Storage and Distribution
This chapter covers the storage of all materials. In general all storage conditions should be established based on stability data or suitability for use information. These data can be derived from formal stability studies for APIs. For intermediates and other materials they might be obtained from scientific considerations, product history and published data or from reanalysis of materials stored for some time. Specific storage conditions are very rarely necessary; they only apply for materials with known stability problems regarding temperature and/ or pick-up of moisture in the standard packaging. Advice on storage conditions (specific and unspecific) is given in USP "General Notices, Storage Temperature and Humidity" where also the concept of applying the mean kinetic temperature approach is explained. The mean kinetic temperature is a calculated value that may be used as an isothermal storage temperature that simulates the non-isothermal effects of storage temperature variations (see also ICH Q1a for reference).
It is not always necessary to have records of storage conditions. This is only necessary when the stored material could be negatively affected by excessive temperatures or humidity over a longer period of time.
For APIs not requiring specific storage conditions, ambient temperature may be adequate without the use of monitoring control devices.
In cases where storage conditions are critical, monitoring control devices should be appropriately calibrated, and it may be necessary to qualify the warehouse itself with respect to temperature distribution.
Separate storage areas are required for quarantined, rejected, returned or recalled materials. Acceptable separate storage areas for such activities may solely be marked shelving or floor spaces with the exception of areas for rejected or recalled products in which physical barriers should be utilised to prevent unauthorised use, e.g. locked cages, areas or rooms.
Alternative systems may be computerised stock control with restricted access. These do not require separated areas.
The focus of this chapter is transportation of APIs and commercial available intermediates to third parties and not on internal transport and/or transport between different sites of the same company.
Distribution under quarantine is only accepted when under the control of the manufacturer of the API or intermediate and not for transport to third parties.
The following examples are not considered as third parties
- Subcontractors (e.g. processing, milling, micronization, drying etc.)
- Warehousing (off site or at a subcontractors site)
- Processing at different sites of the same company
For subcontracted activities the formal quality agreement should cover this scenario as recommended in chapter 16 Research and Development.
Appropriate protective outer packaging and a reliable shipper should be chosen to avoid damage during transport. For sensitive products special shipping conditions should also be specified.
Special transport or storage conditions are only applicable if safety or API / commercial intermediate stability (indicated by stability data) require special conditions and / or instructions. For stable and / or harmless APIs normally no specific conditions are required on the label. Independently from GMPs, national and international laws and regulations have to be followed.
Appropriate transport and storage conditions are typically conveyed to the shipper on the bill of lading. If very special storage conditions are required to avoid alteration, it might be necessary to monitor the shipping conditions.
Full traceability for all shipments from the manufacturer to its customer(s) has to be in place. If APIs or intermediates are delivered to a broker, full traceability has to be ensured by the broker as well. In this case the final user of the API is unknown to the API producer, therefore full traceability to the end customer should be the duty of the broker.
The storage conditions depend on the sensitivity of the material. If the stability data do not result in any specific requirements, monitoring of the storage conditions is not required. If special transport conditions are required, the manufacturer is responsible for ensuring that these are adhered to and recorded. Material under quarantine should be stored in an area designated for this purpose. Rejected and recalled material should be stored in a locked area, unless access to these materials is secured by another means. Transportation under quarantine is only permitted within different facilities of the company. Only released goods can be sent to third parties. A recall procedure must be established.