QC Policy / Main Activities

One of the important sources of the BioDarou standards for establishing of the “Quality System” is the relevant resources of European Guidelines and all relevant requirements. In this regard; we are focused on Directive 2002/98/EC and its commissions or other relevant addendums:

Quality system for blood establishments

Member States shall take all necessary measures to ensure that each blood establishment establishes and maintains a Quality System for blood establishments based on the principles of good practice (GMP).

Good manufacturing practices (GMP)

The implementation and enforcement of Good Manufacturing Practices (GMP) in Blood and Plasma Collection Establishments is considered a priority as a tool to minimize the risk of transmitting currently known and emerging blood-borne diseases. This priority has been consistently highlighted by medicines regulatory authorities at the last International Conferences of Drug Regulatory Authorities (ICDRA) held in Berlin (1999), Hong-Kong (2002) and Madrid (2004).

GMP is a system for ensuring that products are consistently produced and controlled according to quality standards appropriate to their intended use and as required by the product specification. The adherence to GMP at all levels of the production process, from the donor to the recipient, is a prerequisite for consistent quality in the preparation of blood and blood products. The quality and safety of locally-manufactured products can only be ensured if national regulatory authorities with operational inspectorates implement and enforce appropriate GMP standards.

The Commission shall establish the Community standards and specifications referred to in Article 29(h) for the activities relating to a Quality System to be carried out by a blood establishment.

In based on EU guidelines and EC directives the Quality control section is a part of GMP (as a approved Quality System) that is concerned with
- Sampling
- Specifications
- Testing
ِ- Documentation
- Release procedures

This approach ensures that materials are not released for use, and that products (including pharmaceutical and biological) released for sale or supply, until their quality has been deemed satisfactory.

The basic requirements of Quality Control

Adequate facilities, trained personnel, and approved procedures are available for sampling, inspecting and testing of disposable and soft goods, all donated plasma, and process control, and, where appropriate monitoring environmental conditions for GMP purposes;

Samples of raw materials, packaging materials, and intermediate, bulk, and finished products are taken according to procedures approved by the quality control department; in blood establishments and so in the plasmapheresis centers, the QC department is responsible for all screening testing according to the current EU directives.


►Test methods are validated ;
All main instruments are qualified according to a Qualification Plan.

►Records are made that demonstrate that all the required sampling, inspecting, and testing procedures were actually carried out, and any deviations are recorded and investigated;

►The finished products comply with the requirements of the marketing authorization, have the purity required, are enclosed within their proper container and are correctly labeled;

►Records are made of the results of inspection, and to show that testing of materials, and of intermediate, bulk, and finished products is formally assessed against specification;


►Product assessment includes a review and evaluation of relevant production documentation and an assessment of deviations from specified procedures;

►No donated plasma is released for dispatching or supply prior to approval by the quality control department, in accordance with the requirements of the marketing authorization

►Sufficient reference standards, Test kits, reagents, validated instrument and appropriate space for testing is provided.

►The QC system must be ensured that the necessary quality controls in the Centre are performed according to the SOPs. As well as the documentation of the performed quality controls is correct and complete. QA support the planning of corrective action if the results of the quality controls are deficient. In order to ensure the observance of the procedures, they monitor the personnel, the methods of investigation, and the instruments.

So, QC department in BioDarou have specific responsibilities as below:

Layers of Safeguards

The heart of the blood safety system established by FDA is five layers of overlapping safeguards that start at the blood collection center and extend to the manufacturers and distributors of blood products.

1- Donor screening. Potential donors must answer questions about their health and risk factors. Those whose blood may pose a health hazard are encouraged to exclude themselves. A trained and competent health professional then interviews potential donors regarding their medical history.
Donors can be temporarily deferred (excluded from donating blood) for a number of reasons, including having a temperature, cold, cough, or sore throat on the day of donation or taking certain medications, such as Accutane (isotretinoin) or Proscar (finasteride). Reasons potential donors are permanently excluded from donating blood include evidence of HIV infection, male homosexual activity since 1977, a history of intravenous drug abuse, or a history of viral hepatitis.

