At the 2nd European GMP Conference, held in Heidelberg on 21 and 22 June 2007,
Fred Blumenschein, Compliance Officer of FDA's CDER, informed about FDA's
"enforcement trends", i.e. the Agency's inspection developments.
The FDA conducts about 1,200 GMP inspections of manufacturers of medicinal
products for human use ("human drug cGMP inspections") in the USA. For foreign
inspections, Blumenschein gave the number of about 200 FDA inspections per year.
In 2005, in 100 inspections, deficiencies of so-called "moderate significance"
were found, that is to say deficiencies due to which the companies had to induce
changes. Twelve inspections resulted in follow-up measures by the FDA, i.e. they
led to "regulatory actions", like e.g. "warning letter, seizure or injunction".
The top nine cGMP deficiencies listed by Fred Blumenschein were:
Lab controls (211.160)
Validation of production and process controls (211.100)
Cleaning equipment (211.67)
Batch production records (211.188)
Quality Control responsibilities (211.22)
Batch release testing (211.165)
Record review/investigation (211.192)
Complaint investigation (211.198)
And the five most frequent cGMP problem areas are:
Having and following sound lab SOPs; documenting results,
Investigating complaints/issues fully
Following production SOPs
QC not exercising real oversight
Validating manufacturing processes properly
The foreign inspections were discussed in detail. The
illustration (see illustration 1) shows the percentage of foreign inspections by
country. The German-speaking countries are listed twice - Switzerland with 4%
and Germany with 9% (rank 3).
Conspicuous - but comparable to the past years - is the high
share of API inspections with 50% (see ill. 2). The list of individual
deficiencies with reference to API manufacturers (see ill. 3) and manufacturers
of medicinal products (see ill. 4) shows deficiencies that have been observed
for many years:
- Lab Controls (APIs and medicinal products)
- Production Records/Reports (APIs)
- Equipment Cleaning and Maintenance (APIs and medicinal
- Cleaning Validation (APIs and medicinal products)
- Failure/OOS-Investigations (medicinal products)
- Process Validation (medicinal products)
- Equipment Qualification (medicinal products)
Another interesting point are the most frequent cGMP
deficiencies in foreign inspections (see ill. 5). Here, the red spot marks the
position of the deficiencies in 2004.
On behalf of ECA
European Compliance Academy
2nd European GMP Conference in co-operation with University of Heidelberg and
European QP Association from 21-22 June 2007