Systems for quality control remain one of the most important and effective bulwarks for protecting the supply chain and ensuring
patient health and safety. This is true especially in biologically based production. As such, quality must be very high on
the list of the criteria for selecting a provider of fermentation services.
When searching for a contract manufacturer, don't expect the company to have identical standards. However, it must have a
comparable and compatible set of standards that ensures high-quality products using fully compliant operations. Today, no
manufacturer can take the chance of using contract suppliers that do not have the quality and compliance systems already in
place or whose track record meets only the minimal levels of performance. The service provider must clearly demonstrate quality
and compliance in its fermentation offering. One question to ask is whether the supplier's quality and compliance records
in fermentation services are among the best in the industry. If not, don't consider engaging with them; the downside potential
for the supply chain is simply not worth the risk.
When evaluating quality systems, look carefully at the laboratory facilities and trained quality analysts and quality assurance
personnel. Do these elements operate under CGMP conditions, ensuring that even routine updates are made on an ongoing basis
for quality reasons?
A company should also know whether a service provider has a standing quality assurance group that is responsible for ensuring
written procedures are followed so that all components, product containers, closures, in-process materials, and finished materials
conform to appropriate standards of identity, strength, quality, and purity. Request to see samples of written procedures
that cover sampling, identification, storage, handling, testing, and documentation of test results. Auxiliary or support activities
such as training, calibration, maintenance, stability evaluations, and audits must also be described in written procedures.
Trained personnel (according to a formalized certification program) should be the ones performing all laboratory testing,
which is conducted according to current written, validated, and approved procedures. The use of validated analytical procedures
ensures the accuracy, precision, specificity, sensitivity, ruggedness, and reproducibility of test results. The GMP computer
systems in the supplier's laboratory operations should be validated. Record checking systems provide the necessary verification
that the appropriate tests, procedures, and calculations are used and performed correctly and that the transcription of data
is performed accurately. In a service provider's quality assurance process, every item essential to the analysis of the material
or product must be checked; look for such assurances when conducting a supplier capabilities evaluation.
Technology transfer and scale-up
Typically when a company has made a decision to outsource a large-scale fermentation process, it has developed the process
at the laboratory- or pilot-scale, and the contract manufacturer works with the company during the technology transfer stage
to first transfer the process at the same scale and then optimize the process in the contract manufacturer's facility. Sometimes,
however, the relationship starts at the preclinical or early clinical materials stage. In such cases, it's worth identifying
a contract supplier that can offer extensive pilot-scale facilities and commercial-scale facilities.
Once underway, the technology transfer experience becomes one of the most important in the relationship, so vetting a contract
manufacturer on this point in advance is recommended. A supplier must have the technical resources in place to receive technology
from a customer and implement successful scale-up and commercial supply in a timely manner. Evaluate its track record and
its ability to demonstrate success in this key area. Technology transfer includes a number of challenging steps, including
transferring process knowledge, analytical methods, raw material specifications, equipment requirements, and so forth. So
a pharmaceutical firm should look for a strong technical team that can successfully implement every step. A contract manufacturer's
staff should be able to quickly learn how to operate the process themselves.
There is a great deal that can go wrong when lab- or pilot-scale quantities of material are scaled-up. Scale-up can include
various hurdles, and key alterations may need to be made in the process. A contract manufacturer must demonstrate clearly
the capabilities of its project management approach. Without experienced support resources on-hand during this difficult period,
successful technology transfer, scale-up, and implementation will not be possible.
Ensuring the "supply" in supply chain
A final point to consider: none of the above points, from process expertise to scale-up, means anything without the assurance
of supply. A successful fermentation services provider must prove it has the capacity and robust business systems (e.g., raw
material supply, production planning) to provide reliable supply for a customer, both in terms of quantity of material and
timing of deliveries.
Important questions to ask well in advance are: Does the supplier have the available capacity for the fermentation requirements
for the foreseeable future? Are its packaging, shipping, logistics, and customer service infrastructure and procedures adequate
to guarantee your supply requirements on a regional, national, or global basis?