italian medicines agency aifa
TRANSCRIPT
Domenico Di Giorgio Italian Medicines Agency – AIFA
August 2018 | Rome, Italy
* Domenico Di Giorgio in accordance with the Conflict of Interest Regulations approved by AIFA Board of Directors (25.03.2015) and published on the Official Journal of 15.05.2015 according to 0044 EMA/513078/2010 on the handling of the conflicts of interest for scientific committee members and experts
The view and opinions expressed in the following PowerPoint slides are those of the individual presenter and should not be attributed to AIFA
N.B. <I am not receiving any compensation> or <The compensation received is based on the collective bargaining agreement>
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The future safety features framework and its impact
Directive 2011/62/EU
(modifies Directive 2001/83/EC)
Delegated Regulation (EU) 2016/161
Antitampering Device (ATD)
2 kinds of safety features for medicinal products: • To verify the authenticity of each pack as well as its identification.
• To verify whether the outer packaging has been tampered with.
ALL medicinal products subject to prescription shall bear them, except if included in a list.
Medicinal products not subject to prescription shall NOT bear them, except if included in a list.
Unique Identifier (UI)
UI: Possibility to extend the scope by MMSS for the purpose of reimbursement or pharmacovigilance
ATD: Possibility to extend the scope for the purpose of patient safety
Repository system information: Possibility for MMSS to use the information for the purposes of reimbursement, pharmacovigilance or pharmacoepidemiology
The regulation of some aspects of the SF was delegated in the European Commission by Directive 2011/62/EU • UI characteristics • Verifications to be perfomed through the supply chain • The repository system establishment, management and accesibility • The list of medicinal products exempted or included and the related
notification procedures to the EC
DELEGATED REGULATION(EU) 2016/161
• Adopted on the 2nd of October 2015
• Published in the Official Journal of the EU the 9 of February 2016
• Coming into force the 9 of February de 2019 , except in 3 MMSS that may use an extension period (6y)
Medicinal products subject to prescription - unless included in Annex I to the Regulation
Medicinal products not subject to prescription which are included in Annex II to the Regulation
Medicinal products to which Member States have extended the scope of application of the UI or of the ATD in accordance with Article 54a(5) of Directive 2001/83/EC
Content • Product code • Serial number • National reimbursement number, if required • Batch number • Expiry date
Carrier • Two dimensional barcode • Machine readable Data Matrix • Coding schemes
Printing quality requirements
PC: 09876543210982 SN: 12345AZRQF123456789 NRC: 9999999 Batch: 10D14V Expiry date: 06 2020
UI EXAMPLE
The repositories system has to ensure, inter alia: • Verification of authenticity and decommissioning of UIs • The detection of potential incidents of falsification • Interoperability among repositories • Commercial, confidential and personal data protection • Virtually instantaneous response: 300 ms system response time • Records of all operations concerning a UI (‘audit trail’)
Member States will be in charge of supervising the repositories system
The repositories system can be queried by verified users: • Whose identity, role and legitimacy has been verified • And only to the information generated by them
NCAs can access the repositories system and the information contained therein for: • Supervising the functioning of the repositories • Investigating potential incidents of falsification • Reimbursement • Pharmacovigilance or pharmacoepidemiology
The implementation of the SFs legislation is a enormous challenge for all of us that will result in a better protection against falsified medicinal products but will also allow NCAs and stakeholders to be more efficient in their activities
Examples of T&T Intelligence
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VOLCANO OPERATION • Signal about suspect/manipulated products (Germany):
different batch numbers, non matching the ones on the outside box.
• Verification of the unique identifier(s), confirming the supposed destination of the product in Italy – an hospital. The verification on the batch numbers vs AIFA DB on thefts also allowed to identify the possible events related to the “mixed up products”.
German invoice allowed the German product was sourced through an UK trader; the UK supplier bought the product from an Italian wholesaler. Checking the invoice of the Italian wholesaler allowed to identify other hospital-only products, to be checked in the Italian T&T system.
All transactions related to the above mentioned products were verified in the T&T system.
The result of the verification was a list of operators and transactions for exporting/supplying the products: all transactions were traced back to the first visible source.
MAHs were then involved in verifying if the first visible source was actually supplied by them: the confirmation of the absence of supply allowed the identification of a list of “contaminated operators”.
“AVALANCHE EFFECT”: 1 product (Herceptin, in Germany), identified as illegal through T&T, led to 5 products (the ones in the Italian operator invoice to UK), also identified as illegal. Checking the transactions regarding the 5 products in the T&T system allowed to identify more operators, and their transactions led to the development of a larger list of products…
The final figures are summarized in the “Volcano Operation White Paper” for the EC: thousands of illegal trades, tenths of police operations, tenths of millions of euros of seized products, etc.
All Rapid Alerts, black lists of operators, NUI for suspect products/operators were developed by using data from the Italian T&T system, as a data source for preventive intelligence and for reactive initiatives.
“CAR TRUNK” CASE • A side case related to the Volcano Operation: during a search,
police forces found hundreds of packages of an Italian medicine in the car of a foreign operator.
• Checking the batch number in the AIFA DB on thefts allowed to identify them as “suspect” – then an in depth verification in the T&T system and in the MAH db was performed.
T&T system and MAH data allowed to identify the unique identifiers connected to a specific theft, corresponding to the ones found by the police.
The identification of the products as “stolen”, and their connection to a specific filed event, allowed police forces to immediately seize the product and the car, and to charge the operator for illegal trade, laundering, etc.
ILLEGAL EXPORT OF “LOST” PACKAGES • AIFA received an informal signal about “non registered thefts”
(single packages “lost” in hospitals) being used for gathering products to be exported: a possible “model” for controlling this kind of trade was then developed (IE: when checking export activities during inspections in the field, pay attention to supplies involving small quantities of many different batches of the same product).
A first supply of this kind was found a few weeks after the signal: Carabinieri NAS sent AIFA/MoH information about a suspect trade, providing also the available unique identifiers
T&T/MAH data confirmed that at least some of the identifiers were related to a supply to a specific hospital – they were not available to wholesalers, then…
Police investigation on theft is still ongoing
DISTRIBUTION DISRUPTION/SHORTAGES. • Italy started in 2015 an intersectorial cooperation between
central/Regional authorities and manufacturers/ wholesalers/ retailers associations, aimed at verifying the roots for lack of availability of some medicines on the Italian market.
• T&T data allowed to identify some “key products” to be used as a reference in ad hoc verification in the field, with respect to some illegal transactions, used for “raking” products to be exported.
T&T data and intelligence activities performed at central level by AIFA/MoH triggered inspections to wholesalers, identification of illegal trades (EG pharmacies selling to wholesalers) and sanctions to operators.
The interim result of the activity was a reduction of the impact of the phenomenon, and the prevention of the lack of supply for some key products.
Domenico Di Giorgio
Head of Inspection & Certification Department
Italian Medicines Agency - AIFA