PHARMACEUTICAL PRODUCT MANUFACTURING - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 276

vary from lot-to-lot and consistently will meet specifications. A good supplier
management program, which selects a supplier based, at a minimum, on a good
performance, validation status, and compliance with regulations, will improve
the manufacturer's confidence that the materials received will consistently meet
quality specifications. The supplier management program should be documented
with rationales for supplier selection.
11.2.2 Formulation
The exact mixture and concentration of active pharmaceutical ingredient (API)
and excipients are crucial for patient health and safety. Healthcare providers
and patients inherently trust that the product delivers the intended potency and
expected results if taken as listed in the product labeling. Formulation errors can
impact product identity, potency, and stability, resulting in a product that fails to
deliver on its intended purpose. Therefore, every formulation process step must
be assessed for risks starting from selection of raw materials to completion of
the in-process bulk.
In formulating a product, there are inherent risks with equipment so a specific
reference to them will be made here (see Chapter 7 for equipment commissioning
and qualification considerations). Knowing the risks and the potential outcome
when equipment is substituted, incorrectly setup, or is used with the incorrect
operating parameters will be helpful information when quality issues arise during
routine operations. Several examples of how equipment can impact the potency,
safety, or stability of the formulated bulk product are as follows:
• The use of equipment such as balances with less sensitivity than required
may result in insufficient quantities of raw materials used (e.g., measures in
whole numbers only when two decimal places are needed).
• A bulk tank of a different size or shape may result in insufficient space to
allow for proper mixing or blending.
• A mixer of a different design, shaft length, or propeller size or speed capabil-
ity may not be adequate to successfully complete the dissolution or blending
step in the defined timeframe.
• Use of wrong mixer speed may not adequately dissolve materials or provide
a uniform batch by the end of the defined mixing time.
11.2.2.1 Dispensing The steps involved in selecting the correct materials,
weighing or measuring, and protecting them from contamination during the
dispensing operation tend to be manual in nature. Therefore, when identifying
the risks, close attention needs to be paid to the quality of operator instructions
and managing operator performance. Procedures need to be sufficiently detailed
and easy to follow, specifying the equipment or instruments to be used so that
the operator has adequate instruction to execute each step precisely.
Some incoming materials are packaged in large quantities to be used in
multiple batches. The risks of contamination from multiple operators, sampling