Current changes in regulatory areas

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Current Changes in Regulatory Areas in the Second Half of 2012

In Germany

Second Law Amending Medicinal Product Regulations

In October of the past year, the second law amending medicinal product and other related regulations was published. In this legislative act, in addition to two provisions concerning the AMG (Medicinal Products Act), twelve other articles related to medicinal product regulations are amended. This implements two EU directives on pharmacovigilance and falsification security into German law (2010/84/EU and 2011/62/EU).

Regarding the particularly sensitive area of falsification security, various definitions of terms and clear implications for different areas of pharmaceutical distribution, including GMP/GDP relevance, are provided. The following points are addressed:
- Counterfeit medicines
- Counterfeit active substances
- Packaging of medicines
- Security features for medicines
- Impact on wholesale
- Impact on re-packagers
- Notification procedures for approval changes
- Expertise according to § 15 AMG in the manufacture of sera
- Declaration regarding active substances – GMP in the approval documents
- Excipients
- Supplier qualification
- Qualification of pharmaceutical wholesalers
- Medicine brokerage

The Regulation on Designation was repealed, which could significantly simplify internal labeling of transport containers.

The various new regulations will come into force at different times.

In Europe

Revision of the EU GMP Guide Part 1, Chapter 1 and Chapter 7, as well as Annex 2

Chapters 1 and 7 of the EU GMP Guide have been revised by the EU Commission and will become binding on January 31, 2013.

In the case of Chapter 1, adjustments were made to ICH Q 10, not regarding the many individual measures, but emphasizing the systematic approach of a Pharmaceutical Quality System. The revision introduces several innovations, with a noticeable influence from the FDA. Notably, there is a much stronger emphasis on the responsibility of top management for a functioning Pharmaceutical Quality System.

With the revision of Chapter 7, its scope has significantly expanded from solely manufacturing and testing under contract to all outsourced activities. It thoroughly covers
- the applicable basic principles
- obligations of the commissioning party
- obligations of the contractor
- contract design

It should be noted that, due to the new regulations, the commissioning party remains fully responsible under pharmaceutical law, and a responsibility delineation is no longer possible. Instead, a detailed technical agreement between the parties regarding the services to be provided and commissioned is required. The commissioning party must verify compliance with this agreement.

Revised Annex 2 to the GMP Guide

The revised version of Annex 2 of the EU GMP Guide also comes into force on January 31, 2013. It deals with the differing GMP standards for the manufacture of active substances and medicines using biological starting materials. It presents a certain competition to the harmonized regulations according to ICH Q7 and considers the current state of science and technology, including medicines for innovative therapies.

Import of Active Substances from Non-EU Countries – Written Confirmation

On July 10, 2012, the EU Commission published the final version of the written confirmation required under EU Directive 2001/83 and included it as part of the EU GMP Guide Part III. Such a document is mandatory for all active substances imported into the EU from non-EU countries starting July 2, 2013. The document must contain the official confirmation from the authority of the country of origin regarding GMP-compliant manufacturing of the active substance, with EU rules serving as the benchmark. Every shipment must be accompanied by such a document. The manufacturer or importer must verify the authenticity of this document. Without the written confirmation, the active substance may not be used for manufacturing medicines authorized in the EU. Exceptions include:
- Development products
- Clinical trial preparations
- Veterinary medicines
- Active substances intended for re-export

See also: http://ec.europa.eu/health/documents/eudralex/vol-4/index_en.htm#part3

This confirmation is required by all countries outside the EU, even those with an MRA agreement with the EU. The requirement can only be waived if the country of origin has undergone a recognition procedure according to Directive 2001/83. Due to the limited time remaining before this obligation becomes mandatory, it is likely that several important manufacturing countries will not have such recognition, leading to significant issues for affected pharmaceutical manufacturers. Countries seeking or having undergone such recognition can be found on the list published by the European Commission in the Official Journal of the European Union and can also be accessed via the following link: http://ec.europa.eu/health/human-use/quality/index_en.htm.

This regulation does not apply to active substances in imported medicines.

MRA Certificate

Part III of the EU GMP Guide includes the form required for mutual recognition agreements (MRAs), which can eliminate the need for retesting when importing medicines from MRA countries.
See the link: http://ec.europa.eu/health/documents/eudralex/vol-4/index_en.htm#part3