John Roberts, Technology Director, CI Precision explains the role of a computerised system of dispensing medicines to enhance GMP compliance and reduce the risk of rejected batches during manufacturing of pharma products
The challenge is to ensure that the correct quantity of an approved raw material of known origin and quality is used during the manufacture of pharmaceutical products.
The conventional approach requires a standard operating procedure to be followed by a first person and the details of the weighing recorded with a second operator acting as a checker.
With a computerised system, the operator is guided through a predefined sequence of checks and actions and is not allowed to proceed if any of the checks fail. Accurate details of the weighing are recorded automatically, and the system prints barcoded labels for the containers of dispensed material, with the operator acting as the checker at every stage to confirm that the details are correct.
This process ensures consistency of dispensing, enhanced GMP and reduced risk of rejected batches.
The principal benefits of an MES weigh and dispense module highlighted in this white paper are as follows:
As with any manufacturing sector, pharma production varies considerably in scale. At one end, there are plants producing comparatively large volumes of product; at the other end, there are small-scale operations producing ‘specials’ or small batches for clinical trials. In some cases, these ‘specials’ operations are factory-based, whereas others are incorporated within hospitals. Whatever the size of the operation, a computerised weigh and dispense system can bring significant benefits.
The dispensing process
Accurately dispensing raw material ingredients is a fundamental requirement for the manufacture of high-quality pharma products. Furthermore, it is essential that a manufacturer can demonstrate that secure systems are in place to ensure that only the correct quantity of an approved raw material of known origin and quality is used.
Good Manufacturing Practice (GMP) requires that weighing and measuring is adequately supervised and checked to ensure that the component has been released by the quality control unit after test, the weight or measure conforms to the quantity required by the batch formula, and that each container of weighed material is labelled correctly.
When performed manually, the dispensing process requires handwritten records and labels that are produced by a first person and checked by a second person. Separate records are maintained for weighing instrument calibration and for cleaning of weighing equipment and the weighing area.
Although errors occur infrequently in raw material dispensing, they have far-reaching implications in terms of GMP, so systems must be in place to ensure that, as far as reasonably practicable, they do not occur. The elimination of dispensing errors is therefore a prime reason for implementing an MES weigh and dispense module. Common causes of errors and the advantages of a computerised system are listed in the following sections.
Common causes of error
Dispense the wrong ingredient
There is the possibility that an operator can accidentally dispense the wrong ingredient by misreading the material name on the stock label.
A computerised system uses the barcode on the stock label to identify the material to be dispensed. The barcode enables retrieval of key information concerning the contents of the container. For this reason it is not possible to identify and dispense the wrong ingredient.
Dispense the wrong weight
It is possible for an operator to dispense an incorrect raw material quantity. The causes of this are varied, but include: an arithmetical mistake (such as might be the result of dispensing into multiple containers), misreading the balance display, an incorrect potency calculation, an incorrect unit of measure conversion or misreading a quantity from the dispensing instructions (typically by transposing figures – for example, reading 0.912 instead of 0.921).
A computerised system:
- Recalculates the remaining quantity on change of dispensed container
- Forces the balance to be zeroed and the container tared before each weighing
- Enforces the use of calibrated, checked equipment only (e.g. by using daily balance validation checks)
- Performs potency calculations and unit-of-measure conversions
- Requires the dispensed quantity to be within predefined tolerances before the dispensing may be completed (and the ‘dispensed’ label printed)
- Maintains an audit trail of all events
Dispense an invalid lot
It is possible for an operator to pick and dispense an expired lot or a lot with an invalid QC status.
A computerised system reads the barcode on the stock label and, if the lot has expired or has an incorrect status, warns the operator and does not allow the material to be dispensed.
Mistakes can be the result of operators taking shortcuts in the dispensing process or not following the standard operating procedure (SOP). For instance, different operators sometimes have their own dispensing techniques. Mistakes can also occur due to over-familiarity with the SOP. Although periodic audits can be used to ensure SOPs are being followed, there is no guarantee that procedures are being followed in the periods between audits.
A computerised system
- Enforces a consistent means of dispensing the ingredients for an order, so all operators must perform the same steps and dispense the ingredients in the same way
- Enables approval points to be configured to apply during particular stages of the dispensing cycle (eg when acknowledging health and safety warnings or reprinting dispensing labels) to ensure that GMP is adhered to at all times.
Contamination of the ingredients dispensed for a product can occur when the incorrect cleaning procedure has been applied following the dispensing of a material. This is especially applicable to cleaning after the dispensing of active materials.
A computerised system enforces the cleaning regime, electronic signatures can be used to ensure that the correct procedures are always applied. Specific cleaning regimes may be applied to particular materials/ products. And the computerised system may be configured to require a second operator to approve either the cleaning when complete, or each stage of the cleaning process. A log of the cleaning activity is also maintained electronically.
Effects of dispensing errors
In general, errors made in the dispensary are identified by the QA department when they qualify the finished product. This mitigates the risk of bad product being released and a subsequent recall. Therefore, dispensing errors tend to result in GMP issues and costly overheads to the manufacturer.
Even with a computerised system, however, there is a requirement to audit the processes and for the Qualified Person (QP) to sign-off each batch. This all requires a substantial amount of paperwork to be checked, but a computerised system can significantly reduce the time required to produce and check the relevant reports. Firstly, the data is entered in the computerised system automatically during the weighing process, with no need for any additional inputs from the operator. This means that the necessary reports can be output virtually instantly when required, which is very different from the hours that might be needed to manually create reports for auditors. Furthermore, if the manual report creation process requires data to be handwritten or rekeyed into a spreadsheet or other computer-based package, there is a risk that further errors will be introduced or that figures will be rounded up or down.
For the auditor or QP, checking reports is far quicker if they are presented in a consistent way, with all of the data clearly legible.