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Operation Volcano - The Herceptin Case

Authors:

Abstract

Summary of the biggest investigation on pharmaceutical crime held in Europe in recent years: stolen and falsified medicines, sourced from Italian hospitals and from other illegal chains, were recycled in the EU distribution network. This White Paper was submitted to the EC and published by AIFA.
OPERATION VOLCANO
THE HERCEPTIN CASE
story, lesson learned, proposals
AIFA | AEMPS | AGES | IGZ | MHRA
OPERATION VOLCANO
THE HERCEPTIN CASE
story, lesson learned, proposals
AIFA | AEMPS | AGES | IGZ | MHRA
© Agenzia Italiana del Farmaco, Via del Tritone 181, 00187 Roma
http:// www.agenziafarmaco.gov.it | e-mail: d.digiorgio@aifa.gov.it
All rights reserved. No part of this book may be reproduced or distributed by any means
(including photocopying, microlm, or other methods) without written permission from the editor.
Director of the Publication: Domenico Di Giorgio.
Editorial production: Italian Medicines Agency - AIFA.
Editorial Sta: Annalisa Berselli (AIFA), Gianpaolo Derossi (AIFA), Belén Escribano Romero (AEMPS), Marta Gramazio (AIFA),
Paul Hargreaves (MHRA), Manuel Ibarra Lorente (AEMPS), Marcel Moester (IGZ), Serena Panicale (AIFA),
Andrea Ungersbäck (AGES), Hannes Wuerkner (AGES).
Book design and Illustrations: Gianpaolo Derossi.
Thanks to: Gabriele Angiello (AIFA), Mark Cilia (Malta Medicines Authority), Patrick Costello (EMA), Mark Jackson (MHRA),
Alastair Jerey (MHRA), Ruth Mosimann (SwissMedic), Liv Weingartz (EMA), Marcus Wittstock (BfArM).
Special thanks to the Comando Carabinieri Tutela per la Salute - NAS and to all other administrations and WGEO delegates involved in this
investigation for their unvaluable support.
Hearty thanks to Pavle Zelić (ALIMS) for the support to this publication.
Compiling a book is a complex operation, which requires repeated checking of the text, the gures and the relations between these. Experience
shows that it is practically impossible to publish a book free of errors. We will therefore be grateful to readers who will point out such errors.
3
AEMPS Spanish Agency for Medicinal Products
and Medical Devices
AGES Austrian Agency for Health and Food Safety
AIFA Italian Medicines Agency
BASG FederalOfceforSafetyinHealthCare(Austria)
CAP CentrallyAuthorisedProduct
DHPC DearHealthcareProfessionalLetter
DRA Drug Regulatory Authority
EMA European Medicines Agency
EU European Union
FIMEA Finnish Medicines Agency
FMD TheEuropeanUnionFalsiedMedicines
Directive 2011/62/EU
GDP Good Distribution Practice
GMDP Good Manufacturing and Distribution Practice
GMP Good Manufacturing Practice
HMA Heads of Medicines Agencies
IWG Inspectors Working Group
MAH Marketing Authorisation Holder
MHRA Medicines and Healthcare Products Regulatory
Agency(UnitedKingdom)
MoH Ministry of Health
MS MemberStatesoftheEuropeanUnion
NUI NonUrgentInformation
OTC Overthecounter
RA Rapid Alert
RAS RapidAlertSystem
WGEO WorkingGroupofEnforcementOfcers
ABBREVIATIONS
4
The so-called “Operation Volcano”, also known as “Herceptin case”, origi-
nates upon receipt of an alert by a German parallel distributor, soon fol-
lowed by further investigations in respect of which emerged that vials of the
cancer medicine Herceptin (trastuzumab), stolen from Italian hospitals, have
been manipulated and falsied and re-introduced under false credentials by
unauthorized wholesalers into the legal supply chain. Seizures of falsied vials
have been carried out by authorities in Germany, Finland and United Kingdom
(UK). The distribution of the falsied vials to other European Union (EU) Mem-
ber States (MS) was also proved.
Upon further investigation by the Italian authorities, additional medicinal prod-
ucts have been identied as stolen in Italy and, subsequently, re-introduced
under false credentials by a criminal organization connected to Italy.
This has been facilitated through unauthorized wholesalers connected with the
Italian criminal organization, formally based in Cyprus, Hungary, Latvia, Roma-
nia, Slovak Republic, Slovenia and Greece issuing fake invoices to sell the stolen
medicines to authorised Italian and Maltese operators. These authorised oper-
ators have subsequently exported these to other EU markets.
A similar scheme, involving operators from other countries, was also discov-
ered.
The vulnerability of the parallel import channel to this kind of attack and the
lack of enforcement actions with respect to Good Distribution Practice (GDP)
(e.g. inspections to wholesalers) were major causes for the case; strong pro-
tection of the network via strict importing rules for parallel distribution and
traceability systems for medicines, cooperation between enforcement and
health authorities, sharing of information and intelligence knowledge (also via
web tools such as the AIFA/Fakeshare ones) allowed Italy to counteract crim-
inals and to avoid the inltration of illegal medicines and up to July 2015 led
to the arrest of more than 60 people in 8 dierent police operations in Italy,
5
and to the eradication of the hospital thefts
in Italy (passing from 3 cases per week, until
May 2014, to zero, from June 2014), but were
not enough for preventing further possible
theft/falsication/exporting criminal plot, as
demonstrated by the recent RA issued by Ger-
many and other MS with respect to the possi-
ble inltration of counterfeit medicines in the
same channels targeted in this case.
By explaining the case in detail, summarising
the key lessons learned and the possible pre-
ventive actions, this White Paper calls for a
stronger enforcement eort against phar-
macrime, with more resources at MS level
and an ad hoc coordination at EU level.
Investigation period Enforcement unit Arrested people Seized products
November 2013 Police (Lodi) 20 236 boxes
December 2013 Carabinieri (Caserta) 0 52.251 packages
February 2014 Carabinieri (Naples) 2 404 boxes
April 2014 Police (Bari) 4 680.00 euros
February 2015 Carabinieri (Siena) 9 Non declared (tons)
April 2015 Carabinieri NAS (Milano) 19 16.000 packages
June 2015 Guardia di Finanza (Rome, Naples) 10 68.000 packages
UPDATE AUGUST 2015:
police operations related to the
“Operation Volcano” criminal network in italy.
November
Police
(Lodi)
2013
20 236
boxes
December
Carabinieri
(Caserta)
2013
052.251
packages
Arrested
people
Seized
products
February
Carabinieri
(Naples)
2014
2404
boxes
April
Police
(Bari)
2014
4680.000
euros
February
Carabinieri
(Siena)
2015
9ND
(tons)
April
Carabinieri NAS
(Milan)
2015
19 16.000
packages
June
Guardia di Finanza
(Rome, Naples)
2015
10 68.000
packages
6
7
I.
THE STORY (SO FAR)
I.I Thefts of medicines in Italy
Theft of medicines (from hospitals and in the eld i.e. from lorries and pharmacies)
had a big increase in Italy after 2011; the number of thefts in hospitals, in particular, was
so big as to become a “media emergency”, with weekly articles and reports, and even
University research (“Transcrime: the thefts of medicines from Italian hospitals”, http://
www.transcrime.it/pubblicazioni/the-theft-of-medicines-from-italian-hospitals/)
being published and promoted on the general press.
This emergency situation resulted in AIFA (Italian Medicines Agency) Counterfeiting Pre-
vention Unit setting up a project with industry in Italy in order to feed a shared database.
One of the primary functions of this project was for industry to share with AIFA informa-
tion about stolen medicines, i.e. name, manufacturer, “Bollini” number, batch details,
etc.: the database is being fed and the gathered data are analysed in order to understand
the real framework.
Another function was to organise those
information in order to let AIFA both in-
vestigate and respond to theft cases, and
refer to those data against pharmaceuti-
cal crime in general, being the phenom-
enon more complex and articulate than
isolated thefts.
THEFT PROJECT: TIMETABLE
Beginning 2013:
increase of thefts of medicines in Italy since 2012.
Spring 2013:
set up of the “Theft project” in order to share the data of
the phenomenon – AIFA, Farmindustria (manufacturers
association), ASSO-RAM (warehousing services association),
Carabinieri NAS (specialised police force), supported by the
Ministry of Health.
Summer 2013:
set up of a shared database through a platform managed by AIFA.
Autumn 2013:
gathering of data (from MoH, Industries, Distributors) and analysis.
8
“Wherearethestolenmedicinesfromthehospitaltheftsandtrucktheftsgoingto?” To
help answer the question were examined and tested six possible scenarios:
AIFA set up indicators for testing the different scenarios:
AIFA developed all listed instruments, and involved Carabinieri NAS, Customs and other
stakeholders in the test verications: the plan was to use these tools for triggering and
“ltering” signals coming from the different involved actors – e.g. customs, police, in-
dustries, health professionals.
1. Black market in the eld 2. Black market on the web 3. New supply to hospitals
National distribution on “grey/black
channels”
(i.e.toprivatehospitals,clinics,etc.ortodoping
network/beautycenters)
Specialised distribution via the Internet
(e.g.athletesnetworks…)
Mere nancial damage
(i.e.creationofashortagetobere-fullled)
4. Black market
to EU/non EU MS
5. Inltration of the legal
supply chain in Italy
6. Inltration of the legal
supply chain in EU
where medicines are cheaper or less
accessible. Transfer (undercover export)
to eastern Europe for distribution
through pharmacies, etc.
National distribution into the legal
network
(i.e.toItalianpharmacies,OTCpharmaciesand
hospitals)
Transfer (overt export) to northern
Europe
(e.g.paralleltrade)
1. Black market in the eld 2. Black market on the web 3. New supply to hospitals
Blacklist of stolen products and
related batch numbers to be shared and
training (police)
Winter 2013
IT intelligence activities (AIFA, private
companies)
Winter 2013
Evaluation of data (low incidence)
4. Black market
to EU/non EU MS
5. Inltration of the legal
supply chain in Italy
6. Inltration of the legal
supply chain in EU
Blacklist of stolen products and
related batch numbers to be shared and
training (customs)
January 2014
Evaluation of data, blacklist and
training (police)
Winter 2013
Watchlist for EU MS, set up of an alert
procedure (DB/signals)
Winter 2013
9
After some test in the eld, the most probable scenario was considered the last one (6):
a “blacklist” of stolen medicines was prepared and circulated to interested DRAs and
stakeholders in Europe, asking to report AIFA any suspect signal about incidents involv-
ing the listed products.
