Quality Control of biological reagents and legal affairs on Latin America

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Quality Control of biological reagents and legal
affairs on Latin America

• Amadeo Sáez-Alquézar
• Rio de Janeiro - 2005

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Quality of Blood Components
Recruitment
Immunohematology
Selection
Collection
Screening for infectious diseases
Fractioning
Storage
Step of a fundamental importance Specially in
developing countries
Release
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Screening for infectious diseases in Latin
America and Caribbean
Other countries
Brazil - Coverage 100

• Anti-HIV 1/2 (2)
• Anti-HTLV I/II (1)
• Anti-HCV (1)
• AgHBs (1)
• Anti-HBc (1)
• Sífilis (1)
• Chagas (1)
• ELISA

• One test
• 40 - 60 (coverage)
• Less than 100
• One test
• 15 - 60 (coverage)
• One test
• One or two tests
• Less than 100

RDC 343 Dec / 2002 RDC 153 Jun / 2004
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Blood Units collected in Latin America and
Caribbean Region during the period from 2000 to
2003
These data correspond only to public blood banks
and were obtained by PAHO from one person
responsable for the management of national
information in each country.
PAHO THS/EV- 2005/005 E
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Serological Screening () for Infectious diseases
Latin America - 2003
PAHO THS/EV- 2005/005 E
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Blood Units that were not Screened for Infectious
diseases (Latin America/2003)
PAHO THS/EV- 2005/005 E
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Blood Units that were not Screened for Infectious
diseases Latin America (2000 - 2003)
PAHO THS/EV- 2005/005 E
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Serological Screening () for Infectious diseases
Caribbean Region - 2003
PAHO THS/EV- 2005/005 E
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Blood Units that were not Screened for Infectious
diseases Caribbean Region (2000 - 2003)
PAHO THS/EV- 2005/005 E
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Reliable Serological Screening of Blood Donors

• Participation of well-trained and periodically up
  to date professionals
• Quality management system
• To use good quality diagnostic kits
• To adopt internal quality control procedures
  (IQC)
• To participate on programs for external quality
  evaluation (EQAS).

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Evaluation of the diagnostic kits as a
pre-requirement for commercialization

• Beneficial practice for avoid the
  commercialization of products with untruthful
  quality
• As the stipulated period between evaluations is
  quite long (up to five years), the performance of
  different batches is not evaluated for each
  product, what might represent a great number of
  non-evaluated products

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Procedures for Quality Control of Infectious
Disease Screening

• QUALITY ASSURANCE
• INTERNAL QUALITY CONTROL
• Internal control sera (ICS)
• Kits evaluation (Performance panel)
• Before to be used
• Batch to batch
• QUALITY ASSESSMENT
• External Quality Control

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The Most Important Items of the Internal Quality
Control

• Use of internal control sera (ICS), for daily
  validation of the tests performed.
• OD/CO 2 - 4,5 or 0.3 - 0.8 for the competitive
  methods
• Monthly determination of the variation
  coefficient for each method performed.
• Use of serum panels to evaluate the kits, before
  they are used.
• Use of serum panels to evaluate each new batch of
  kits before their use in laboratory routine.

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Batch-to-Batch Changes of Kits Performance

• Different levels of reactivity.
• Changes in sensitivity and specificity that put
  the truthfulness of the final results at risk

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Batch to Batch changes

• Different levels of reactivity, making the
  adoption of internal quality controls for daily
  validation of serum reactions hard and expensive.
• This problem is continuously present in the
  Brazilian and Latin America laboratories

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The Use of the ICS to validate the assays
performed in the laboratories
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Batch Changes (n 7) during a 66 days period in
a serological screening laboratory
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Batch Changes (n 3) during a 66 days period in
a serological screening laboratory
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Results obtained for the standardization of
Levey-Jennings chart, using the same ICS on Batch
Changes (n 3) during a 66 days period in a
serological screening laboratory
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Batch to Batch changes

• When a change of batch results in significant
  losses of sensitivity and/or specificity.
• In order to evaluate each new batch before use,
  the application of internal laboratory
  performance panels has shown good results

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Internal Kits EvaluationBefore to be used and
batch to batch control

• Panel sera with 20 samples
• Positive samples N 7
• Negative samples N 13

All samples are analyzed for all tests used in
the serological screening of blood donors
anti-HBs. Also for other tests when necessary.
Confirmatory tests are performed in positive
samples
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Performance Panel to HBs Ag
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Performance Panel to Anti-HIV
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Procedures for Quality Control of Infectious
Disease Screening

• INTERNAL QUALITY CONTROL
• Internal control sera (ICS)
• Kits evaluation (Performance panel)
• Before to be used
• Batch to batch
• QUALITY ASSESSMENT
• External Quality Control

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External Quality Assessment (EQA) or External
Quality Control Programs (EQCPs)

