IMPLEMENTING THE FALSIFIED MEDICINES

DIRECTIVE: A MAMVO UPDATE

THE BACKGROUND

Directive 2001/83/EC of the European Parliament and the Council of 6 November 2001 on the Community code relating to medicinal products for human use. Transposed into Medicines Act and Subsidiary Legislation.

Directive 2011/62/EU of the European Parliament and of the Council of 8 June 2011 amending Directive 2001/83/EC on the Community code relating to medicinal products for human use, as regards the prevention of the entry into the legal supply chain of falsified medicinal products. The ‘Falsified Medicines Directive’

Introduced the concept of safety features and the requirement of a Delegated Regulation

Transposed into local legislation

THE BACKGROUND

Commission Delegated Regulation (EU) 2016/161 of 2 October 2015 supplementing Directive 2001/83/EC of the European Parliament and of the Council by laying down detailed rules for the safety features appearing on the packaging of medicinal products for human use. It is a Regulation therefore does not need to be

transposed into local legislation, but has full legal force like any Maltese Act of Parliament and Subsidiary Legislation.

It will come into force in Malta on the 9th February 2019

WHAT ARE THE SAFETY FEATURES?

Safety features (unique identifier, UI) enabling

wholesale distributors and persons authorised or

entitled to supply medicinal products to the public

to

verify the authenticity of the medicinal product, and

identify individual packs

Device (anti-tampering device, ATD) allowing

verification of whether the outer packaging has

been tampered with.

THE UNIQUE IDENTIFIER CONSISTS OF…

‘product code’ (identifying name, common name, form, strength, pack size, pack type, maximum 50 characters, globally unique) [PC, AI 01]

‘serial number’ (numeric/alphanumeric, maximum 20 characters, randomised, less than 1 in 10,000 chance of guessing) [SN, AI 21]

batch number [Lot, AI 10]

expiry date [Exp, AI 17]

national reimbursement number, if required by MS (not required by Malta but may be required by other Member States and therefore may be present)

THE UNIQUE IDENTIFIER

The unique identifier shall be encoded in a 2-D barcode Machine-readable Data Matrix with internationally

recognised coding scheme (The PC is a 14-digit GS1 GTIN/NTIN or 12-digit IFA PPN)

Product code, serial number, national reimbursement number shall also be printed in human-readable format as long as sum of two longest dimensions is > 10 cm. (Should be printed next to the Data Matrix whenever dimensions allow)

Batch number and expiry date are already printed as per “Labelling and Package Leaflet” section in the Directive.

Combination of product code and serial number is unique to a given pack until at least 1 year after expiry or 3 years after release for sale or distribution, whichever is longer.

THE UNIQUE IDENTIFIER

QR Code Data Matrix

WHICH MEDICINAL PRODUCTS?

Medicinal products

Subject to prescription shall bear the safety features,

unless they have been included in the “white list”

Not subject to prescription shall not bear the safety

features, unless they have been included in the “black list”

WHICH MEDICINAL PRODUCTS?

WHICH MEDICINAL PRODUCTS?

Medicinal products Subject to prescription shall bear the safety features, unless

they have been included in the “white list”

Not subject to prescription shall not bear the safety features, unless they have been included in the “black list”

However, member states may

For the purpose of reimbursement or pharmacovigilance extend the scope of the UI to any medicinal product subject to prescription or subject to reimbursement

For the purpose of patient safety, extend the scope of the ATD to any medicinal product

Note: Malta is not extending the scope of either the UI or the ATD but plans to allow the placing on the market of any medicinal products that should not bear the safety features, but do so because of requirements of other Member States.

THE REPOSITORIES SYSTEM

THE REPOSITORIES SYSTEM

THE REPOSITORIES SYSTEM

Malta Medicines Verification Organisation (MaMVO)

Full members (minimum of three): PRIMA, GRTU, Malta

Chamber of Pharmacists

Founding members and any other association admitted as such at a

later time, represented on Board of Directors (2 per member)

The right to participate in and vote at the General Assembly

meetings, participate in working groups and task forces, request an

independent audit of NMVS security and performance

The obligation to pay a yearly membership fee

Affiliate members: CPSU as part of Health Dept, MQPA

Right to receive notice of General Assembly and attend in a non-

voting observer capacity, and right to be consulted on the activities

of the MaMVO

THE REPOSITORIES SYSTEM - FUNDING

WHAT HAPPENS ON SCANNING?

If the market is supplied with original market-specific

or multi-market packs, or packs that have been

repackaged specifically for Malta with a new safety

features

the pack data is available in the Maltese repository.

the response time of 300 milliseconds is the response time

of the repository, and does not take into consideration the

internet connection speed.

WHAT HAPPENS ON SCANNING?

If the market is supplied with packs originally

intended for other markets that have not been

repackaged, or have been repackaged without the

need to replace the safety features

the pack data is not available in the Maltese repository.

an out-of-market query will be triggered (i.e. the system will

need to communicate with the hub, find the market for

which the product was intended, and verify and

decommission the number in the foreign repository).

transaction will take longer (the 300 millisecond-response

time applies to each step, and does not take into

consideration internet connection speed from the

pharmacy/wholesaler and between the repositories).

THE REPOSITORIES SYSTEM

WHAT HAPPENS IF?

There are technical problems?