The database was also made available to industries and operators as a tool for process-
ing signals from the eld: any suspicion about a medicine could be processed by using
also the data regarding stolen medicines.
When in March 2014 the signal arrived, the system helped to identify
it in a timely manner: a manipulation occurred in Germany on
a medicine in AIFA blacklist was forwarded to the Market-
ing Authorisation Holder, that informed AIFA in real time,
since the reported batch number matched an entry of
the database.
I.II The case
A “signal” was received on March 31st, 2014, from a Ger-
man parallel distributor who received Herceptin 150 mg
from a wholesaler in UK, concerning what initially looked
like a defective vial that had been traded in the Parallel Im-
port system.
On March 31st the signal was forwarded to the manufacturer (Roche)
and to AIFA.
As reported in the NUI that Paul-Ehrlich Institute (released on April 2nd), during the de-
livery control of medicinal products from the UK wholesaler the following was observed:
the batch number of the primary and the secondary packaging differed;
the products were partially liquid (although it is a powder);
residue of product was observed on the outside of the vial;
some products seemed to have been reopened and closed.
10
Samples from each of the affected batches (H4319B02; H4129B01; H4284B04) were
seized.
Further investigation of the case was performed by involving also the manufacturer and
the AIFA Counterfeiting Prevention Unit: data were evaluated by using also the theft
database tools.
The check determined that the batch number could be related to a theft from a truck in Italy.
The quality signal and the theft data gave a possible explanation to what had been ob-
served: the mix up of batch numbers can be caused by the assembly of single stolen
vials in big packages, easier to replace on the market since importers prefer single batch
numbers; the manipulation may be explained since criminal organisations make
use of inltrators and those, besides stealing intact or “prepared” vials, might
recycle also products’ packages from garbage by relling and sealing
them in a way acceptable to non experts, in order to get more money.
Following the above mentioned initial NUI issued by Paul-Ehr-
lich Institute (April 2nd, 2014), whereby vials of the cancer
medicine Herceptin (trastuzumab), stolen from Ital-
ian hospitals/distributors, were reported to have been
re-introduced under false credentials by unauthorized
operators as falsied medicines into the supply chain,
a number of Member States have taken action where
required.
Seizures of manipulated vials have been carried
out by national competent authorities in Germany,
Finland and UK, while the MHRA inspected the UK
wholesaler and the Carabinieri NAS inspected the
Italian wholesaler who supplied to the UK: AIFA sup-
11
ported the identication of the products
as “illegally exported”, and “falsied”
with respect to the origin (as for the Dir.
2011/62 denition of “falsied medicine”).
The distribution of similar vials to other
EU MS was also veried.
In the invoices from the UK wholesal-
er two other products were detected,
namely Alimta and Remicade. The evi-
dence pointed rmly at a signicant dis-
tribution channel having been discovered
and not just a one-time case.
Upon further investigation by the Italian
authorities, additional medicinal prod-
ucts were identied as stolen in Italy and
subsequently re-introduced under false
credentials. This was facilitated through
the unauthorized operators operating in
Cyprus, Hungary, Latvia, Romania, Slovak
Republic and Slovenia issuing fake invoic-
es pretending to sell the stolen medicines
legally to authorised Italian operators.
These authorised legal Italian operators
subsequently exported these to other EU
markets.
Apparently, there was a consolidated
scheme: the criminal organisation behind
IDENTIFIED UNAUTHORIZED (“BOGUS”) WHOLESALERS
CARNELA LIMITED
str. Michalaki Karaoli 8, Nicosia, Cyprus, VAT CY10308068X
ABLE POWER INTERNATIONAL HOLDINGS
str. Podmaniczky Utca 57. 2/14, Budapest, Hungary
AVIMAX HEALTH AND TRADE KFT
Fòti U. 4 Szàm, HU-2161 Csomàd, Hungary, VAT HU24206028
MARS DISTRIBUTIONS KFT
Tompa M. Utca 9, HU-8360 Keszthely, Hungary, VAT HU11779074
EURORIGA MED Import Export
str. Akademika Mstislava Keldisa Iela 12-158, Riga, Latvia,
VAT LV40103517211
LATVAMED INTERNATIONAL Imp. Exp
str. Akademika Mstislava Keldisa Iela 12-158, Riga, Latvia,
VAT LV40103572887
PERSONAL COMMODITY RINGSIDE
Municipiul Arad, str.Tribunal Dobra n.18 Judet Arad, Romania,
Fiscal code RO31031066 dated 19.12.2012
ZEAPHARMA S.R.L
Municipiul Targu Jiu, Victoriei, bloc196, scara 3, etaj 2, ap. 10,
Judetul GORJ, Romania (note:Zeapharmaisauthorisedas
pharmacy,notaswholesaler)
EXIMP AZ - sros
Bratislava, Slovak Republic
PIRAMID D.O.O
Brniceva Ulica 31, 1231 Ljubljana, Slovenia, VAT 61869937
TAIN D.O.O
Nova Gorica, str. Kridiceva Ulica n.19, Slovenia, VAT 76488632
HILDONS
Feidiou 3, Thessaloniki, Greece, VAT number EL 800528668
NIXERTRON IBERICA S.r.l.
via Novara 123, 20153 Milan, Italy, VAT 01063770323
12
this criminal operation hired local crimi-
nals in Italy to break into hospitals and to
hijack distribution trucks.
The stolen products were transferred to
an Italian licensed wholesalers and it ap-
pears that falsied receipts were creat-
ed for the shipments. Fake non licensed
wholesalers were set up in numerous EU
Member States, e.g. Hungary, Latvia, Cy-
prus, Czech Republic.
Authorised wholesalers in Italy received
(fake) invoices from one of the “bogus
wholesalers” in another country, e.g.
Hungary, and received the stolen medici-
nal products: It is likely that the medicinal
products never left Italian territory during this stage, the unauthorised operators’ mo-
dus operandi was aimed at legitimise the supply chain. The whitewashed shipment was
then sold by the licensed Italian wholesalers, e.g. in the UK.
The non Italian wholesalers, apparently, never asked anything more than the Italian au-
thorisation of the legal wholesaler1; they apparently believed they bought from a genu-
ine wholesaler for selling the medicines to other MS in that belief.
Since organisations in e.g. Latvia, Hungary etc. are unauthorised operators, the products
were considered as “falsied”; due to the falsication of the origin, they were not con-
sidered safe or effective, and consequently quarantined.
1 According to GDP guidelines, wholesalers have to verify only the direct wholesalers they are
buying from (see FMD).
LIST OF OPERATORS WHICH DIRECTLY BOUGHT
MEDICINES FROM THE “BOGUS WHOLESALERS”
FARMA GLOBAL Srl
Via Boscofangone Snc, 80035 Nola, Napoli, VAT 06474151211
FARMACEUTICA INTERNAZIONALE Srl
Via Dell’industria Snc, 83030 Pietradefusi, Avellino, VAT
02715470643
FARMACIA COZZOLINO DI MARIO & CIRO S.N.C.
Corso Italia 15, 80056 Ercolano, Napoli, VAT 02778921219
FARMACIA DELLA ROCCA
Via Sottotenente Ernesto Cirillo 207, 80041 Boscoreale, Napoli,
VAT 06345681214
PHARMA-TRADE SPA
Via Roma,12 (Operative site: Via S.Abbondio, 158), 80045 Pompei
(NA), VAT 07034161211
PHARMASEA Ltd.
11, Dingli Street, Sliema, Malta
13
With respect to the already investigated products, Italy traced all internal transactions:
the Italian operators that were supplied, directly or indirectly, by the unauthorised
wholesalers mentioned above were also inspected.
Member States were requested by AIFA in a NUI launched on May 14th to contact whole-
salers, relevant organisations and parallel distributors in their territory to temporarily
quarantine medicinal products bought from the unauthorized operators above, until the
outcome of the current investigations provide evidence of their safety and efcacy, and
to inform AIFA of any medicine bought from the Italian operators listed in the NUI, in
order to allow the “validation” of the purchase with the data made available to AIFA by
the Traceability System of the Ministry of Health.
Follow up NUIs were launched by AIFA on 28th of May, 1st and 25th of July and 26th of Au-
gust, aimed at disseminating a list of spe-
cic batches of medicinal products that
were conrmed as affected by the case,
updating the list of involved operators
and proposing specic activities of veri-
cation and inspection, when required, to
the competent authorities of other MS.
Further investigations allowed to dis-
cover that the “undercover distribution
network” sourcing stolen medicines from
Italy was applying similar schemes also in
other MS (a Malta/Romania connection
was demonstrated) and with other kind
of illegal products (falsied Herceptin,
Pegasys, Avastin were spotted between
2013 and 2014, in channels clearly related
to this one).
THE SUPPLY CHAIN MODELS
A) Bogus Operator sells to Italian Operator who sells to German
operator.
B) Bogus Operator sells to Italian Operator who sells to operator in
another MS who subsequently sells to a German operator.
At this stage it is estimated that this has been going on for three
years at least and involves hundreds of medicines.
14
The list of operators which directly bought medicines from the “bogus wholesalers”
mentioned above was also released as an Annex to NUI issued on the 14th of May, and
updated in the follow up NUIs (see box for the list)
Italian and Maltese authorities are progressing with regulatory action against the whole-
saler authorisations of the above listed operators.
To date, the licence for three of the operators was suspended for three months by the
competent local authority, Regione Campania:
FARMA GLOBAL (degree n. 161, 29/7/14),
FARMACIA DELLA ROCCA (n. 160, 29/7/14),
PHARMA-TRADE (degree n. 162, 29/7/14).
