EU GMP Annex 1 compliant inspection of BFS bottles

EU GMP Annex 1 of the European Medicines Agency (EMA) is the governing regulatory document related to “Manufacture of Sterile Medicinal Products”; the latest revision took place in 2022. The new Annex is active now, companies need to comply with the requirements since 25 of August 2023. Especially for products that are closed by fusion, such as BFS bottles, fall into this category.

WILCO automated leak tester for BFS bottles

Annex 1 explicitly states the requirements

Containers closed by fusion, e.g. BFS bottles, demand a 100% Container Closure Integrity Testing. In draft versions of the latest Annex 1 revision a 100% integrity testing of containers independent of the volume using a validated method was discussed, the final version was changed to include containers up to a volume of 100 mL (SVP - Small Volume Parenterals) and BFS units (it is arguable if the volume limit is also applicable to blow fill seal products).

Our approach: Highest precision in BFS bottle leak testing

When investing into a fill finish project manufacturers of BFS products now need to decide for the best fitting and most reliable technology / equipment to comply with Annex 1 regarding container closure integrity testing.

The WILCO LFC method® is best suited for CCI testing of BFS products as highest measurement accuracy is achieved and the entire container is tested at once.

For achieving sterility after the filling of BFS plastic bottles in frequent cases terminal sterilization within an autoclave is being used. Steam parameters reach temperatures >= 121°C and pressures up to 2 bar (abs.) for periods of 15 min. In case of dry heat sterilization even higher temperatures are being used. Conditions during the sterilization process often affect bottle shape - while bottles have an "as designed" shape after the BFS process, the shape after sterilization can vary significantly.

We have developed a transport system that solves these challenges to ensure proper through transport of the LVP bottles.

Our solution for reliable 100% leak detection of BFS bottles

The R DPPB leak tester is designed to compensate for such uncertainties and provide reliable transport through the machine, including the test chambers.

Through its tried and tested LFC method® for leak detection using the deep vacuum technology lowest sensitivities can be achieved. WILCO's proprietary differential pressure inspection technology tests the entire bottle in a single pass. This reliably detects even the smallest leaks in both the filled and empty areas.

Being capable to handle a wide variety of bottle sizes, a transport system proven in several projects, as well as WILCOs standard MAVIS HMI makes it an ideal solution for 100% inline testing system for blow-fill-seal bottles bringing ease of use and flexibility to the next level.

The advantages of our BFS inspection solutions

  • High sensitivity of the LFC method®
  • Testing of entire bottle at once
  • Applicable for various shapes and sizes of BFS bottles
  • Non-destructive and deterministic test method preferred acc. USP <1207>
  • Applicable for oily and non-conductive liquids in BFS bottles
  • Applicable for BFS with low filling volume