14/15 April 2021
GMP News No. 218
5 August 2002
New FDA Guidance for Industry ContainerClosure Systems for Packaging Human Drugs and Biologics – Questions andAnswers
In May 2002, FDA(CDER and CBER) published a Guidance for Industry giving answers toquestions asked by applicants in relation to the 'Guidance onContainer Closure Systems for Packaging Human Drugs and Biologics' issuedin May 1999.
Two of the three questions refer to thestorage and shipping of 'bulk drug products'. A footnote explainsthat bulk drug product means 'finished dosage form that has not yet been packaged into the containerclosure systems intended for market and/or sale.'
Information on container closure systemsused for bulk drug products only needs to be included in the applicationfor biologics (e.g. proteins). For all other products, no such informationhas to be provided in the application. However, FDA does require that thesuitability of the containers for the intended purpose can be proven bymeans of adequate data. These data also should be made available duringFDA inspections on demand.
As reason why more data have to beincluded in the application concerning biologics FDA cites the fact thatthe probability of adverse effects on the product quality during storageor shipping is much higher with biologics and proteins than with otherproducts.
Note: In FDA's Human Drug cGMP Notes ofDecember 1995, Paul Motise wrote about the storage of bulk drug productsthat physically/chemically stable bulk drug products can be stored up to30 days under suitable storage conditions without having to providestability data. For unstable bulk drug products or for materials that areplanned to be stored for more than 30 days, stability data have to beprovided according to a stability testing plan approved in advance.
The above-mentioned FDA Guidance on packagingmaterials of May 1999 also included the item 'Containers for Bulk DrugProducts': the storage containers should provide adequateprotection and be manufactured from materials that are compatible and safefor the intended use. In case a firm intends to hold bulk drug products instorage, the maximum storage time has to be described and justified. Ifthe storage is meant to be extended, stability data have to be provided.However, Paul Motise's concrete indication from which storage time onstability data have to be provided (30 days) is not included in theGuideline.
As to shipping containers for bulkdrug products (e.g. for the transportation to the contract packager), FDAconsiders the suitability to be proven when annual batches of the packagedproduct are included in post-approval stability studies. It goes withoutsaying that the shipping containers, too, have to protect the productsufficiently and be manufactured from appropriate materials.