In the name of Allah
XXXth International congress of
ISBT, June 7-12, 2008, Macao
Plasma for Fractionation
IRAN Experience
Dr. H. Abolghasemi
Managing Director
Iranian Blood Transfusion Organization
XXXth International congress of
ISBT, June 7-12, 2008, Macao
Product demand
Annual need for blood
products is increasing
Marketing research Bureau 2006-2007
•
Clotting factors
• IVIg
• Albumin
Average annual growth rate of factor
VIII, factor IX, AAT, fibrin sealant,
IVIg, and albumin being
3%,1.9%,13%,3.4%,6-8% , 2%
respectively.
XXXth International congress of
ISBT, June 7-12, 2008, Macao
Worldwide plasma market including recombinant
products
10
9
8
US$ bn.
7
6
1.9
5
1.72
0.98
4
0.58
3
0.9
0.8
1.5
1.5
2
1
1.2
1.4
1996
1998
1.08
0.9
0.8
0.9
1.1
0.95
0.95
1.9
2.3
2.6
2000
2003
2005
Others
Andere
rec. FIX
pd FIX
rec.FVIII
pd FVIII
Albumin
IVIG (incl. I.m.)
0
MRB-Report: Feb 2005
Figures 2005 estimated
24.03.2006
Dr. M. Kloft
XXXth International congress of ISBT, June 7-12, 2008, Macao
1
Worldwide need of immunoglobulins
120
CAGR 2004/10 = 6,5 %
99.0
100
88.8
78.5
IVIG (tons)
80
68.0
58.2
60
47.4
40
35.5
36.6
1996
1998
27.7
19.7
20
15.7
7.4
8.9
9.7
1984
1986
1988
0
1990
1992
1994
2000
2002
2004
2006
2008
2010
MRB-Report: Feb 2005
24.03.2006
Dr. M. Kloft
XXXth International congress of ISBT, June 7-12, 2008, Macao
2
Why contract fractionation?
• National blood services play crucial role in
providing safe and adequate plasma to be
fractionated to the very important medicine
including clotting factors,albumin and
immunoglobulines.Although importing these
medicines might be a prompt aproach to furnish
national market with these medicines, worldwide
shortage of these medicines and limited
resources available in countries health care
system make this approach far from ideal
XXXth International congress of
ISBT, June 7-12, 2008, Macao
Why contract fractionation?
• An alternative would be either to produce
these medicines locally or use contract
fractionation approach in order to meet
needs of local market
• Due to its financial and technical
requirements and considerations
establishing a facility for local production
at least in developing countries has not
been fruitfful
XXXth International congress of
ISBT, June 7-12, 2008, Macao
Why Contract Fractionation in
IRAN?
Cost-effectiveness because of
• Rich resource of blood
donors in our country
• The number of plasma units
in our blood centers being
higher than the hospital
demand rate.
• Decrease in import demand
of blood products including
IVIg and factor VIII.
XXXth International congress of
ISBT, June 7-12, 2008, Macao
XXXth International congress of
ISBT, June 7-12, 2008, Macao
Iranian Blood Transfusion
Organization
• Integral part of the national health system
• Blood donation being voluntary and nonremunerated (100%)
• Centralized. All blood centers throughout the
country are under supervision of IBTO
headquarters. All procedures, kits, and
equipment are the same and follow a similar
standard in all blood centers. All organizational
policies mandated by the headquarters are
issued to all centers.
