Ethically Speaking at the CMO Level

CMOs serve a broad spectrum of customers — from well-established big pharmaceutical companies on one end to emerging pharma and startups on the other. Knowing when and how to support their partners when questions of ethics come up is a key value add CMOs bring to the table. The perspective CMOs bring of distance and independence can keep customers large and small on the path of doing the right thing. Whether a CMO is helping accelerate most pressing NCE, API, or custom chemistry projects, guidelines and values must not only address the spirit but also the letter of the law.

When it comes to ethical decision-making in drug manufacturing, big pharmaceutical companies walk in familiar territory, bringing experience, practice and a solid understanding of the boundaries and positions they take in all manufacturing issues. CMOs working with these companies, then, are a natural extension of their team and comply with the same values and approaches that big pharmaceutical companies have adopted. They also serve as a sounding board or quality check when processes or systems seem to stray from the norm.

The role of the CMO changes when working with the other end of the spectrum — with emerging pharma or startups that have no knowledge of pharma. These could be a venture capital funded enterprise or even a university lab.  When they approach a contract manufacturing organization, it’s likely they do not have an understanding of what can and cannot be done. In this situation, the CMO assumes the role of an advisor, providing expert guidance on the rules and boundaries. The customer is in learning mode, assessing and absorbing what is “appropriate” as it goes through the development process for the first time. For example, a new company with a molecule that has documented therapeutic properties may want to move from a health supplement stage to a full clinical trial. That start-up doesn’t know the rules; it just wants to move to the trial as quickly as possible. In that type of situation, CMOs serve as not only vendors who manufacture the product but also mentors who help the emerging pharma or startup organization navigate the various regulatory and compliance hurdles. These emerging or startup companies may have pre-conceived expectations or a false set of assumptions — such as how quickly the product can be made, for example — that need to be informed by more seasoned expertise.  In these situations, the CMO can guide them on the timing of every step, the prep work involved and so on.  It is up to the CMO to put the brakes on, to let its customers know how to achieve that balancing act of efficiency, quality and compliance.

Innovative CMOs find new ways to accomplish certain tasks while meeting compliance. Being flexible is key, and understanding that the rules get stricter as you go through various stages of development is also important. For example, processing materials for clinical supply can be a somewhat flexible process as you go through FDA approval, but when the materials are processed for commercial manufacturing, the regulations are more specific. In API manufacturing, ICHQ7 is the primary document that provides guidance. The rules for releasing raw materials, defining a process validation, the expectations for analytical methods and more vary according to the practice and experience of the customer.  A CMO will need to understand that experience with its customer and ensure that its own values match that of its client.  It will also need a good understanding of how the regulations change from country to country and where the drug is supplied.

Increasingly, the global nature of the market reminds us of the importance of being in sync with your customer. There may be contractors who take a different view of how to do things based on their cultural heritage. Ethical questions will have a variety of responses based on the location and cultural background of the contractor. Explore these before you enter into a working relationship.

The FDA, for example, is increasing its level of scrutiny on companies throughout every stage on the supply chain, rather than only the traditional last leg of the journey.  How organizations respond to this new level of challenge will be telling.

This won’t stem the growth of CMOs/CROs but it will separate out the serious players. The years of just skating by with a minimalist approach are gone.  Companies will need to step it up or step away. Based on our years of experience, we offer the following tips and suggestions to CMOs evaluating where they fall in term of ethical decisions:

  • Take a close look at the use of the product. One of the familiar tenets of medical ethics is “First, do no harm.” If the product you are manufacturing is something that humans will use, seriously and carefully consider what you are doing in every step of your process to ensure it is safe for human consumption or application. This is the central ethical issue at PCI that we consider every day.  Our own conscience keeps us accountable.
  • Err on the side of caution. When you have to search for wisdom and make tough choices about a particular batch of product, ask yourself: Is it recoverable? Can you use it?  Erring on the side of caution is the better part of wisdom. PCI Synthesis, Inc. (www.pcisynthesis.com), a 12-year-old custom chemical manufacturer of new chemical entities (NCEs), generic active pharmaceutical ingredients (APIs), and other specialty chemical products
  • Don’t stifle creativity. When it comes to matters of compliance, you need to be able to rethink but not overthink. Don’t be paralyzed by regulations. Instead, question: What are we doing? Is it a good practice, habit, or just a cow path we’ve been following for years? How can we solve this problem in a way that no one has tackled it before?

These are just a few of the ways CMOs can successfully deliver both product and ethical choices from post-discovery to commercial application.