Two of the operators are no longer active:
FARMACEUTICA INTERNAZIONALE ceased its activities (as stated in the Regione
Campania degrees n. 72, 27/5/14 and n. 111, 3/7/14);
PHARMASEA license was revoked by the Maltese authorities.
Between April and July 2014, Italian Prosecutors and joint investigation teams coordi-
nated by AIFA and Carabinieri NAS identied the involved operators, the distribution/
export channels and, moreover, even the undercover warehouses of the criminal organ-
isations.
In July 2014 three warehouses were found near Naples; police forces enforced the with-
drawal of the stolen medicines from the exporting channels, and local authorities acted
against the operators which directly bought from the bogus wholesalers.
It is now known that some wholesalers are not adhering to the regulations and this has
permitted falsied medicines to contaminate the parallel import/distribution network.
15
II.
CASE MANAGEMENT
II.I The verication process
II.I.I Validation of trades
Since the NUIs launched by AIFA recommended quarantining all products sourced by
operators that were “contaminated” by the bogus wholesalers, all EU MS started an
in-depth check of all trading activities which were in connection
with such operators; AIFA, Carabinieri NAS and other com-
petent authorities performed targeted inspections of the
whole supply chain and, after the July 1st NUI, all availa-
ble invoices related to possibly “contaminated” trades
were forwarded to AIFA and EMA for a systematic ver-
ication of the legitimacy of the trades.
The result of this exercise was double:
AIFA worked on the data disclosed by the com-
petent Prosecutor, following the trades from the
bogus wholesalers to the rst EU MS outside of Italy,
with EMA and other MS followed up the next steps up
to the nal customer (top-down approach: nal goal, RA/seizure of the illegal
quarantined goods).
EMA and AIFA led all invoices received by the MS, trying both to reconstruct
the full picture of the illegal trades (since some of the bogus wholesalers related
transactions appeared to be missing in the available seized documentation), and
to validate the legitimate trades, by verifying the origin of the products and the
traceability of the supply (bottom-up approach: nal goal, release of the quar-
antined products non related to the illegal network, and reconstruction of the
full picture of the illegal trades for the next follow up RA/seizures).
16
On the basis of the data collected and disclosed by Carabinieri NAS and by the com-
petent Prosecutor, AIFA have painstakingly identied the medicinal products that were
supplied via Route A listed above. They are involving other MS in the supply chain review
when one of the 5 authorised Italian wholesalers supplied product to a non-German
wholesaler/PDs (Route B above).
EMA and other involved EU MS authorities supported the verication and trades recon-
struction exercise, nalised at the compilation of the annex to the RA that AIFA issued
on August 8th.
The investigation has identied 100 products that have been supplied via the bogus op-
erators listed in the previous table. The products are listed in the RA issued by AIFA on
August 8th, including an Annex that was updated on August 14th, September 1st and Janu-
ary 29th, 2015. This Annex will be furtherly updated as more information becomes avail-
able.
Italian authorities continued to identify the supply chains for the medicinal products
concerned. On review of documentation from the bogus operators to Italian Oper-
ators (purchasers) it became evident that a large number of various medicines
(but in small volumes) were supplied utilising the same supply chains as for
the rst ve medicinal products identied and listed in the previous
NUIs. It was evident that in most cases the country of nal desti-
nation was Germany.
AIFA proposed recall of the medicines con-
rmed as falsied related to specic
trades, as listed in the RA Annexes, and
not the entire batches. Each Member State
had to search for trades in which they are
the last customer in the supply chain. Once
identied, these trades form the basis of a
specic MS recall.
17
It is important to note that AIFA proposed recall of the specic trade not the entire batch
referenced.
II.I.II Validation of operators
As part of the general investigation, AIFA and Carabinieri NAS enforced the proposal in-
cluded in the previous NUIs: Italian wholesalers were inspected by Carabinieri NAS and
all invoices related to the “bogus wholesalers” were led, and their trades traced to the
rst non Italian customer, as for the RA annex development process.
This inspection exercise was extended to all Italian operators who bought products from
the operators listed, and all new data regarding trades and operators were disclosed in
real time to all MS, via EMA mail list and AIFA restricted “fakeshare” web platform: the
new bogus operator HILDONS was for instance identied in July 2014 during the inspec-
tion campaign, its nature conrmed through direct contacts between AIFA and Greek
authorities, and the distribution of the information to the network authorised in real
time by the Prosecutor.
After the RAs were issued, a new inspection campaign was launched as a result of the
new data gathered by EMA and EU MS authorities; the results of the new campaign will
be disclosed by AIFA through the same authorisation process and distribution channels
used previously.
The results of this campaign should conrm the security of the distribution network in
Italy, allowing all EU MS to consider as “safe” any trade related to the validated opera-
tors, with no need for further statements by the competent Italian authorities. There are
no illegal activities recorded and conrmed after the third NUI launched by AIFA (July 1st,
2014). Invoices forwarded by EU MS authorities have been conrmed as legitimate.
It is likely that this new campaign, in combination with the RA follow up activities, will
trigger the identication of new actors and trades. For example, Italian authorities
have suspended the licence of another operator (ITAFARM SRL, Strada del Piano 49/E-
51, 06135 Ponte S. Giovanni, Perugia, VAT 04944591009), even if for infringements that
currently seem unrelated to the targeted illegal channels, whilst Italian and other EU
18
PRODUCTS SOLD MOSTLY TO HOSPITALS
These are products for which the dispensation is exclusively at
hospital level. AIFA contacted the MAHs of these products in order
to verify the distribution chain and validate the data through the
Italian Traceability System of the Ministry of Health. This let AIFA
identify the products sold directly to hospitals
without any wholesalers’ involvement. Hospitals
are not allowed to export or resell these
products: any of these products found at level
of wholesalers’ channel should be regarded as
“suspect” at least, and evaluated further.
BRAND MAH MAH STATEMENT
AFINITOR Novartis Farma S.p.A. Note to AIFA, 3 September
2014
ATRIPLA Gilead Sciences S.r.l. (for Bris-
tol Myers Squibb) Note to AIFA, 8 August 2014
AVASTIN Roche S.p.a. TWIMC 16 May 2014
CAELYX Janssen-Cilag SpA Note to AIFA, 28 August 2014
ECALTA Pzer Italia S.r.l. Note to AIFA, 3 September
2014
EVIPLERA Gilead Sciences S.r.l. Note to AIFA, 8 August 2014
EXJADE Novartis Farma S.p.A. Note to AIFA, 3 September
2014
FASLODEX AstraZeneca S.p.a. Note to AIFA, 6 August 2014
GILENYA Novartis Farma S.p.A. Note to AIFA, 3 September
2014
HERCEPTIN Roche S.p.a. TWIMC 17 April 2014
IRESSA AstraZeneca S.p.a. Note to AIFA, 2 September
2014
MABTHERA Roche S.p.a. TWIMC 16 May 2014
NPLATE (250mg) Amgen S.r.l. Note to AIFA, 11 August 2014
PREZISTA Janssen-Cilag SpA Note to AIFA, 28 August 2014
ROACTEMRA Roche S.p.a. Note to AIFA, 7 August 2014
STELARA Janssen-Cilag SpA Note to AIFA, 28 August 2014
MS authorities are currently investigating
suspect movements connected with the
“bogus wholesalers” activities.
II.I.III Triggers for new signals
One of the key lessons learned during this
phase of the investigation is that since
the counterpart is a criminal organisa-
tion, it is impossible to rely on informa-
tion sourced from the paperwork facade.
Moreover, some of the information relat-
ed to the illegal channels emerged only
after repeated police inspections and
in depth IT verications; and since the
comparison between the number of sto-
len medicines (as for the available Ital-
ian data), the disclosed invoices and the
“Italian sourced medicines” highlighted
visible outliers and unbalances, it is like-
ly that there are still more undercover
channels to be discovered.
In order to generate more signals to be
investigated, AIFA asked MAHs and the
Ministry of Health for support in order to
identify products that were not legally
exported after April 1st 2013: this exercise
was aimed at giving all MS new referenc-
es for identifying suspect invoices and
trades.
AIFA then checked all available tracea-
bility data, and asked MAHs of hospital
>
19
medicines listed in the RA annex to spec-
ify if they sold products to wholesalers
(i.e. the only wholesalers legally export-
ing medicines) after April 1st 2013. MAH
declarations were validated using the
traceability data gathered by the Italian
Ministry of Health through the medicines
track & trace system in place in Italy.
On August 26th, a list of products for
which the distribution was intended for
Italian hospitals (which are not allowed to
export these medicines) was released via
NUI: since any trade related to the above mentioned list of products should be regarded
as “suspect” at least, and evaluated further, AIFA asked all operators to send any infor-
mation regarding trades of those products which occurred after 1st April 2013, that were
not already listed in the 8th August RA, and recommends to quarantine the suspect goods
until further verication of the trade.
The goal of this exercise is to support the research of any other illegal channel that is
still out of the investigation: any signal will be evaluated (through traceability data and
verication with MAH) and, if conrmed as “suspect”, forwarded to police/prosecutor for
the follow up activities (e.g. inspections and seizures), in preparation of further update
of the RA Annex.
II.I.IV Restoring of the security of the italian supply chain beyond the Herceptin case
During the crisis period, Italy put in place additional checks and verications that are
currently guaranteeing the safety of the supply chain: NAS inspections, reinforced veri-
cation on MoH traceability data, cooperation with MAHs and wholesalers associations
for data verication and invoices check, support to other MS in invoices verication were
all major triggers for the enforcement of the proper GDP processes validation, with re-
spect to the criminal inltration that was highlighted by the AIFA/NAS investigation.
