Changing Regimes & Facility Zones in Pharmaceutical Facilities

There may be variety of changing regimes within a pharmaceutical factory. It is noted that no two factories exhibit identical regimes. These regimes will vary for a number of reasons including historically accepted practice and the design of the facility. It is the intention of this guide to identify Best Practice and to describe the appropriateness of a particular practice.

Garment change regimes will vary depending on the use of the rooms in which the person changing is expected to enter. A changing regime for a processing area where raw materials or product are exposed will differ from that found in offices, laboratories, or workshops. SOP’s should be in place for changing regimes for every zone, and for changing following emergency evacuation.

Zone Definitions

It is useful if floor plans are available for a factory which show the boundaries of each zone.

A Factory Grey Zone is an area within a factory building where production of non- sterile products takes place. Raw materials, bulk intermediates, and bulk products prior and during primary packaging, contact equipment associated with their processing, and primary containers can be exposed to the environment in these areas.

A Factory White Zone is an area where sterile products are manufactured.

A Street Black Zone is an area either inside or outside a factory building where there are no production activities and no GMP requirement for any garment change. Areas which are normally classified as Street Black are given below. Although there is no GMP necessity for a garment change to enter these areas, it is noted that in certain areas may require some form of change for Health & Safety reasons.

• Offices with no access to production
• Workshops with no access to production
• Warehouses for enclosed materials and finished Other areas which are located in Street Black Zones are:
• Wherever possible these should be located in Street Black Zones.
• Cafeterias where food is both prepared and consumed should be located in Street Black This implies that people entering cafeterias should do so in their Street Black clothes, and should not enter in working garments. Separate changing rooms and toilets must be provided for canteen staff.
• Exterior walkways between buildings

A Factory Black Zone

Its is an area within a factory building where production takes place, but such production is limited to secondary packaging operations and other operations where product or components are not exposed. Factory Black Zones are those production and related areas within a factory where raw materials and bulk pharmaceutical products are not normally exposed to the environment. The extent of a garment change is correspondingly less rigorous than the requirements for Grey Zone changes. The most usual production operation in Factory Black Zones is secondary packaging. Laboratories can be considered as Factory Black which implies that laboratory staff are required to change before entering a cafeteria, for example, which is located in a Street Black Zone.

Objectives of a Garment Change to a Factory Black Zone

To provide a uniform for operator

To protect the operator during packaging operations from the results of any accidental spillage/breakage.

To maintain an area such as secondary packaging ( and the floor in particular) in a clean & hygienic state.

To comply with general custom and practice in the pharmaceutical

 Location of Changing Room

 The changing facilities should be located in the production building at the entrance to the Factory Black Zone. Personnel should therefore not wear Factory Black garments in the Street Black Zone.

The concept of ‘Deemed Factory Uniform’

The recommendation above in section 5.2 contrasts with general practice in some countries, where the concept of a ‘deemed factory uniform’ is employed. In this system, at the beginning of their shift, employees change from street clothes into a ‘deemed factory uniform’. Unless Grey Zones are entered, there are then generally no further garment changes. The deemed factory uniform is worn both inside and outside the factory building – to the cafeteria for example. Whilst it is judged that this practice does not violate minimum GMP standards, it is not Best Practice, as outside the building, the uniform may become soiled with mud and dirt that may be expected to be brought into the Factory Black Zones such as the secondary production floor. It  is noted that under this system, there is no differentiation (and no garment change) between ‘Factory Black’ and ‘Street Black’.

Recommended Garments for Factory Black Zones

Head Covering

A close fitting cap which covers all hair and is worn over the ears. A disposable hat with an elasticated edge made of non-shedding material is recommended. Other types of non-disposable caps may be used only if they cover the hair completely.

Shoes/Overshoes

Shoes should be non-slip and provide the appropriate degree of protection to the feet and toes. There should be a shoe change from ‘street shoes’.

Overalls

A separate change of factory trousers is optional. Some factories choose to do this by adding light over-trousers at a subsequent change into Factory Grey operations. Close fitting at the ankles is not necessary. A jacket or coat should be worn which may have pockets and may be fastened with zip or buttons. Close fitting at the wrists is not necessary. The coat may be disposable or re-usable. For visitors, a comfortably fitting coat, easily put on and taken off, is recommended. Garments worn in different areas may be colour coded for identification and access control.

Masks & Gloves

Masks are not normally required for GMP purposes. Appropriate gloves may be required for operator protection.

Food and Drink

Best Practice will have no food consumed or stored in a Factory Black Zone. Minimum GMP standards would not be violated if cold ‘pre-prepared’ food (e.g. sandwiches, biscuits) are dispensed and consumed in a Factory Black Zone provided that this is not in or immediately adjacent to secondary packaging operations, and such consumption is limited to the room where the dispensers are located. Chewing should not be permitted in any production area.  Drinks dispensers may be present in Factory Black Zones, but they should be positioned in a separate room and not in the production areas. Water fountains may be present, but not immediately adjacent to production areas.

