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Questions and Answers
What was the primary use of serum from recovered patients in the late 1800s?
What was the primary use of serum from recovered patients in the late 1800s?
What substitute became widely used instead of whole blood and plasma for transfusion purposes?
What substitute became widely used instead of whole blood and plasma for transfusion purposes?
Which major event contributed to the advancement of fractionation techniques in the 1940s?
Which major event contributed to the advancement of fractionation techniques in the 1940s?
What is indicated as an important clinical benefit of using plasma-derived therapy in the early 20th century?
What is indicated as an important clinical benefit of using plasma-derived therapy in the early 20th century?
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What was a predominant use of antibodies from fractionated plasma during its early history?
What was a predominant use of antibodies from fractionated plasma during its early history?
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What is the purpose of using AF9 filter sheets in the IMIG process?
What is the purpose of using AF9 filter sheets in the IMIG process?
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During the powder formulation stage, what is added to stabilize proteins?
During the powder formulation stage, what is added to stabilize proteins?
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What is the target protein concentration aimed for in the dissolved powder solution?
What is the target protein concentration aimed for in the dissolved powder solution?
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How long is the freeze drying process carried out?
How long is the freeze drying process carried out?
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At what stage is the batch filled after the IMIG process?
At what stage is the batch filled after the IMIG process?
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What is the primary purpose of the depth filtration in the IMIG process?
What is the primary purpose of the depth filtration in the IMIG process?
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What happens to the powdered formulation after it is dried?
What happens to the powdered formulation after it is dried?
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Which step comes directly after the dissolution of Fraction II paste?
Which step comes directly after the dissolution of Fraction II paste?
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What is the primary purpose of adding castor oil during the bioplasma process?
What is the primary purpose of adding castor oil during the bioplasma process?
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What is the size of the filter used in the second filtration stage of the bioplasma process?
What is the size of the filter used in the second filtration stage of the bioplasma process?
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Which step follows the decantation in the bioplasma process?
Which step follows the decantation in the bioplasma process?
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What is added to the filtered plasma to remove Triton X-100?
What is added to the filtered plasma to remove Triton X-100?
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What does the quality assurance system aim to guarantee?
What does the quality assurance system aim to guarantee?
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Which of the following is NOT part of the Integrated Safety Approach in the bioplasma process?
Which of the following is NOT part of the Integrated Safety Approach in the bioplasma process?
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In the quality control system, what does the Certificate of Analysis signify?
In the quality control system, what does the Certificate of Analysis signify?
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What type of products have their specifications defined by SPCs in the quality control system?
What type of products have their specifications defined by SPCs in the quality control system?
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During what temperature and duration does the viral inactivation process occur?
During what temperature and duration does the viral inactivation process occur?
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What is the bioplasma fill dose?
What is the bioplasma fill dose?
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What is the role of in-process testing in the quality control system?
What is the role of in-process testing in the quality control system?
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How is the plasma separated from the oil in the bioplasma process?
How is the plasma separated from the oil in the bioplasma process?
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Which step ensures the removal of active raw materials in the quality control system?
Which step ensures the removal of active raw materials in the quality control system?
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What is a key aspect of the quality control system's validation process?
What is a key aspect of the quality control system's validation process?
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What is a primary aim of Good Manufacturing Practice (GMP)?
What is a primary aim of Good Manufacturing Practice (GMP)?
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Which factor is NOT listed as a consideration for minimizing contamination in sterile manufacturing?
Which factor is NOT listed as a consideration for minimizing contamination in sterile manufacturing?
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Who is NOT involved in the final product release panel?
Who is NOT involved in the final product release panel?
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What does QA audit confirm before product release?
What does QA audit confirm before product release?
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Which of the following is an element of viral safety in the summarized process?
Which of the following is an element of viral safety in the summarized process?
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What is one of the critical steps in a GMP system?
What is one of the critical steps in a GMP system?
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Which method is NOT mentioned as a measure for minimizing contamination?
Which method is NOT mentioned as a measure for minimizing contamination?
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What is the role of properly trained operators in the GMP system?
What is the role of properly trained operators in the GMP system?
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What is a key aspect of the QA process before the release of a product?
What is a key aspect of the QA process before the release of a product?
