variety of nonharmonized risk management
programs.
Similarly, sertindole. In this case, the marketing
authorization for this anti-psychosis agent was
initially suspended by a single member state
(some would claim with too little advance notice).
This was followed by complete withdrawal of the
product, on a voluntary basis, by the Marketing
Authorization Holder. Again, a CHMP/EMEA
pan-European review took place for all the phar-
macovigilance data that was available. Again, the
product has now been reintroduced, albeit with risk
management programs of different designs in var-
ious European countries.
Intra-County (sic) problems implementing risk
management programs. If there was ever any need
to emphasize the need for flexibility of approach in
risk management programs, then no better illustra-
tion could be than dealing with problems that can
arise within a single county! San Diego County is
the most southwestern within the 48 contiguous
United States, bordering on Mexico and the Pacific
Ocean. It is quite a large county (about the size
of the country of Lebanon) and has substantial
Spanish-speaking, Italian-speaking, Mandarin-
speaking, Anglophone, Roman Catholic, Protes-
tant, Buddhist and non-religious communities.
Pity, then, the San Diego pediatrician trying to
copewiththe nationally designed risk management
program for isotretinoin when used in adolescent
girls with acne vulgaris. Advice to avoid sunlight,
given the local climate and architecture might be
somewhatpro forma. But the ability to hold effec-
tive discussions about contraception and repeated
pregnancy testing with supposedly under-aged,
tattooed, Californian, surfers, as well as conserva-
tive, teenage Latinas accompanied by their
mothers, can only inspire awe.
41.3 Summary
Risk managementprogramsare not a new invention
(e.g. ‘Scheduling’ of drugs with abuse liability).
There are classes of drugs for which risk manage-
ment programs are clearly indicated beyond those
that are routinely required for product approval and
marketing. The menu of measures that can be used
is long, and should be scaled against the clinical
hazard that has been identified or is suspected.
Political, national and cross-cultural factors have
a large impact on the success of risk management
plans; the most effective ones are likely not to be
internationally harmonized.Acknowledgments
For this chapter, much is owed to analysis offered
by the following experts at the 5th Scripps-
BIO Drug Development Conference (La Jolla,
California, February 2003): Rear-Admiral Marlene
E. Haffner USPHS MD MPH FRCP (US Food and
Drug Administration), Professor P. Kurki MD
(National Agency for Medicines, Finland), M.
Toivonen MD PhD (CHMP, EMEA), H.Greenaway
MD (Scripps Clinic, California), and R. Wagner
PharmD (Kaiser Permanente, USA). The views
expressed at that conference were those of the
experts themselves, and were not necessarily those
of their employers.Further reading
Daniel DG, Wozniak P, Mack RJ, McCarthy BG. 1998.
‘Long-term efficacy and safety comparison of
sertindole and haloperidol in the treatment of schi-
zophrenia’.Psychopharmacol. Bull. 34 : 61–69.
Honein MA, Moore CA, Erickson JD. 2004. ‘Can we
ensure the safe use of known human teratogens?
Introduction of generic isotretinoin in the US as an
example’.Drug Safety 27 : 1069–1080.
Kartzinel R. 1981. ‘Guidelines for scheduling drugs
under the Controlled Substances Act [Proceedings]’.
Psychopharmacol. Bull. 17 : 40–42.
Mechcatie E. 2004. ‘Risk management program for IBS
drug on track: alosetron was reintroduced to the
market in 2002 with a few caveats, including a
narrower indication’. Clin. Psychiatr. News 32 :
78–81.
Schaefer C, Hannemann D, Meister R. 2005. ‘Post-
marketing surveillance system for drugs in preg-
nancy – 15 years’ experience of ENTIS’.Reprod.
Toxicol. 20 : 331–343.562 CH41 RISK MANAGEMENT IN PRODUCT APPROVAL AND MARKETING