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

2. 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 .“

3. 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

4. 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.

5. 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

8. 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.

9. 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. “

10. Microbial Contaminants
Endospores
Quality Degradation
Potential Harm
Endotoxins
Mycoplasmas

11. Bacterial Structures

13. Endospore Formation Process
Typically takes hours
SURVIVAL!
Extraordinary Resistance!

15. MYA Bacteria!
New Oldest “Living” Endospores MYA

16. Microbial Contaminants
Endospores
Quality Degradation
Potential Harm
Endotoxins
Harmful effects
Indicate contamination
Mycoplasmas

17. Gram - Cell Wall Composition
contains endotoxin
***
***
Fig. 3.34

18. Endotoxin Effects

19.  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

20. Endotoxin Assay Most commonly used assay:
LAL Kinetic Assay - Lymulus (horseshoe crab) amoebocyte lysate (LAL) test
Manufactuer’s of LAL:

21. LAL assay background

22. Microbial Contaminants
Endospores
Quality Degradation
Potential Harm
Endotoxins
Harmful effects
Indicate contamination
Mycoplasmas

23. Mycoplasmas

24. 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 ( 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.

25. Mycoplasma Assays
QA/QC Forms

26. General “Sanitary” Monitoring Techniques
Petrifilms (3M)