Since February 2002, the FDA has been following a new inspection approach
that aims at conducting and evaluating inspections with regard to specific
systems. In doing so, the Agency distinguishes between the following
systems:
- Quality System
- Facilities and Equipment System
- Materials System
- Production System
- Packaging and Labeling System
- Laboratory Control System
The idea underlying this approach is that deficiencies in one system
will affect all other systems as well.
Therefore, these systems are not congruent with the subparts B - K of
21 CFR 211.
As an example, we will have a look at the "Quality System."
One can assign the following paragraphs of the CFR 211 subparts to the
individual parts of the quality system:
|
Failure Investigations |
211.22 ("Responsibilities of quality control unit") |
|
Training / Qualification |
211.25 ("Personnel qualifications") |
|
Validation / Computer |
211.68 ("Automatic, mechanical, and electronic
equipment") |
|
Rejects |
211.89 / 110 ("Rejected Components, drug product containers,
and closures"/ "Sampling and testing of in-process
materials and drug products") |
|
Validation / Manufacturing |
211.110 ("Sampling and testing of in-process materials and
drug products") |
|
Change Control |
211.100 / 160 ("Written procedures; deviations" /
"Lab controls - General requirements") |
|
Reprocessing / Rework |
211.115 ("Reprocessing") |
|
Quarantine Products |
211.142 ("Warehousing procedures") |
|
Stability Failures |
211.166 ("Stability testing") |
|
Product Reviewers |
211.180 ("Records and Reports - General Requirements") |
|
Validation / Lab. Method |
211.194 (Laboratory records") |
|
Complaint Files |
211.198 ("Complaint Files") |
|
Returns / Salvages |
211.204 / 208 ("Returned drug products"/ "Drug
product salvaging") |
The new inspection approach is reflected by the kind and frequency of
the citations in the Warning Letters issued since February 2002.
Practically all of the CFR paragraphs (except for 211.89; 211.115; 211.204;
211.208) appeared with increasing frequency in the Warning Letters issued
after February 2002, reaching a peak in the second half of 2002.
This trend can be verified quite well with the example of the
"Laboratory Controls" system. There was e.g. a rapid increase in
the Warning Letter references to paragraph 211.165 ("Testing and release for distribution")
towards the end of 2002. Batch release testing is certainly one of the
most important tasks of the QC laboratory, and it is no wonder that the
FDA inspectors have more and more often an especially critical look at
this point within the framework of the new inspection approach.
The same is true of 211.166 ("Stability testing"), which is
also more and more frequently referenced in Warning Letters.
If this hot topic is also of interest to you, we recommend you to visit
the international conference on "Stability Testing"
that takes place in Barcelona on 18 and 19 November 2003. Top-level
speakers from industry and authority will inform you about the most
important innovations in this field.
What is also in the focus of FDA inspections is the topic of
computerised systems in the laboratory, above all the consequences of
FDA's new Part 11 approach for the QC lab. Hear all about the current
state of affairs at our GMP Education Course "FDA/EU
Requirements for Laboratory Computers and Records."
The University of Heidelberg organises a conference with workshop on
Process Analytical Technology (PAT) titled "NIR
and FDA's PAT Initiative." An FDA official will be among the
speakers.
Author:
Dr Gerhard Becker
CONCEPT HEIDELBERG
