Therapeutic Proteins and Advanced Therapy Medicinal Products

Abstract

This chapter is divided in two parts: Therapeutic proteins and Advanced Therapy Medicinal Products (ATMPs). Therapeutic Proteins. Therapeutic proteins are large molecules that are different from low molecular weight medicines. They consist of amino acid chains, sometimes decorated with polysaccharides (glycoproteins) that fold in space in secondary and tertiary structures. The first section describes the production process which is divided into upstream and downstream processing. It encompasses cell line development and expression of biopharmaceutical products in Upstream Processing (USP), the purification of the products during Downstream Processing (DSP), as well as the subsequent formulation process (which may be part of DSP or done afterwards). Therapeutic proteins are sensitive to chemical and physical degradation. The formulation section describes the forces that stabilize a therapeutic protein and potential degradation pathways. It then discusses the challenges a formulator encounters when developing a protein medicinal product: (1) the development of analytical techniques for monitoring critical quality attributes, (2) the selection of the relevant tests to optimize stability and the excipients available, (3) the options for primary packaging materials and (4) the link with the preferred routes of administration. Ultimately, this should lead to achieving the predefined target product formulation profile for a biological. The predominant routes of administration for therapeutic proteins are the intravenous and subcutaneous (s.c.) route. In contrast to intravenous administration, absorption of the protein from the subcutaneous reservoir upon s.c. injection is an extra step, resulting in a longer time to reach the maximum plasma concentration (Cmax) as compared to intravenous administration. Therapeutic proteins are very important treatment options for a variety of diseases. An adverse event specifically linked to therapeutic proteins is immunogenicity. An immune response against a therapeutic protein can have a major impact on efficacy and/or safety and can be influenced by either patient-, disease-, and product-related factors. Especially, the product-related factors are important to take into consideration during product development. ATMPs. The second part of the chapter is devoted to the discussion of Advanced Therapy Medicinal Products (ATMPs). These are medicines made from, or consisting of, cells, genes or tissues. They have introduced a new area of specialism to the pharmacy workforce. The section about ATMPs will explore the role of the pharmacy team in the delivery of ATMPs recognising that operationalising ATMPs requires a collaborative multidisciplinary approach to ensure that the medicines are optimised for patients. This involves ensuring that whilst appropriate pharmacovigilance and pharmaceutical procedures are in place, handling is undertaken by a trained workforce that is competent in the handling of cellular products. The second part describes the legislation applicable to ATMPs and focuses on specific operational considerations including the logistics and product handling requirements related to ATMPs and the implications for pharmacy.