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On 11 March 2008, the European Commission published the paper PUBLIC
CONSULTATION IN PREPARATION OF A LEGAL PROPOSAL TO COMBAT COUNTERFEIT MEDICINES
FOR HUMAN USE - KEY IDEAS FOR BETTER PROTECTION OF PATIENTS AGAINST THE RISK OF
COUNTERFEIT MEDICINES. With this paper, the European Commission reacted to
recent events caused by
- Active Pharmaceutical Ingredients (APIs) not manufactured in
compliance with GMP,
- counterfeited medicinal products,
- and uncontrolled streams of goods via brokers, traders and
agents
The numbers and facts are alarming. The number of counterfeit
medicinal products identified within the EU alone has risen by 384% since 2005.
In England, cases have become known where counterfeit medicines were secretly
introduced into the regular supply chains of pharmaceutical companies.
Non-GMP-compliant API manufacturers have gained access to the international
markets. Equipped with CEPs or DMFs, they signal a GMP compliance that is not
really controlled. The changes now proposed by the European Commission are very
far-reaching and will change the existing system of pharmaceutical quality
assurance considerably. The following main theses and proposals
are planned:
I Control of the Supply Chain
-
Clarify that the obligations for wholesalers apply to all parties in the
distribution chain, except for those directly distributing or administering to
the patient. Brokers, traders and agents would be considered as wholesalers,
with the respective obligations stemming from the pharmaceutical legislation.
-
Make regular audits of GMP/GDP compliance mandatory by qualified auditors
- of (contract) manufacturers by manufacturers;
- between suppliers (wholesalers, manufacturers) at least in cases of suspicion
of non-compliance with GMP and/or GDP.
II Inspections and Supervision
-
Strengthen provisions on inspections and supervisions, in particular
regarding inspections in third countries. For example, make application of the
Community procedures on inspections and supervision ("Compilation of Community
Procedures on Inspections and Exchange of Information") mandatory..
-
Include specific harmonised provisions for inspections by competent
authorities of parties in the distribution chain (e.g. wholesalers, brokers,
traders, agents, business-to-business platforms).
III Packaging requirements
Require the outer packaging of medicinal products to be sealed. This would
reveal any subsequent opening of the packs. Such a requirement could be applied to certain categories of products chosen
on a risk-based approach, i.e. by taking into account the public health impact
of the appearance of a counterfeit product and the profit strategies of
counterfeiters. The right to opening the outer packaging would be restricted to the market
authorisation holder and end-user (hospital, health care professional, or
patient).
IV Tracing of ownership (pedigree)
-
Require the possibility of tracing ownership and transactions of a specific
batch. This should be achieved by making a specific record (pedigree)
obligatory. The record should be accessible by all actors in the distribution chain.
-
Require the possibility to trace each pack and perform authenticity checks.
This could be attained by a mass serialisation feature on the outer packaging.
Technical details would be further defined in implementing legislation and/or by
standardisation organisations.
V Good Distribution Practices Certification of
wholesalers and GDP Database
-
Require GDP certificates to be issued after each inspection of a wholesaler.
-
Establish a Community database of wholesalers (including distributing
manufacturers25) documenting GDP compliance. This could be achieved via
extension of the EudraGMP database.
VI Imported Medicinal Products for Export will be
subject of Inspection
Directive 2001/83/EC would be clarified to the effect that imported medicinal
products intended for export (i.e. not necessarily subject to marketing
authorisation) are subject to the rules for imports of medicinal products. The
corresponding rules on inspections would apply.
VII Mandatory Notification procedure for APIs
Submit the manufacturing/import of active ingredients to a mandatory
notification procedure. Render information on notified parties available in a
Community database. This could be achieved via extension of the EudraGMP
database.
VIII Increased Control of APIs
Make regular audits of active substance suppliers on GMP compliance by
manufacturers and importers of medicinal products mandatory. Auditors should be
sufficiently qualified.
Require, where scientifically feasible, control of active substances via
sufficiently discriminating analytical techniques, such as fingerprint
technologies, Near Infrared Spectroscopy (NIR), as a mandatory method for
identification by the manufacturer of the medicinal product. Such a testing is
meant to identify deviations of the manufacturing process and manufacturing site
for each batch.
Turn principles of good manufacturing practice for active substances placed
on the Community market into a legal act of Community law (e.g. a Commission
Directive) in order to enhance enforceability.
IX Unannounced Inspections of API Manufacturers
The competent authority may carry out announced or unannounced inspections of
active substance manufacturers in order to verify compliance with the principles
of good manufacturing practice for active substances placed on the Community
market. The competent authority shall carry out these inspections if there is
suspected noncompliance with GMP.
X Repeated Inspections of API Manufacturers in Third
Countries with different GMP
standards
The competent authority shall carry out repeated inspections in the exporting
country if the third country applies standards of good manufacturing practice
not at least equivalent to those laid down by the Community or if mechanisms for
supervision and inspections are not at least equivalent to those applied in the
Community. To this end, a Member State, the Commission or the Agency shall
require a manufacturer established in a third country to undergo an inspection.
The proposals mentioned above are far-reaching and would result in a better
control of counterfeit products and non-GMP-compliant APIs. The Commission has
asked for contributions from all stakeholders and interested parties by 9 May
2008.
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