platelets
(§ 606.145)
• E. Records (§ 606.160)
• F. Test Requirements (§§ 610.40, 640.5, 640.71(a))
• G. Donor Deferral (§ 610.41)

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Organization of the Final Rule - 2
• H. Purpose and Scope (§ 630.1)
• I. Medical Supervision (§ 630.5)
• J. General Donor Eligibility Requirements(§ 630.10)
• K. Donor Eligibility Requirements Specific to Whole
Blood, Red Blood Cells and Plasma Collected by
Apheresis (§ 630.15)
• L. General Exceptions from Donor Eligibility
Requirements (§ 630.20)

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Organization of the Final Rule -3
• M. Exceptions from Certain Donor Eligibility
Requirements for Infrequent Plasma Donors
(§630.25)
• N. Donation Suitability Requirements (§ 630.30)
• O. Requalification of Previously Deferred Donors
(§630.35)
• P. Requirements for Notifying Deferred Donors
(§630.40)

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Organization of the Final Rule - 4

• Q. Platelets: Eligibility of Donors (§ 640.21)

• R. Source Plasma: Plasmapheresis
(§ 640.65(b))
• S. Source Plasma: General Requirements
(§640.69)
• T. Source Plasma: Records (§ 640.72)
• V. Alternative Procedures (§ 640.120)

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Relevant Transfusion-
Transmitted Infection (RTTI)

• Regulatory framework to provide for testing,

screening, educational material
• Identifies specific agents
• Provides for the addition of new agents
• Flexible approach
– Allows for removal of testing and
screening
• Incorporates current recommendations
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RTTI Definition
§ 630.3 (h) (1) -
(i) Human immunodeficiency virus, types 1 and 2 (referred to,
collectively, as HIV);
(ii) Hepatitis B virus (referred to as HBV);
(iii) Hepatitis C virus (referred to as HCV);
(iv) Human T-lymphotropic virus, types I and II (referred to,
collectively, as HTLV);
(v) Treponema pallidum (referred to as syphilis);
(vi) West Nile virus;
(vii) Trypanosoma cruzi (referred to as Chagas disease);
(viii) Creutzfeldt-Jakob disease (referred to as CJD);
(ix) Variant Creutzfeldt-Jakob disease (referred to as vCJD); and
(x) Plasmodium species (referred to as malaria).

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 RTTI Definition (part 2)
§ 630.3 (h)(2) -
• A transfusion-transmitted infection not listed in paragraph
(h)(1) of this section when the following conditions are met:
• (i) Appropriate screening measures for the transfusion-
transmitted infection have been developed and/or an
appropriate screening test has been licensed, approved, or
cleared for such use by FDA and is available; and
• (ii) The disease or disease agent:
• (A) May have sufficient incidence and/or prevalence to affect
the potential donor population; or
• (B) May have been released accidentally or intentionally in a
manner that could place potential donors at risk of infection.

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New RTTIs

• FDA would issue draft guidance for public comment

to address
– Appropriate donor screening measures, including
medical history assessments, in accordance with
§ 630.10(e)
– Appropriate donor testing in accordance with
§ 610.40(a)(3)
– Educational materials in accordance with
§ 630.10(b)

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Testing 610.40
• An establishment that collects blood and blood
components for transfusion or for use in manufacturing
a product, including donations intended as a
component of, or used to manufacture, a medical
device, must comply with the following requirements
– Test for HIV, HBV, HCV
– Test for HTLV, syphilis, West Nile virus, and Chagas disease
• Source Plasma donations do not have to be tested for
HTLV, West Nile virus or Chagas disease
• Source Plasma donors must be tested for syphilis in
accordance with 640.65(b)

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 Flexible Approach to Testing

• Allows for alternate testing schemes when approved

by FDA, e.g. one time testing for Chagas disease

• FDA may allow testing to be discontinued for a

specific relevant transfusion transmitted infections
other than HIV, HBV, and HCV, if testing is no longer
necessary to reduce adequately and appropriately the
risk of transmission of such infection
– Factors FDA would consider include epidemiology,
geography, or pathogen reduction technology

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Control of Bacterial Contamination of Platelets
• Blood collection establishments and transfusion
services must assure that the risk of bacterial
contamination of platelets is adequately controlled
using FDA approved or cleared devices or other
adequate and appropriate methods found acceptable
for this purpose by FDA
• Allows for use of testing or pathogen reduction
technology to control risk
• Donors must be notified of a bacterial infection likely
to be endogenous to the blood stream of the donor

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Medical Supervision - 1
• Definitions provided for responsible physician,
physician substitute, trained person

• Who must determine the eligibility of a donor?

The responsible physician must determine the
eligibility of a donor of blood or blood
components in accordance with this
subchapter.

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Medical Supervision - 2
• The responsible physician may delegate certain
activities to a physician substitute or other trained
person
– The responsible physician need not be present at the
collection site provided that the responsible physician has
delegated oversight of these activities to a trained person who
is adequately trained and experienced in the performance of
these activities and is also adequately trained and experienced
in the recognition of and response to the known adverse
responses associated with blood collection procedures

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Medical Supervision - 3
Must rapid emergency medical services be available?