XXXth International congress of
ISBT, June 7-12, 2008, Macao
Ministry of
Health
A Provincial
Transfusion Center
BCC
BCC
BCC
BCC
BTC
IBTO
HEADQUARTERS
BCC
BCC
BTC: Blood Transfusion Center
BCC: Blood Collection Center
XXXth International congress of
ISBT, June 7-12, 2008, Macao
Trend of Blood Donation in
Iran (1974-2007)
2000000
1735000
1800000
1600000
1,448,149
1,183,630
1200000
1000000
800000
746,868
600000
400000
200000
12,354
XXXth International congress of
ISBT, June 7-12, 2008, Macao
07
20
05
20
00
20
95
19
90
19
85
19
80
19
74
0
19
Units
1400000
Trend of Yearly Donation Index
in Iran(1974-2007)
30
24.7
22.1
19.4
20
14.7
15
10
5
0.39
XXXth International congress of
ISBT, June 7-12, 2008, Macao
06
20
04
20
02
20
00
20
98
19
96
19
94
19
92
19
90
19
88
19
86
19
84
19
82
19
80
19
78
19
76
19
74
0
19
Per 1000
25
Trend of Transition to 100%
Voluntary Blood Donation in Iran
(1996-2007)
99
100
95
95
97
92
77
80
80
77
100
79
64
60
40
20
XXXth International congress of
ISBT, June 7-12, 2008, Macao
07
20
06
20
05
20
04
20
03
20
02
20
01
20
00
20
99
19
98
19
97
19
96
0
19
Percent
96
National Blood Program
Donor Screening
Blood Testing
Blood Donor Recruitment Program
National
Blood Centers
1) Develop and implement a
continuous national awarenessraising program to highlight the
importance of regular blood donation
2) Oversee the recruitment, retention,
and recognition of blood donors to
ensure an adequate supply of safe
blood for use by all hospitals in Iran
3) Have accessibility to more than
185 fixed blood donation centers
throughout the country
4) Work in partnership with mass
media to encourage voluntary blood
donation
5) Provide training to blood centers’
staff in the field of donor recruitment
1) Follow the program of recruitment,
retention, and recognition of blood
donors
2) Build effective communication
between staff and blood donors
3) Embark on establishing blood drives
in safe places and make efforts for
their being improved so that demands
are met
4) Provide training to volunteers and
exert management to maximize impact
of the public awareness-raising
program
XXXth International congress of
ISBT, June 7-12, 2008, Macao
Q.C
• IBTO started to send the recovered plasma for
fractionation to two fractionation facilities in
Europe following the contract concluded in
2005.
• End products are returned to our country.
• Our goal is to have a safe and sufficient plasma
derivatives to meet the majority of needs of our
population in the country
XXXth International congress of
ISBT, June 7-12, 2008, Macao
volume of plasma
70000
2007
60000
2005
50000
liter
2006
40000
30000
20000
10000
0
1
year
XXXth International congress of
ISBT, June 7-12, 2008, Macao
Plasma derived medicines used in 2006
IVIG (kg)
HA (X 10kg)
FVIII (MIU)
IBRF
230
168
7
Total
385
874
128
XXXth International congress of
ISBT, June 7-12, 2008, Macao
Flow work for plasma shipment to fractionation center
agreement of medicines
regulatory Authority
Assessment of the
shipment volume
Audit of the selected
centers by an appointed official auditor from Europe
Audit of the fractionation center by an
Iranian auditor
(appointed by supplier party and Health Minister)
Approval of
plasma
contract for
fractionation
Licensing
XXXth International congress of
ISBT, June 7-12, 2008, Macao
Increase
Quantity
of Plasma
Increase
Total Number
of Donations
Quantity shipment of
plasma can still raise
because
• just 16 out of 30 blood
transfusion centers
across Iran have already
been active contributing
to contract fractionation.
• We have formulated and
started to implement the
program to increase the
total number of blood
centers eligible to send
plasma
XXXth International congress of
ISBT, June 7-12, 2008, Macao
3 kinds of products:
1) Haemoctin
2) Intratect
3) Human Albumin
XXXth International congress of
ISBT, June 7-12, 2008, Macao
Improvements in IBTO system
• Plasma fractionation caused
improvement in the system
specially Documentation,take
PCR sample and cold chain.
• More strict standards for
plasma fractionation.
• Several external audits from
certified body of Europe.
• pushing toward implimentation
of automation in our system.
XXXth International congress of
ISBT, June 7-12, 2008, Macao
Automation of lab tests and
implementation of the new software
XXXth International congress of
ISBT, June 7-12, 2008, Macao
Automation of lab tests
XXXth International congress of
ISBT, June 7-12, 2008, Macao
Home made Blast
freezers replaced
mechanical
freezing.
The plasma core
temperature
reaches -30°c
within less than 1
hour in blast
freezer.
XXXth International congress of
ISBT, June 7-12, 2008, Macao
Improvement of the cold rooms and
freezing rooms
• Freezer temperature shall be less than -25°C during the
whole storage period.
