Biomedical Engineering Reference
In-Depth Information
software. The role of a vendor in Part 11 compliance resides in their duty to summarize
the technical attributes of their system in a way that the end user can leverage them to
build their own system. In a flow cytometer validation we conducted at Amgen, we
defined our system as everything used from the generation of the electronic data to its
final resting place in the archives. This included validated file servers where the data
were saved, a third party file backup and archiving engine, an electronic file security
software service, third party components (e.g., plate loaders), and the SOPs we wrote
that govern the use of the instruments. For this reason, we were not able to simply
purchase the vendor's validation package and consider our system validated.
13.2.2.4 Are There Exemptions from Part 11 Compliance? It may be surprising
to some that Title 21CFR Part 11 does not require organizations to use electronic
records or signatures. In the case that an organization exempts itself from the need to
demonstrate the accuracy and trustworthiness of electronic records that aregovernedby
the predicate rule, Part 11 guidance defines the requirements that must be met. In this
case, the organization cites paper documents as the sole authoritative source for
regulatory purposes. The problem is that this creates the obligation to demonstrate
that hard copies produced froman electronic source are complete and accurate, and that
computer usewas incidental. Theburdenof proof here is high andunderlainby resource
intensive activities with high potential for error. In this day and age, it is difficult to
envision an organization opting to exempt itself from Part 11 compliance; we rely on
electronic records andcannot retract fromour responsibility to ensure their compliance.
An important distinction should nonetheless be made between “enforcement
discretion” and exemption from Part 11 compliance. This topic has roots tracing
back to February 2003 when FDA re-examined the breadth of 21CFR Part 11
enforcement [7]. The key branch point in this argument is whether the work stream
was conducted under the predicate rule; if not, a documented risk assessment is
advisable and is discussed in the guidance document. In the case of flow cytometry
experiments, the heavy reliance on a variety of software packages to recover data
through gating processes and fluorescence compensation algorithms markedly tip the
balance toward enforcement of many of the elements of Part 11 compliance. Even if
not guided by formal mandate, these principles simplymake a sound practice for those
leveraging flow cytometers in their drug development campaigns.
13.2.3 GCP
The idea that GLPs are required for the conduct of clinical studies is a misconception.
The introduction to the OECD principles of GLP [5] makes it clear that they apply
only to preclinical studies, excluding clinical studies such as pharmacokinetic and
efficacy studies. The relevant documents for clinical studies are the various codes such
as the International Conference on Harmonisation (ICH) [8]. Because data supporting
a clinical trial have the same assurances as what is more typically cited at GLP - such
as accuracy, traceability, reproducibility, and retrievability -many investigators find it
convenient to exert the practices and principles of GLP to GCP efforts (and there is
nothing inherently wrong in this approach).
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