The Biologics License Application (BLA) for Marketing Approval in the USA

Formulating biologics is an intense and complex process that requires strict adherence to regulations. Any sponsor wanting to market and sale a biologic must receive a license to do so from the Food and Drug Administration (FDA). The application for this license centers around the Biologics License Application (BLA).

Biological products have come to dominate the market for medicines in recent decades. To introduce a biological product into interstate commerce in the USA, the sponsor of the product must gain FDA approval of a Biologics License Application (BLA). This enormous compilation of information and data is the culmination of years of effort and financial investment in the research and development of the product by the sponsor company. Biological products require manufacturing processes of greater complexity than those for small-molecule drugs, and control of the processes is critical to assurance of the products’ safety, purity and potency. The processes and manufacturing establishments are subject to extensive inspection by the FDA before approval.

This course is intended primarily for regulatory affairs professionals who are new to the BLA or who seek a refresher course. It will also be of interest to others involved in drug development and/or who interact with the FDA. It will take a dive deep into the role of the BLA, including reviewing key criteria for licensure, the expected process control and manufacturing procedures, and the procedural requirements for its submission to the FDA.

The course covers:

• Introduction – In this session we describe the role of the BLA, define biological product, and outline the legal basis of the regulation of such products in the USA. We specify key criteria for licensure of biologics. We identify, by product type, the Centers within the US Food and Drug Administration (FDA) to which a BLA must be submitted for review and approval. We emphasise the importance of good communication between the agency and the sponsor of a BLA before submission. We set out the high-level structure of the electronic Common Technical Document, with which BLA submissions must comply.
• Quality information – Biologics manufacture involves many complex processes which must be described in the parts of the eCTD concerning quality of the product. In this session we discuss characteristics of biologics manufacture and we outline the chemistry, manufacturing and controls (CMC) information that needs to be included in a BLA.
• INonclinical information – In this session we briefly outline the information required on pharmacological actions, toxicological effects, pharmacokinetics, and reproductive toxicity from studies in animals.
• Clinical information – Module 5 of a BLA, containing clinical information, is the largest and most complex part of the application. The data and analyses it provides are key to the FDA’s understanding of the safety and effectiveness of the biological product. In this session, we describe the components of the information required, according to the categorisation of form FDA 356h.
• Administrative information and summaries – In this session we discuss Modules 1 and 2 of a BLA. Module 1 contains administrative and prescribing information specific to the USA, including the draft labeling for the product. Module 2 contains summaries and overviews of the quality, nonclinical and clinical information included in Modules 3 to 5 of the application.
• BLA submission and FDA review – By submission of a BLA to the FDA’s Center for Biologics Evaluation and Research (CBER) or Center for Drug Evaluation and Research (CDER), a sponsor formally proposes that the agency license a new biological product for sale and marketing in the USA. To gain a biologics license the applicant must convince the reviewers that their product is safe, pure and potent. In this extensive session we describe the process of BLA submission and review, including the FDA’s responsibilities and actions, the obligations of the applicant, and the options available.
• Expedited development and review – The FDA has established several processes that enable patients to gain access to new medicines earlier than would be the case under the normal development and review process. In this session we describe four mechanisms potentially available to sponsors of biological products regulated by CDER or CBER that address unmet medical need in the treatment of a serious condition: priority review, accelerated approval, fast track development, and breakthrough therapy designation. We then discuss the most recently introduced expedited programme, applicable to some products regulated by CBER: regenerative medicine advanced therapy designation.

Learn

• The requirements for obtaining a license to market and sell biologics in the US
• What process control and manufacturing criteria the Food and Drug Administration (FDA) require
• To identify the content and format requirements for a BLA
• To ensure the BLA also complies with the International Council for Harmonization (ICH)
• To understand FDA requirements for expedited drug development and review