Every pharmaceutical manufacturing plant features an area in which raw materials are weighed and transferred to clean containers. This area goes by various names, including Weighing, Weighroom, Central Weigh, Pharmacy, Dispensary, Dispensing, Fractionation and Subdivision. No matter what it’s called, its design is essential. This article outlines some best practices for design, layout and operation of these areas.
Three basic principles should drive the design of any pharmaceutical weighroom:
- Unidirectional flow of materials and personnel
- Segregation between hazardous and non-hazardous materials
- Separation of storage and manufacturing items and spaces.
In the past, convenience dictated the placement of weighrooms, traditionally located right near warehouses where materials were stored. Today, the weighroom is viewed as the entry point to manufacturing and the transition point for materials coming from the warehouse and entering process areas, so specific criteria will determine the best location.
The typical weighroom is made up of three sections: raw material staging, weighing and work-in-process staging.
Weighroom design depends on the type of processing that will take place in the process area. Manufacturing operations can include: active pharmaceutical ingredients (API), solid dose forms (SDF), liquids, ointments and creams (LOC), sterile injectables (SI), and biopharmaceuticals (cell culture and fermentation).
Raw Material Staging
Raw material and work-in-process staging should be directly adjacent to the weighroom, thus reducing the requirement for transition spaces. When weighing is complete, there may still be material left in the containers received from the client. Large quantities are usually returned to the warehouse, but small quantities, especially of those materials that will be used again soon, can be stored on pallets or on shelving in raw material staging areas.
Many ingredients require special conditions for storage, such as temperature and humidity control. If the materials are to be held for any length of time in the area, appropriate measures should be taken.
Large Lot Dispensing
With APIs, SDFs and LOCs, large quantities of material can be weighed into intermediate bulk containers (IBC) of up to 2,000 liters in size. In the case of SDFs like tablets and capsules, excipients typically make up the largest percentage of raw materials. These inert ingredients, such as corn starch and lactose, are used as fillers and binding agents for the formation of tablets and the filling of capsules.
Figure 1. Sterile material weighing room layout.
The weighing equipment in these rooms is normally a pit-mounted floor scale with minimum dimensions of 48 x 48 in., or load cells mounted on a support frame or a post hoist. In either situation, powder should be transferred by gravity or vacuum.
Small and Intermediate Lot Dispensing
In the case of the remaining operations, small quantities of materials will be weighed out and placed on clean pallets to create “kits.” The kits will usually contain all of the materials required to make one batch.
Weighing in these suites is handled manually, with operators using scoops and drum-tipping devices. Scale size is determined by the load capacity and by the ergonomic capabilities of the operators. Platform floor scales that can be accessed with a hand truck are used for weighing 50- to 100-kg quantities into plastic and stainless steel drums and tubs. Platform scales can be used for pails or plastic bags of materials ranging from 10 to 50 kg. One or two bench scales will also typically be present, the first for 1- to 10-kg quantities and the second – with a much higher level of accuracy – for weighing materials from 0 to 1 kg.
Equipment Wash and Preparation
All equipment that comes in contact with materials must be cleaned to reduce the risk of cross-contamination from previously weighed materials and airborne particulates. Small items such as scoops, small containers and sample thiefs can be cleaned in a specifically designed washroom or within the weighing room.
Larger equipment, such as pails, drums and small IBCs (holding less than 100 liters), are usually cycled through the manufacturing washroom before being returned to the weighroom. Large IBCs, particularly those above 1,000 liters, are normally cleaned with Clean-In-Place systems, in which spray balls are inserted through the top opening. A more sophisticated system involves the use of a fully automated bin washer. The IBC is placed inside the washer and the doors are sealed. The washer will open the access ports on the top and bottom of the bin and wash the inside and outside surfaces. This system is particularly beneficial when cleaning equipment used in the process of making potent compounds because it dramatically reduces operator exposure.
Specialized Suites – Potent Compounds
Potent compounds are materials that would be harmful if operators were exposed to a specified amount as defined by the Operator Exposure Limit (OEL). The OEL for each compound is set by the manufacturer and is based on the normal patient dosage compared with a Time-Weighted Average (TWA) of operator exposure during handling. A general description of containment categories follows:
• Category I: >100 mcg/m3
At this level, following normal cGMP is usually enough protection for an operator. This should include hair and shoe covers, as well as the requirement to change into a uniform that is laundered or replaced.
• Category II: <100 mcg/m3 -
This is the first category that requires the use of special equipment to create an additional separation between the operator and the materials being handled. At the Category II level, containment can usually be accomplished using laminar flow booths.