BRAND MAH MAH STATEMENT
SUTENT Pzer Italia S.r.l. Note to AIFA, 3 September
2014
TASIGNA Novartis Farma S.p.A. Note to AIFA, 3 September
2014
TRUVADA Gilead Sciences S.r.l. Note to AIFA, 8 August 2014
TYSABRI Biogen Idec Italia S.r.l. Note to AIFA, 6 August 2014
VELCADE Janssen-Cilag SpA Note to AIFA, 28 August 2014
VIRAMUNE Boehringer Ingelheim Italia
S.p.a. Note to AIFA, 6 August 2014
VIREAD Gilead Sciences S.r.l. Note to AIFA, 8 August 2014
VOTRIENT GlaxoSmithKline S.p.a. Note to AIFA, 7 August 2014
>
20
Since GDP inspections are not specically targeting criminal behaviours, Italy is putting
in place extra verications to be applied in order to avoid the possible resurfacing of this
kind of criminal inltrations: the inspection systems will be strengthened through the
cooperation between NAS and competent authorities, allowing to maintain the degree
of condence on the validation that was conrmed through the extraordinary proce-
dures put in place during the investigation, and the already established procedures for
tracing legal operations will be put in transparency, in order to allow other EU MS to
easily check by themselves the legitimacy of the supplies.
With respect to this, it is important to note that legally distributing/exporting operators
are currently obliged to send to the Traceability System of the Ministry of Health all data
about the medicines they export: products, number of pieces, batch numbers, dates and
MS of destination.
Lack of communication of those data is considered as a relevant infringement, since it
impacts on the traceability of the medicines; specic sanctions are already considered
in the Italian regulation, and could trigger not only administrative nes, but also licence
suspensions.
These data may be automatically correlated by the tracea-
bility system to the MAH supplies, highlighting any suspect
activity (i.e. export non related to previous supplies);
MoH and AIFA will develop a system for giving MSs
access to the validation data and will also prepare
an ad hoc “certication le” that all MS opera-
tors could request from their Italian suppliers,
as an ofcial conrmation that the distribution/
export is traced and legal.
AIFA currently publishes on its website alerts,
blacklists and data about stolen medicines:
the restricted “fakeshare” web platform, ac-
tive since January 2014, was made available to
operators and authorities for the sharing of infor-
21
mation during the crisis, and will be developed further as a current tool for operators,
whilst the ad hoc “open” webpage (already active: http://www.agenziafarmaco.gov.it/
en/content/falsied-illegal-and-stolen-medicines-0) will be used for the dissem-
ination of guidance documents, such as guidelines (e.g. the “WGEO due diligence” for
wholesalers, a “list of suspect signals for wholesalers” that AIFA is currently developing,
and a list of available web resources for checking the National authorisations of whole-
salers), alert on stolen medicines, and the explanation of the verications on the Italian
supplies for the interested operators.
Some of the measures could be easily implemented at EU level as preventive actions
against the resurfacing of the contamination.
II.II Coordination activities
Upon the rst alerts for Herceptin, BASG/AGES required the parallel distributors, which
are located in Germany, to recall the batches identied (April 16th to 18th, 2014). Within
the recall correspondence BASG/AGES not only asked for delivery data, but also for pur-
chase data (name of the supplier). For getting an overview EMA set up spreadsheets to
collect the delivery routes of Italian-origin Herceptin batches. By checking the spread-
sheets and contacting the relevant DRAs, the original supplier in Italy could be identied
for mostly all quantities of Herceptin which were distributed to Austria within few days.
One route was traced back to a Maltese supplier, and after contacting the DRA in Malta,
an inspection took place which revealed that this supplier sourced Herceptin from an
unauthorized supplier.
In the mid of May 2014, all parallel importers based in Austria were inspected or ofcially
contacted to provide the names and status of their suppliers for special parallel traded
medicinal products. Afterwards a check was done whether the named companies under
suspicion were on the circulated list of the bogus wholesalers.
A focus project was started to collect all purchase data of all medicinal products affect-
ed in this case to check whether all actors involved in the distribution chain possess an
authorization according to Directive 2001/83/EC.
22
BASG/AGES coordinated and required all data relevant for the Austrian market (e.g.
asked DRA to provide data on suppliers for Herceptin delivered to Austria) and analysed
the data.
A coordination of all investigative measures and outcomes (e.g. collecting the analyses
reports) as well as asking for required data all over Europe (which was partially done by
EMA) and an analysis of the data given with investigative measures to follow on DRA side
would be useful. In this case, analysis of data was done on DRA level only by those DRAs
affected as end user countries – to different extent.
II.II.I Roles of dierent entities during this case
Role of EMA
Coordination and set up of spreadsheets completed by member states;
Providing data on parallel distribution notications;
Coordination activities and requests to affected DRAs from DRA side for CAPs.
Role of WGEO Task Force Volcano (founded in Vienna during the annual WGEO - Meeting)
Discussion of next steps and recommendations from enforcement side;
Keeping in mind the broader involvement of other branches of the illegal net-
work in other MS.
Role of AIFA
Providing data and analysing data, primarily related to the Italian case;
Linking the prosecutor in Italy to European DRAs and EMA;
Summarising all information and coordination of discussion/joint activities
between DRAs and investigators (via organisation of webinars, teleconferences,
development of documentation, publication of NUIs, RA and press releases);
Sharing of information between DRA/enforcement activities through the “fake-
share” web tools (restricted web area, webinar platform, etc.).
Role of DRAs
Providing data on distribution of medicinal products affected in this case follow-
ing requests from EMA, Italy or other concerned MS;
23
Some DRAs are not affected as target country, which may have inuence on
setting priorities in corresponding.
Investigative Coordination
Is currently done by AIFA for the Italy case which is a heavy workload;
Information is missing whether further suspicions are addressed/followed-up/
coordinated from enforcement side (e.g. the Romanian/Malta case, the Roma-
nian Herceptin/MabThera/Sutent cases, evaluation of notications of parallel
distributed medicinal products and trade that gain no nancial benet for the
involved companies when legally bought).
24
III.
KEY LESSON LEARNED
The management of the “Operation Volcano” made it clear that additional enforcement
resources are necessary to tackle any cross-border illegal trafcking of this magnitude.
These resources have to be allocated within DRAs to handle such cases adequately in
order to protect public health.
GMDP inspections are mostly focused on the pharmaceutical quality system. Empiri-
cally, signals of criminality cannot be found that way. Although irregularities might be
addressed by GMDP inspectors, further enforcement investigations are necessary to
tighten the suspicion. DRAs are well staffed with personnel to narrow down the risk and
danger to public health caused by falsied medicines. GMDP personnel is competent
to set up guides and measures to prevent falsied medicines entering the legal sup-
ply chain, but when this occurs many different professional experiences in the phar-
maceutical area have to be considered before a case can be xed. Only specialised DRA
enforcement personnel are trained to address and prove irregularities especially of the
provisions of FMD. Coordinated surveillance of the market and communication between
these two groups is necessary. Finally, each other’s experiences have to be implemented
in prevention programs to secure public health.
Another evidence stands out: there is no common procedure for handling in a coordi-
nated way transnational enforcement cases in healthcare. The “Herceptin case” proved
how spread and interconnected illegal activities in Europe are, while the operations set
in motion proved the importance of sharing a common procedure at a European level to
tackle such activities which have European impact and require proactive measures to
identify signals by all involved MS.
25
Training of GMDP inspectors should attract more attention to nding signals of irregu-
larities/illegal practices and criminalities, which can never be found by using standard
procedures. Every inspector should be aware, that no criminal case is like the last one.
The supply chain to parallel importers and distributors can be complex and there is cur-
rently no system that enables visibility of the full audit trail, even in MS where existing
regulations support traceability.
Looking closer to complex criminal cases will mostly end up in nding several other non
compliant activities conducted by well known and inspected authorised companies, like
the fact that vials were detected during delivery control as manipulated but no notica-
tion was carried out to the National Competent Authorities or buying from not author-
ised wholesalers.
The same illegal structure can be driven in another country at the same time, following
the same set up, like the Romanian signals indicate. Awareness raising and the will to
preserve condence in the parallel trade system can strengthen the ambition for com-
pliance.
26
IV.
PROPOSALS
IV.I Enforcement coordination
The medicines supply chain is constantly being challenged by criminal activity and this
paper and associated proposals appear to be a positive step towards managing this risk.
It is clear from the lessons learned that well-coordinated, effective and efcient en-
forcement collaboration by member states is key in ghting medicines crime. It is there-
fore suggested that, in complex cross border cases involving more than two member
states, an ad hoc medicrime enforcement taskforce, comprising of staff from enforce-
ment departments within drug regulatory agencies and associated bodies, should be
formed.
The formation of an enforcement taskforce will enable members to share information
and partake of intelligence and best practice, as well as gauge enforcement capabilities/
limitations and provide assistance in capacity building and training. Tools and guidelines
can also be developed, for example the WGEO due diligence document, and shared with
appropriate stakeholders. The ad hoc enforcement taskforce will also endeavour to co-
operate with competent international bodies such as EMA, EUROPOL, INTERPOL, and
others at eye level.
One of the primary roles of the medicrime enforcement taskforce will be to gather intel-
ligence by collection and analysing each signal and supporting national competent au-
thorities such as police, DRAs and customs with concrete questions to be able to conduct
investigations in a timely and efcient manner, share information and focus on evidence.
The team should also adopt proactive measures and move away from the traditional
reactive enforcement activities, which stand the risks of losing relevant evidence and
investigative leads
27
In terms of setting up and implementing the taskforce the following issues will be ad-
dressed:
A task force leader similar to a Rapporteur shall be appointed.
Reassure that the WGEO SPOC system is in place in each country.
Support from the highest level (HMA) must be provided to inuence member
states to provide requested data within the set time frame and to actively col-
laborate.
Members shall be assigned to prioritise their work on the taskforce in order to
protect the public health within Europe.
Financing for the taskforce personnel should be guaranteed and provided by the
respective agency.
Training is available for specic enforcement duties.
A joint communication strategy should be agreed.
Cooperational meetings, webinars and telecons can be performed.
Mapping and structured intelligence gathering can be guaranteed.
Recommend actions for member states affected will be documented.
A focused enforcement project shall be set up to proactively collect and docu-
ment all data in the case (as done during this case by using the AIFA/EC “fake-
share” platform and tools).
IV.I.I Further proposals
The MHRA collaborated with AIFA, and other agencies, to produce this document with a
view to formalising a process that would allow effective joint working in relation to com-
plex, European, cross border investigations. In terms of enforcement coordination, the
MHRA support the formation of an ad-hoc taskforce approach to manage this type of
enquiry.
