Biopharmaceutical companies often look to specialized contract service companies to help them meet regulations, before and after market approval, and to maximize their resources. But they may be overlooking the expertise of their process equipment suppliers. Aside from equipment, some suppliers also provide consulting services for equipment documentation, process validation, automation, and compliance.
The September 2003 draft guidance "Sterile Drug Products Produced by Aseptic Processing" recommends that drug manufacturers validate their sterilizing filtration processes specific to each drug, but it also acknowledges that suitable testing is probably beyond the capabilities of most drug manufacturers. This work can be outsourced, and FDA has recognized that some filter suppliers are experts in validation.
It is an established practice for qualified filter suppliers to conduct drug product-specific bacteria or mycoplasma retention testing; related tests for filter compatibility, extractables, and integrity test values; and to provide "FDA-ready" documentation substantiating that the selected filters can sterilize the drug product.With the emergence of new technologies, suppliers are providing even more extensive validation documentation and services. For example, to make sterile pathways, drug manufacturers historically have relied on manual tubing connections; this approach requires specialized capital equipment — laminar flow HEPA filtered hoods and tubing welders, for example — and highly trained operators. With the introduction of new aseptic connection devices, sterile pathways can be created on the open production floor without extensive training. These devices can provide a higher level of sterility assurance, they are free of capital costs, and they allow aseptic connections to be more easily performed.
The question for any new technology is how to validate it. Suppliers can apply the worst-case uses of their products and conduct, in advance, all the applicable validation work at their own facilities. Thereafter, the supplier's product is launched with much of the user's validation work already documented.
This greater degree of supplier testing and documentation is a significant advance. Today, suppliers are helping users meet 21 CFR Part 11 regulations for electronic records. The "Good Automated Manufacturing Practice Guide for Validation of Automated Systems" was developed by an industry forum and establishes how suppliers' design and development documentation can eliminate users' need to generate their own. Beyond easing the drug manufacturers' documentation and validation learning curve, this practice is also more cost effective. The supplier does it once and costs can be spread broadly among its many customers.
Suppliers are also expanding their consulting services, such as troubleshooting and pre-inspection reviews of equipment usage. One supplier provides experts who visit a plant to review equipment usage, record observations, and provide recommendations to the client. This is a cost-effective means to reduce adverse FDA observations and retrieve information which can, in the event of a compliance issue, help scientifically justify a manufacturing practice.
With the pharmaceutical industry becoming increasingly globalized, major suppliers must prepare themselves to support customers everywhere. They must monitor regulatory practices in Canada, Europe, Australia, Japan, and elsewhere. Although equipment usage, validation, and compliance requirements tend to have commonalities worldwide, local support is necessary to ensure sensitivity to national regulations or regional practices and to allow the supplier to provide an approach that is applicable globally.
Major equipment suppliers can play an important role in helping pharmaceutical manufacturers meet diverse requirements. Many are experts in the technology they offer, including its use. Ultimately, that expertise is what regulators want drug manufacturers to have. Obtaining that knowledge from suppliers is faster, easier, and more cost effective than when users try to develop it internally. Global suppliers are focusing on expanding their offerings by providing related services. The pharmaceutical industry will benefit by viewing their equipment suppliers as experts in the validation and compliant use of their equipment — not simply as vendors. BPI