June 2015

& Cross & Cross ContaminationContamination

Sreenath.SSreenath.S

QC-Micro

WelcomeWelcome

Microbial Impacts on Products Microbial Impacts on Products

-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"

 

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).

 

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

 

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

 

FDA-RECALL- Physical Contamination

 

FDA-RECALL- Physical Contamination

 

FDA-RECALL- Chemical Contamination

 

FDA-RECALL- Biological Contamination

Gowning Procedures Gowning Procedures

• 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

 

Cross-contamination:

 

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

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

 

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.

 

EnvironmentTemp. & RH

Pressure DifferentialAir velocityAir changes

Filter IntegrityViable & Non-Viable particles

HVAC Controls

 

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.

 

Microbial contamination of pharmaceuticalsMost 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 productsThe 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.

 

 

Contamination

Contaminants from

Environment& Operators

Contaminants from

Equipment

CrossContamination

Productfrom

Environment& Operators

Productfrom

Equipment

 

• 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

 

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)

 

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

 

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.

 

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.

 

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

 

Bata-Lactam Cross contamination

(Attix Pharma, Canada- June 2015)

 

Bata-Lactam Cross contamination

FDA -483 (Attix Pharma, Canada- June 2015)

 

Bata-Lactam Cross contamination

FDA -483 (Attix Pharma, Canada- June 2015)

 

CAUSIONS

House keeping

AHU/HVAC Systems

Personnel Hygiene

Microbial Monitoring

cGMP

FDA SURPRISE VISIT FDA SURPRISE VISIT

 

Post Script....!!!!

The challenge in aseptic processing is always personnel:

•As a source ofmicrobial andparticlecontamination.

•As a brake on theimplementation ofimprovedtechnology.

 

Do U Really Wanna Screw UP….????

THANKS THANKS FOR YOUR FOR YOUR

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