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.
Michael S. Wyand
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
ESTABLISH A GxP MINDSET
Quality in biopharmaceutical parlance is often narrowly viewed as representing the quality assurance and quality control groups.
Many in research see themselves outside of the regulated environment and consider themselves free of the quality regulations
that interfere with the creative process and result in excessive paperwork. A limited view of quality in an early-stage biotechnology
company should be avoided. The regulated component of quality is just a subset of overall quality in an organization. Data
review, principles of documentation, protocols, validated methods and equipment, and change control and deviations all represent
good science and management; these are not merely arcane system requirements favored by government regulators.
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.