All biopharmaceuticals (inclusive of both biologics and biosimilars) are produced by living organisms or cells and contain complex molecules in the form of mostly proteins or polypeptides.1 Proteins are made from amino acids and a single protein can contain many such amino acids.
The Science
Manufacturing biosimilars
Cloning and protein expression
Polypeptides are linear chains of amino acids. Apart from amino acids, sugars or carbohydrate groups may also be incorporated in such amino acid chains. Once the amino acids and other sugars or carbohydrates have been joined together, the protein will fold into a specific shape. This is important, because this 3-dimensional shape will determine who well the protein binds to its receptor on cell membranes or other surfaces.
Once produced by an organism or living cell, the desired end product has to be purified (or separated) from the thousands of other proteins or molecules present in the cell or organism. The production process for a biosimilar is therefore complicated and requires sophisticated and validated technologies.1 It often calls for the use of sophisticated cell systems and recombinant DNA technology.3
Cloning and protein expression
Protein production, purification and validation
Once produced by an organism or living cell, the desired end product has to be purified (or separated) from the thousands of other proteins or molecules present in the cell or organism. The production process for a biosimilar is therefore complicated and requires sophisticated and validated technologies.1 It often calls for the use of sophisticated cell systems and recombinant DNA technology.3
Production sequence
The standard production sequence for biopharmaceuticals starts off with culturing (or growing) of the desired cells, followed by fermentation, harvesting, purification and formulation to produce the finished medicinal product.1
Clinicians and patients can rest assured that both originator reference products and biosimilar products are manufactured under stringently controlled conditions to ensure that the products are consistently produced and manufactured to the required quality. This is what is known as Good Manufacturing Practice (GMP). Manufacturing facilities are regularly inspected by the relevant Regulatory Authorities (including SAHPRA) to ensure compliance with GMP specifications and standards.1,3 In some instances, GMP requirements may have been specifically adapted to consider the specific nature of biopharmaceuticals allowing for the use of appropriate aseptic techniques, refrigeration and other storage conditions, stability, transport, and so forth.3