In relation to regulatory coordination, the MHRA support the closer cooperation with the
EMA GMDP Inspectors Working Group in relation to improving the due diligence require-
ments for wholesale dealers and enhanced cold chain provisions.
28
The paper clearly addresses matters from an “enforcement” perspective which would
include collaboration in relation to the investigative strategy. However, an area that
does not seem to be clear, and that the paper may benet from, is in relation to the
management of the higher level strategic issues. The question arises, should there be a
strategic group that sits above the operational taskforce to ensure appropriate coor-
dination of the issues?
It is suggested the group could maintain an overview of the emerging issues, draw up
terms of reference for the operational taskforce, ensure sufcient resources are availa-
ble, consider transnational risk and strategic linkages with other agencies. This strategic
group could also review progress of the taskforce and would provide a useful structure
to escalate critical issues.
Depending on the nature and the scale of the event, it would be drawn from the member
states most affected by the incident.
It is suggested to pull a steady strategic group out of senior DRA enforcement ofcers
alongside the active WGEO taskforce, whose members would change case by case. Only
a few of the European agencies could facilitate a bigger operational group with their re-
sources. Smaller countries could handle cases better with the supervisory help of both
the strategic group and the active colleagues involved in the taskforce. Financing and
resources for both strategic group and WGEO taskforce have to be ensured in order to
better tackle criminal activities at a European level.
IV.II Regulatory approach
The current regulations and controls are clearly insufcient with regard to due diligence
by wholesalers in order to prevent the criminal penetration of the legitimate supply chain.
It is recommended that the EMA, GMDP IWG and HMA-WGEO be requested to develop
common position documents to explain how to apply the due diligence requirements in
the EU GDP Guide by wholesalers and strengthen its compliance providing examples of
how to carry out this activity, e.g. requiring nancial credit checks, conrming VAT num-
29
ber, checking Duns number, conrming EORI number and conrming that the address is
a registered business premise, like listed in the WGEO Due Diligence paper.
The creation of the EMA GMDP database will help resolve the problem of wholesale deal-
ers unknowingly purchasing from unlicensed sources. However, it will take approximate-
ly ve years for the database to be fully operational as it depends upon the inspection
of wholesale dealers and the issue of a GDP certicate. One possible proposal could be
for an enhanced inspection programme by all MS with a commitment to complete the
database within an agreed time limit. This would have signicant resource consequences
for most MS and may detract from their GMP inspection programmes.
In order to make out of the thefts’ database a useful tools at a European level, there
should be legal obligations for all stakeholders to report stolen medicines to the DRA.
The “Operation Volcano” highlighted the importance of such a tool in support of inves-
tigations.
Ways should be sought to see if a quicker implementation of the serial number system
introduced in FMD would be possible, along with the permission to use this structure for
all medicines and medical products.
Lastly, in order to ensure the quality of products, it is recommended that the Commis-
sion, through the auspices of the EMA GMDP Inspectors Working Group, be requested
to review the current requirements in the EU GDP Guide for cold chain medicines and
determine whether the current requirements can usefully be strengthened by requir-
ing a temperature data logger (or similar) to accompany all shipments so as to assure a
complete temperature audit trail.
IV.III Preventive measures
Prevention can only be based on tools to gather and share information among author-
ities involved in law enforcement. The following tools currently appear to be the most
useful ones:
30
A constantly and timely updated database (similar to EudraGMP) and/or web
platforms of thefts of medicines where data about stolen medicines are pub-
lished: AIFA already started a project on this involving authorities, administra-
tions, associations and operators in the pharmaceutical and healthcare elds.
Real time alert on stolen/illegal medicines (AIFA will start using new ad hoc pag-
es for that - http://www.agenziafarmaco.gov.it/it/content/furti-di-medicinali,
and will promote the use of the AIFA/EC “fakeshare” platform as tool for inves-
tigators).
Development of risk proles on suspect offers as included in the HMA-WGEO
due diligence document in Annex VI.
Guideline for wholesalers how to proceed when a batch listed in the “Stolen
Medicines Database” is offered.
Training for DRA enforcement employees and for GMDP inspectors.
All of these measures should be discussed by involving the appropriate international
fora (e.g. Inspectors Working Party – EMA, PIC/S, PDA, ISPE etc.).
31
V.
RAs and NUIs
RAs issued by AIFA
August 8th, 2014 | IT - Italian Medicines Agency (AIFA)
AIFAtriggeredawiderecallofillegallymedicinesthroughalistofveriedtradeswheretheprimary
sourcewasaboguswholesaler.ThedocumentwasupdatedonAugust14th,September1st2014,
January 29th 2015 and on July 2nd 2015.
Other RAs
April 2nd, 2014 | DE - Paul-Ehrlich-Institut (PEI)
SuspectedcounterfeitofHerceptin(Trastuzumab)150mg.ThedocumentwasupdatedonAugust12th.
April 8th, 2014 | FI - Finnish Medicines Agency (FIMEA)
Suspect counterfeit herceptin.
April 11th, 2014 | European Medicines Agency (EMA)
Herceptin150mgPowderforconcentrateforsolutionforinfusion.
April 17th, 2014 | DE - Paul-Ehrlich-Institut (PEI)
FalsiedRemicadebatchesandtheactionstakeninGermany.
May 23th, 2014 | CZ - State Institute for Drug Control (SUKL)
NoticationofaQualityDefect/Recall.ThedocumentwasupdatedonJune26th.
July 1st, 2014 | DE - Paul-Ehrlich-Institut (PEI)
ConcerningfalsiedsyringesofGardasil.
July 28th, 2014 | DE - Federal Institute for Drugs and Medical Devices (BfArM)
Recall,noticationforparallelimportedmedicinalproductsoftheCompanyCC-PharmainGermany.
July 28th, 2014 | DE - Paul-Ehrlich-Institut (PEI)
Recall,noticationforparallelimportedmedicinalproductsoftheCompanyCC-PharmainGermany.
August 4th, 2014 | DE - Paul-Ehrlich-Institut (PEI)
Recall of batches of products of Italian origin.
August 6th, 2014 | DE - Federal Institute for Drugs and Medical Devices (BfArM)
ConcerningfalsiedViramune.
32
August 8th, 2014 | N – Norwegian Medicines Agency
Recalloffalsiedmedicinalproducts(Ipstyl,Orifarm).ThedocumentwasupdatedonAugust11th.
August 14th, 2014 | DE - Paul-Ehrlich-Institut (PEI)
ConcerningthecompanyHaematoPharmaGmbh,regardingrecallsofbatchesofproductsofItalianorigin.
August 14th, 2014 | DE - Paul-Ehrlich-Institut (PEI)
ConcerningthecompanyInophaGmbH,regardingrecallsofbatchesofproductsofItalianorigin.
August 19th, 2014 | DE - Paul-Ehrlich-Institut (PEI)
RecallsofparalleldistributedmedicinesofItalianorigin(RACC-Pharma).
August 19th, 2014 | DE - Paul-Ehrlich-Institut (PEI)
RecallofsuspectedmedicinalproductsofItalianorigin(Remicade100mg).
August 19th, 2014 | DE - Paul-Ehrlich-Institut (PEI)
RecallofsuspectedmedicinalproductsofItalianorigin(Humira40mg).
August 26th, 2014 | DE - Paul-Ehrlich-Institut (PEI)
Recallofillegalproductsofitalianorigin(RAOrifarm).
August 26th, 2014 | DE - Paul-Ehrlich-Institut (PEI)
RecallofillegalproductsofItalianorigin(RAMilinda).
August 26th, 2014 | DE - Federal Institute for Drugs and Medical Devices (BfArM)
Recall,noticationforparallelimportedmedicinalproductCelebrex200mgoftheparalleldistributer
CC-PharmainGermany.
August 26th, 2014 | DE - Federal Institute for Drugs and Medical Devices (BfArM)
Recall,noticationforparallelimportedmedicinalproductViramune400mgoftheparalleldistributer
CC-PharmainGermany.
August 26th, 2014 | DE - Federal Institute for Drugs and Medical Devices (BfArM)
Recall,noticationforparallelimportedmedicinalproductsoftheparalleldistributerOrifarmGmbHin
Germany.
August 27th, 2014 | DE - Paul-Ehrlich-Institut (PEI)
RecallofillegalproductsofItalianorigin(ClexaneeRemicade).
August 29th, 2014 | DE - Federal Institute for Drugs and Medical Devices (BfArM)
Qualitydefect,ClassII,medicinalproductCialis20mgtabletsoftheMAHEliLillyNiederlande,parallel
distributionbyOrifarmGmbH,DE.
September 9th, 2014 | DK - Danish Health and Medicines Authority (SST)
33
Illegalsupplychain(ZonegranandIpstyl).
September 25th, 2014 | FI - Finnish Medicines Agency (FIMEA)
Truvada parallel trade.
November 5th, 2014 | UK - Medicines and Healthcare Products Regulatory Agency (MHRA)
SuspectedFalsication,SymbicortTurbohaler320/9.ThedocumentwasupdatedonNovember6th.
May 18th, 2015 | DE – Federal Institute for Drugs and Medical Devices (BfArM)
Recallofsuspectedcounterferitmedicinalproductsofitalianorigin(SpirivaRespimat)
May 18th, 2015 | DE – Federal Institute for Drugs and Medical Devices (BfArM)
Recallofsuspectedcounterferitmedicinalproductsofitalianorigin(Clexane40mg)
NUIs
April 4th, 2014 | DE - Paul-Ehrlich-Institut (PEI)
Follow-upinformationonsuspectedcounterfeitofHerceptin150mg.
May 14th, 2014 | IT - Italian Medicines Agency (AIFA)
Identicationofthe“boguswholesalers”andrstlistofoperatorshavingtradedillegalmedicines.
May 28th, 2014 | IT - Italian Medicines Agency (AIFA)
Listofinvolvedbatchesforsomeoftheproductstradedbytheboguswholesalers(Mabthera,Avastin,
Herceptin).
