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Good Distribution Practices for Active Substances

Good Distribution Practices for Active Substances
Good Distribution Practices for Active Substances

In the future, the distribution of active substances will be regulated by the «Principles of Good Distribution Practices for Active Substances».

The Guidelines (hereinafter: GDP Guidelines for Active Substances) will have to be elaborated as a delegated legal act resulting from the Falsified Medicines Directive 2011/62/EU.1 A draft was presented by the European Commission for public consultation.2 The commentary period ended on 30 April 2013. Position statements have been submitted by the affected industry.3

This article describes the existing legal requirements for the distribution of Active Substances. The changes expected to arise from the GDP Guidelines for Active Substances are listed and discussed.

 

Current statutory requirements for the distribution of Active Substances
The GDP Guidelines for Active Substances have not yet been adopted, but the distribution of Active Substances is actually not performed without any legal requirements. The EU GMP Guidelines (Part II) contain a series of requirements relating to the distribution of Active Substances (see table 1 below).4

Directive 2001/83/EC also governs the execution of audits at the distribution sites of the distributor by the holder of the manufacturing authorization.5

For areas governed by German law, the qualification and auditing of importers/distributors of Active Substances used for the manufacture of medicinal products intended for use by humans already must be carried out in accordance with written procedures.6

Furthermore, importers, manufacturers and distributors of active substances are obligated to register with the competent authorities.7 The right of inspection of the competent authorities has also been established.8 The specification setting for the storage and transport conditions for Active Substances must comply with the «Guideline on Declaration of Storage Conditions».9

 

Planned new requirements of the GDP Guidelines for Active Substances
The draft of the GDP Guidelines for Active Substances takes up already existing rules and regulations and adds greater depth and details. New requirements have also been added that are analogous in type and scope to the GDP Guidelines for Medicinal Products for Human Use. Table 2 provides an overview of the planned new requirements.

 

Discussion
The distribution of Active Substances is currently partially regulated by provisions in the EU GMP Guidelines Part II. Further requirements are based on Directive 2001/83/EC and have been implemented in areas governed by German law in the German Ordinance on the Manufacture of Medicinal Products and Active Pharmaceutical Ingredients (AMWHV). The present draft of the GDP Guidelines for Active Substances contains new requirements. Parts of existing requirements from the EU GMP Guideline Part II have been adopted verbatim. Both documents thus require revision to prevent redundancies. The newly introduced definition of the term «Distribution of Active Substances» provides clarity; this is mostly identical to the definition of the term used by wholesalers of medicinal products for humans11, but also includes the term «import». Repackaging, relabeling and re-filling as manufacturing activities are governed by the provisions set out in the EU GMP Guidelines Part II. The comments submitted during the consultation phase indicate that harmonization with the Guidelines for Good Distribution Practices for Medicinal Products for Humans, which took effect in 2013, would be desirable.

The following requirements should encourage you to review your company’s own preparations:

  • the right of the competent authorities to inspect distribution companies
  • the obligation of the manufacturers to audit offices/plants of the distribution companies.

Both rules aim for transparency throughout the entire supply chain. It is expected that in the event of the occurrence of falsification or suspicion of falsification, an inspection of the companies involved will ensue.

In preparing for the implementation of the existing and new legal requirements, it must be noted that in the German Drug Law the definition of a falsified active substance also includes its incorrect labeling on the package and inaccurate accompanying documentation. The latter must reflect all manufacturers involved and the actual distribution channel.12

Putting falsified active substances into circulation or trading with them is subject to prosecution and must be reported upon any suspicion thereof by the regulatory authority – without room for discretion. This reflects the duty specified in the GDP Guidelines for Active Substances to notify the relevant authorities in potentially life-threatening situations with regard to the quality and integrity of the distributed Active Substance.13 The publication of the GDP Guidelines for Active Substances will probably be scheduled in 2015. A critical review of your company’s own distribution channels for the procurement of active substances is necessary regardless of these new guidelines in order to ensure that your company meets the existing applicable legal requirements. A dialog should be initiated between distributors of active substances and the processing companies to reconcile the mutual expectations and opportunities.

Chemgineering supports the implementation with specific expertise in Good Distribution Practice based on its own experience in industry and regulatory authorities.

1    Article 47 of Directive 2001/83/EC
2    Guidelines on the Principles of Good Distribution Practices for Active Substances for Medicinal Products for Human Use, Draft submitted for Public Consultation, SANCO/D/6/ SF/mg/ddg1.d.6(2013)179367
3    http://ec.europa.eu/health/human-use/quality/developements/index_en.htm#pc20132
4    Ibid. Chapters 7, 10 and 17.
5    Article 46 f of Directive 2001/83/EC
6    Section 11, paragraph 3, sentence 2 of the German Ordinance on the Manufacture of Medicinal Products and Active Pharmaceutical Ingredients (AMWHV) dated 3 November 2006 (Federal Gazette I, p. 2523) in the current version.
7    Article 52a (1) of Directive 2001/83/EC
8    Article 111 (1b (a)) of Directive 2001/83/EC
9    Guideline on Declaration of Storage Conditions, CPMP/ QWP/ 609/96/Rev 1, 3 April 2003
10  Reference is made to the relevant chapter of the Guidelines on the Principles of Good Distribution Practices for Active Substances for Medicinal Products for Human Use, Draft submitted for Public Consultation, SANCO/D/6/SF/mg/ddg1.d.6(2013)179367
11  Article 1 of Directive 2001/83/EC
12  Section 4 (41) of the German Drug Act, redrafted via publication dated 12 December 2005
I 3394 in the current version
13  See No. 44 of the submitted Guidelines for Good Distribution Practices for Active Substances.

 

Dr. Martin Melzer|Senior Consultant GMP Compliance|Chemgineering - The Business Designers

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