Contract Sterile Manufacturing of Generics

Quality standards are often difficult to meet, creating challenges for manufacturers.

by Raymond E Peck, CEO of VxP Pharma

Injectable generics need to be safe, sterile and pure. Manufacturers, patients and regulators can all agree on that. The questions of how quality standards should be formulated and enforced, on the other hand, continues to spark heated debate. Many facilities around the world still struggle to comply with excessively strict guidelines; while many other rules remain vague, full of gray areas that are open to interpretation.

The consequences of excessively stringent regulations can be just as critical as the consequences of excessively vague ones,. Many worldwide drug shortages occur because of late or inconsistent release dates, as facilities scramble to meet guidelines. Meanwhile, other batches whose quality fails to measure up to standard end up having to be discarded. Some manufacturers even use the wrong active pharmaceutical ingredients (APIs) or excipients in their formulations, or ship non-sterile batches, putting patients’ lives at serious risk.

In light of these issues, it’s important for regulators and manufacturers alike to begin taking a more holistic view of quality standards, with a primary focus on the actual goals they aim to achieve.

Pharmaceutical companies need more insight into CMO practices.

Once a pharmaceutical product development company hands over manufacturing to a contract manufacturing organization (CMO), they often give up the ability to monitor practices and supply lines. They may feel no responsibility to actively monitor whether the CMO is following good manufacturing practices (GMP) or good distribution practices (GDP). In fact, they may not have any way of finding out where the materials in their products are coming from, or how those materials move through the supply chain.

This lack of transparency creates major issues for any pharmaceutical company aiming for full regulatory compliance. The EXCiPACT Certification Scheme for Pharma Excipients (in the US) and the Eudralex guidelines (in Europe) both lay out specific GMP and GDP standards for marketing authorization holders (MAHs) of pharmaceutical products. For example, facilities are expected to be sterile, to undergo regular inspections, and to have systems in place for area monitoring and air handling. But since the MAH is rarely directly responsible for the supply chain and manufacturing, it can be extraordinarily difficult for them to know, for sure, whether the CMO is complying.

Contract manufacturing organizations need to be clearer about their standards.

For all these reasons, the bulk of the responsibility for following GMP and GDP falls squarely on the shoulders of the CMO. One might expect that all CMOs would do their best to follow guidelines rigorously, given that their success as a business depends on their ability to consistently deliver sterile, effective batches of pharmaceuticals. And while this is true to some extent, slight variations in quality standards between the CMO, the pharmaceutical developer, and various regulatory bodies can (and often do) lead to miscommunications and mistakes.

For example, different organizations uphold different standards for the testing of raw materials. Various CMOs use different procedures for validating analyses of formulations; and those may differ from the methodologies at the pharmaceutical firm. Even logistical parameters like security tagging and acceptable temperature ranges can vary slightly from one company to the next. This is why it’s crucial for CMOs and pharmaceutical developers to communicate clearly and consistently about the standards to which they’re holding their production and distribution lines.

Quality standards need to be clearer, more standardized, and simpler to follow.

While US and European regulatory bodies have gone to great lengths to word their guidelines as specifically and clearly as possible. Even so, the ongoing instances of miscommunication between pharmaceutical firms and their CMOs reveals that a significant amount of room for interpretation still exists.

To cite just one concrete example, many suppliers mislabel certain containers of products shipped to the CMO, causing the CMO to proceed through the entire manufacturing pipeline with an incorrect source material. And while regulations stipulate that manufacturers must test incoming raw materials to ensure accuracy, they don’t necessarily specify that every container needs to be tested. Thus, many CMOs test only a few containers, and end up using mislabeled containers to manufacture useless (or dangerous) batches of pharmaceuticals.

The more clearly and transparently pharmaceutical developers and CMOs are able to communicate about GMP, and the more stringently they interpret and follow existing regulations, the more likely they’ll be to consistently ship safe, sterile and effective generics.


In addition to being a writer and speaker, Raymond E Peck is the Founder and CEO of VxP Pharma Services and VxP Biologics, both based in Indianapolis Indiana.


About the Author:

Ray Peck