Microbial Impacts on Pharma Products & Cross Contamination


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Microbial Impacts on Pharmaceutical dosage forms & Cross Contamination.

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  • Dust carries bacteria, much like a dog carries fleas.
    Dust can be categorized into 3 groups:
    COARSE DUST (50-500 microns) – settles rapidly
    FINE DUST (1,0 – 50 microns) – settles slowly
    ULTRA FINE DUST (< 0,5 – 1 micron) – remains suspended.
  • Microbial Impacts on Pharma Products & Cross Contamination

    1. 1. June 2015 & Cross& Cross ContaminationContamination Sreenath.SSreenath.S QC-Micro WelcomeWelcome Microbial Impacts on ProductsMicrobial Impacts on Products
    2. 2. -He successfully introduced carbolic acid (now known as phenol) to sterilize surgical instruments and to clean wounds, which led to a reduction in post-operative infections and made surgery safer for patients. By applying Louis Pasteur's advances in microbiology, he promoted the idea of sterile surgery (pioneer of antiseptic surgery) "Kills germs that cause bad breath"
    3. 3.    Definition of Cross-Contamination Cross-Contamination is the presence in a particular product of small, traceable quantities of other pharmaceutical products manufactured at the same time in the same premises previously on the same equipment or in the same premises Definition of contamination: The introduction of impurities of a chemical or microbiological nature, or of foreign matter, into or onto a raw material, intermediate, or API (e.g., occurring during production, sampling, packaging or repackaging, storage or transport).
    4. 4.    Types of contamination: 1.Physical: Ex. Particles/ Fibers /Paint flakes/ Metal parts 2.Chemical: Ex. Moisture/gases/ Molecules/ vapors 3.Biological: Ex. Microorganisms Examples of Cross-contamination: 1.Physical: Ex. Leakage of oil seal form the reactor 2.Chemical: Ex. If a product exposed to a high RH environment---- Increase in Moisture content 3.Biological: Ex. Improper Cleaning of equipment/ Use of unclean equipment for the process
    5. 5.    Biological contamination is due to : Improper sanitization of hands Improper Gowning procedures Open Lesions Suffering from Infectious diseases Use of contaminated water for cleaning equipments
    6. 6.    FDA-RECALL- Physical Contamination  
    7. 7.    FDA-RECALL- Physical Contamination  
    8. 8.    FDA-RECALL- Chemical Contamination  
    9. 9.    FDA-RECALL- Biological Contamination  
    10. 10. Gowning ProceduresGowning Procedures
    11. 11. • What are contaminants? • Contaminants are the presence of anything in the manufactured product which should not be there. • Contaminants can originate from: • Environment (particles, micro-organisms, dust containing other products/materials) • Equipment (residues of other products, oil, particles, rust, gaskets, metal) and can be brought into the product by air movements. • Personnel
    12. 12.    Cross-contamination:
    13. 13.    Where Do Contaminants Come From? • Outside air carries dust which is a contaminant • People generate contaminants: We completely shed our outer skin every 24 hrs. Particles of 0,3 micron & greater are liberated at a rate varying between of 100 000 to 10 million per minute A person walking will liberate 5000 bacteria/minute and a single sneeze can produce up to 1 million bacteria. • The manufacturing process itself can generate contaminants • Ex. paint off equipment, dust from belt drives, etc ∆
    14. 14. Why All the Concern About Dust? Typical size relationship between  dust, bacteria and viruses Virus  (0,006µm to  0,03µm) Dust Particle (0,5µm to  500µm) Bacteria  (0,2µm to  2µm) Dust Is a Bacteria Carrier
    15. 15.    Removal of Dust • As dust is a carrier, dust must be controlled. • Ambient bacteria is removed by filtration. • Internal bacterial distribution can be controlled by directional air flow and air flushing or dilution. • Surface bacteria is controlled by adherence to strict cleaning sop’s.
    16. 16.    Environment Temp. & RH Pressure Differential Air velocity Air changes Filter Integrity Viable & Non-Viable particles HVAC Controls 
