Gradation in Pharmaceutical
■ By Brigitte Mangiarotti, SAFC Manager of Quality Services - EMEA
A look at industry trends and how suppliers help
Drug development is a lengthy process, some- times taking up to 15 years to get to the final commercial manufacturing phase. Whether biologics or small molecules, all medicines have
to meet strict regulatory and quality standards to ensure
patient safety and product integrity. Within these standards
there are different ranges of quality for the raw materials
used in biopharmaceutical manufacturing depending on
where manufacturers are at in the development process.
Often times, the quality of raw materials used in discovery
and pre-clinical phases can be very different than those in
Involving quality raw material suppliers from the beginning of drug development can reduce
many risk factors.
the clinical trial phases and through to review and commercial manufacturing.
As drug manufacturers are increasingly looking to minimize costs in the research and development phases of a
product, they may choose a lower-quality version of the
regulated raw material, not wishing to pay for full traceability or GMP-standard manufacture when it is not necessary.
When looking at the right level of quality to use through the
different phases of manufacturing, it is important to take all
factors into consideration. In this paper, we take a look at
raw materials, why grade matters, the responsibilities of a
supplier, and the importance of a clear remediation policy.
QUALITY ALONG THE WAY
While the regulatory demands are clear for commercialized drug products, they tend to be much less specific during development phases. It is true that many potential medicines will go through the scale-up process only to fail in
Phase III trials. In other cases, they may successfully make
it through clinical trials, only to have regulatory authorities
reject them when a market authorization application has
been made. Yet a biopharmaceutical manufacturer should
be looking to the final manufacturing process even at this
early, uncertain stage of the development process.
As the product moves through the pipeline, from the medicinal chemist’s lab bench to the commercial product, the
approach should change. Ideally, the raw materials being
used are subject to a grading system to determine whether
they comply with industry regulations at each point.
To save costs during scale-up, a company may be willing
to accept non-critical raw materials that do not meet all the
stringent requirements for items of GMP or other high quality
standards. However, pursuing supply chain transparency and
demanding extensive documentation earlier should minimize
risks and help to avoid problems further down the line.
WHY GRADE MATTERS
Undocumented materials introduce the risk that undefined or unquantified contaminants might be introduced
into the process, which could impact the final product.
Those may also affect the manufacturing process itself, altering the yield or even the product of a chemical reaction,
or the composition of a peptide for a biologic.
As the quality level of a raw material increases, the risks
it poses decrease. The most difficult decision for a manufacturer is frequently balancing cost and risk in the early stage
of development in terms of raw material choices. While
those higher-quality products do increase costs, there are
other advantages on top of the reduced risk – should the
product advance into clinical trials, the necessary supply
chain transparency documentation will already be in place-with certificates of origin for those raw materials.
Consequently, biopharmaceutical manufacturers have
become increasingly reliant on their suppliers to assist with
product compliance. They are looking to meet all the necessary standards without engendering excessive cost and will
consult on what grades are appropriate. Raw materials must