Contains Nonbinding Recommendations
laboratory personnel, the laboratory phase of the investigation, additional testing that may be
necessary, when to expand the investigation outside the laboratory, and the final evaluation of all
test results.
The Agency, in accordance with its August 2002 “Pharmaceutical CGMPs for the 21st Century”
initiative, encourages modern approaches to manufacturing, monitoring, and control to enhance
process predictability and efficiency. Process Analytical Technology (PAT) takes a different
approach to quality assurance by using process controls and in-process data as the release
specification instead of relying on single laboratory determinations to make batch acceptability
decisions. This guidance is not intended to address PAT approaches, as routine in-process use of
these methods might include other considerations. For information on timely in-process testing,
see the CGMP guidance entitled PAT — A Framework for Innovative Pharmaceutical
Development, Manufacturing, and Quality Assurance.
FDA's guidance documents, including this guidance, do not establish legally enforceable
responsibilities. Instead, guidances describe the Agency's current thinking on a topic and should
be viewed only as recommendations, unless specific regulatory or statutory requirements are
cited. The use of the word should in Agency guidances means that something is suggested or
recommended, but not required.
II. BACKGROUND
Laboratory testing, which is required by the CGMP regulations (§§ 211.160 and 211.165), is
necessary to confirm that components, containers and closures, in-process materials, and finished
products conform to specifications, including stability specifications.
Testing also supports analytical and process validation efforts.
4
General CGMP regulations
covering laboratory operations can be found in part 211, subparts I (Laboratory Controls) and J
(Records and Reports). These regulations provide for the establishment of scientifically sound
and appropriate specifications, standards, and test procedures that are designed to ensure that
components, containers and closures, in-process materials, and finished drug products conform
to the established standards. Section 211.165(f) of the CGMP regulations specifies that finished
drug products that fail to meet established standards, specifications, or other relevant quality
control criteria will be rejected.
Both finished pharmaceuticals and active pharmaceutical ingredients (APIs) are to be
manufactured in accordance with current good manufacturing practice under section
4
Specifications must be scientifically sound and appropriate (§ 211.160(b)), test procedures must be validated as to
their accuracy, sensitivity, specificity, and reproducibility (§ 211.165(e)), and the suitability of the test procedures
under actual conditions of use must be documented (§ 211.194(a)(2)). For products that are the subjects of new drug
applications (NDAs), abbreviated new drug applications (ANDAs), or investigational new drug applications (INDs),
specifications are contained in the application or DMF. Specifications for nonapplication products may be found in
official compendia or established by the manufacturer.
2