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Abstract
Background: Reports from the World Health Organization have suggested that counterfeit medicines
pose a serious problem in developing countries. An investigation of anti-erythropoietin
antibody—mediated pure red cell aplasia in Thailand found evidence of drug smuggling,
which may have serious safety implications.
Objective: This study assessed the authenticity and quality of epoetin alfa samples in Thailand.
Methods: Samples of epoetin alfa—prefilled syringes were collected from the pharmacies at
2 major hospitals (62 samples), 8 retail pharmacies (41 samples), and Thai authorities
(30 samples confiscated from smugglers at 2 airports, and 6 samples from a condominium
used by smugglers). These samples were tested against the European Union Pharmacopeia
specifications for aggregate content in epoetins of <2%. The integrity of epoetin
alfa distribution channels, coldchain processes (maintenance at 2°C–8°C), primary
and secondary packaging components (eg, batch number, expiration date, appearance,
letter size), and company's confidential features (eg, nature of the ink, type and
quality of the paper, other covered features) were also investigated. The main outcome
measures were protein aggregate content, determined by sodium dodecyl sulfate polyacrylamide
gel electrophoresis and Western blotting; and isoform distribution, assessed by isoelectric
focusing and Western blotting.
Results: Epoetin alfa samples obtained from the company's cold-chain and authorized distribution
channels met all quality standards, as did all epoetin alfa samples obtained from
the hospital pharmacies. However, evidence showed that some samples were being smuggled
or sold illegally through certain unauthorized retail pharmacies. The epoetin alfa
samples obtained from both airports and the condominium were stored improperly at
room temperature. Aggregate levels exceeded the specification of <2% in 11 samples
from 2 of the retail pharmacies (range, 1.2%–3.1%), 15 samples from the Dongmuang
Airport (range, 2.2%–17.0%), and all 6 samples from the condominium (range, 10.5%–19.8%).
All samples from the 2 hospitals, 8 retail pharmacies, and Suvarnabhumi Airport had
the authentic 6 isoform bands. Samples from Dongmuang Airport and the condominium
appeared to have the 6 characteristic bands, but positive confirmation was difficult
because of band smearing caused by a high level of aggregates. All features of primary
and secondary packaging were found to be authentic.
Conclusions: This investigation found evidence that some epoetin alfa samples were smuggled into
Thailand without proper cold chain, contained high levels of protein aggregates, and
were sold illegally through certain retail pharmacies. The Thai authorities have intervened
to stop such unauthorized products from reaching patients. Strenuous efforts must
be made to prevent illegal cross-border smuggling of biopharmaceuticals without proper
cold chain because of the serious safety implications for patients in developing countries.
Key words:
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Article info
Publication history
Accepted:
January 9,
2009
Identification
Copyright
© 2009 Excerpta Medica Inc. All rights reserved. Published by Elsevier Inc.