• The programs intend to assess the performance of
  the participating laboratories and should be
  considered a challenge to check the efficacy of
  the Quality Assurance and the Internal Quality
  Control, in each laboratory.
• Possible failures in the internal procedures of
  the laboratories may give rise to FPR and / or
  FNR in processing the Multipanel

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Multipanel for EQASBlind Panel

• 12 or 24 serum samples
• Positive samples of
• HIV
• HTLV
• HBV , Anti-HBc
• T. cruzi
• Syphilis
• HCV
• Negative samples

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Organizing Laboratory
Participanting Laboratories
Shipment
Samples Processing
Multipanels Manufacturing
Results
Disclosure of the correct results
Acknowledging the correct results
Final Report Evaluation
Analysis of the results
Self Evaluation
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EQCPs - Final Report Contents

• Number, type and geographic distribution of the
  Participant Laboratories
• Charaterization of the Multipanel
• Strategies (type of methodologies) used by each
  Participant Laboratory
• False Positive and False Negative Results
• Number, and distribution by methodology, by
  disease and by trademark of the used kits
• Relevant information

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Evaluation of the LaboratoriesCriteria

• A Correct Results
• Without FPR or FNR
• B1 False Positive Results
• lt 5 of the total assays
• B2 False Positive Results
• gt 5 of the total assays
• C False Negative Results

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Development of External Quality Control Programs
in Serology
BRASIL 1994 - 1995
BRASIL 1995 - 2005
PANEL PUBLIC AND PRIVATE BLOOD
BANKS 30 PROGRAMS 120 LABS Options External QC
and Internal QC
MINISTRY OF HEALTH / FPS PUBLIC BLOOD BANKS 1st
32 Labs 2nd 58 Labs 3th 60 Labs 4th
61 Labs
()PANEL / SBHH 1995-2001
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DEVELOPMENT OF PAHO/WHO EQAS
1995 / 96
2001/ 2003
1996
FPS/HSP
PANEL
FPS/HSP
1997 / 2000
LATIN AMERICA 15 countries (21PLs) 4
Programs CARIBBEAN 21 Countries (24 PLs) 4
Programs
FPS/HSP
CENTRAL AMERICA and Colombia (3 Programs)
LATIN AMERICA One Program
LATIN AMERICA 5 Programs 16 countries (21 PLs)
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Main problems detected during EQAS development

• Contamination of samples, creating FPR that might
  occur as a consequence of human mistakes or by
  failure of the equipment used.
• Errors in the transcription of the results (FPR
  and FNR)
• Lack of sensitivity and/or specificity of the
  kits used (FPR and/or FNR)
• Unsuitable procedures for ICQ (FPR and/or FNR)

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Distribution () of evaluation criteria in 7 EQAS
developed in Brasil (2002 2004)
PANEL Final reports 2002 - 2004
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Performance Evaluation of the Participant
Laboratories of EQAS in Brasil (2002 / 2004) -
HCV
PANEL Final reports 2002 - 2004
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FPR (B1/B2) and FNR (C) for HCV EQAS Brasil -
PANEL (2002 / 2004)
PANEL Final reports 2002 - 2004
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overall rate of false negative and false positive
results ovserved in 5 EQAS / PAHO Latin America
- (1997 2000)
Sáez-Alquézar, A et al. Pan Am J Public Health
13(2/3), 2003
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Rate of false negative results ovserved in 5 EQAS
developed by PAHO in Latin America(2001 2003)
PAHO / PANEL Final reports 2001 - 2003
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Rate of false positive results ovserved in 5 EQAS
developed by PAHO in Latin America(2001 2003)
PAHO / PANEL Final reports 2001 - 2003
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EQAS - PAHO / CAREC False Positive and False
Negative Results for HIV (2001 / 2003)
PAHO / PANEL Final reports 2001 - 2003
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EQAS - PAHO / CAREC False Positive and False
Negative Results for HBs Ag (2001 / 2003)
PAHO / PANEL Final reports 2001 - 2003
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EQAS - PAHO / CAREC False Positive and False
Negative Results for Syphilis (2001 / 2003)
PAHO / PANEL Final reports 2001 - 2003
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Screening Coverage in Reference Laboratories of
16 Latin America Countries
PAHO / PANEL Final reports 2001 - 2003
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Screening Coverage in Reference Laboratories of
23 countries from Caribbean Region
PAHO / PANEL Final reports 2001 - 2003
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Final Comments. Our suggestions (1)

• To strengthen internal quality control
  procedures
• Adequate application of ICS for daily validation
  of the reactions.
• Batch-to-batch evaluation, by panel performance
  application

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Final Comments. Our suggestions (2)

• Participation in the EQAS
• By careful analysis of the information on final
  reports
• Disclosure of the results obtained in each
  program by the organizing centers to guide the
  regulation authorities
• To reinforce the implementation of kit evaluation
  systems as a pre-requirement to commercialization
  in each country.

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Thank you

• amadeosaez_at_uol.com.br