Michael S. Wyand

Building a compliant supply chain and preparing for product launch at an emerging biotechnology or pharmaceutical company can be a challenging task. The infrastructure and systems that larger companies take for granted need to be built from the ground up, usually on a just-in-time basis with limited resources and little room for contingency planning. Frequently, the focus of companies approaching their first commercial product is research-based, with a mission to generate proof-of-concept data, which will propel the product to a profile that justifies increased investment in building development infrastructure. In such an environment some companies find themselves playing catch-up in the areas of chemistry, manufacturing, and control (CMC), and risk serious, costly delays in product approval or launch. Although step-by-step guidelines for success exist and every complex biotechnology product presents its own set of unique challenges, careful planning and management of the transition from an early-stage research company to a later-stage development organization can pay huge dividends downstream during new drug application or biologics license application submission and product approval.

Therion Biologics is a private, cancer immunotherapy company with two cancer vaccines in late-stage clinical development, one in phase 3 for pancreatic cancer and the other in phase 2 for prostate cancer. With 90 employees and 11 successful years in a Cooperative Research and Development Agreement relationship with the National Cancer Institute (treating over 700 patients with at least 12 prototype pox virus vaccines), Therion quickly changed its focus from research to later-stage development. This transition included developing a supply-chain infrastructure sufficient to meet the demands of product submission, approval, and launch. In managing this transition from research to development, Therion identified three key success factors critical to building a supply-chain infrastructure and executing an aggressive project timeline:

• Establishing a GxP mindset
• Committing to process development
• Identifying an effective strategy to produce cGMP-compliant manufacturing capacity for approval and commercial launch

Why is this broad view of quality important for a successful transition from research to development? Scientists operating outside the traditional regulated environment are usually the source of the initial manufacturing processes as well as the assay technology that will be the foundation for quality control testing, product characterization, and other CMC data necessary for major regulatory submissions. Any gaps in data documentation or lack of appreciation for the regulatory process by these early-stage research groups can result in major CMC problems during later-stage method validation, product characterization, and process validation.

GxP is an acronym referring to any or all of laboratory, manufacturing, and clinical regulations encompassed under Good Laboratory Practices (GLP), current Good Manufacturing Practices (cGMP), and Good Clinical Practices (GCP). In order to institute a GxP mindset across the organization, support and respect for quality systems should come from the top down. Senior quality representation must be fostered at the highest management levels in the company. Quality guidelines and policies should be applied to all areas of the company — not just quality assurance, quality control, and manufacturing. This does not mean that the entire organization will be converted to cGMP- or GLP-compliant status, since an FDA inspection and evaluation will look at those systems with a clear designation as compliant. But it does mean that adherence to protocols and procedures, rigorous documentation, and submission of quality reports will be the standard across the entire organization. Remember, critical decisions regarding which drug to develop are made based on "research" data.