In Germany there is currently no legal obligation to manufacture bulk
pharmaceutical excipients (BPE) in accordance with GMP. On the other hand,
however, the pharmaceutical entrepreneurs are responsible for the quality
of the BPEs they process. Owing to 'customer pressure' from the
pharmaceutical industry, GMP-conform manufacture and distribution of bulk
pharmaceutical excipients plays a key role.
But even
the
pharmaceutical entrepreneur's obligation to obtain starting materials from
qualified suppliers and to inspect the quality of the starting materials
have not been able to prevent the distribution and processing -
intentional or not – of active ingredients and excipients of inferior
quality and their sometimes tragic consequences for the patient. For
instance, in Haiti in 1996 some 80 children died after taking paracetamol
syrup containing glycerol contaminated with diethylene glycol.
While the manufacture and distribution of medicinal products are
governed by law, in many countries there are no legal provisions
concerning active ingredients and excipients. With the ICH Q7a 'Good
Manufacturing Practice Guide for Active Pharmaceutical Ingredients', which
was passed in November 2000, we now have a global harmonized GMP guideline
for active ingredients requiring the adherence to GMP rules also for
'Agents, Brokers, Traders, Distributors, Repackers and Relabellers' and
therefore covers the entire marketing chain. Nevertheless, this Guideline
still has no statutory relevance, for instance, in Europe, where the
relevant legal foundations still have to be created.
Therefore regulations for medicinal products and, meanwhile, for active
ingredients do exist. But as the case described above shows, excipients
may also be the cause of disastrous incidents involving medicinal
products.
Against this backdrop IPEC (International Pharmaceutical Excipients
Council) was founded in 1991 as an international interest body
representing the chemical, pharmaceutical and foodstuff industries. IPEC
is an umbrella organization divided into three regional association in the
USA (IPEC Americas), in Europe (IPEC Europe) and in Japan (JPEC) and which
was founded for the purpose of making an active contribution towards
improving the safety and efficacy of medicinal products throughout the
world. Within the framework of its activities IPEC is particularly
concerned with the harmonization of excipient standards and has meanwhile
published several guides for excipients:
- GMP Guide for Bulk
Pharmaceutical Excipients
GMP Audit Guideline
for Bulk Pharmaceutical Excipients
GMP Audit Guideline
for Distributors of Bulk Pharmaceutical Excipients
Significant Change
Guide for Bulk Pharmaceutical Excipients
Certificate of
Analysis Guide for Bulk Pharmaceutical Excipients
The 'GMP Guide for BPEs', which was originally published in 1995, was
revised in November of last year to take into account current cGMP
requirements pertaining to BPEs and new requirements for the ISO Quality
Management System. The revised version of the GMP Guide adopted the ISO
9001:2000 numeration system.
The 'GMP Guide for BPEs' issued in 1995 serves, for instance, the World
Health Organization (WHO) as a guideline for the manufacture of
pharmaceutical starting materials for its member states. This Guideline
was also adopted in USP 24/NF 19 and in Pharmeuropa, the journal
of the European Pharmacopoeia.
The Guidelines can be obtained from IPEC. The contact
addresses for IPEC Europe and IPEC
Americas are as follows:
Dr Evert Izeboud
IPEC Europe
Tel.: +31-70-320-9894
Fax : +31-70-320-3759
E-Mail : eizeboud@worldonline.nl
Mr Alan Mercill
IPEC Americas
Tel.: +1-703-875-2127
FAX: +1-703-525-5157
E-Mail: ipecamer@aol.com
Writer:
Dr. Barbara Jentges,
CONCEPT HEIDELBERG
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