14/15 April 2021
European Commission Plans Far-Reaching Changes to GMP and GDP in the Fight against Counterfeit Medicines
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
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
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