In the midst of a pandemic raging across the world, pharmaceutical companies are more and more alerted to the dangers and risks of drug product contamination. The recent FDA-ordered destruction of 60 million vaccine doses is one very prominent example. One source of contamination is particulate generation. Pharma companies are researching smarter control of particulate in hopes to specifically reduce or eliminate particulate in injectable products.
Particulates can be of two types:
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Visible particulates are greater than or equal to 100 microns
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Sub-visible particulates are less than or equal to 100 microns.
Sources of particulates can be inherent, intrinsic, or extrinsic. They may be introduced as part of the process itself or from external sources such as packaging materials. Particulate generation can also impact the biological response from a patient. For example, presence of particulates in the vascular system can cause blockage, emboli, or accumulation or chronic damage to organs. In the case of extravascular particulates, it may impact the immune response in patients and may cause tissue damage.
As expected, there are several regulatory standards that specify the requirements for control of particulate in pharmaceutical applications. The list of requirements is long. The main standard to evaluate is ISO 11040-7, Prefilled syringes - Part 7: Packaging systems for sterilized sub-assembled syringes ready for filling. We previously covered that standard in more detail here. Other standards, such as USP788 (Injections) and USP789 (Ophthalmic), specify the number and the size of allowable particulates within a drug container. Particulate is typically counted through two methods, a Light Obscuration Test or a Microscopic Test.
During the production process for prefillable syringes, the syringe tub is moved into an isolator or controlled environment. The lid is peeled and removed from the syringe tub, usually by a robotic process. It must be stressed that particulate generation is minimized during this peeling process. The right material selection is important here. Coating on the lidding material can help lessen particulate from peeling, as described in our technical evaluation of lidding removal.
Maintaining a highly sterile environment during the entire drug delivery process is of critical importance. This includes the selection of an uncompromising sterile barrier system. Since the entire drug process is so long (taking years between development and final launch), pharma companies rely on their partner network to interpret regulatory procedures and operationalise standards in the manufacturing process. The tragedy of the vaccine destruction story is a big reminder of how much is at stake.