According to the Delegated Regulation, if technical problems prevent verification and decommissioning, it must be possible to record the UI, and as soon as the technical problems are solved, verify and decommission the UI (e.g. if the system is off-line client software could queue the scans and send them as soon as the system comes back online)

A manual pack entry option will also be available (e.g. if the scanner or the software is not working) – in this case only the product code and serial number have to be entered. This option is deliberately onerous (deliberately designed not to accept scanner input) in order to prevent this mode of input being used systematically.

WHAT HAPPENS IF?

I have many products to verify/decommission

Some (but not all) operations can be carried out in “Bulk-of-

Pack” mode (i.e. instead of scanning each number and every

time waiting for a response, a group of products can be

scanned, and the numbers sent in bulk; the system will then

respond with an aggregate response, that can be opened to see

the individual responses)

Asynchronous operation since the system has to wait for the

operation to be performed on all numbers.

Out-of-market transactions are not available in “bulk-of-pack”

mode.

Software viewed by MaMVO has shown it is actually faster to

send e.g. 10 × 1 individual transactions, than 1 × 10 “Bulk-of-

Pack” transactions.

IS THIS PRODUCT ACCEPTABLE?

The basic principle is very simple: one unique identifier, one integral antitamper device.

There may be more than one barcode or datamatrix on the product, but only one can be used for the purpose of identification and verification of the authenticity of the product.

A sticker can be used to place the UI on the product, but

it must be tamper-evident

it should not be possible to remove it without damaging the packaging or the sticker or leaving visible signs

it must not impair readability

it must not be placed on top of an existing sticker

IS THIS PRODUCT ACCEPTABLE?

The basic principle is very simple: one unique identifier, one integral antitamper device.

Replacement of ATD’s is permitted, even with equivalent (rather than identical) ATD’s but the new ATD

must completely seal the pack and cover any visible sign of the original, broken ATD

must not impact the readability of the Data Matrix containing the unique identifier

shall not prevent the human-readable batch number and expiry date from remaining readable when the medicinal product is subsequently opened

THE REPOSITORIES SYSTEM

HOW IS EVERYTHING CONNECTED?

WHAT DO YOU NEED?

A computer or other IT device with internet connection

A scanning device that recognises Data Matrix 2-D barcodes (ISO/IEC 16022:2006 standard) and communicates with the computer.

Software that can receive and interpret input signal from the scanner

communicate with the repositories system, via appropriate authentication

allow the users to perform their obligations at law

WHAT NOW AND WHEN?

Now would be good, yesterday even better.

WHAT NOW AND WHEN?

The Malta Medicines Verification System needs to connect to the European Medicines Verification System (Part 1 passed, Part 2 underway)

Draft legal notice to be issued (does not contain any legal obligations that apply directly to community pharmacists)

IT Supplier Onboarding:

Make contact with IT suppliers and organise workshop

Contractual onboarding: IT Suppliers sign nondisclosure agreement

Technical onboarding: Connect first to a test environment for software development and interface / connectivity testing and, when ready, then to a quality environment for system testing and self-certification, in preparation for a known End User.

WHAT NOW AND WHEN?

Pharmacy and Wholesaler Onboarding

Contractual onboarding: registration online via

MaMVO website (soon available), to include

submission of certified true copy of pharmacy /

wholesaler licence, details of responsible and

contact persons for the End User Organisation, and

identity of IT Supplier. MaMVO will perform eligibility

checks, and if approved, End-User Agreement will be

signed between the Licence Holder and MaMVO.

WHAT NOW AND WHEN?

Pharmacy and Wholesaler Technical Onboarding MaMVO will create an account for the end-user organisation. This will

require a Prime Contact, a Prime Contact e-mail (which cannot be changed for the Organisation) and up to 5 Test Questions.

Prime Contact will receive an e-mail to register as an organisation in the MaMVO portal. Note: If multiple pharmacy owners wish to register each pharmacy as a separate organisation, a unique e-mail will have to be provided for each pharmacy.

Organisation will be created with a single Super User, who then has to create: Locations and equipment, to obtain the Client ID and Client Secret, to put into

software, communicate with EMVO, create end-user audit trails (Note: these will be shown once and there is no way of ever retrieving them again – new equipment would have to be “created”).

Users, to be able to use Solidsoft emergency portal. Any other control of individual pharmacist functionality / audit trails in day-to-day activities occurs through the pharmacy software.

WHAT DO I DO NEXT?

Familiarise yourself with the information (https://ec.europa.eu/health/human-use/falsified_medicines_en) .

Delegated Regulation (https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-1/reg_2016_161/reg_2016_161_en.pdf)

Commission Questions and Answers (https://ec.europa.eu/health/sites/health/files/files/falsified_medicines/qa_safetyfeature_en.pdf)

MaMVO website (http://www.mamvo.org)

Contact:

Your IT Supplier if you already have software systems in place.

Your stakeholder representative within the Malta Medicines Verification Authorisation (MaMVO).

WHAT DO I DO NEXT?

Liaise with your suppliers

Establish when you will be receiving serialised stock and/or stock that will be placed on market under transitional arrangements.

Take necessary steps, where applicable, to establish status as “a wholesaler who is designated by the marketing authorisation holder, by means of a written contract, to store and distribute the products covered by his marketing authorisation on his behalf”, to avoid unnecessary verification legal requirements by yourselves and your wholesaler clients.

Update QRD templates.

Review your pharmaceutical quality system

The provisions of the Delegated Regulation do not replace GDP requirements, neither should they run independently. Your legal requirements under the Delegated Regulation need to be integrated into the way you implement GDP.

QUESTIONS?