Aseptic Production

Question 1

What is Aseptic production ?

Answer 1

The assembling of sterile ingredients or products using sterile equipment and appropriate techniques within a clean room environment

Question 2

State the most common flora found on walls and ceilings

Answer 2

Mould (they’re able to feed off plaster)

Question 3

Walls and ceilings of a clean room should be ?

Answer 3

Smooth, Impervious and Washable

Question 4

Generally walls of clean rooms are clad with what type of plastic ?

Answer 4

Laminated plastic

Question 5

Why do aseptic clean rooms have a ‘false ceiling’

Answer 5

It contains air filtration systems and light fittings

Question 6

In a clean room, Electrical wiring, pipework etc should be fitted within the walls rather than on the wall. TRUE or FALSE

Answer 6

TRUE

Question 7

State requirements for Floors and drains in a clean room

Answer 7

• Floors should be flat, impervious to water, easy to clean
• Floor joints should be adequately sealed
• Floor to wall junction should be coved (curved laminated plastic)
• Floor surface must be able to withstand cleaning products
• There should be NO open sinks or drains in a clean room (handwash facilities will be exterior to the clean room)

Question 8

State requirements for Doors, Windows and Fittings in a clean room

Answer 8

• Must be fitted flush with the walls to prevent dust collecting
• Doors must be well fitting to prevent entry of microorganisms
• Doors must be easy to open (usually no door handles, push plates used instead). If doors have handles they are flush fitted
• Windows for light only, not ventilation
• Fittings such as door plates must be easy to clean (often stainless steel used)

Question 9

The EU guidance gives four grades of air. State them

Answer 9

Grade A: Cleanest possible air. For ‘high risk’ operations. e.g: Aseptic connections and filling. (Withdrawing a liquid from a vial using

Grade A environment has to be situated within a; Grade B: minimum background environment.

Grade B: Almost as clean as Grade A. Minimum background environment for grade A zones.

Grade C and D: Less critical stages of aseptic production. e.g: labelling and packing

Question 10

Air supply (whatever grade) before it enters the clean room must be filtered. What filter is used to achieve this ?

Answer 10

HEPA filters

Question 11

How many changes per hour are there in a clean room and what is this dependent on ?

Answer 11

20-35. Depending on room size, activity and number of operators

Question 12

State the two types of air flow patterns

Answer 12

1) Unidirectional (ensures hyper clean and safe environments)
2) Non-directional (Grade C and D environments)

Question 13

What does HEPA stand for

Answer 13

High-efficiency Particulate Air

Question 14

HEPA filters trap particulate contamination. TRUE or FALSE

Answer 14

TRUE

Question 15

HEPA filters are made up of pleated fibreglass filters. What does the glass spindles on the fibreglass ensure ?

Answer 15

Large surface area

Question 16

HEPA filters exhibit

Answer 16

• Air passing through filter at a high flow rate
• High particulate holding capacity
• Low pressure drop across the filter

Question 17

HEPA filters can remove particles in 3 ways. State them

What british standard must the HEPA filter conform to ?

Answer 17

1) Removal of large particles by; Inertial impaction
2) Removal of medium particles by; Interception
3) Removal of small particles by; Brownian diffusion
- Must conform BS5295

Question 18

Clean rooms generally operate under negative pressure. TRUE or FALSE

Answer 18

FALSE. They usually operate under POSITIVE PRESSURE; 10-15 pascals above surrounding environment. Prevents ingress/entry of particles

Question 19

When is negative pressure (10-15 pascals below surrounding environment)
used in a clean room

Answer 19

If products are deemed to be a risk to operators

Question 20

A clean room suit is usually a room within a room. Multiple rooms have multiple pressure differentials.

Answer 20

LEARN

Question 21

State the two types of Laminar airflow cabinets

Answer 21

Horizontal and Vertical

i.e; Air will blow horizontally or vertically at the operator.

Question 22

Laminar Airflow cabinet is always situated in a positively pressured area. TRUE or FALSE

Answer 22

TRUE

Question 23

Horizontal laminar airflow cabinets have an open front

Answer 23

LEARN

Question 24

Where is the HEPA filter situated in an horizontal laminar airflow cabinet ?

Answer 24

At the back of the cabinet

Question 25

Horizontal laminar airflow cabinets are for products with risk or no risk to the operator ?

Answer 25

Products with no risk e.g: TPN

Question 26

Vertical laminar airflow cabinets are for products with risk or no risk to the operator ?

Answer 26

Products with some risk to the operator e.g: Cytotoxic drugs

Question 27

Where is the HEPA filter situated in a vertical laminar airflow cabinet ?

Answer 27

At the top of the cabinet

Question 28

Vertical laminar airflow cabinets are usually more difficult to work in as they do not have an open front. Instead they have a …

Answer 28

Perspex barrier

Question 29

Horizontal and Vertical laminar airflow cabinets have to be situated in an environment with what grade of air ?

Answer 29

Generally Grade A air but Grade B may be used also

Question 30

What is an alternative to Grade A and B air ?

Answer 30

Isolators

Question 31

State the 2 types of Isolators

Answer 31

Type 1 (Positive pressure Isolator)

Type 2 (Negative pressure Isolator)

Question 32

Isolators are self contained sealed units.

Answer 32

LEARN

Question 33

State an advantage of a Negatively pressured isolator ?

Answer 33

It can be situated in a positively pressured room. Doesn’t need to be in a negatively pressured room to operate

Question 34

Type 1 isolators are used for the production of what type of products ? Give examples

Answer 34

Non-harmful products e.g: TPN, Injections, eye drops

Question 35

Type 2 isolators are used for production of harmful products such as ?

Answer 35

Cytotoxics, BCG vaccines

Question 36

Type 1 isolators protect products from operator and aseptic process

Answer 36

LEARN

Question 37

Type 2 isolators protect products from operator and operator from product

Answer 37

LEARN

Question 38

What type of isolator is used for industrial/ large scale manufacture ?

Answer 38

Half-suit isolators

(generally used for making electronic components for the space industry)

• Can be type 1 or type 2
• Allows operator greater movement (operator comes from the bottom)

Question 39

There is a specification for clean room clothing

Answer 39

LEARN

Question 40

Why is Clean room clothing is worn ?

Answer 40

To prevent particulate contamination from the human body

Question 41

State some specification required for clean room clothing

Answer 41

• Must not shed particles or fibres
• Must be washasble
• Must be sterilisable (usually autoclaving or radiation)

Question 42

To maintain asepsis, we have to ensure ?

Answer 42

• Operators work efficiently and with good technique (Staff training, validation and revalidation)
• Appropriate disinfection of products
• Microbiological monitoring on a daily basis and this includes;
• Finger dabs
• Settle plates
• Surface testing
• Active air sampling

Question 43

GMP applies to all aseptic processes.

• There must be a system in place to trace patients should a problem be identified
• Documentation should be kept up to date
• All processes should be validated (reviewed) regularly

Answer 43

LEARN

Question 44

Give examples of 2 incidents where aseptic processes went wrong

Answer 44

1) Manchester Children’s Incident 1994
(2 children died after receiving TPN which was contaminated with Enterobacter cloacae)

2) Germany Incident 2010
(3 babies dies and 4 critically ill after receiving TPN contaminated with Enterobacter cloacae)