July 1st, 2014 | IT - Italian Medicines Agency (AIFA)
Updateofthelistofinvolvedoperators,proposalofinspectionandvericationsaimedatdiscovering
other possible channels and triggering new signals.
July 25th, 2014 | IT - Italian Medicines Agency (AIFA)
Updateofthelistofoperatorsandsummaryofthecase.
August 26th, 2014 | IT - Italian Medicines Agency (AIFA)
UpdateonthestatusoftheItaliandistributionnetwork,summaryoftheongoingvericationsand
proposal of follow up.
October 14th, 2014 | IT - Italian Medicines Agency (AIFA)
Update on the status of the Italian distribution network.
34
RAs related to similar patterns
September 3rd, 2014 | DE - Paul-Ehrlich-Institut (PEI)
Counterfeit/manipulatedMabthera500mg(Bactch:H0656B03)withromanianorigin.
September 9th, 2014 | RO - National Agency for Medicines and Medical Devices (ANMDM)
Notication-productsdistributedbyChemomedIntertrading.
September 11th, 2014 | DE - Paul-Ehrlich-Institut (PEI)
Notication-productsdistributedbyChemomedIntertrading.
October 2nd, 2014 | DE - Paul-Ehrlich-Institut (PEI)
Recall,illegallytraded/counterfeitedmedicinalproductAbilify;wholesalerChemomedinRO,
manufacturerhvdmedicalGmbHinDE.
October 8th, 2014 | DE - Paul-Ehrlich-Institut (PEI)
RecalloffalisiedmedicinesbyparalleldistributorInophaGmbH.
October 22nd, 2014 | DE - Paul-Ehrlich-Institut (PEI)
NoticationonTarceva150mg.
November 19th, 2014 | DE - Paul-Ehrlich-Institut (PEI)
FalsiedAvastinRomanianorigin.
December 4th, 2014 | DE - Paul-Ehrlich-Institut (PEI)
SuspectedfalsiedMabTheraofRomanianorigin.
35
VI.
WGEO DUE DILIGENCE
by wholesalers and other actors involved in the purchase and sale of
medicinal products in the legal supply chain
VI.I Introduction
The legal supply chain of medicinal products has become increasingly more complex
during recent decades, with more and more actors being involved. Brokers are intro-
duced and more than one distributor is usually involved in the purchase and sale of
the same batch of product. Consignments of medicinal products are often
moved across several countries’ borders before entering the market they
are intended for. One important reason for this being the large extent
of movement/change of production sites producing medicinal prod-
ucts from Europe to third countries.
This ever increasing complexity calls for a well regulated and mon-
itored supply chain. As the saying goes “a chain is as strong as its
weakest link”, and to this end every player, every actor in the sup-
ply chain has a crucial responsibility and role to play to ensure that
the right medicines of the right quality reach the right market and
thereby also ensuring that no falsied medicines penetrate the legal
supply chain. Falsied medicines enter the legal supply chain either by
someone’s criminal intentions, by negligence of actors in the legal distribu-
tion chain or by both. So though one cannot eliminate the former, which will be dealt
with through the enforcement systems of the respective countries, there is much room
for improvement in the latter.
One of the key issues one has to address in order to ensure a safer supply chain is to
exercise appropriate due diligence. Due diligence involves ensuring that the person with
whom wholesalers are dealing and thus sourcing (in case of purchases) and supplying
to (in case of selling) are duly authorised in line with required legislation to handle (re-
ceive and supply) the medicinal products involved in the transaction. Though this might
36
seem as a simple and quite straight forward task, experience has shown that this is often
overseen or poorly adhered to.
VI.II Scope
The scope of this document is to list a set of questions with recommended answers which
will help wholesalers to highlight the risk areas and thus exercise necessary due diligence
when entering into deals especially with new potential suppliers and/or customers.
VI.III Questions and Answers
Q. Do you have a procedure available for Qualication of Suppliers?
A. A procedure delineating how a potential supplier should be assessed before becoming
an approved supplier from the point of view of your business operations should always
be available and followed up. A person should be identied within the company, ideally
the Responsible Person, who should be responsible for the execution of this procedure
and thereby approving new suppliers.
Q. What should be checked before a new supplier can be approved?
Does the company actually exist? Was the verication documented?
A. To ascertain that the company does indeed physically exist, ask for the UID or VAT
number and check this against appropriate country registers, before documenting that
the verication has taken place.
Alternatively, or additionally, search for the number on:
(www.ec.europe.eu/taxation_customs/vies/vatRequest.html). In this way you will at
least ascertain that the company is actually a registered one (and thus a legal entity
subject to legal proceedings). Open source checks on the internet can often be very use-
ful too.
What is the licensing status of the company?
A. Once the company has sent you a copy of their licence or a GDP-certicate, then the
authenticity of the document and the validity of the authorisation are very important.
This verication can be done by checking the website of the competent authority issuing
the licence or if it is registered in the EUDRA-GDP/GMP database as GDP/GMP compli-
37
ant. If the licence has an expiry date and it is expired, or if it has no expiry date and was
issued more than 3 years ago, check if it is still valid. The process of how and when such
verication is to be done should be described in your procedure and the verications
documented. It is crucial that the company licence status is conrmed before you issue
a purchase order.
Was an audit performed of the supplier?
A. You should have a policy of auditing your suppliers, especially new suppliers with
whom you have not previously had any business dealings with and which are not known
as trusted sources to your medicinal supply trading network. There should be a docu-
mented policy of audits including whom and when to audit based on a risk assessment
approach. Frequency of such audits is also to be listed. An audit should, as a minimum,
include a check of the supplier’s procedure for supplier qualication, ensuring that the
supplier has a process in place to verify that licences/certicates are checked prior to
any purchase orders being issued.
Q. Is the product offered a new product for your company?
A. Verify that the product has a Marketing Authorisation in an EEA country. You have to
consider if this product by nature or by source may be falsied. If so, do not assume that
the Marketing Authorisation number on the packaging is authentic/legitimate, check
with MAH or with the competent authority of the destination country to conrm the
products marketing status. Your quality system should have a procedure which incor-
porates a mandatory provision to notify the authorities in cases of suspicious products.
Q. Is the product being offered available in quantities or volumes unusually high or is
the price being offered considerably lower than the usual price?
A. If the answer to any of these questions is ‘yes’, as part of due diligence, the wholesal-
er accepting the deal should investigate the reason why, to try to establish a plausible
explanation before entering into a transaction. This holds true especially for products
which one does not usually come by in large quantities, or it is a known fact that cur-
rently there is a shortage of a particular product (example GMP problems in a site / sites
38
where the product is manufactured). Low prices should also raise a red alert and the
wholesale dealer should enquire the reason as to why such a low price is being offered.
Q. Is the supply chain of this transaction transparent?
A. The supply chain, i.e. the movement of goods from the storage of your supplier until
they reach your warehouse should be as transparent as possible. Is the complete chain
accountable? If not, it may pose a risk. A risk assessment should be conducted in this
regard to establish whether all points and handlers involved in the consignment journey
are known. If brokers are involved, check whether these brokers are adequately regis-
tered with the competent authority where they are established. Brokers must register
with the competent authorities of the country in which they are situated. If a broker
involved who is situated in the EEA is not registered, you should not enter into an agree-
ment but notify the competent authority.
Q. What will be the method of transportation? Will there be groupage?
A. The transport of the consignment should be well planned and it should only be han-
dled by shipping/transportation companies with whom there are written agreements
and with whom you have experience and condence in. Another important point to con-
sider is whether there would be groupage. If this is the case this should be known prior to
shipping so that adequate measures are taken by the handlers/shippers not to leave the
consignments exposed which increases the risk of someone tampering with the consign-
ment. For products requiring special storage conditions such as cold chain medicines the
transportation has to be well planned in advance.
39
VII.
OFFICIAL WEB RESOURCES
allowing to check if a wholesaler is authorised to trade in medicines by the
competent authorities of the MS where it is established
EMA
The Community database EUDRAGMDP may not be fully populated as Member States
are currently working to bring it into operation so the database can be complimented
with further information from the sources listed above and even through direct contact
with the concerned National Competent Authorities if no listing can be found.
http://eudragmdp.eudra.org/inspections/logonGeneralPublic.do
AUSTRIA
http://www.basg.gv.at/inspektionen/good-manufacturingdistribution-practice/
arzneimittelbetriebe/
CYPRUS
Cyprus Regulatory authority, Pharmaceutical Services/Ministry of Health, has published
a catalog of all authorized wholesalers in Cyprus. Here is the relevant link:
http://www.moh.gov.cy/MOH/phs/phs.nsf/All/
B67DD58A5E16809AC2257B2E0026D869?OpenDocument
All authorized wholesalers are also registered in the EudraGMDP database.
DENMARK
Information about Danish companies with a valid WDL can be found at the link:
http://sundhedsstyrelsen.dk/en/medicines/regulation/company-
authorisations-and-registrations/wholesale-distribution
By clicking at “Companies authorized to distribute medicines by wholesale in Denmark”
an excel le will be downloaded.
40
Another list for companies authorized to manufacture and import medicines and inter-
mediates in Denmark can be downloaded here:
http://sundhedsstyrelsen.dk/en/medicines/regulation/company-
authorisations-and-registrations/manufacture-and-import-of-medicines-
and-intermediates
A manufacturer must hold a wholesale dealer’s authorisation if it wholesale deals med-
icines that are not manufactured at an address approved on the MIA, or if the manu-
facturer chooses to wholesale their own manufactured medicines from other addresses
than those authorised on the MIA (e.g. separate storage addresses).
FINLAND
Name list of authorized wholesale license holders in Finland (for more detailed requests,
contact qdefect@mea.)
http://www.mea./valvonta/laaketehtaat_ja_-tukkukaupat/toimiluvat/
kotimaiset_laaketukkukaupat
FRANCE
List of authorised pharmaceutical companies in France, including notably wholesalers,
importers and exporters.
http://agence-prd.ansm.sante.fr/php/etapharm/index.php
ICELAND
List of Information about Icelandic companies with a valid WDL:
http://www.lyfjastofnun.is/Eftirlit/Lyfjaheildsolur_og_dreing/Listi_yr_
lyfjaheildsolur/
All authorized wholesalers are also registered in the EudraGMDP database.
