Accreditation & Inspection + cGMP

What is blood component considered?

Biological and Blood

What is the goal of drugs?

Safe, Potent, effective

What is the goal of biologic?

Safe, pure, potent

What is the steps to getting approval?

1) Congress writes laws

2) President signs law and authorizes FDA

3) FDA enforces the laws and oversees compliance

What is CLIA’88?

Clinical Laboratory Improvement Amendments (FDA, CMS and CDC)

What is the purpose of CLIA’88?

1) Regulate laboratory testing (proficiency testing, competency, ect)

2) Establish laboratory standards for laboratory testing performed on specimens from humans eg. blood, body fluids + tissues

3) CLIA regulations established requirements for certification

What does FDA regulate?

Blood and blood components

What does CMS do?

Regulates all US medical laboratories under CLIA

What are the FDA agencies?

• Center for Blood Evaluation and Research (CBER)

• Office of Blood Review and Research (OBRR)

• Office of Regulatory Affairs (ORA)

What is the functions of FDA?

1) Enforce and oversee the laws

2) Issue Guidance Documents

3) Perform inspections

4) Impose penalties

What is the FDA requirement for unregistered TS/BB?

• Performing compatibility testing, pooling platelets and cryoprecipitate only

• they are not required to be FDA registered

What is a blood product manufacturers?

A company or institutions involved in collection, preparation, processing of reagents, equipment, supplies, devices, computer program

• includes hospitals performing component preparation and compatibility testing

What is the FDA requirement for Blood Product manufactures?

1) FDA registrations, FDA license (biologic license application

2) Follow current Good Manufacturing Practices (cGMP)

3) FDA inspections

What are other FDA requirements?

1) Biological product deviation reporting (BPDR)

• Lvl 1 = Sentinel event, blood was transfused before error was caught

• lvl 2 = near miss event

• lvl 3 = clerical error

2) Product recall - voluntary market withdrawals

3) Fatality reporting

Who are the inspection authorities?

• Pre-license inspection

• pre-approval inspection

• for-cause investigation

• routine cGMP inspection

What are the procedures FDA is inspecting for blood centers?

• Quality assurance system

• Donor eligibility criteria

• product collection

• product testing system

• quarantine/inventory management system

• documentation

What are the procedures FDA is inspecting for test centers / blood banks?

• Quality assurance system

• Quality control reagents/ instruments

• Patient testing

• Handling of blood products and components modifications

• quarantine/inventory management system

• documentation

What is in the DFA form 483?

Enforcement action

1) Advisory action —> warning letter

2) Administrative action —> suspension, revocation

3) Judicial action —> Seizure, injunction, prosecution

What are the accrediting agencies?

1) The Joint Commission (JC) formerly called JCHO

2) College of American Pathologist (CAP)

3) AABB (Formerly American Association of Blood Banks)

What is the goal of the Joint Commission?

Improve accuracy of patient identifications by requiring 2 identifier in blood samples

What are the goal of AABB and CAP?

AABB —> Developed standards for Blood Banks and Transfusion services

CAP —> established Transfusion medicine checklist

What is GMP?

The minimum legal requirement for the manufacture of drug, which will ensure the safety of the products produced

What is a biologic product?

Any virus, therapeutic serum, toxin, anti-toxin or analogous product applicable to the prevention, treatment or cure or disease or injuries to man

What does SQUIPP stand for?

• Safety

• Quality

• Identity

• Purity

• Potency

What is safety?

Refers to the chance that a blood component may cause harm to a recipient

What is identity?

Refers to the labeling of a blood component

What is purity?

Refers to the content of a blood component

• avoid bacterial contamination

What is potency?

Refers to the ability of the product to be effective = correct dosage, not expired

What are some consequences of Non-compliance?

• Purity, potency, safety compromised

• FDA citation (483)

• FDA Warning Letter

• FDA Intent to revoke licensure

• FDA consent decree

What is some benefits of GMP?

• Improve products via consistent and reliable system for production

• decrease component discard, rework and shortage

What are the elements in GMP?

• Record keeping

• Personnel

• Calibration

• Validation

• Error management

• SOP

• Production controls

• Labeling/Lot release

• Facilities/Equip/Supp

• QA and auditing

What is record keeping?

Effective documentation should provide trackability and traceability of each step

What is back date?

Documentation of date and/or time which implies that a process was performed at an earlier date/time

What is falsification of records?

Documentation that does not accurately reflect what actually occurred

What is indelible?

Making marks that cannot be easily removed, washed away, or erased

What is legible?