    17. 17.    Microbial contamination of pharmaceuticals A pharmaceutical raw material is an active or inactive substance used in the manufacture of a pharmaceutical dosage form. Non-sterile pharmaceutical products with a high degree of water content may be contaminated with microorganisms. The contaminating microorganisms may cause spoilage of the product with loss of its therapeutic properties.
    18. 18.    Microbial contamination of pharmaceuticals Most raw materials for pharmaceutical products support some forms of microbial growth, depending on the nutritive properties and moisture contents. Hence, dry powder or tablets are capable of undergoing some form of microbial spoilage or degradation. The more serious problem of microbial contamination of tablets is where there are no obvious signs of spoilage; Survival of microorganisms within pharmaceutical products The survival of microorganism in particular environments is sometimes influenced by the presence of relatively inert materials. Thus, microbes can be more resistant to heat or desiccation in the presence of starch, acacia or gelatin.
    19. 19.   
    20. 20.    Contamination Contaminants  from Environment & Operators Contaminants  from  Equipment Cross Contamination Product from Environment & Operators Product from Equipment
    21. 21.    • Cross-contamination  is a sure indication of bad  practices,  as it shows that there is insufficient control over, 1.Design of premises and systems quality 2.Air handling and dust extraction systems 3.Operation and maintenance of air handling and dust extraction systems 4.Procedures for cleaning of equipment and for restriction of movement of personnel 5.Procedures for cleaning of premises
    22. 22.    Cross-contamination can be minimized by 1. Personnel procedures (Skilled Manpower, Technical Awareness) 2. Adequate premises (Proper Lay out, Area Classification) 3. Use of closed production systems (Man & Material movement) 4. Adequate, validated cleaning procedures 5. Correct air pressure cascade (HVAC design & Air Distribution)
    23. 23.    Prevention of Cross-contamination during Processing Clothing/ Gowning/PPE Proper washing of cloths Dedicated clothing for sensitive products (Hormones)/BP/GP separate washing facility Minimize the exposed body surfaces Clothing/Linen should be changed after every product change over Utilities  Ensure monitoring of Water/Compressed air on a regular basis
    24. 24.    Bata-Lactam Cross contamination Separation from BP to GP -penicillin products may cross contaminate other medicines -cross-contaminated products can cause severe anaphylactic reactions and death in sensitive patients -more than one drug is manufactured in the same production line. This is the source of cross- contamination since residuals of former drug may be passed to the latter drug.
    25. 25.    Bata-Lactam Cross contamination Separation from BP to GP -The cGMP requires that production of penicillin and other preparations liable to be contaminated shall be carried out in dedicated areas Penicillin can be a sensitizing agent that triggers a hypersensitive exaggerated allergic immune response in some people.
    26. 26.    21 CFR 211.42(d), 211.46(d), and 211.176. Non-penicillin beta-lactam drugs also may be sensitizing agents. Cross-contamination with non- penicillin beta-lactam drugs can initiate the same types of drug-induced hypersensitivity reactions that penicillins can trigger, including life-threatening allergic reactions. Therefore, manufacturers of non- penicillin beta-lactam drugs should employ similar control strategies to prevent cross-contamination, thereby reducing the potential for drug-induced, life- threatening allergic reactions. Bata-Lactam Cross contamination Separation from BP to GP
    27. 27.    Bata-Lactam Cross contamination (Attix Pharma, Canada- June 2015)
    28. 28.    Bata-Lactam Cross contamination FDA -483 (Attix Pharma, Canada- June 2015)
    29. 29.    Bata-Lactam Cross contamination FDA -483 (Attix Pharma, Canada- June 2015)
    30. 30.    CAUSIONS  House keeping  AHU/HVAC Systems Personnel Hygiene Microbial Monitoring cGMP
    32. 32.    Post Script....!!!! The challenge in aseptic processing is always  personnel: •As a source of microbial and particle contamination. •As a brake on the implementation of improved technology.