ITALY
Permalink to the updated page:
http://www.dati.salute.gov.it/dataset/distributori_farmaci.jsp
41
Download link (refences: D – Depositario = warehousing service shipping/distributing
medicines on behalf of manufacturers; P – Produttore = manufacturer; G – Grossista =
wholesaler):
http://www.dati.salute.gov.it/imgs/C_17_dataset_4_download_
itemDownload0_upFile.CSV
MALTA
A webpage listing various pharmaceutical activities licensed/certied/registered after
establishing that the relevant GxP requirements and provisions of the Medicines Act are
achieved. This webpage lists various headings for facilities with a: GMP certicate, man-
ufacturer’s licence, wholesale dealer’s licence, plus registered brokers and API importers
and distributors. Clicking on the individual listed heading opens a document with the
relevant listed entities under that heading.
http://www.medicinesauthority.gov.mt/licensed-pharmaceutical-activities
ROMANIA
The list of authorized Romanian wholesalers can be found at the following link:
http://www.anm.ro/anmdm/_/Lista%20depozite.pdf
The suspended wholesalers are marked in red.
SPAIN
The list of authorized Spanish wholesalers can be found at the following link:
https://labofar.aemps.es/labofar/registro/entidadesDistribucion/consulta.
do?metodo=detalleBusqueda
By clicking in the name of the company, in blue, it is possible to access to more detail
data. Some of these details are still missing pending of the update of the authorisations
to the new format but all the authorised companies are listed. Also it is indicated wheth-
er the wholesale dealer’s licence is temporarily suspended.
SWITZERLAND
Link to the authorized wholesalers in Switzerland:
42
https://www.swissmedic.ch/bewilligungen/00155/00241/00253/index.
html?lang=en
THE NETHERLANDS
There are currently 229 wholesale dealers listed on EudraGMDP under WDA - Nederland.
There may be more wholesalers with a license that are not yet transferred to EudraGM-
DP, and for those you could search the list of licensed manufacturers and wholesalers at
http://www.farmatec.nl/geneesmiddelen/vergunningen/farmacie/
Lijstvergunninghouders.aspx
This is a pdf list that you could search for the name or address of the wholesaler. WDA is
indicated by the letter G in the column “Registernummer” (number in the register).
UNITED KINGDOM
List of UK MHRA licensed wholesalers:
http://www.mhra.gov.uk/Howweregulate/Medicines/Licensingofmedicines/
Manufacturersandwholesaledealerslicences/index.htm
43
VIII.
Q&A
At the beginning of the use of the “fakeshare” web tools, AIFA gathered questions from
all interested MS authorities, and prepared an ad hoc Q&A document, that was present-
ed during the second “fakeshare” webinar, and shared through the restricted web area,
in order to create common consensus on some issues related to the case: the following
list of Q&A is an excerpt from that document, with the exclusion of the questions related
to practicalities or to aspect that are now out of date.
Q. Can medicinal products, that are related to the illegal wholesalers outside Italy, be
dened as falsied?
AIFA (ITALY). We consider these medicines as “supplied with fake documentation” (e.g.
invoices stating that they were supplied by non authorized/non active wholesalers), and
consequently FALSIFIED. See Dir. 2001/83, as amended by Dir. 2011/62. TITLE I, Deni-
tions, Art. 1.
33.Falsiedmedicinalproduct:
Anymedicinalproductwithafalserepresentationof:
(a) itsidentity,includingitspackagingandlabelling,itsnameoritscompositionasregardsany
oftheingredientsincludingexcipientsandthestrengthofthoseingredients;
(b) itssource,includingitsmanufacturer,itscountryofmanufacturing,itscountryoforiginorits
marketingauthorisationholder;or
(c) itshistory,includingtherecordsanddocumentsrelatingtothedistributionchannelsused.
Thisdenitiondoesnotincludeunintentionalqualitydefectsandiswithoutprejudiceto
infringementsofintellectualpropertyrights.
Q. Where in the European legislation can I nd the right paragraphs to force the Par-
allel distributors/Wholesalers to give us the requested information?
POINT FOR DISCUSSION. Dir. 2001/83, TITLE IV considers together “Manufacture and im-
portation”; TITLE XI (“Supervision and sanctions”), art. 111, states that
44
1g.Inspectionsshallbecarriedoutbyofcialsrepresentingthecompetentauthoritywhoshallbe
empoweredto(…)
(c) examineanydocumentsrelatingtotheobjectoftheinspection,subjecttotheprovisionsin
forceintheMemberStateson21May1975placingrestrictionsonthesepowerswithregardto
thedescriptionofthemanufacturingmethod;
(d) inspectthepremises,records,documentsandpharmacovigilancesystemmasterleofthe
marketingauthorisationholderoranyrmsemployedbythemarketingauthorisationholder
toperformtheactivitiesdescribedinTitleIX.
With respect to wholesalers, there are clear provisions under Art. 80:
Holdersofthedistributionauthorizationmustfullthefollowingminimumrequirements:(…)
(e) theymustkeeprecordseitherintheformofpurchase/salesinvoicesoroncomputer,or
inanyotherform,givingforanytransactioninmedicinalproductsreceived,dispatchedor
brokeredatleastthefollowinginformation:
date,
nameofthemedicinalproduct,
quantityreceived,suppliedorbrokered,
nameandaddressofthesupplierorconsignee,asappropriate,
batchnumberofthemedicinalproductsatleastforproductsbearingthesafetyfeatures
referredtoinpoint(o)ofArticle54;
(f) theymustkeeptherecordsreferredtounder(e)availabletothecompetentauthorities,for
inspectionpurposes,foraperiodofveyears;
Q. What do we do if the Parallel distributors/Wholesalers refuse to give information
or refuse to do a recall and send their lawyers against us?
AIFA (ITALY). Lack of compliance with Directive 2001/83 would be a major infringement
with respect to any authorization.
Q. What measures are planned for the suspected Italian wholesalers, will there be a
withdrawal of licences?
Q. Are the above mentioned Italian operators declared GDP non-compliant? If so, has
this been entered into Eudra GMDP?
45
AIFA (ITALY). The ones who bought from “non authorized wholesalers” (i.e. the ones in
Latvia etc.) will undergo sanctions from the competent authorities (i.e. local Authorities).
Article80Holdersofthedistributionauthorizationmustfullthefollowingminimum
requirements:
(a) theymustmakethepremises,installationsandequipmentreferredtoinArticle79(a)
accessibleatalltimestothepersonsresponsibleforinspectingthem;
(b) theymustobtaintheirsuppliesofmedicinalproductsonlyfrompersonswhoarethemselves
inpossessionofthedistributionauthorizationorwhoareexemptfromobtainingsuch
authorizationunderthetermsofArticle77(3);
(…)
(ca)theymustverifythatthemedicinalproductsreceivedarenotfalsiedbycheckingthe
safetyfeaturesontheouterpackaging,inaccordancewiththerequirementslaiddowninthe
delegatedactsreferredtoinArticle54a(2);
(d) theymusthaveanemergencyplanwhichensureseffectiveimplementationofanyrecall
fromthemarketorderedbythecompetentauthoritiesorcarriedoutincooperationwiththe
manufacturerormarketingauthorizationholderforthemedicinalproductconcerned;
(e) theymustkeeprecordseitherintheformofpurchase/salesinvoicesoroncomputer,or
inanyotherform,givingforanytransactioninmedicinalproductsreceived,dispatchedor
brokeredatleastthefollowinginformation:
date,
nameofthemedicinalproduct,
quantityreceived,suppliedorbrokered,
nameandaddressofthesupplierorconsignee,asappropriate,
batchnumberofthemedicinalproductsatleastforproductsbearingthesafetyfeatures
referredtoinpoint(o)ofArticle54;
(f) theymustkeeptherecordsreferredtounder(e)availabletothecompetentauthorities,for
inspectionpurposes,foraperiodofveyears;
(g) theymustcomplywiththeprinciplesandguidelinesofgooddistributionpracticefor
medicinalproductsaslaiddowninArticle84;
In particular, the Italian implementation of Dir. 2001/83 indicate the art. 80 requirements
as “essential” for granting the wholesale authorization; this aspect will be covered even
46
before the trial, and (if relevant) the update of the EUDRA GDMP system will be consid-
ered.
Q. Is it true that in Italy hospitals have no licence as wholesalers?
AIFA (ITALY). Yes.
Q. Are Italian labelled medicinal products that are hospital only in Italy to be classi-
ed as falsied if they are in the legitimate supply chain elsewhere in EU/EEA?
Q. Is it illegal for an Italian wholesaler to export hospital only medicines to other
EU-countries?
AIFA (ITALY). No: Italian wholesalers may legally export also hospital only medicines.
Q. Is there a list of Italian medicinal products that are hospital only?
AIFA (ITALY). Yes: it is published and updated regularly by AIFA, it is available on the
web. http://www.agenziafarmaco.gov.it/it/content/tabelle-farmaci-di-classe-e-
h-al-15052014 (Excel le: http://www.agenziafarmaco.gov.it/sites/default/les/
Classe_H_per_Principio_Attivo_15.05.2014. xls)
Q. If Italian medicinal products that are hospital only are found in the legitimate sup-
ply chain in EU/EEA, what action should be taken, i.e. company to quarantine, Na-
tional Competent Authorities to seize, company to return to marketing authorization
holder, etc?
AIFA (ITALY). We should rene the question: since it is possible that hospital only drugs
are legally exported, we should focus on ILLEGAL products. If Italian medicinal products
that are hospital only and are conrmed as “falsied”, e.g. paired to fake documentation
with respect to the origin are found in the legitimate supply, the rules for falsied med-
icines should be applied.
Q. For the stolen cold chain medicines is there any evidence that the cold chain has
been maintained, i.e. by data-logger records that cover the relevant periods of time?
