INSTRUMENT VALIDATION FOR REGULATED STUDIES - Flow Cytometry in Drug Discovery and Development - page 265

retrievability. Whenever possible, automated data generation and transfer should be
aggressively pursued to enable validation of the entire process, reduce risk of error,
and increase efficiency. When a validated pathway is not an option, as is the case with
most flow cytometers, areas of risk must be identified and manual verification steps
added to the process. In addition, electronic data supporting a GLP study are required
to be archived in a secure location and indexed to ensure expedient retrieval. To ensure
this requirement is met, a procedure defining electronic file nomenclature (how files
shall be named) and transfer to a secure file location (how, when, and where files shall
be transferred) for storage/archiving is essential. For example, in the case of
nondigital flow cytometers, we chose to save raw data files and exported text files
to the local hard drive as recommended by the vendor. However, procedure dictated a
manual transfer of files to a secure file location until a technical (automated) solution
could be identified.
Ultimately, appropriate access control and data integrity are best accomplished by
carefully analyzing the data generation process from system to archive, identifying
technical gaps, and applying procedural controls as necessary to assure GLP
compliance.
13.2.2.3 21CFR Part 11: What is Part 11 Compliance? Title 21CFR Part 11 of
the Code of Federal Regulations provides important guidance for those who are
responsible for the equivalency of electronic records to paper documents [1]. The
guidance provides clear requirements for those charged with establishing and
upholding the reliability of electronic records and signatures; however, the FDA
also recognizes the need for flexibility in execution. For those required to ensure
compliance for activities governed by the FDA predicate rule (i.e., GLP), the need to
develop unambiguous philosophies regarding audits and audit trails, system
validations, electronic signatures, and software systems that warehouse and process
electronic data is paramount. There are no turnkey systems that can adequately cover
the case-by-case requirements of any individual organization or work stream. All drug
makers, including medical device manufacturers and biotech and pharmaceutical
companies, are charged with meeting the requirements of these regulations by
assembling a coherent program after selecting from of a mosaic of commercially
available resources in combination with system components that may be organically
derived from in-house expertise. Although the tangible degree of uncertainty generated
from this approach may be initially unsettling, the growing expertise in this field is
noteworthy and can be reassuring. Awide variety of experts are emerging as a function
of maturation, and presentations/resources addressing practical solutions to Part 11
compliance [1, 6] that do not unnecessarily overengineer solutions have become
common in public domain. Thus, development of a risk-based approach anchored by
sensible but robust philosophies regarding Part 11 compliance is the kernel bywhich an
individual can build an appropriate and effective Part 11 compliant system.
One should bewary of any vendor that offers a turnkey “Part 11 compliant system.”
To practice Part 11 compliance, both procedural controls (i.e., notification, ongoing
training, governance via SOPs, and administration) and administrative controls are
required in addition to technical controls provided by the instrument and associated