Quality requirements for medicines do not end after production and packaging.
Medicines and APIs are often shipped over long distances and different climate zones and stored in various warehouses. Once the WHO has taken the lead with its guidelines „Good Storage Practices for Pharmaceuticals“ (2003) and „Good Distribution Practices for Pharmaceutical Products“ (2010), more and more compliance with good storage, transportation and distribution practice was emphasized worldwide. Another milestone were the EU-GDP guidelines from 2013 with a lot of intensified demands.
Since 1 July 2015, the EU GDP guidelines do also apply for Switzerland. This was realized through an adaptation of Annex 2 of Ordinance on Establishment Licences (Arzneimittel-Bewilligungsverordnung – AMBV or Ordonnance sur les autorisations dans le domaine des médicaments – OAMéd)
With the EU Falsified Medicines Directive (Directive 2011/62/EU) the application of GDP (2013/C 343/01) for APIs has become mandatory.
The EU Commissions Guideline on the Principles of GDP for APIs is the first regulatory binding document specifically for distribution activities of APIs. This also applies for distribution between sites within a single corporation.“GDP is that part of quality assurance which ensures that the quality of medicinal products is maintained throughout all stages of the supply chain from the site of manufacturer to the pharmacy or person authorized or entitled to supply medicinal products to the public.”
The GMP Part II/ICH Q7 for the manufacturers of API have been the only Guideline partially covering GDP for API. These affect more the handling of APIs at the manufacturing site, but not the distribution outside the manufacturing site.
For the purpose of this document, the distribution of active substances for medicinal products for human use is the procuring, importing, holding, supplying or exporting active substances. Activities consisting of re-packaging, re-labelling or dividing up of active substances are manufacturing activities and as such are subject to the guidelines on Good Manufacturing Practice of active substances.
For the purpose here “distributors” includes those parties involved in trade and distribution e.g. (re)processors, (re)packagers, transport and warehousing companies, forwarding agents, brokers, traders, and suppliers other than the original manufacturer.
The word « should » is used several times in the EU Guideline on the Principles of GDP for APIs. It indicates requirements and recommendations that are expected to apply unless shown to be inapplicable or replaced by an alternative that can be shown to provide at least an equivalent level of quality assurance. Hence, « should » does not mean that because it is only a «should», and not a «must», then this requirement does not have to be met.
The holder of a manufacturing authorization shall at least be obliged to use only active substances, which have been manufactured in accordance with good manufacturing practice for active substances and distributed in accordance with good distribution practices for active substances. Distributors of active substances may, according to Article 111 of the same directive [2001/83/EC] , become subject to inspections by the competent authority. On the other hand the holder of the manufacturing authorization shall verify compliance with good manufacturing practices and good distribution practices by conducting audits at the manufacturer and distributors sites of active substances.
With a subdivision in 13 chapters, following the Pharmaceutical Inspection Convention; Pharmaceutical Inspection Co-operation Scheme (PIC/S) Guide to GDP (PE 011-1) and Q7A from the FDA, with the emphasis on GDP for API (chapter 9 & 10).
1. Quality Management
IMPACT: No impact expected because a mature quality system is anticipated to be in place.
2. Organization and Personnel
IMPACT: Potential, Responsibility and Accountability between Operations and Logistics/Supply Chain for the different stages of the Supply Chain pertaining to API needs to be clarified, agreed, and documented.
3. Premises
IMPACT: Potential, buildings and facilities used for the distribution of API manufacturers should be defined areas or under other control systems for the following activities: receipt, identification, sampling, and quarantine of incoming materials, pending release, rejection or further disposition.
4. Warehousing and Storage
IMPACT: Potential, warehouse and (cold-) storage areas used for the API manufacturers (also those within manufacturing area’s) should be defined areas or under other control systems for the following activities: receipt, identification, sampling, and quarantine of incoming materials, pending release, rejection or further disposition.
5. Equipment
IMPACT: Potential; Impact needs to be assessed for the validation of distribution and transport processes together with the identification, training, and monitoring of staff responsible for initiating, designing, performing, reviewing, and tracking of distribution and transport validation, inbound and outbound, not just for raw materials and finished product(s), but for intermediates, and DS or Bulk DP as well.
6. Documentation
IMPACT: Potential; Impact needs to be assessed for documentation for Intermediates, DS, and Bulk DP as batch record, logbook, validations, cleaning procedures and standard SOP for API manufacturers are required according to GMP rules equally as for Finished Products.
7. Repackaging and relabeling
IMPACT: Potential, API manufacturers also involved in the distribution of active substance, Intermediate, DS, and Bulk DP, as intended in the GDP guideline, must be in compliance with the above requirements.
8. Complaints
IMPACT: Potential, Responsibility & Accountability for complaints and complaints handling between Operations and Logistic s/Supply Chain pertaining to Intermediates, DS, and Bulk DP needs to be clarified, agreed, and documented.
9. Recalls
IMPACT: Potential, Responsibility & Accountability for handling recalls between Operations and Logistic s/Supply Chain pertaining to Intermediates, DS, and Bulk DP needs to be clarified, agreed, and documented.
10. Returned goods
IMPACT: Potential, API manufacturers also involved in the distribution of Intermediates, DS and Bulk DP, as intended in the GDP guideline, must be in compliance with the above requirements.
11. Handling of non‐conforming materials
IMPACT: Yes, API manufacturers also involved in the distribution of Intermediates, DS and Bulk DP, as intended in the GDP guideline, must be in compliance with the above requirements.
12. Dispatch and transport
IMPACT: Yes, API manufacturers also involved in the distribution of Intermediates, DS and Bulk DP, as intended in the GDP guideline, must be in compliance with the above requirements (selection of correct transporters, qualification, quality agreement, certifications risk analysis, monitoring of temperature, declaration for use of second transporter in the chain, cleaning of truck, etc).
13. Contract activities
IMPACT: Yes, API manufacturers also involved in the distribution of Intermediates, DS and Bulk DP, as intended in the GDP guideline, must be in compliance with the above requirements as part of correct GMP approach.
Much to check and maybe update, upgrade, and-or put in place!
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