Dispensing Technique in GMP

There are a number of critical steps in the manufacture of a medicinal product. These steps include the weighing out of starting materials, the formulation of a batch, clearing the production line to start up, cleaning production equipment, and using correct labels and printed matter in packaging, along with many others.

Since incorrect dispensing of starting material, either by incorrect weight or selecting wrong materials has a significant impact on the purity and strength of products and may not be detected by laboratory testing, it is definitely a critical step.

This is why the dispensing must be verified by a second person or a validated computer system, such as a bar code reader inked to formulation control software.

US FDA CFR 21 Regulations 

Subpart F–Production and Process Controls

Sec. 211.101 Charge-in of components.

Written production and control procedures shall include the following, which are designed to assure that the drug products produced have the identity, strength, quality, and purity they purport or are represented to possess:

(c) Weighing, measuring, or subdividing operations for components shall be adequately supervised. Each container of component dispensed to manufacturing shall be examined by a second person to assure that:

(1) The component was released by the quality control unit;

(2) The weight or measure is correct as stated in the batch production records;

(3) The containers are properly identified

(d) Each component shall be added to the batch by one person and verified by a second person 

International GMPs

– Starting materials should only be dispensed by designated persons, following a written procedure, to ensure that the correct materials are accurately weighed or measured into clean and properly labeled containers.

– Each dispensed material and its weight or volume should be independently checked and the check recorded.

The dispensary is where the chemical is weighed out prior to the bulk formulation, the dispensary presents an “opportunity” to introduce problems if not managed well.

Specific production controls such as dust extractors, protection from cross-contamination, accurate weighing of the right material and correct labeling are essential. Some of the GMP rules include:

• Checking that the room is clear of all previous materials, labels and documents.
• Verifying that the equipment, materials and documents needed for the current operation are correct and are all identified.
• Verifying the identification and weighs of all materials dispensed. It’s a GMP requirement to formally double-check a critical product as steps. Accurate dispensing of chemicals is one of these steps.
• Cleaning the area after use.

Any error in dispensing will definitely result in a significant problem later on in production.

The dispensary is the first place where materials are processed, obviously, any error here has major implications for all downstream processing.

It is important to take particular care when dispensing out the starting material.

Dispensing Out Starting Materials

Step 1: Room clearance

Room Clarence prior to introducing any new chemical is a GMP rule. Removing all previous chemicals and dust residues ensures that the next raw material being introduced will not be contaminated.

This is accomplished by physically inspecting the room, the weighing station, the dispensing utensils, and the dispensing booth to make sure that they are free from all contaminants.

Step 2: Setup

The dispensing setup is a critical step. This is where the operator matches the paperwork to dispensing chemicals. Take particular care and double-check that the right chemical and the right lot or batch number has been issued by the warehouse against the paperwork.

Step 3: Weighing

When weighing chemicals first make sure that the scales are within calibration. Carefully weigh the exact amount prescribed in the paperwork.

Double-check that the right chemical the right lot number and the right amount are weighed.

Step 4: Clean-up

After finishing weighing, there will be residual dust that must be cleaned up immediately. There should be procedures describing this clean-up plus paperwork to verify that the clean-up has occurred.

After clean-up, unused chemicals can be returned to the main store accompanied by the paperwork.

Record and sign each weighing on the official record as you go. Ensure that you lake all personal protection prescribed in your company’s procedures.

Dispensary Room Clearance

A room area clearance is a critical manufacturing control, which equally applies to the dispensary. GMP rules require:

• Before starting a dispensing operation, the area is checked to ensure that all materials labels and documents from previous operations have been removed.
• Equipment has been cleaned.
• The status of the room has been checked to ensure the room is clean and ready to use.
• Where air pressure controls are used. they are working and recording pressures in the correct ranges.
  

Dispensary Room Setup

During setup:

• Ensure that only materials required for the current operation are in the dispensary area.
• Check the identification of each raw material and its testing status. Record the testing status on ‘the batch records.
• Ensure and check all equipment and instrumentation are clean and dry.
• Wear correct garments.
• Check that scales and measures are calibrated and appropriate for the quantities being dispensed.
• Carry out performance checking of equipment according to standard procedures.

Checking Dispensary Scales 

The dispensary scales must be accurate or each formulation will be incorrect. Most companies have a combination or all of the following mechanisms for checking dispensary scales:

– Annual or biannual formal calibration across the working range of the scales (e.g. 100mg -100g). Typically, five different weights within this range would be checked for accuracy and precision.

– Labels attached to the scales identifying their dates of calibration, status, and next date calibration is due. The allowed “working range” is also displayed.

– Regular performance checks to verify the ongoing accuracy of the scales at “upscale” and “downscale” limits. In the dispensary, this is typically done daily before first use.

– Automatic lockouts of scales once they reach their next calibration date if they are out of calibration.

GMP Rules for Dispensary 

– Identifying and documenting the previous material processed within the dispensary provides traceability within the records.

– It is a GMP requirement to identify in the dispensary the current material being processed and the date of processing.

Weighing

During the weighing operation, ensure:

• Only authorized persons are permitted to dispense materials following a written procedure.
• Only one container is opened at any one time and is closed immediately after it has been used.
• Only clean dispensing/weighing scoops are used.
• Each weighing step must be checked by a person and verified either by another person or by an electronic system. Weighing chemicals is a critical step, so it requires double-checking.
• The weighed amounts and signed, dated evidence of the checks are recorded on the batch documentation.

The Use of Computers in the Dispensary

Computerized systems are often used for weighing out raw materials. However, this does not change the nature of the GMP requirements.

The equipment must be calibrated and checked at regular intervals, and the system must be qualified and validated before use.

One of the advantages of using a computerized weighing control system is that it eliminates the need to have a second person verify the operation.

Of course, this is only true if a validated barcode system is used to identify the materials. Without a validated barcode system, a second actual person will need to independently verify that the correct material is being weighed. 

Identifying Dispensed Material

Dispensed materials should be transferred to new or clean containers, which are clearly identified with:

• the standard name
• the quantity
• the raw material lot number
• the product processing batch number
• Always label the container, not the lid.

Dispensary Room Clean-up

Cleaning up at the end of the process is another very important control, you must ensure that:

• Labels on emptied containers are defaced, canceled or removed
• The area and equipment used are cleared.
• All materials and paperwork are removed
• The dispensed materials are stored in such a way as to prevent damage, loss or deterioration