2- Blood testing. After donation, the blood is tested for such blood-borne agents as HIV, hepatitis and syphilis.

3- Donor lists. Blood establishments must keep current a list of deferred donors and check donor names against that list.

4- Quarantine of untested blood. Blood products are not available for general use until the products have been thoroughly tested.

5- Investigation of problems. Blood establishments must investigate any breaches of safeguards and correct deficiencies. Licensed firms must report to FDA any manufacturing problems, errors or accidents that may affect the safety, purity or potency of their products. Registered firms, although not required to report problems, are required to thoroughly investigate problems and maintain accurate records for FDA to review during an annual inspection.

Blood Testing

One of the cornerstones of maintaining a safe blood supply is testing. FDA requires that all blood establishments test each unit of blood for a variety of blood-borne diseases. Furthermore, FDA reviews and approves all assay test kits used to detect infectious and transmittable diseases in donated blood. Each unit of blood must be tested for:

Hepatitis B, using HBsAg ( an indicator of the virus)
Hepatitis C, using a Hepatitis C antibody test HCV Ab
HIV-1 (AIDS virus), using an HIV-1 antibody te HIV-2
Syphilis for evidence of this sexually transmitted disease.

In the early 1970s, the risk of contracting some form of hepatitis from a unit of blood was as high as 6 to 8 percent. Now the risk of contracting hepatitis B per unit of blood is approximately 1 in 250,000, and the risk for contracting hepatitis C is less than 1 in 3,300. For HIV, the virus that causes AIDS, the risk of infection has decreased from 1 in 2,500 in 1985 to around 1 in 225,000 today.

In 1985, FDA licensed the first test, HIV-1 enzyme immunoassay, capable of detecting HIV antibodies in blood. In 1987, the agency licensed the more precise Western Blot Test, which is used as a confirmatory test. Screening tests are continually being improved. The test for hepatitis C detects the antibody in about 90 percent of chronic non-A, non-B hepatitis cases. However, more sensitive tests are being developed. The screening test for HIV is among the most sensitive, detecting evidence of infection in more than 99 percent of infectious samples.*

*A reprint from FDA Consumer Magazine Printed May 1995

RELEVANT TERMINOLOGY

Aphaeresis: Process by which one or more blood components is selectively obtained from a donor by withdrawing whole blood, separating it by centrifugation or filtration into its components, and returning those not required to the donor.

Blood (Whole blood): Whole blood collected from a single donor and processed either for transfusion or further manufacturing.

Blood component: Therapeutic components of blood (red cells, white cells, plasma, platelets) that can be prepared by centrifugation, filtration, and freezing using conventional blood bank methodology.

Blood establishment: Any enterprise or body that is involved in any aspect of the collection and testing of human blood or blood components, whatever their intended purpose, and their processing, storage and distribution when intended for transfusion.
1 July 2004 Page 19 of 21 PE 005-2

Blood product: Any therapeutic product derived from human blood or plasma. Encompasses both labile blood components and stable plasma and cell derivatives.

Closed system: System developed for the aseptic collection and separation of blood and blood components, manufactured under clean conditions, sealed to the external environment and sterilized by an approved method.

Open system: System in which a breach has occurred but every effort is made to prevent microbial contamination by operating in a clean environment using sterilized materials and aseptic handling techniques.

Donor: A person in normal health with a good medical history who voluntarily gives blood or plasma for therapeutic use.

First time donor: Someone who has never donated either blood or plasma GMP Good Manufacturing Practice: All elements in the established practice that will collectively lead to final products or services that consistently meet appropriate specifications and compliance with national and international regulations.

Manufacture: All operations of purchase of materials and products, Production, Quality Control, release, storage, dispatch of blood components and the related controls.

Preparation: All operations from the receipt of blood or blood component (after its collection) to its completion as a finished blood component.

Procedure: Description of the operations to be carried out, the precautions to be taken and measures to be applied directly or indirectly related to the manufacture of a blood product.

Product release: Process which enables a product to be released from a quarantine status by the use of systems and procedures to ensure that the finished product meets its release specification.
PE 005-2 Page 20 of 21 1 July 2004

Production: All operations involved in the preparation of blood components, from the collection of blood or blood component, through processing to its completion as a finished blood component.

