Are Sterile Bioprocess Containers A Source Of Particulate Contamination?

We suggest that containers which are not produced to a recognized standard of cleanliness are a potential source of contamination. This article discusses why this is a problem for biopharmaceutical and vaccine manufacturers, the nature and source of possible contaminants, and a recommended solution.

50 Micron particulate in a well-known sterile, ready-to-use brand.
(Click to enlarge)

Sterile, ready-to-use bottles and carboys used in biopharma are assumed by many to be clean. Is this assumption valid? The graph shows liquid particle analysis of sterile ‘ready- to-use’ bottles from a well-known manufacturer. Test articles consisted of 120 each of PET and PC bottles and are shown in the chart vs. the USP 788 limit. As can be seen these bottles do not meet the USP 788 criteria for Particulate Matter in Injections. Any solution stored in such bottles will be contaminated by this particulate and may require further processing to meet the USP 788 standard.

Rigid bioprocess containers are typically molded in ‘controlled’ but uncharacterized environments. Some manufacturers recognize the need to reduce environmental contamination, but choose to avoid the cost of certifying controlled environments. This means these ‘controlled’ environments are not monitored or held to any standard. The cleanliness of containers produced under these conditions is therefore unknown.

Why Is Particulate A Problem For Bottle Manufacturers?

Production runs for sterile single use bottles are often as short as one to two weeks depending on the popularity of the container. Mold changes between production runs are necessarily dirty activities that impact the controlled environment. After each mold change and cleaning, re-certification of the environment would be necessary, with the associated expenses of testing and extended downtime for the production line. Many manufacturers consider such costs prohibitive.

Container molders, like other manufacturers, wish to use their existing equipment and facilities and avoid new investment whenever possible. This leads to compromises in the choice of processes, environment and employee training. For example, extrusion blow molding (EBM) is commonly used to mold containers because the cost of manufacture is low. Also EBM is an old process many established molders have EBM molding machines already. Unfortunately EBM processing generates significant particulate and is not amenable to clean production. One should expect high particulate levels and other manufacturing flaws in EBM containers. See  EBM vs. ISBM: For Bottles

Many molders produce a variety of products on the same equipment for dissimilar markets; products that may have different cleanliness requirements. The standard process environment for multipurpose molders is for non-sterile, non-clean production. Manufacture for clean-sterile products is an exception to general practice in these facilities. This can produce confusion for machine setup technicians and operators who may fail to implement procedures necessary for clean production.

Ideally, equipment choice, configuration and facilities should be dedicated and optimized for molding of clean products for sterilization.

Coming next, in Part II: Where Does Particulate Come from? And The Implication Of Particulate In Your Production Process.

 Download full article Go to Part 2 –>