• Establishments that collect blood or blood components must

establish, maintain, and follow standard operating
procedures for obtaining rapid emergency medical services
for donors when medically necessary. In addition,
establishments must assure that an individual (responsible
physician, physician substitute, or trained person) who is
currently certified in cardiopulmonary resuscitation is located
on the premises whenever collections of blood or blood
components are performed

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Donor Acknowledgement
• Prior to each donation, you must provide
information to the donor to address:
– Donor has reviewed educational materials
– Donor agrees not to donate if potential risk to
recipient
– Sample of blood testing for RTTI
– Donor will be notified of unsuitable donation
– Risks and hazards of donation procedure
– Donor has opportunity to ask questions and
withdraw from donation procedure
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Donor Acknowledgement
• Information on risks and hazards may be provided
in donor educational materials
• Must not include exculpatory language through
which donor is made to waive legal rights
• You must establish procedures to assure donor has
reviewed materials and provide for donor signature
or other documented acknowledgement (electronic
signature acceptable)
• Is in addition to informed consent requirements in
§ 630.15 and § 640.21

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 Alternative Procedures
• FDA may issue an exception or alternative to any
requirement in subchapter F of chapter I of title 21 CFR
regarding blood, blood components, or blood products in
response to a written or oral request from an
establishment. (§640.120 (a))
• To respond to a public health need, the Director CBER
may issue a notice of exception of alternative, if a variance
is necessary to assure availability (§640.120 (b))
– To address an urgent and immediate need for blood
– To provide for appropriate donor screening and testing

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 Donor Eligibility
• What factors determine the eligibility of a donor?
– The donor must be in good health and
– Free from diseases transmissible by blood as required in
this chapter

• What factors make the donor not eligible?

– The donor is not in good health or
– If you identify any factor(s) that might affect the
(1) The health of the donor; or
(2) The safety, purity, or potency of the blood or blood
component
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When Must You Determine the Eligibility of a Donor?
• On the day of donation, and before collection
– Except if the component cannot be stored for more than 24
hours, you may determine eligibility no more than 2 days
before donation

• Incomplete responses regarding the donor’s medical

history may be clarified within 24 hours of collection
– Does not include failure to perform or document part of the
physical assessment

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How Must You Determine the Eligibility of a Donor?

• You must consult the records of deferred donors

– If you cannot check the cumulative record prior to

collection, you must do so before release of the product

• Assure donation interval is appropriate

• Assess the donor’s medical history
• Perform a physical assessment of the donor

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How Do You Assess the Donor’s Medical History?-1
• Before collection, you must conduct a medical
history interview

• Assess and identify risk for, or evidence of, a

relevant transfusion-transmitted infection
– Behaviors associated with an RTTI
– Receipt of blood or blood components or other
medical treatments
– Signs and/or symptoms of an RTTI

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How Do You Assess the Donor’s Medical History? -2

• Assess and identify risk for, or evidence of, a

relevant transfusion-transmitted infection
– Institutionalization for 72 hours or more
consecutively in the past 12 months
– Intimate contact with risk for a relevant
transfusion-transmitted infection
– Nonsterile percutaneous inoculation

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Other Factors Affecting the Donor’s Health
or Blood Product
• Symptoms of a recent or current illness
• Certain medical treatments or medications
• Travel to, or residence in, an area endemic for a transfusion-
transmitted infection
• Exposure to accidentally or intentionally released disease or
disease agent
• Pregnancy at the time of, or within 6 weeks prior
• Unreliable answers
– Donor appears to be under the influence or test seeking
• Xenotransplantation product recipient (products with exposure
to live, nonhuman cells, tissues or organs)
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How Do You Perform a Physical Assessment
of the Donor?
• On the day of donation and before collection
• Temperature
– Not to exceed 37.5 C (99.5F)
• Blood pressure
– Systolic between 90 and 180 mmHg
– Diastolic between 50 and 100 mmHg
• Hemoglobin
– Males > 13.0 gm/dL or 39% hematocrit
– Females > 12.5 gm/dL or 38% hematocrit
• Females > 12.0gm/dL or 36% hematocrit with FDA approval

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How Do You Perform a Physical Assessment
of the Donor?
• Pulse
– Must be regular and between 50 and 100 beats per minutes
– A donor with measurements outside these limits may donate
only when responsible physician determines and documents
that the health of the donor would not be adversely affected
by donating
– Procedures for one time determination by responsible
physician for athletic donors with pulse rate less than 50 beats
per minute may be acceptable to qualify the donor for future
donations
• Weight > 110 lbs
• Skin examination
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When Must Donors Be Weighed?
• Plasmapheresis donors must be weighed at
each donation (630.15 (b)(3))
– Applies to all plasmapheresis donors, including
infrequent plasma donors and when plasma is co-
collected with other apheresis components
– A current weight measurement permits the
collecting establishment to calculate accurately
the plasma volumes to be collected based on a
weight specific nomogram

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Exceptions for Certain Ineligible Donors
• Permits donation from certain ineligible donors provided
– The donation is for autologous use only as prescribed by the
donor’s physician;
– The donor has a hemoglobin level no less than 11 grams of
hemoglobin per dL of blood or a hematocrit value no less
than 33 percent; and
– The responsible physician determines and documents that
the donor’s health permits the collection procedure
• Responsible physician may make this determination by
telephonic or other offsite consultation
• Responsible physician is the best person to determine
that the donor’s health permits the collection procedure

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Implementation of the Rule
• Rule becomes effective May 23, 2016
• If a new requirement is more stringent than the current
requirement, you may implement prior to effective date
• Licensed blood establishments
— We recommend that required submissions be sent to FDA as
soon as possible
— Refer to FDA Guidance for Industry: Changes to an Approved
Application: Biological Products: Human Blood and Blood
Components Intended for Transfusion or for Further
Manufacture (November 2014)
— For implementation questions, please contact your CSO

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