To document in a manner that can be easily read and understood

What is write-over?

The unacceptable practice of writing over a previous entry or comment

What is traceability?

The ability to tell who did what, when, and with what instrument

What is trackability?

The ability to follow a process (from beginning to end) through record review

What is calibration?

The comparison of measurement performed with an instrument to those made with more accurate instrument or standard for the purpose of detecting, reporting, and eliminating error in measurement

What is required in calibration?

• Documentation of calibration is required

• Identification of the equipment and standard use

• Performed at suitable intervals following written procedures

What is validation?

Validation establishes documented evidence which provides a high degree of assurance that a specific process will consistently produce a product that meets its pre-established quality and performance specification

What is error management?

A process or a system for identifying errors and observing patterns that occur in any phase of the manufacturing operation

What are 3 things error management is looking out for?

1) Accidents —> unexpected occurrences

2) Error —> Mistakes attributable to a person

3) Deviations —> Variance from the SOPs

What are some example of reportable error?

• Unsuitable units released for transfusion

• QC on the equipment used for testing not documented

• microbiologically contaminated

• Release of the wrong component for transfusion

• Transfusion reaction due to mis-transfusion

• missing special needs

What is Form 483?

A list of all things discovered during a FDA (CBER) inspection that the transfusion services is expected to correct

What is error management?

The responsible head must be informed of all complaints, errors, component investigation, recalls or regulatory action

What is the definition of Standard Operating Procedures?

A living document that provides instruction on how to perform a task in order to achieve consistency and control in operations

What is process control?

1) Control: To regulate

2) Process: set of activities that use resource to transform inputs to outputs

3) Process Control: Activities intended to minimize variation within a process to produce a predictable output that meets specification

What is the laboratory control?

Standards and test procedures ensure that blood products are safe, pure, potent and effective

• Reliable methods for monitoring test procedures and instruments

What does the compatibility testing control requires?

1) Positive identification of recipient samples

2) Fresh samples for pre-transfusion testing

3) Crossmatching procedure

4) Procedure for emergency release of unxm blood, including complete documentation signed by the doctor requesting the procedure

What does the equipment and facility control?

1) Cleaning and maintenance logs

2) Equipment identification

3) Equipment status

What is labeling?

Labeling/Lot Release is the system that ensures that each final container is correctly labeled

• The labeling system consists of multiple processes, including record review, determination of component suitability for labeling, the labeling process, verification of labeling

What are the parts included in the labeling process?

• Proper name of the component

• Name, address of manufacturer

• Expiration date, including day, month and year and if dating period is 72 hours or less

• Donor classification e.g. “volunteer donor”

• Volume of the component accurate within 10%

• recommended storage temperature

What are some labeling control?

• Labeling must be separate from other operations

• labels for different components stored separately

• obsolete labels destroyed

• labels must be clear & legible

• New labels compared to an approved copy

• components unsuitable for transfusion labeled “NOT FOR TRANFUSION”

What is responsibilities of quality management?

Review records, SOP and training program approval, internal and external assessments, error investigation, approval of validation protocol, and QC review

What is quality assurance program?

Activities involving quality planning, control, assessment, reporting and improvements necessary to ensure that a product or service meets define quality standards and requirements

• Blood manufactures must have a QC/QA unit that reports independently from productions/operations to the Responsible Heads

What is QA auditing?

A mechanism for evaluating the effectiveness of the total QA program

• must be documented and must include assessment of effectiveness of corrective action and process improvement

What is the responsibilities of the QA units?

• Assess impact of SOP changes

• Review and approval of SOP

• Index SOP

• Archive obsolete SOP

• Ensure SOP are accessible to staff

• Ensure validation protocol are written

• Ensure changes to SOP are documented

• Approve validation protocols

• Approve traning program content

• Approve test procedures used in QC

• Error management

• record review

• internal audits

What is FOCUS PDC

• F —> Find a process to improve

• O —> Organize a team that knows the process

• C —> Clarify current knowledge

• U —> Understand the sources of variation

• S —> Start the PDCA cycle

• P —> Plan the improvement

• D —> Do the improvement

• C —> Check the results

• A —> Act to hold the gain

What are the 10 commandments of GMP?

1) Thou shalt read procedures

2) Thou shalt follow written procedures

3) Thou shalt validate

4) Thou shalt document thy work

5) Thou shalt design and build proper facilities and equipment

6) Thou shalt maintain thy facilities and equipment

7) Thou shalt be competent

8) Thou shalt be clean

9) Thou shalt control for quality

10) Tho shalt audit for compliance