PHARMACEUTICAL PRODUCT MANUFACTURING - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 278

Inadequate drying parameters (e.g., time and temperature) could result in a bulk
that is too moist, which may ultimately impact product stability or its inability
to be further processed. If the bulk is held too long in a wet state before drying,
the wet conditions may allow chemical reactions between the materials to take
place. These chemical reactions may change the final composition of the bulk
such as forming a different product or by-products that could be detrimental to
patient safety. There may be a need for wet holding times to be defined to avoid
conditions that support chemical reactions.
11.2.2.4 Milling After drying, the bulk is typically processed through a mill
or metal screens that break up clumps that may form as a result of the granulation
and drying processes. In this process, it is important that the operating parame-
ters and equipment setup are correct. Inadequate milling time or the wrong size
milling screen can result in a nonhomogeneous batch, with clumps that will not
be blended correctly. In addition, incorrectly fitted screens or warped screens
can cause the metal screens to rub against each other, causing a risk of metal
shearing and contaminating the batch with metal particulate.
11.2.2.5 Mixing/Blending The bulk granules are combined with a solution that
will act as a lubricant to aid in the flow of the powder to the compression area,
the next step in the process. In this process, there is a risk that the solution being
added or that the amount of solution being added is incorrect. Material error
will result in a product that is mislabeled and may be a risk to patient safety.
Insufficient solution or insufficient blending time may result in a batch that will
not compress properly, putting the patient at risk to receive a product that has a
variable or an incorrect potency.
11.2.3 Finish Processing
11.2.3.1 Compression A powder bulk is compressed into metal cylinders or
forms that determine the size, shape, and weight of a tablet. The tablet weight
directly determines the delivered dose; and if the tablet weight varies so that
some may be underweight, the patient is at risk of not receiving the intended
treatment. Some of the common risks associated with weight variation are as
follows:
• Inadequate or inconsistent powder flow as the result of equipment operating
problems or inadequate humidity control causing the powder to cake. It is
important that the powder flows freely at a consistent rate so that the forms
are always correctly filled.
• Incorrect equipment setup using the wrong size or type dyes or punches.
• Incorrect pressure and speed operating parameters for the required weight
or hardness. Incorrect hardness can result in chipping or flaking of the table
or susceptibility to further cracking.