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Which of the following describes a proper recall system in a GMP framework?
Which of the following describes a proper recall system in a GMP framework?
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What type of plasma is primarily used for the production of NBI products?
What type of plasma is primarily used for the production of NBI products?
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Which factors influence the extraction and separation of therapeutic proteins?
Which factors influence the extraction and separation of therapeutic proteins?
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What was one of the major contributions made by Cohn in the field of protein extraction?
What was one of the major contributions made by Cohn in the field of protein extraction?
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Which regulatory body must approve all plasma materials imported into South Africa?
Which regulatory body must approve all plasma materials imported into South Africa?
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What is a primary characteristic of the plasma collection process?
What is a primary characteristic of the plasma collection process?
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Which protein is included as a therapeutic protein extracted from human plasma?
Which protein is included as a therapeutic protein extracted from human plasma?
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What is the purpose of pasteurization in the plasma processing procedure?
What is the purpose of pasteurization in the plasma processing procedure?
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What are the implications of the FDA CFR in the context of plasma fractionation?
What are the implications of the FDA CFR in the context of plasma fractionation?
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Which of the following factors is NOT typically varied in the fractionation of plasma proteins?
Which of the following factors is NOT typically varied in the fractionation of plasma proteins?
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What does the pooling and controlled thawing process ensure in plasma processing?
What does the pooling and controlled thawing process ensure in plasma processing?
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What is the minimum information required from plasma material suppliers according to regulatory frameworks?
What is the minimum information required from plasma material suppliers according to regulatory frameworks?
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Which plasma-derived factor is crucial for blood coagulation?
Which plasma-derived factor is crucial for blood coagulation?
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What is the function of the quality management system in plasma collection?
What is the function of the quality management system in plasma collection?
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Study Notes
Plasma-derived Therapy History
- Blood serum from recovered patients treated acutely ill patients during the 1918 influenza pandemic.
- Plasma use was expanded to treat a wider range of infections, including measles, polio, and bacterial infections in the first half of the 20th century.
- Dried plasma was used in WWII to replace plasma as a volume expander.
- Fractionation, the purification of antibodies and clotting factors, advanced in the 1940s and 1950s.
- This led to separation of blood into components, with albumin replacing plasma as a volume expander.
Fractionation History
- Dr. Edwin J. Cohn studied the nature and structure of proteins, developing the foundation principles of cold ethanol fractionation.
- The separation of blood into components was advanced during WWII, leading to a significant increase in fractionation between the 1940s and 1950s.
- The equipment and procedures developed during this period are still the basis for current plasma fractionation production.
- Kistler and Nitschmann improved the process in the 1970s.
Fractionation Principles
- Fractionation uses varying parameters such as alcohol concentration, temperature, pH, ionic concentration, and time to precipitate plasma proteins (fractions) based on physical characteristics, including solubility, charge, affinity, and stability.
Regulatory Framework
- Fractionation is governed by a complex regulatory framework, including pharmacopoeias, FDA CFR, Council of Europe, European Law, WHO Technical Report series, EMA Note for Guidance, SAHPRA, PICS Annex 1 & 14, and the Blood Directive.
Blood Components
- Blood is composed of plasma (55%), red blood cells (45%), white blood cells (<1%), and platelets (<1%).
- Plasma is a pale yellow liquid that is separated from blood and contains clotting factors, nutrients, hormones, and antibodies.
Plasma Collection
- Plasma is collected from both “recovered plasma” donation and “source plasma” donation.
Plasma Material Sources for Fractionation in South Africa
- The South African National Blood Service (SANBS) and Western Cape Blood Service (WCBS) are primary starting plasma material sources for fractionation in South Africa.
- Additional plasma sources include:
- Voluntary non-remunerated and paid donors from South Africa.
- Fresh Frozen Plasma from Namibia.
- Anti-D, anti-hepatitis B, and anti-rabies plasma from the USA.
- Cryoprecipitate for FVIII and Fraction V for Albumin.
- All imported plasma materials must be approved by the South African Health Products Regulatory Authority (SAHPRA).
Minimum Information Required from Plasma Material Suppliers
- Suppliers must provide details about their regulatory framework, national standards, quality management system, donor selection, blood/plasma collection, processing, cold chain management, testing, and donor epidemiology data for HIV, HBV, HCV, and emerging diseases.
