For
many manufacturing QA/QC laboratories, chromatography data systems
(CDS) and laboratory information management systems (LIMS) manage the
bulk of their scientific quality data. Traditionally, the integration
of these discrete systems has been limited to sequence creation and
upload of the final results. This approach, while less than ideal, has
been reasonably successful in meeting past expectations of the U.S. Food and Drug Administration
(FDA). Yet in September 2004, the FDA issued the final report of the
"Pharmaceutical cGMPs (current Good Manufacturing Practices) for the 21st
Century – A Risk-Based Approach," which outlines the FDA's perspective
on pharmaceutical quality and manufacturing process improvement. In it,
the FDA acknowledges that pharmaceutical companies have been hesitant
to adopt new technology, even if it will make manufacturing more
efficient and provide higher quality products to patients. It
attributes this reluctance, in part, to the heavy burden of regulatory
compliance and system validation. This was not the FDA's intent, and
clearly it is not in the best interest of either pharmaceutical
companies or the general public. The FDA wants pharmaceutical companies
to use modern science and technology to ensure product quality and to
increase the confidence of the FDA and the general public. While the
cGMP initiative focuses heavily on the manufacturing process, it also
emphasizes the importance of the associated quality data. Under the
cGMP, tight integration of LIMS and CDS is more important than ever.
Integration ensures a high level of data integrity, allows
pharmaceutical manufacturers to make better business decisions and
track investigations, and has the potential to lighten the burden of
regulatory compliance.
The report focuses on two areas: the FDA's new risk-based approach to
validation and the use of modern pharmaceutical technology by
manufacturers to improve quality. For the FDA to best utilize its
resources moving forward, it needs to concentrate on those areas it
deems to be high risk. Risk will be based upon several factors
including the manufacturer's compliance history and the public health
impact of their products. It also includes the "manufacturer's product
and process understanding and the robustness of the quality system
controlling their process." The manufacturer's control of their process
will determine the extent of the FDA's oversight. The FDA states that a
key way for pharmaceutical manufacturing to improve their process is to
take advantage of the latest technology.
As with the initial 21 CFR Part 11 guidelines, it is difficult to
determine the true impact of the report and how it will be implemented.
The Office of New Drug Chemistry
(ONDC), within the Center for Drug Evaluation and Research, is
responsible for the chemistry, manufacturing, and controls (CMC)
section of new drug applications. The ONDC is one of the first groups
to incorporate the risk-based approach into their current process.
Moving forward, the ONDC intends to focus on the critical
pharmaceutical attributes and will rely heavily on the summary
documentation, e.g., the comprehensive quality overall summary and the
pharmaceutical development report, and not on the raw data output
itself. The onus is on pharmaceutical companies to interpret their data
and to put it in the appropriate context. Through cGMP, it is more
important than ever to ensure that the data is available to create
these output documents effectively.
The ONDC also emphasizes "reduction in variability through product
understanding." By demonstrating less variability in manufacturing
processes, pharmaceutical companies will increase the FDA's confidence
in their manufacturing techniques; this confidence could potentially
lessen their regulatory oversight. (continued)
