QA/QC, (c)GMP, SOP, BSL, etc.

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QA/QC, (c)GMP, SOP, BSL, etc.
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Quality Control

• Quality control is involved in developing
  systems to ensure products or services are
  designed and produced to meet or exceed customer
  requirements and expectations .

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Quality Assurance

• Covers all activities from design, development,
  production, installation, servicing and
  documentation
• Includes
• the regulation of the quality of raw materials,
  assemblies, products and components
• services related to production and
• management, production, and inspection processes

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PDCA (aka the Shewhart Cycle)

• An iterative four-step quality control strategy
• Ensure that the product fulfills or exceeds
  customer expectations
• PLAN
• establish the objectives and processes necessary
  to deliver results in accordance with the
  specifications.
• DO 
• implement the processes.
• CHECK
• monitor and evaluate the processes and results
  against objectives and specifications and report
  the outcome.
• ACT
• apply actions to the outcome for necessary
  improvement.

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Good Manufacturing Practice

• A set of regulations, codes, and guidelines for
  the manufacture of drugs (known as medicinal
  products in Europe), medical devices, diagnostic
  products, foods products and Active
  Pharmaceutical Ingredients (APIs).
• cGMP current GMP

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Standard Operating Procedures

• Written descriptions of routine methods
  (standardize).
• Referenced or provided in an appendix of the QA
  project plan.
• Procedures benefiting from SOPs include
• routine measurements
• chain-of-custody
• sample handling and shipment
• routine analytical methods for chemical
  analyses.
• Ensure that all persons conducting work are
  following the same procedures and that the
  procedures do not change over time.
• All personnel should be thoroughly familiar with
  the SOPs before work is initiated.
• Deviations from SOPs may affect data quality and
  integrity.
• If it is necessary to deviate from approved SOPs,
  these deviations must be documented and approved
  through an appropriate chain-of-command.
• Personnel responsible for ensuring the SOPs are
  adhered to must be identified in the QA Project
  Plan.

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Biological Safety Levels (BSLs)

• Biosafety Level 1 suitable for work involving
  well-characterized agents not known to
  consistently cause disease in healthy adult
  humans, and of minimal potential hazard to
  laboratory personnel and the environment.
• The laboratory is not necessarily separated from
  the general traffic patterns in the building.
  Work is generally conducted on open bench tops
  using standard microbiological practices. Special
  containment equipment or facility design is
  neither required nor generally used.
• Laboratory personnel have specific training in
  the procedures conducted in the laboratory and
  are supervised by a scientist with general
  training in microbiology or a related science.

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Microbial Contaminants

• Endospores
• Quality Degradation
• Potential Harm
• Endotoxins
• Mycoplasmas

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Bacterial Structures

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Endospore Formation Process
Typically takes hours
SURVIVAL!
Extraordinary Resistance!
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25 - 40 MYA Bacteria!
New Oldest Living Endospores - 250 MYA
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Microbial Contaminants

• Endospores
• Quality Degradation
• Potential Harm
• Endotoxins
• Harmful effects
• Indicate contamination
• Mycoplasmas

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Gram - Cell Wall Composition
contains endotoxin


Fig. 3.34
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Endotoxin Effects
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 Fever (Pyrogenicity)      Circulatory system
effects   Leukopenia followed by leukocytosis
  Leukopenia an abnormal reduction in the
number of leukocytes   Leukocytosis an abnormal
increase in the number) of leukocytes  Increased
vascular permeability (vasodilation)   Decreased
peripheral circulation   Decreased perfusion
(blood flow) of blood to major organs  
  Effects on blood coagulation   (DIC)
Disseminated intravascular coagulation
  Activation of clotting pathway   Thrombosis
Formation of blood clot (thrombus) in heart or
blood vessel      Effects on metabolic and liver
functions   Decreased iron availability
  Hypoglycemia Abnormally low glucose levels
  Cellular death (cytotoxicity)   Organ
necrosis   Sum of morphological changes
indicative of cell death and caused by the
progressive degradative action of enzymes
  Shock   Characterized by failure of the
circulatory system to maintain adequate
blood flow to the vital organs   Symptoms
include Hypotension Weak pulse Rapid and
shallow breathing Low body temperature CNS
(central nervous system) effects (e.g., nausea)
  Death  
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Endotoxin Assay

• Most commonly used assay
• LAL Kinetic Assay - Lymulus (horseshoe crab)
  amoebocyte lysate (LAL) test
• Manufactuers of LAL

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LAL assay background
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Microbial Contaminants

• Endospores
• Quality Degradation
• Potential Harm
• Endotoxins
• Harmful effects
• Indicate contamination
• Mycoplasmas
• Harmful effects
• Indicate contamination

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Mycoplasmas
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Mycoplasma Silent Infections

• long implicated in a variety of frustrating and
  expensive cell-culture contaminations.
• Lack rigid cell wall
• not affected by the presence of beta-lactamase
  antibiotics
• small in size (0.3 - 0.8 µm)
• do not produce turbidity
• very hard to see with light microscope.
• Presence/growth can result in severe metabolic
  changes and production of deleterious
  metabolites affecting valuable data and results.
• Contamination of cell cultures can result in loss
  of valuable cell lines, production time and
  batches of biologicals.
• Monitoring cell cultures on a routine basis can
  help identify the source of contaminations as
  well as prevent future cross-contamination
  events.

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Mycoplasma Assays
QA/QC Forms
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General Sanitary Monitoring Techniques

• Petrifilms (3M)

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