Therapeutic Proteins Extracted from Human Plasma
- Therapeutic proteins extracted from human plasma for parenteral use include:
- Immunoglobulins
- Albumin
- Coagulation Factors (e.g., Factor VIII, Factor IX)
- Other proteins (e.g., C1 esterase inhibitor, fibrinogen, α-1 antitrypsin)
Plasma Processing at NBI
- NBI manufactures its products from fresh frozen plasma, which is shock-frozen to less than -30°C within 24 hours of donation.
Plasma Handling and Processing
- Plasma arrives at the NBI plasma stores from a refrigerated truck.
- Plasma is reconciled, quarantined, and pool-tested for HIV-1, HBV DNA, HCV RNA, Parvovirus B19 DNA, and HAV RNA.
- A plasma pool consists of approximately 1,600 recovered or 700 source donations.
- The pooled plasma (± 450 liters) is thawed in a controlled manner.
- Plasma is then formulated, sterile filtered, filled, and pasteurized.
Pasteurization
- Terminal pasteurization is a process in which plasma is treated with liquid heat (60°C) for 10 hours to inactivate enveloped and non-enveloped viruses.
IMIG and Bioplasma Processes
- The IMIG process includes freeze drying, powder formulation, and dissolution. The Bioplasma process includes viral inactivation, phase separation, filtration, and column application.
Integrated Viral Safety Approach
- A comprehensive integrated viral safety approach is implemented to minimize the risk of viral transmission.
- This approach includes donor selection, donation screening (serology and NAT), inventory management, plasma pool testing, manufacturing of plasma derivatives, purification, and virus inactivation steps.
Quality Assurance and Quality Control
- Quality Assurance (QA) is a management plan that ensures the integrity of data and inspires confidence in the quality of products.
- QA encompasses all aspects that influence product quality and outlines arrangements to ensure products are suitable for their intended use.
- Quality Control (QC) is a system that ensures product quality through validated analytical methods, equipment, specifications (SPCs), procedures (SOPs), and testing at various stages of production (raw materials, in-process, and final product).
Good Manufacturing Practice (GMP)
- Aims to ensure accurate and controlled implementation of viral inactivation and elimination treatments.
- Prevents cross contamination through:
- Medical testing of personnel
- Environmental monitoring
- Segregation of areas
- Flow of materials
- Flow of people
- Ensures quality assurance and process validation
GMP System
- Includes clearly defined and systematically reviewed processes
- Validates critical steps
- Requires appropriate resources:
- Personnel
- Buildings
- Equipment
- Materials
- Emphasizes clearly written procedures and trained operators
- Requires complete records and failure investigations
- Focuses on proper storage and distribution
- Features a recall system and complaint handling
Sterile Manufacturing
- Minimizes risks of:
- Microbiological contamination
- Particulate matter contamination
- Pyrogen contamination
- Considers:
- Premises
- Equipment
- Personnel
- Environment
- Processing
- Finished product
QA Assurance & Final Product Release
- Reviews all manufacturing documentation
- Reviews any incidents or deviations during the process
- Reviews test results
- Involves a panel consisting of:
- QA
- Responsible Pharmacist
- Head: Manufacturing
- Decides to release or reject product
Summary
- Combines elements of product safety from donor to end user
- Uses plasma processing methods to preserve therapeutic proteins
- Implements measures to minimize contamination of starting material
- Enhances safety through viral inactivation methods
- Tests samples throughout manufacturing process for compliance
- Performs a QA audit of process documents and test results before product release
- Includes adverse event, product complaint monitoring, and management
Viral Safety, Quality, and Donor Testing
- Includes viral safety measures
- Emphasizes quality control
- Utilizes donor testing for:
- HIV 1, 2
- HCV
- HBV
- Processes plasma pool testing
- Employs cold ethanol fractionation and pH 4
- Includes pharmacovigilance
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Description
Explore the significant milestones in the history of plasma-derived therapies and the development of fractionation techniques. From the use of blood serum during the 1918 influenza pandemic to advancements in protein separation during WWII, this quiz covers pivotal moments that shaped modern medical practices. Test your knowledge on how these developments have influenced the treatment of various infections and conditions.
