CORE VALIDATION OF FILTERS
When validating disposable filters, processors must first quantify the materials extracted from a pre-sterilized unit by measuring
the nonvolatile residue, or the chemicals extracted from the test sample. Then, the unique footprint of the extracted material
should be analyzed through infrared spectrum or Fourier Transform Infrared (FTIR) spectroscopy. Liquid or gas chromatography
and mass spectroscopy are more sensitive methods of identifying semivolatile compounds, but are not typically applied in generic
filter studies.
CORE VALIDATION FOR FLEXIBLE CONTAINERS (BAGS)
The process for testing disposable bags is similar to testing filters, but there are some important differences, including
consideration of the bags' integrity and tensile strength. Physiochemical tests for disposable bags used in drug processing
seek to characterize the nonvolatile residue; residue on ignition (inorganic residue); the presence and type of heavy metals;
and the buffering capacity, or the estimated strength of the buffering effect caused by extractable chemicals. All disposable
materials used should meet the requirements of the United States Pharmacopeia or the European Pharmacopoeia upon manufacture and also over their lifecycle.
SYSTEM-WIDE ANALYSIS
In any testing program, it is important to look at the whole system, taking into account potential interactions over time
and through all the steps of a dynamic manufacturing process. For example, consider the length of time that a product is in
contact with various components of the system. This is especially important when using disposable bag systems for filtration
and storage. Generally, as the period of contact lengthens, the potential for leachables to appear becomes greater. Also,
consider the ratio of the product volume to the surface area of various components: the greater the surface area, the greater
the potential for the creation of extractables.
Q Are there any standards applicable to extractables studies?
A Although standards for extractables testing do not exist today, the industry is working through the Bio-Process Systems Alliance
(BPSA) to establish guidelines for selecting, using, and disposing of single-use technologies. The goal of BPSA is to promote
confidence in the application of single-use technologies in the biotech and biopharmaceutical manufacturing industry. The
organization comprises leading companies engaged in the manufacture and testing of single-use technologies.
Q I am currently using a stainless steel assembly. What qualification work would I need to perform if I were to use a single-use
system?
A Just as for stainless steel equipment, the qualification of single-use systems requires that manufacturers verify that every
aspect of the system is performing as intended. The difference between qualifying single-use systems and stainless steel equipment
is the hastened timeline. Since single-use systems are installed in as few as four to six weeks, processors must be prepared
to conduct qualification studies in a very short time.
Q How long does it typically take to get a single-use system into operation?
A Single-use systems can be installed in just a few weeks—approximately three to four times faster than stainless steel systems.
This makes single-use systems especially useful for production of "fast track" drugs and at development scale, where flexibility,
speed of installation, and safety are critical. Particularly with clinical batches of investigational drugs, elimination of
equipment cleaning by using single-use systems greatly reduces the risk of cross-contamination. However, as with any system,
getting all parties to agree on the design can be one of the most time-consuming steps, along with sourcing all of the components.
Q What are the lesser-known advantages of single-use processing?
A Seemingly unimportant characteristics of single-use technologies can add up to significant time and labor savings. For example,
single-use systems have clear tubing and clear or translucent capsule filter housings, which enable operators to observe fluid
levels and flow. This allows fluid discoloration and air pockets to be readily detected, so that problem areas can be immediately
identified and isolated from the rest of the process. Single-use technologies can also be supplied pre-assembled and pre-sterilized
to significantly reduce setup time.
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