PHARMACEUTICAL PRODUCT MANUFACTURING - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 281

package integrity requires that the packaging components fit together to form a
proper seal. In the case of blister packs and sample packets, the packaging mate-
rials (e.g., foil thickness, plastic or paper stock, or glue) and sealing parameters
(e.g., temperature, pressure) are critical to the seal formation. Any shortage in
the amount of sealant applied or any mistake in setting the temperature, pres-
sure, or timing parameters may result in an inadequate seal. For example, if the
sealing temperature was set too low, the adhesive may fail to liquefy and could
not be activated to form a seal. Likewise, if the amount of sealant is inadequate
or misaligned to the sealing area, a seal would not be properly formed and the
patient would be at risk of receiving a contaminated or degraded drug product.
11.2.4 Facility
11.2.4.1 Material Flow Facilities should be designed to allow for ease and
efficiency of material and personnel flow, to allow for easy cleaning, and to
safeguard product quality by avoiding the possibility of product contamination or
cross-contamination. The risk of cross-contamination of one product with another
is of particular concern where product areas or facilities are not dedicated to the
manufacture of just one product. The risk increases if superpotent or highly
allergenic products are being manufactured. There are inherent risks for product
cross-contamination associated with the movement of personnel, equipment, and
materials in shared production hallways, staging or preparation areas, and in
nonproduction areas such as lavatories or cafeterias where employees interact. It
may be necessary to modify the facility design to provide dedicated pathways
or rooms for each product manufacture, control the use of a common cafeteria
to avoid employee-to-employee contact, and have a qualified cleaning program
that ensures removal of residual product for multiproduct production rooms or
equipment.
11.2.4.2 Cleaning Cleaning agents, technique, and equipment and the required
level of microbial bioburden control are factors to be considered in the risk
assessment to support the cleanliness level required for the product. General
area cleaning, product-contact surface cleaning, and, where applicable, surface
sanitization practices should be assessed to ensure that, at a minimum, they
adequately reduce the likelihood of environmental and product-to-product cross-
contamination. The cleaning process, similar to dispensing, tends to be manual in
nature. Therefore, the details of the cleaning program should be clearly defined
in procedures that can be easily followed.
The assessment of the cleaning program should include the following:
• the type of cleaning agents;
• cleaning technique;
• cleaning equipment; and
• frequency of cleaning.