Toilets

Toilets may be present in Factory Black Zones, but they should not be located immediately adjacent to production areas

FACTORY GREY ZONES

Examples of Factory Grey Zones are sampling rooms, dispensaries, secondary manufacturing, and primary packaging areas. Areas where materials are exposed require the most extensive garment change. The trend in the design of equipment and processes is to increase the degree of containment, so reducing the exposure of operators, either by inhalation or through skin contact, to potentially harmful materials. The advent of automated “clean in place”, CIP, systems also reduces exposure of operators during cleaning processes. The time of exposure may be short and the quantity of materials handled small – for example during sampling procedures. In such situations, after a formal risk assessment.

Objectives of a garment change to a Factory Grey Zone

• To protect the product from contamination from the Such contamination may be from skin or hair.
• To protect the product from contamination from the exterior of the Grey The main source of such contamination is liable to be brought in on shoes.
• To minimise as far as is reasonably practical cross contamination between materials of different products.
• To protect the operator from the
• To prevent materials adhering to garments from being removed from the Grey

Location of Changing Room to a Factory Grey Zone

 The changing rooms should be located at the personnel entrance to the Grey Zone. In a general-purpose tableting facility there should be a changing room for operators engaged in the dispensing, granulation, compression and coating processes. All supporting personnel and visitors entering the Grey Zone would be expected to undergo the same change procedure. The exception is that occasional visitors may be provided with overshoes in place of a complete shoe change. In general, it is not practical to locate changing rooms for general-purpose production areas, at the entrance to each processing room (for example at the entrance to each granulation room). However, if there are manufacturing facilities which are dedicated to the production of a single potent product.

In order to comply with best practice, it is not necessary to have a ‘primary’ change ( into a Factory Black Zone) followed by a ‘secondary’ change into the Grey Zone. It is quite possible, and indeed is recommended for designs of new factory buildings, that separate parallel changing rooms are built for Grey Zones and Factory Black Zones, so that personnel enter either the Factory Black or the Factory Grey Zone. However, it is recognized that considerations of people flow need to be addressed at the design stage, and it is often very difficult to design retrospectively additional change facilities into an existing production building. Staff wearing Factory Grey uniforms should not be allowed entry into Factory Black Zones.

Food and Drink

Food and drink should not be consumed in a Grey Zone ( therefore there should not be food or drinks dispensers present). Water fountains may be present and in some countries are required by law.

Toilets

Toilets should not be present in Grey Zones, though they may be located on the ‘black’ or ‘dirty’ side of the changing room to the Grey Zone. The implication of this arrangement is that there should be a garment change between a Grey Zone and toilets.

Recommended Garments for Factory Grey Zones 

Head: A close fitting cap which covers all hair and is worn over the ears. A disposable hat with an elasticated edge made of non-shedding material is recommended. Other types, and most non-disposable caps do not cover the hair completely.

Excess Facial Hair :All excess facial hair must be covered with suitable masks.

Shoes: There must be a shoe change (or addition of overshoe for visitors- see below). The shoes must only be worn within the confines of the designated Grey Zone and must not therefore be worn in secondary packaging, warehouse, or cafeterias or other areas outside the Grey Zone. Shoes should cover all toes, and be made of non-absorbent, resilient, cleanable material. Shoes should be non-slip and provide the appropriate level of protection to the feet and toes.

Overshoes: Overshoes are normally worn by occasional visitors to the processing area. They are held at the ankle with elastic and are normally disposable, though certain types may be re-washed and re-used.

Overalls: Outdoor clothing should be removed, and then protective clothing put on which should cover completely, the body, arms to the wrist, and legs. A one piece ‘boiler suit’ is preferred. The suit should allow freedom of movement and have no external pockets. A two piece design of separate trousers and jacket is acceptable providing that the length of the jacket extends to the lower thigh. A separate trousers and short waist length jacket would be unacceptable. Overalls should be fastened at the wrist but not at the ankle. There should be no turn-ups at the feet or wrist. Overalls should be made of non-shedding material should be securely fastened for example with a zip. They may be disposable or reusable.

Gloves: Gloves must be used at all times when handling materials and machine parts which contact materials. The design should be sufficient to ensure that the wrist is not exposed. Long sleeves are recommended for operations which could entail significant contamination of the forearm and should be worn over the sleeve of the garment. Gloves are normally disposable vinyl or latex, though cotton can be used in non- critical applications. A design with an anti-slip embossed palm is useful for wet operations.

Protective masks: The degree of protection will be determined by the materials processed and the degree of exposure. An assessment of the operation to be performed should be done before selecting the most appropriate mask. Protective facemasks should cover the nose and mouth. They are disposable. For dispensing operations and other processing where more protection is required a ‘Pure flow’ helmet or similar is often used.

Jewelry: In general, there should be no jewelry or wristwatches worn in production areas. In some countries, there are local custom and practices that make this difficult and in such cases, jewelry may be covered by tape. However, this is not recommended where materials are exposed, and the tape may become detached and contaminate the materials. If jewelry is worn then steps must be taken to prevent it or small parts such as stones falling into product.

Sampling Areas

 Sampling areas are classified as Factory Grey Zones. The same principles therefore apply to sampling areas as to dispensaries. However, as the time of exposure of materials is more limited, then a full overall change is not essential. The minimum that should be changed are hat, shoe (or overshoe) and gloves. The ‘overall’ may be a coat, and it is not essential to change trousers. It is noted that under some circumstances there may be no garment change for the sampling operation- for example for the sampling of bulk supplies of materials, both solid and liquid