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Jul 21, 2015

European Supply Chain: A Series of New Regulations in Force



Director Operations
CONCEPT HEIDELBERG GmbH

The new EU Directive 2011/62/EU and its delegated acts keep on changing the pharmaceutical supply chain. The directive introduced numerous Delegated Acts with different time schedules and had some impact on revisions of several chapters of the EU-GMP Guidelines.

Here is the status quo of the Directive and the delegated acts:

Already in 2011, the European Commission published Directive 2011/62/EC, the so-called Falsified Medicines Directive (or FMD).The main goal was the fight against counterfeit medicines. In 2014 the technical characteristics of one key requirement were defined, the unique identifier delivering the possibility of verification of the authenticity of single folding boxes. This will be a 2D barcode (data matrix). As this new requirement will become active in 2018, it is time to start defining strategies for both technical implementation and change control strategy.

The new GDP Guidelines apply not only to the wholesalers and manufacturers of pharmaceuticals; they also incorporate the specific requirements for the Brokers dealing with pharmaceutical products. The responsibility for the product during storage and distribution will remain with the manufacturers up to the point of sale, where wholesale dealers will take ownership of the products. It is clear that those playing a role in the pharmaceutical supply chain now have to comply with these requirements. Therefore, the service providers such as transportation companies and logistic service providers need to gain good understanding of what is required to be able to provide appropriate service to their clients.

In 2014, the Pharmaceutical Inspection Co-operation Scheme PIC/S published a PIC/S Guide to Good Distribution Practice for Medicinal Products (PE 011-1). This Guide is based on the EU GDP-Guidelines (2013/C 343/01) and quotes the EU Guide almost completely.

However, EU-specific references have been deleted and the term "must" is often replaced by the term "should." A dedicated Responsible Person is not introduced by the PIC/S document. It talks about "designated responsible person(s)" or "designated person(s)." Chapter 2.2 "Responsible person" of the EU GDP Guide is not quoted in the PIC/S document.

This article is related to the Whitepaper: Managing Change Control to Comply with FDA and EU Regulations.To get the full details, please download your free copy.

GDPs for APIs are still on their way. The "Guidelines on the principles of good distribution practices for active substances for medicinal products for human use" were published for consultation by the EU early in 2013. The new guidelines are addressed to distribution organisations and distributors involved in procuring, importing, exporting, holding or supplying active substances. 

GMPs for APIs: Whereas for medicinal products a GMP Directive (Directive 2003/94/EG from 8 October 2003) and detailed guidelines (Part I of the EU GMP Guide) have existed for many years, there has been no equally binding act in all the EU member states for APIs. Only the detailed guidelines as Part II of the EU GMP Guidelines are in place. This has now been updated. On 25 November 2014, the "Commission Delegated Regulation (EU) No 1252/2014" was published in the Official Journal of the European Union. As the subtitle shows, this regulation is to be seen as "supplementing Directive 2001/83/EC... with regard to principles and guidelines of good manufacturing practice for active substances for medicinal products for human use."

Now, the set of rules for APIs is complete.  The new regulation provides the necessary legal framework of GMP principles for APIs; the long-lived Part II of the EU GMP Guide delivers further solidification of these principles.

EMA has published a template for the QP's declaration concerning GMP compliance of the API used as starting material and verification of its supply chain called "The QP declaration template."

The QP Declaration should be provided in support of an application for a new marketing authorisation, variation or renewal of a medicinal product(s) authorised in the Community, using EU or national procedures within the scope of the respective Directives.

With this document, the Qualified Person confirms that an API used in manufacture of a Medicinal Product submitted for approval meets EU GMP standards. It includes all sites of full or partial manufacture of the API and the confirmation has to be based upon an audit of the API manufacturer(s).

In 2013, hardly any other topic was as extensively discussed in the pharmaceutical environment as the so-called Written Confirmation (confirming the GMP compliance of an API / of the API manufacturer). From 02 July 2013, all APIs manufactured outside the EU had to be accompanied by a Written Confirmation, issued by the Competent Authority of the exporting country. Otherwise there would have been almost no possibility to import an API into the EU. One alternative to a Written Confirmation is the admission to the list of "Third Countries" with comparable inspection standards. Authorities from countries on that list do not have to issue Written Confirmations. Countries currently on the list are Australia, Japan, Switzerland and the USA. Countries under assessment are Brazil, Israel, Singapore and New Zealand.

Is your supply chain affected by these changing guidelines?  How are you coping? Tell us below!



Wolfgang Schmitt studied pharmacy at the University in Heidelberg, Germany and the School of Pharmacy in London, U.K. He also holds a degree in total quality management from the University of Kaiserslautern, Germany. 

After functions in the community pharmacy, he started in 1999 in the GMP-Coordination (R&D) of the former Knoll AG in Ludwigshafen, Germany (later Abbott). Subsequently he was head of quality management at SOLIQS (Abbott’s global Drug Delivery Business Unit).

From 2005-2006 he was an associate director and Qualified Person at Abbott’s Global Pharmaceutical Research and Development Quality Assurance, responsible for the GMP/GLP-Compliance. In July 2006 he joined CONCEPT HEIDELBERG as
project manager where he is now Director Operations. Email him at w.schmitt@concept-heidelberg.de.






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