3.D Room classes

Here you will find answers to the following questions:

  • Which room classes exist?
  • How can the required room classes be achieved?

At pharmaceutical companies, hygiene, ventilation and constructional design requirements of the rooms vary according to their function. The most fundamental requirement, which applies in all areas, is that the penetration of animals and insects must be prevented. Moreover, rooms must be designed to prevent the accumulation of dust and dirt and facilitate easy cleaning. The requirements for the rooms must be defined according to the products and the procedure.

Figure 3.D-1 Classification of air quality for the production of sterile products [EU GMP Guideline]

 

At Rest

Operational

Class

Max. permitted numer of particles/m3
(equal to or above than)

Recommended limits for microbial contamination

 

0.5 mm

5 mm

0.5 mm

5 mm

 

A

3.500

0

3.500

0

<1

B (a)

3.500

0

350.000

2.000

10

C (a)

350.000

2.000

3.500.000

20.000

100

D (a)

3.500.000

20.000

not determined (c)

not determined (c)

200

(a) In order to achieve the air purity classes B, C and C, the frequency of the air exchange must be relative to the size of the room, the facility and the number of personnel in the room. The ventilation system should be fitted with suitable filters, such as HEPA filters for cleanliness classes A, B and C.

(b) The guidelines listed under "at rest" for the maximum permissible particle count approximately correspond to the US Federal Standard 209 E and the ISO classifications: Cleanliness classes A and B correspond to class 100, M 3.5, ISO 5, cleanliness class C to class 10 000, M 5.5, ISO 7 and cleanliness class D to class 100 000, M 6.5, ISO 8.

(c) The requirements and limits for this area depend on the type of work processes carried out.

(d) The values given are averages

According to the first supplementary guideline of the EU GMP Guideline, the production of sterile dosage forms places special demands on rooms that must be satisfied. The law requires that the various operations are assigned different room classes. In categories A-D, the maximum permissible number of particles and microbial counts in the air of a room are specified.

The particle requirements specified in figure 3.D-2 for cleanliness class A with operational status table "should be maintained in the zone immediately surrounding the product whenever the product or open container is exposed to the environment." [EU GMP Guideline, Annex 1.3] to minimise the risk of product contamination. The categories for the various dosage forms are defined in the EU GMP Guideline depending on whether products can be sterilised in the final container or whether aseptic processing is required.

Figure 3.D-2 Example of a zonal concept

GMP zonal concept

Area

Definition

Comment

Warehouse
Offices
Laboratories
Secondary packaging

not defined

-

Production
Primary packaging

Rooms and equipment according to the requirements of the EU GMP Guideline, Chapter 3

Standard arrangement
Filter corresponds with room class D, but without regular monitoring

Sterile production

Class A, B, C, D

See EU GMP Guideline - supplementary guidelines for the production of sterile medicinal products

Derived from clean room classes A-D, it is recommended for all other areas that a zonal concept (see figure 3.D-2) for room classes is laid down in the form of an SOP and corresponding construction and building services criteria are defined. For the case of crossing particle and microbiological limits, procedures must be specified as counteractive measures.

In order to satisfy the requirements of the various room classes, not only the ventilation technology (see chapter 3.H Heating Ventilation Air Conditioning (HVAC)) plays a decisive role - a range of technical details must also be configured correctly (see figure 3.D-3)

Figure 3.D-3 Technical details for rooms

Technical details for the layout of rooms

Ventilation technology

Filter stages, pressure characteristics, air exchange, air flow

Components

Walls, doors, ceilings, floors, windows

Layout

Personnel and material locks, material and personnel flow

Other building services

Gases, water, waste water, plumbing, lighting

Control systems for

Pressure differential, temperature, moisture, particles

Equipment

Cleanability and sterilisability; no shedding of wear debris, oil, particles, micro-organisms; ease of operation, maintenance and repair

Summary:

The EU GMP Guideline defines room classes A-D for sterile production.

It is also recommended that room requirements are defined for other pharmaceutical areas according to what is known as a zonal concept.

For the case of crossing particle and microbiological limits, procedures are specified as counteractive measures.

Compliance with the particulate and microbiological limits may be achieved through appropriate harmonisation of the building and ventilation facilities.