asepsis 2

Question 1

what methods are used to assess risk of microbial contamination?

Answer 1

–Hazard analysis critical control points (HACCP)
–Failure mode and effects analysis (FMEA)
–Fault tree analysis (FTA)
–And many others

Question 2

what are the 7 principle of HACCP?

Answer 2

1. Perform hazard analysis and identify preventative measures for each stage
2. Determine Critical Control Points (CCP)
3. Establish target levels and critical limits
4. Establish a monitoring system of CCPs
5. Establish what corrective action occurs when something goes wrong
6. Establish a verification system to make sure its working properly
7. Establish a record keeping system

Question 3

what are the 4 grades for the manufacture of sterile medicinal products?

Answer 3

• Grades C and D:Clean areas for carrying out less critical stages in the manufacture of sterile products.
• Grade B:In case of aseptic preparation and filling, the background environment for grade A zone.
• Grade A:The local zone for high risk operations, e.g. filling zone, stopper bowls, open ampoules and vials, making aseptic connections.

Question 4

what class of ISO is the cleanest?

Answer 4

class 1 is the cleanest and class 8 is the least clean

Question 5

what classes of ISO correspond to the WHO/EU grades?

Answer 5

ISO 5= A/B
ISO 7=C
ISO 8=D

Question 6

What is a cleanroom?

Answer 6

A cleanroom is a contained space where airborne particulates are controlled and environmental conditions controlled as needed

Question 7

what is important in a clean room design?

Answer 7

design and layout?
floors,walls and ceilings: coated with chemically resistant materials
•All exposed surfaces are smooth and sealed to minimize accumulation of dirt
•Equipment and fixtures may be on movable surfaces to facilitate cleaning

Question 8

what are the general considerations when designing a cleanroom?

Answer 8

• Air-locks: buffer zone prevention of contamination entry of all substances/personnel into a clean room must occur via air-lock systems
• An interlocking system: System which ensures that doors are never open at the same time
• Can be mechanical(at high risk areas) or an alarm(at lower risk areas)•Stops a direct connection between dirty and clean areas
• Separate entries and exits: For personnel, raw materials, and products

Question 9

how are personnel a major source of potential contaminants?

Answer 9

microbes that humans carry
- normal talking can emit 1-50 particles per second
skin sheds 28-85mg of skin per hour

Question 10

how do we reduce the risk of people contaminating the clean room?

Answer 10

• Ensure staff are adequately trained
• Provide specialized protective equipment (sterile gloves, face masks etc)
• Minimize personnel in the clean area at any given time

Question 11

what kind of airflows are used in clean rooms?

Answer 11

Airflow in cleanrooms use either HEPAor ULPA filters
•HEPA removes 99.95% of particles ≥0.3μm
•ULPA removes 99.999% of particles ≥0.1μm

Question 12

what are the two possible airflow principles that the airflow and airlocks use?

Answer 12

• Laminar: unidirectional (horizontal or vertical), constant velocity•Can be influence/directed by walls curtains, machinery etc (created air turbulence)
• Turbulent: random directions, non specific velocities

Question 13

what are the 3 main types of airlocks in pharma?

Answer 13

cascade, bubble and sink

Question 14

how does airflow and airlocks work?

Answer 14

• Uses pressure differences between spaces to stop particles moving between areas (usually 10-15 Pa between areas)
• The difference between the 3 is the way the air is handled

Question 15

how do we environmentally monitor cleanrooms?

Answer 15

Takes regular samples from the following based on the risk analysis;
•Physical (pressure, particles, temperature, relative humidity etc)
•Microbiological
•Personnel (gloves, nails etc)
•Surfaces (swabs, contact plates)

Question 16

what is particulate monitoring?

Answer 16

Generation of particles during routine operations is unavoidable but can be controlled and monitored

Question 17

how are particulate levels monitored?

Answer 17

• Particulate levels monitored under 2 conditions
• At rest: All equipment, environmental control systems in place but not running & no staff present.
• Not part of routine environmental monitoring

Question 18

how are particles measured?

Answer 18

by a light scattering instrument

Question 19

what happens if something goes wrong?

Answer 19

• If limits are broken, need to establish how and where problem has come from–Microbial/particulate results will give you a clue where to start but not the complete picture
• Other systems will be in place to monitor mechanical processes, maintenance procedures, cleaning regimes etc etc