CLEANING VALIDATION STRATEGY
The cleaning processes for product-contact surfaces for all products manufactured in GMP equipment must be demonstrated to
be effective. Product-contact surfaces are surfaces that make direct contact with product or materials introduced into equipment
as part of the normal manufacturing process by their very design. Indirect-product-contact surfaces (such as buffer tanks),
where there is a significant risk of residues on surfaces contaminating a subsequently manufactured product, also undergo
To demonstrate the effectiveness of a cleaning process, the process is challenged. This challenge involves at least three
consecutive successful cleaning process runs, after which residues are measured and results are compared to predetermined
Mock soiling is also used. Mock soiling refers to the soiling of equipment by a process other than routine manufacturing that
creates a dirty equipment state equivalent to that following routine manufacturing. Mock soiling of equipment for validation
purposes can be performed when equipment is not available for manufacturing soiling. Mock soiling procedures must be adequately
described to simulate normal manufacturing processes.
Cleaning validation includes the establishment of dirty hold times and clean hold times. Dirty hold time is the amount of
time between the end of the use of the equipment and the start of equipment cleaning. Clean hold time is the amount of time
between the completion of the equipment cleaning and the next cycle of use. Cleaning processes are challenged for maximum
dirty hold times during cleaning validation runs.
For clinical products, infrequently made products, or infrequently used equipment, a cleaning verification approach may be
used in lieu of cleaning validation.
Single-use product-contact equipment (used once and then discarded) is excluded from cleaning validation. Single-use items
include beakers, pipettes, weigh boats, silicone tubing, sample tubes, storage bags, and normal-flow filtration filters.
Product-dedicated refers to equipment that is used for a single product and then is removed as part of changeover procedures.
Product-dedicated items, such as chromatography resins and tangential-flow filtration membranes, are used with one product
only. The requirement for residues in dedicated equipment may differ from that for residues in equipment used for multiple
products; nevertheless, the cleaning of product-contact surfaces of dedicated equipment requires cleaning validation. The
validation of product-specific resin and membrane cleaning is captured in process validation protocols.
Multi-use equipment may be used to process one or more products or media components. At Genentech, the main emphasis of the
equipment cleaning validation program is on multi-use equipment, because this equipment type has the highest risk of process
contamination (run-to-run or product-to-product).
NEW PRODUCT INTRODUCTION
Before introducing a new product into equipment used for manufacturing a marketed product, a cleanability study is performed
to determine the effectiveness of the cleaning process, using the new product on similar equipment surface types. The new
product introduction (NPI) method has two purposes: to avoid cross-contamination of commercial products, and to collect development
data on new products.
The cleanability study is divided into two parts: the laboratory-scale study, and the representative-scale runs. The cleanability
study starts with an evaluation of the characteristics of the product and soiling at laboratory scale to determine the effectiveness
of the rinse, swab, and visual inspection methods. Results of the laboratory-scale study are verified at representative scale.
Representative-scale runs include three successful consecutive cleaning runs, conducted on equipment used for marketed products,
which include sampling and analysis for residues, and comparison to predetermined acceptance criteria.