Quality in a Time of EUAs and Fast-Track Drugs

There was a time when terms such as Emergency Use Authorization and fast track drugs were not a part of the ordinary vernacular, but then along came COVID-19. As of March 31, 2021, ten COVID-19 treatments were authorized by the FDA for emergency use and many more are in the works; and three vaccines have been approved by the FDA.

But aside from COVID-19, the growing trend of expedited drug approvals from the FDA has actually been happening for a few years now. Today, drugs are released faster than ever through expedited approval. These programs mostly target drugs that the FDA considers to be highly needed for critical diseases with very few treatment options. The approvals often rely on signs of effectiveness in early research rather than on long-term studies.

While drugs or treatments may receive fast track status or become authorized for emergency use, what is unwavering is the need for them to be effective and safe. 

The question becomes how can Contract Development & Manufacturing Organizations (CDMOs) and other API manufacturers meet rapid production processes while adhering to quality?  In essence, it begins with following the same quality protocols and processes that should be in place regardless of the circumstances.

There are ICH guidelines and FDA recommendations that articulate how to manage quality. For example, the ICH says that Quality Risk Management (QRM) “is designed to ensure that each drug’s critical quality attributes (CQAs) are defined and maintained from phase to phase during product and process development and manufacturing.” Yet, it still remains up to individual CDMOs and other drug manufacturers as to how they go about accomplishing it.

Below are four best practices that CDMOs should follow to ensure that quality remains paramount through all stages of API manufacturing:

1. Concur on the most effective regulatory strategy. A regulatory strategy is a game plan for obtaining approval or clearance of a novel drug, the definitive blueprint and timeline for meeting key goals and requirements. A CDMO should work closely with the internal team, project managers, the sponsor and consultant to develop a sound regulatory strategy that will guide the entire process. In developing the strategy, the team will quantify the attributes of the novel compound to determine the regulatory implications of its use, design, and performance. Many firms use a regulatory affairs managers or a Quality Assurance (QA) manager to lead the development of the regulatory strategy. And, since API manufacturing is constantly changing, CDMOs must stay current with regulatory developments and changing policies.
2. Focus on method development. Especially when it comes to meeting shortened drug delivery timelines, it’s important to establish a bold but realistic approach to developing an API. To accomplish this, reliable and reproducible analytical methods should be developed that are shown to be suitable for their intended use. To accomplish this, in conjunction with the process chemistry, the analytical scientists would develop a method for each step of the process. The analytical department, organic scientists, engineers and regulatory experts then design suitable specifications for each step and develop methods suitable for its intended use.  A well-equipped and well-staffed analytical department is crucial for a manufacturing facility.  It is the type of expertise sought by savvy sponsors.
3. Qualify and validate early on in the process. ICH Q10 guidelines state that qualification and validation are important in establishing and maintaining a state of control and product quality. Qualification means proving and documenting that equipment or ancillary systems are properly installed, work correctly, and comply with the documented requirements. Qualification is part of validation, but it also involves the documented evidence that a specific step will consistently meet its  predetermined specifications. In early stages of process research and pre-clinical development, it’s important to qualify your methods, but often that is all that is necessary. It’s critical, however, to validate your analytical methods in later stages – Phase II and Phase III when you are getting closer to filing for FDA approval.
4. Audit your internal systems, procedures often. A good way for a CDMO to ensure it is covering all the bases is to formally evaluate its key operations – from production systems, facilities and equipment; to laboratory controls, materials and packaging & labeling systems.  And, an effective internal audit needs an audit plan, and timely reporting that communicates the audit’s findings to the organization. This report should include an assessment of compliance risk and a comparison to current industry standards, regulations and guidelines to ensure compliance.

All the internal audits in the world, however, are meaningless without proper action. All of the follow-up corrective and preventative steps related to the audit observations must be addressed, even if it means retraining staff or amending Standard Operating Procedures (SOPs).

Despite EUAs and fast-track status, the CDMOs and drug manufacturers that make quality the hallmark and number-one priority of their organizations, not only secure more drug approvals and meet specific needs among countless patients looking for effective treatments, but they also stand out in an increasingly competitive marketplace where there’s little room for error.

To learn more about quality operations in API manufacturing read our blog posts:  “Why the FDA and EMA Want You to Implement QbD” or “The Role of ICH and How to Meet Quality Guidelines in API Manufacturing.”