47
AIFA (ITALY). No direct evidence. With respect to the medicines under investigation, as
far as we know, up to now none reported EMA complaints/pharmacovigilance data/etc.
clearly related to cold chain issues; the criminals were using a certain degree of care
in handling things, apparently, since they were working on a “long term business”; and
they wanted to avoid incidents. The “Herceptin incident” starting the case seems to be
an indication of the “enlargement of the platform” – i.e. the central coordination unit of
the criminal organization started using “non specialized burglars” for “supplying” the
network, which was the cause for the incident. We know Police is studying the camera
recordings of recent thefts, in order to identify “people carrying portable refrigerators”.
Q. Can you conrm that the tampering/adulteration of Herceptin is a one-off incident
and, in principal, is not related to the theft of medicines?
Q. How many of the involved medicinal products are at the moment conrmed to be
manipulated? (I think it is only Herceptin!?)
AIFA (ITALY). The only manipulation we found up to today is the Herceptin one. We have a
series of indications supporting the interpretation of the manipulation as a “bad quality
supplier tampering”: the very low incidence of the case, the bad quality of manipulation,
the presence of water in all tampered vials, support this interpretation of the incident.
We suppose that someone working in the targeted hospital took the medicines, some
empty vials and some labels, and tried to arrange some “extra vials” to be added to the
supply.
Q. What are the specic reasons for the Italian companies being on the list of concern?
Q. Does the Italian wholesalers mentioned on the list of operators identied as having
supplied medicines sourced from the illegal operators identied outside of Italy have
a valid WDA in Italy?
AIFA (ITALY). The list we published includes authorized operators, which according to
the medicines traceability data/seized invoices/customs data, were directly or indirectly
“victims” of the fake wholesalers, i.e. they exported medicines “arriving” from the Lat-
vian/Hungarian/ etc. wholesalers - as the documents pretended. Please, note that since
48
they simply traded medicines from this network, they should simply considered as “un-
der reinforced checks” – the Italian names in the list are not blacklisted.
Q. What is AIFA’s recommendation to member states for any consignments of the
products of its watchlist? Immediate recall or quarantine of all those products of
Italian origin following precautionary principle as there is an illegal supply chain (un-
authorised wholesaling activity)?
Q. Do you have batch numbers for any of the medicines on the list of concern?
Q. Of the 64 products identied by AIFA, is it possible for AIFA to differentiate this list
of medicinal products into those that have a potential legitimate supply route out of
Italy and those which have no potential legitimate supply route out of Italy?
AIFA (ITALY). AIFA (ITALY). The list was considered as a “support for inspections”, a sort
of watchlist, being based on documents issued by fake wholesalers; so, at this stage the
recommendation is to use it for extra verication, not for recalls or seizures. In the ex-
amined documentation we have batch numbers, but since the batch numbers come from
fake invoices, we are performing extra checks, connecting the purchase invoices with the
selling ones. Our plan is to send MS Authorities data and copies of all conrmed invoices/
trades by next week, including conrmed batch numbers; in this way, we will cover also
the EMA point, i.e. the possible “nal destination” of medicines. According to the picture
we are building and to other ongoing investigation we are trying to liaise with, it seems
that some specic medicines (doping substances and Botox, for instance) were destinat-
ed to the national black market, or to the web.
Q. What dates does your information regarding stolen medicines cover? i. e. how long
have the companies been dealing in stolen/falsied medicines?
Q. When did this begin? What would be the recommended exclusion dates for consign-
ments supplied to member states?
AIFA (ITALY). We have industry data for 2013-2014, and all Ministry of Health data from
2012 to 2014. According to our information, the case started at least 3 years ago (i.e.
end of 2011, beginning of 2012). Since we are speaking about products with a very quick
turnover, we performed a risk assessment, deciding to ask the Prosecutor the more re-
49
cent data; we would then recommend to focus on 2013-2014 purchases, at least for the
moment.
Q. How can you state for a specic medicine (i.e. Mabthera and Avastin) that no legal
export has taken place the last 12 months? Have you decided whether or not to extend
the range of “12 months”? Also it would be helpful to know exactly when “12 months
ago” is - is it April or May 2013, or what is behind this timeframe?
AIFA (ITALY). Italy has a full medicines traceability in place: all medicines packages are
identied with an unique code, so we may check all trades/export/movements of medicines.
You nd some explanation (in Italian) and a picture (easier to understand) here http://www.
salute.gov.it/portale/temi/p2_6.jsp?lingua=italiano&id=1373&area=tracciabilita%20
farmaco&menu=monitoraggio. The “12 months” window means “after April 1, 2013”.
Q. What kind of documentation does an Italian wholesaler need to export medicines
to other EU-countries (special documents?, notication to authorities in Italy? Other?)
AIFA (ITALY). Only authorized wholesalers (authorized at local level; the authorization is
notied to Ministry of Health) may export medicines; they may only export authorized
medicines, obviously. There is an obligation to send all data about the export (i.e. medi-
cine name and number of pieces) to the Traceability Repository.
Q. What enforcement measure is being undertaken against the Italian wholesale
dealers involved? Have we an assurance that this pipeline has now been stopped?
AIFA (ITALY). They were inspected by the Police forces, all their transactions were ex-
amined and doublechecked by AIFA/Ministry of Health, and also the Italian Customs are
verifying their trades. Some of the operators already stopped their activities, and the
Prosecutors and the local authorities are planning direct actions on them. We noted a
strong reduction in thefts after the beginning of investigations, even if we cannot be sure
to have identied all channels – we still have thefts, but we don’t know if they are relat-
ed to a “delay” in stopping the “suppliers”, or to another exporting channel. An update on
the activities performed in Italy is already part of this White Paper.
Q. Is there any evidence of supply to the Italian market?
50
AIFA (ITALY). For the moment, we have no evidence with respect to the already evalu-
ated products (i.e. the hospital ones), which we may conrm as being out of our legal
distribution network. In Italy, parallel import procedures are related to a centrally is-
sued authorization (managed by AIFA), so we already know that no parallel import was
authorized for any of the already evaluated products. As mentioned above, according to
the picture we are building and to other ongoing investigation we are trying to liaise with,
it seems that some specic medicines (doping substances and Botox, for instance) were
destinated to the Italian black market, or to the web (targeting Italian market) ; then, we
will better evaluate this in the follow up investigations we are starting.
Afterword
Review by the HMA
On February 2015, this White Paper was provided to the HMA for evaluation, prior to submit-
ting the paper to the European Commission.
Dr Ian Hudson, MHRA Chief Executive Ocer, commented on the document as reported at p.27
under the heading “Further proposals”.
On May 11-13, 2015, in the occasion of the 80th HMA Meeting held in Ljubljana, Slovenia, copies
of the publication were distributed to the participants. The publication of the White Paper on
the HMA Website under the WGEO page was approved. Submission of the White Paper to the
EC was also approved.
TABLE OF CONTENTS
I THE STORY (SO FAR) 7
I.I Thefts of medicines in Italy 7
I.II The case 9
II CASE MANAGEMENT 15
II.I The verication process 15
II.I.I Validationoftrades
II.I.II Validationofoperators
II.I.III Triggers for new signals
II.I.IV Restoringofthesecurityoftheitaliansupplychain
beyond the Herceptin case
II.II Coordination activities 21
II.II.I Roles of different entities during this case
III KEY LESSON LEARNED 24
IV PROPOSALS 26
IV.I Enforcement coordination 26
IV.I.I Furtherproposals
IV.II Regulatory approach 28
IV.III Preventive measures 29
V RAS AND NUIS 31
VI WGEO DUE DILIGENCE 35
VI.I Introduction 35
VI.II Scope 36
VI.III Questions and Answers 36
VII OFFICIAL WEB RESOURCES 39
VIII Q&A 43
Afterword: Review by the HMA 51
TABLES
Theft project: Timetable 7
Identied unauthorized (“bogus”) wholesalers 11
List of operators which directly bought
medicines from the “bogus wholesalers” 12
The supply chain models 13
Products sold mostly to hospitals 18
AIFA will keep in updating all documentation and databases
related to the case, using the same web tools developed in
the FAKESHARE/FAKESHARE II projects framework, already
used during this crisis.
The restricted area of the www.fakeshare.eu website will be
accessible to all registered users from interested institutions
and stakeholders.
... As mentioned before, in the last decade more advanced biologicals such as different blockbuster monoclonal antibodies have been falsified. Major oncology drugs such as adalimumab, trastuzumab, rituximab and bevacizumab are prone to falsifications and have been found in the legal supply chains in the USA, Western Europe, India, Western Africa, Northern-Cyprus and Turkey [18,92,[130][131][132][133]. Analysis of the seized samples however showed that, in contrast to the earlier mentioned anabolic proteins, in most cases no API was found to be present. ...
... The incidents with trastuzumab in Europe, in 2014, bear the hallmarks of organised pharmaceutical crime. 59 In this case, a criminal network provided stolen batches of authentic trastuzumab with fake documentation and reintroduced them into the legal supply chain in the EU. The stolen batches were stored and distributed in facilities that did not have temperature control, which risked the degradation of the active ingredients in the compound. ...
Article
Oncology drugs clearly have become a target for pharmaceutical crime. In 2016, falsified oncology drugs ranked fifth in the most commonly falsified drug category among the reports received by the Pharmaceutical Security Institute. Although the prevalence of illicit oncology drugs in the legal supply chains appears to be small, these drugs are difficult to detect, particularly in clinical practice. Forthcoming countermeasures to detect illicit drugs in high-income countries include compulsory antitampering devices and product verification technology for a risk-based selection of medicines. Health-care professionals must implement these new procedures into their workflow and remain vigilant about those medicines that are not selected. Although countermeasures should firmly tighten supply chain security, there are concerns about how quickly pharmaceutical crime will adapt to these protections. Because patients and health-care professionals have shown a lenient attitude towards purchasing medicines from unreliable sources, measures against the highly accessible illegal medicine supply chain remain necessary. To improve detectability in clinical practice, reporting of ineffectiveness and unusual drug effects as adverse events or adverse drug reactions is essential.
ResearchGate has not been able to resolve any references for this publication.