Biopharmaceutical manufacturing is the manufacture of protein-based therapies that include recombinant proteins, monoclonal antibodies, and vaccines (to name a few). With such an extensive repertoire of products, there are many aspects of testing specific to the type of product being assessed. However there are typical tests that are universal for all these types of products in addition to your traditional synthetic pharmaceuticals (small molecules) that are performed during the manufacturing processes.

This article will discuss the typical routine sampling and testing requirements associated with the aseptic processing of a biopharma-ceutical from the perspective of a contract aseptic manufacturer. Specifically, the focus will be on what many consider the most critical part of a biological drug product’s manufacturing life cycle: going from the purified bulk drug substance (PBDS) to the sterile final drug product (FDP).

While it’s a given that no two products and processes are alike, the approach described herein provides a good generic basis for establishing the testing “where and when” (and in some instances, the “why”) for manufacturing formulation and fill/finish activities. While the focus is on processing of biologics, this approach is also applicable for the most part to small molecule drug products formulation and fill/finish (F/F).

TYPICAL TESTING PERFORMED DURING ASEPTIC PROCESSING
The typical sequence of testing activities associated with formulation and aseptic F/F of small volume parenteral drug products is schematically representedin Table 1.

RAW MATERIAL/INCOMING BULK DRUG TESTING
As with any GMP manufacturing process, incoming raw materials, as well as PBDS, need to be minimally tested to verify their identity. Often times it’s necessary to evaluate the bioburden and endotoxin levels of the raw materials. This testing is performed to insure that these materials are not adding bioloador endotoxin to the formulated product.

Biopharmaceuticals can pose some unique challenges to F/F contractors relative to small molecule-based drug products. Typically, the PBDS is sent to the fill house either as a refrigerated liquid or frozen material. This means that special considerations need to be taken during the usual incoming testing to verify the product’sidentity.

Refrigerated products generally need to be sampled so that temperature increases of the bulk container(s) during sampling are minimized. This sample then needs to be temperature controlled until the time of analysis. These types of handling precautions should be clearly delineated on the incoming PBDS’s raw material specification (RMS) document and may be supplementedby a standard operating procedure (SOP) specific for raw material sampling.