Quality: Totality of characteristics of an entity that bear on its ability to satisfy stated and implied needs. Consistent and reliable performance of services or products in conformity with specified standards.

Quality assurance: All planned and systematic activities implemented within the quality system and demonstrated as needed to provide adequate confidence that an entity will fulfill requirements for quality.

Quality control: Operational techniques and activities that are used to fulfill requirements for quality in compliance with the specification.

Quality management: All activities of the overall management function that determine the quality policy, objectives, and responsibilities and implement them by such means as quality planning, quality control, quality assurance, and quality improvement within the quality system.

Quality monitoring: That part of a quality assurance program concerned with maintenance and improvement of quality which deals with the identification and use of indicators to detect variations from standards or specifications.

Reconciliation: Comparison and assessment of any discrepancy between the amount of material entering and leaving a given operation or series of operations.

Regular donor: Someone who routinely donates their blood or plasma (i.e. within the last two years), in accordance with minimum time intervals, in the same donation centre.

Repeat donor: Someone who has donated before but not within the last two years in the same donation centre.

Responsible personnel: Individuals with relevant qualifications and experience for the scope of activities carried out in a blood establishment.

Self-inspection: An audit carried out by people from within the organization to ensure compliance with GMP and regulatory requirements.
1 July 2004 Page 21 of 21 PE 005-2

Validation: That part of a quality assurance system that evaluates in advance the steps involved in operational procedures or product preparation to ensure quality, effectiveness, and reliability.

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Refrences:

• WHO: Requirements for collection, processing and quality control of blood components and plasma derivatives. Requirements for Biological Substances No. 27, revised 1992

• Commission of the European Communities: Good manufacturing practice for medicinal products in the European Community. The rules governing medicinal products in the European Community, Volume IV, 1997

• Commonwealth Department of Human Services and Health, Therapeutic Goods Administration, Australian Code of Good Manufacturing Practice for Therapeutic Goods - Blood and Blood Components, December 1995

• Council of Europe: European Pharmacopoeia, current version

• Council of Europe: Guide to the preparation, use, and quality assurance of blood components, current version

• Council recommendation on the suitability of blood and plasma donors and the screening of donated blood in the European Community, 29 June 1998 (98/463/EC)

• ISO 9000:2000: Quality management systems – Fundamentals and vocabulary, current version

• PIC/S: Aide Memoire for Inspection of Blood Donation and Plasmapheresis Centers, 13 December 1996 (PS/W 5/96)

• United States Food and Drug Administration, Code of Federal Regulations, 21 Parts 600 - 799, revised as of April 1, 1997

Related Documents:

• WHO Recommendations for the Production, Control and Regulation of Human Plasma for Fractionation

• WHO Guidelines on viral inactivation and removal procedures intended to assure the viral safety of human blood plasma products. WHO Technical Report Series (TRS) No. 924, Annex 4 (Adopted by ECBS 2001) [pdf 630kb]

• WHO Requirements for the collection, processing and quality control of blood, blood components and plasma derivatives. TRS No 840, Annex 2 (Adopted by ECBS 1992) [pdf 3.27Mb]

• PIC/S GMP Guide for Blood Establishments (Jul 2004) [pdf 209kb]

• Eleventh International Conference of Drug Regulatory Authorities (ICDRA); Workshop on Assuring quality and safety of blood products. Madrid, Spain (2004)

• Tenth International Conference of Drug Regulatory Authorities (ICDRA); Workshop on Safety of blood-derived products. Hong Kong, China (2002)

• Ninth International Conference of Drug Regulatory Authorities (ICDRA); Workshop on Safety issues of plasma-derived medicinal products. Berlin, Germany (1999)

Related links:

• International Conferences of Drug Regulatory Authorities (ICDRA)

• Pharmaceutical Inspection Convention / Pharmaceutical Inspection Cooperation Scheme (PIC/S)

• WHO Expert Committee on Biological Standardization (ECBS) Mission

• WHO Expert Committee on Biological Standardization (ECBS) Reports

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