Microbial Impacts on Pharmaceutical dosage forms & Cross Contamination.

1. June 2015
& Cross& Cross
ContaminationContamination
Sreenath.SSreenath.S
QC-Micro
WelcomeWelcome
Microbial Impacts on ProductsMicrobial Impacts on Products

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.
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.
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.
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.
FDA-RECALL- Physical Contamination

7.
FDA-RECALL- Physical Contamination

8.
FDA-RECALL- Chemical Contamination

9.
FDA-RECALL- Biological Contamination

10. Gowning ProceduresGowning Procedures

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.
Cross-contamination:

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. 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.
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.
Environment
Temp. & RH
Pressure Differential
Air velocity
Air changes
Filter Integrity
Viable & Non-Viable particles
HVAC Controls

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.
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.

20.
Contamination
Contaminants
from
Environment
& Operators
Contaminants
from
Equipment
Cross
Contamination
Product
from
Environment
& Operators
Product
from
Equipment

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.
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)

24.
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

25.
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.

26.
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.

27.
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

28.
Bata-Lactam
Cross contamination
(Attix Pharma, Canada- June 2015)

29.
Bata-Lactam
Cross contamination
FDA -483 (Attix Pharma, Canada- June 2015)

30.
Bata-Lactam
Cross contamination
FDA -483 (Attix Pharma, Canada- June 2015)

31.
CAUSIONS
House keeping
AHU/HVAC Systems
Personnel Hygiene
Microbial Monitoring
cGMP

32. FDA SURPRISE VISITFDA SURPRISE VISIT

33.
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.

34.
Do U Really Wanna Screw UP….????
THANKSTHANKS
FOR YOURFOR YOUR
KIND ATTENTIONKIND ATTENTION