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In February 2011, the European Union showed its commitment to fighting against counterfeit medicinal products and ensuring patient safety by adopting the amendments to Pharma Directive 2001/83/EC of the Community Code in relation to medicinal products for human use.

This article outlines the proposed amendments to Pharma Directive 2001/83/EC and is based on the text, which is not the final version. It should only be used as an indicator of possible future changes to this Directive. Further documents can be found at the bottom of the article.

The amendments not only recognise the risk of counterfeit medicinal products by recognising counterfeiting as a crime, but also include strict rules on internet pharmacies and places increased importance on a secure supply chain through the implementation of Good Distribution Practice principles.

The EU is aware that “there is an alarming increase of medicinal products detected in the Union which are falsified, thus posing an important threat to public health.” Most alarming is the fact that these falsified products not only come from illegal supply channels, but also via the legal supply chain.

The increasing complexity of the supply chain (from raw materials and active substance to the final product and end consumer) and the evolution of new products (temperature controlled) makes it necessary to strengthen current regulations. It is important that in order to ensure reliability, consistency and security of the supply chain, legislation in relation to medicinal products should address all protagonists in the supply chain. A key safety measure is the introduction of a Europe wide system of verification and safety features that will allow for the verification of the authenticity and identification of individual packs.

This also affects wholesale distributors, who need to verify that their suppliers are authorised. The role of the inspectors in ensuring that all agents involved in the manufacturing and supply chain of medicinal products will be also strengthened.

For those online pharmacies selling medicinal products legally they will need to comply with a series of rules to ensure the security of the products for the end user. A logo will be created to identify these legal businesses, and the business will also be linked to the website of the respective competent authority.

Several Articles have been amended. Below is a summary of the most significant changes.
- Article 1: Introduces a definition of falsified products (both medicinal and active substance).

- Article 8: A written confirmation that the manufacturer of the medicinal product has verified compliance that the manufacturer of the active substance complies with GMP principles and guidelines by conducting audits.

- Article 46:

• 46f: comply with GMP guidelines and only use GMP and GDP compliant manufacturers and distributors. The holder of the manufacturing authorisation shall verify compliance by the manufacturer and distributors of active substances with GMP and GDP by conducting audits at the manufacturer and distributor sites.
• 46g: to inform the competent authority and the marketing authorisation holder if he has information that medical products under the scope of his manufacturing authorisation are, or are suspected of being falsified.
• 46h: to verify that supplier manufacturers, importers or distributors are registered with the competent authority.
• 46I: to verify the authenticity and quality of the active substances and the excipients.
  

• They have been manufactured in accordance with GMP at least equivalent to those established by the EU.
• Active substances are accompanied by written confirmation from the competent authority that GMP standards have been followed.
• The plant is subject to regular inspections and in the event of non-compliance, the information is supplied by the exporting third country to the Union without any delay.
• If a plant manufacturing APIs has been inspected and is found to be in compliance, then inspection can be waived by any other Member State.
  

- Article 47: Third and fourth paragraphs are modified, stressing that the principles of Good Distribution Practices for active substances shall be adopted by the Commission in the form of guidelines.

- Article 47a: New article included to ensure that the safety measures shall not be removed or covered unless:

• The manufacturing authorisation holder verifies that the medicinal product concerned is authentic
• The manufacturing authorisation holder replaces the safety feature with an equivalent
• These operations are conducted in accordance with GMP
• The replacement is subject to supervision by the competent authority

- Articles 52a and 52b:

• Article 52a: Importers, manufacturers and distributors of active substances shall register their activities with the competent authority, which shall include their name and permanent address, active substances being imported and any additional information regarding their premises and technical equipment. The competent authority will be able to carry out an inspection when necessary.
• Article 52b: Member States will have to take the necessary measures to prevent falsified medicinal products entering the supply chain.
  

- Article 54: This article has been amended to require safety features that make it possible for wholesale distributors and authorised persons to verify the authenticity of the products and identify individual packs.

- Article 54a: Medicinal products subject to prescription will have to incorporate the safety measures outlined above. Any other medicinal products may be subject to these security features if there is a potential risk of falsification.

- Section VII: The new title for this section will read “Wholesale distribution and brokering of medicinal products”

- Article 76: Article 76 is amended as follows:
a) paragraph 3 is replaced by the following:
"Any distributor, not being the marketing authorisation holder, who imports a product from another Member State shall notify the marketing authorisation holder and the competent authority in the Member State to which the product will be imported of his intention to import it. In the case of products which have not been granted an authorisation pursuant to Regulation (EC) No 726/2004, the notification to the competent authority shall be without prejudice to additional procedures provided for in the legislation of that Member State, including fees payable to the competent authorities for the examination of the notification."

b) the following paragraph is added:
In the case of products which have been granted an authorisation pursuant to Regulation (EC) No 726/2004, the distributor shall submit the notification in accordance with paragraph 3 to the marketing authorisation holder and the Agency. The notification shall be accompanied by a fee payable to the Agency for checking that the conditions laid down in Union legislation are complied with.’

- Article 80: Holders of distribution authorisation must also verify that the medicinal products they purchase are not falsified by checking safety measures on the outer packaging. They must also maintain a quality system setting out responsibilities, processes and risk management in relation to their activities. Additionally, where the product is obtained from another wholesale distributor, they must verify compliance with the principles and guidelines of GDP; where the product is obtained from the manufacturer, they must verify that the manufacturer or importer holds a manufacturing authorisation.

- Article 85: It has been amended to add requirements for brokers such as having a permanent address in the Union; they also have to be registered:

“the natural or legal person or the body provided for by national law offering medicinal products for sale at a distance is authorised or entitled to supply medicinal products to the public, also at a distance, according to national legislation where that person or body is established”

- Title VIIa – Sales at a distance to the public: For the first time it addresses the reality that the point of sales have evolved and take into account the effect that the internet has had on sales of medicinal products. It outlines the conditions under which these entities can operate such as being registered with the competent authority, being in a European Union wide database and having a common logo identifying the organisation as being legitimate.

- Article 111: Stringent pharmacovigilance rules, with stronger and more regular inspection to both manufacturers located in the European Union and in third countries.

- Article 117a: "48 Member States shall have a system in place which aims at preventing medicinal products that are suspected to be dangerous from reaching the patient.

To this end the system shall cover the receipt and handling of notifications of suspected falsified medicinal products as well as of suspected quality defects of medicinal products and cover recalls by marketing authorisation holders or ordered by national competent authorities from all relevant actors in the supply chain both during and outside normal working hours. The system shall also allow recalls from patients, who received them, where necessary with the assistance of health professionals.

If the medicinal product in question is suspected to present a serious risk to public health, the competent authority of the Member State in which the product was first identified, shall without any delay transmit a rapid alert notification to all Member States and all actors in the supply chain in that Member State. In the case where such medicinal products are deemed to have reached patients, urgent public announcements shall be issued within 24 hours in order to recall the medicinal products from the patients. These announcements shall contain sufficient information on the suspected quality defect or falsification and the risks involved.

Member States shall within two years after the entry into force of this Directive notify the Commission of the details of their respective national systems mentioned in this Article."

- Article 118b: The Member States shall lay down the rules on penalties applicable to infringements of the national provisions adopted pursuant to this Directive and shall take all necessary measures to ensure that these penalties are implemented. The penalties must be effective, proportionate and dissuasive.

The European Union is taking serious steps to ensure patient safety and reduce the risk of counterfeit products entering into the supply chain and reaching the end consumer.

Further Documents:

DIRECTIVE 2001/83/EC

DIRECTIVE OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL amending Directive 2001/83/EC