• Because we already have a contract with a European
country, our freezing storage standards shall comply with
European Pharmacopoeia.
•
The European Pharmacopoeia has a provision stating that if the
temperature of the plasma is between -20°C and -15°C for a
maximum of 72 hours, or if it is above -15°C (but colder than - 5°C)
in no more than one occurrence, the plasma can still be used for
fractionation.
XXXth International congress of
ISBT, June 7-12, 2008, Macao
Donor
Look back
• Improvement of our
look back system.
• Every blood donor can
be recalled if the follow
up is necessary.
• System is established
to immediately notify
fractionation center
once a test is positive.
Fractionation
center
XXXth International congress of
ISBT, June 7-12, 2008, Macao
Responsibilities and roles of blood establishment
who expert committee 2007
• Collects and analyses the epidemiologic data and surveilance
of donor population based on results of screening tests.
• Develops and implements the criteria in selection and interview
of donors.
• Performs validated tests (or the tests maybe sub-contracted).
• Hemovigilance:Informs plasma fractionator (and when
appropriate the regulatory authority) when relevant information
is obtained.
• Collects blood plasma, prepares, freezes, and stores the
plasma, according to good manufacturing practice (GMP).
• Prepares the NAT samples following fractionators' specifications
• Implements GMP.
XXXth International congress of
ISBT, June 7-12, 2008, Macao
Responsibilities and roles of plasma fractionators
who expert committee 2007
• Review the epidemiological data.
• Verifies donor selection criteria set by national regulatory authority are
met; may provide additional selection criteria.
• Agrees on the tests kits used and audits the virology laboratory.
• Hemovigilance: Takes appropriate measures if plasma pool or product
quality is compromised.
• Preparation of plasma : Sets the specifications and audits.
• Provides the standard operating procedure for NAT samples and
performs (or sub-contracts) the validated testing.
• Applies the fractionation methods including viral inactivation following
GMPs and processes described in marketing authorization.
• Prepares of plasma product regulatory files
• GMP : Audits the blood establishment.
• Does pharmacovigilance studies and informs regulatory authorities and
blood establishment when relevant side-effects are found.
XXXth International congress of
ISBT, June 7-12, 2008, Macao
Responsibilities and roles of regulatory authorities
who expert committee 2007
•
•
•
•
•
•
•
•
•
•
•
Review the epidemiological data.
Sets the criteria and inspects the blood establishment.
Approves test kits and inspects the blood establishment.
Evaluates haemovigilance/post-donation reports with regards to
product quality and safety.
Approves and inspects the blood establishment.
Approves the procedure and inspects the plasma fractionator.
Evaluates the data presented in the dossiers prepared by the
fractionator, and inspects fractionation facility.
Reviews and evaluates regulatory files.
Inspects blood establishment and enforces GMP.
Grants the marketing authorization.
Evaluates pharmacovigilance reports with regards to product quality
and safety.
XXXth International congress of
ISBT, June 7-12, 2008, Macao
Notification obligation
:
 Deviation is subsequently discovered in any of screening
tests performed on the plasma unites supplied
 A regular donor is found to be positive for a marker
although the previous donation was found negative.
(starting look back procedure)
 A donation is found to have transmitted an infectious
disease potentialy transmissible by plasma.
 We are informed that a donor previousely contributing to
plasma for fractionation has developed an infectious
disease potentially transmissible by plasma
 Post transfusion infection following transfusion of blood
components obtained from a donor who has also
donated one or more unites of plasma for fractionation
 A unit positive for viral markers has been sent by
mistake
XXXth International congress of
ISBT, June 7-12, 2008, Macao
Conclusion : Advantages of plasma
fractionation contract in IRAN
• Prevention of 200,000 liters of fresh frozen plasma to be
wasted
• 35% cost reduction of plasma derivatives and a
reduction in products import with foreign resources
• Prevention of patient exposure to foreign biological
products and patient protection against unwanted
infections
• Standardization of plasma for fractionation leading to the
improvement of all the procedures in preparation of
blood components
• Implementation of a look back system and tracing back
based on the NAT results
XXXth International congress of
ISBT, June 7-12, 2008, Macao
XXXth International congress of
ISBT, June 7-12, 2008, Macao
Thank you
XXXth International congress of
ISBT, June 7-12, 2008, Macao