PHARMACEUTICAL PRODUCT MANUFACTURING - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 277

equipment, and environmental exposure are greater for these materials than for
the materials packaged for use in a single batch. The assessment would determine
if controls are adequate to protect the material from chemical and environmental
contamination during the weighing step. In addition, operators would need to
employ procedural controls to protect the material's identity, making sure that
the material is properly relabeled, reconciled, and returned to the proper storage
area after use.
The obvious risk associated with incorrect weighing or measuring of materi-
als is producing a batch that is subpotent or superpotent. Human errors such as
operator technique, calculation, and labeling errors are common for weighing and
measuring steps. Any of these errors can result in formulating a batch with the
wrong amount of ingredients or the wrong ingredients. Errors can often be miti-
gated by a check by a second operator. A determination should be made if second
checks are needed for calculations, measuring, or labeling and if they will ade-
quately mitigate the risk. Operator technique can impact the final potency result if
materials are not handled with care so that already weighed or measured material
is completely transferred into the dispensing container without spillage. Controls
should define what action is taken if accidental spillage occurs to ensure only
the correct amounts of materials are used and to protect subsequently dispensed
materials from potential cross-contamination.
Other factors play a role in this part of the manufacturing process includ-
ing work flow. Operational steps that are handed-off from one department to
another can lead to product error. For example, materials can be delivered to
the incorrect formulation area, creating a risk that the bulk product will not be
made in accordance with the correct batch instructions. Once materials are deliv-
ered, formulation operators should verify that the materials received are correct
before use.
11.2.2.2 Granulation It is important to know what steps in the process of
adding materials together to form a batch are critical in achieving the correct batch
formulation that supports product potency and stability and include them in the
risk assessment. For example, in some formulations the order of materials added,
the amount of material per addition, or the timing between material additions is
critical to product potency or stability. Once the critical steps are identified and
defined, they should be fully described in written instructions such as SOPs or
batch instruction records for personnel to follow.
Other common risks in the granulation process involve improper mixing of
materials as a result of operator error. Installing the wrong chopper blades or
applying the wrong mixing speed or time parameters can result in the risk that
the granulation process is incomplete, leading to product instability or incorrect
potency.
11.2.2.3 Drying If the granulation is a wet granulation process, a drying step
is typically applied at the end of the process. The risks associated with this
step include inadequate drying and uncontrolled or improper wet holding times.