GMP News No. 218
5 August 2002
In May 2002, FDA (CDER and CBER) published a Guidance for Industry giving answers to questions asked by applicants in relation to the 'Guidance on Container Closure Systems for Packaging Human Drugs and Biologics' issued in May 1999.
Two of the three questions refer to the storage and shipping of 'bulk drug products'. A footnote explains that bulk drug product means 'finished dosage form that has not yet been packaged into the container closure systems intended for market and/or sale.'
Information on container closure systems used for bulk drug products only needs to be included in the application for biologics (e.g. proteins). For all other products, no such information has to be provided in the application. However, FDA does require that the suitability of the containers for the intended purpose can be proven by means of adequate data. These data also should be made available during FDA inspections on demand.
As reason why more data have to be included in the application concerning biologics FDA cites the fact that the probability of adverse effects on the product quality during storage or shipping is much higher with biologics and proteins than with other products.
Note: In FDA's Human Drug cGMP Notes of December 1995, Paul Motise wrote about the storage of bulk drug products that physically/chemically stable bulk drug products can be stored up to 30 days under suitable storage conditions without having to provide stability data. For unstable bulk drug products or for materials that are planned to be stored for more than 30 days, stability data have to be provided according to a stability testing plan approved in advance.
The above-mentioned FDA Guidance on packaging materials of May 1999 also included the item 'Containers for Bulk Drug Products': the storage containers should provide adequate protection and be manufactured from materials that are compatible and safe for the intended use. In case a firm intends to hold bulk drug products in storage, the maximum storage time has to be described and justified. If the storage is meant to be extended, stability data have to be provided. However, Paul Motise's concrete indication from which storage time on stability data have to be provided (30 days) is not included in the Guideline.
As to shipping containers for bulk drug products (e.g. for the transportation to the contract packager), FDA considers the suitability to be proven when annual batches of the packaged product are included in post-approval stability studies. It goes without saying that the shipping containers, too, have to protect the product sufficiently and be manufactured from appropriate materials.
In the next months, we offer you the following events on the topics of stability and packaging:
ECA Education Course
Testing in the Pharmaceutical Industry