API Quality Risk Management


The ICH guidelines and FDA recommendations about how to effectively manage quality risk in drug manufacturing are clear and plentiful. But the truth is that the amount of qualification and validation that take place is really left to the discretion of drug manufacturers and their CMOs.

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Some sponsoring companies want to cut corners and save costs in their approach to quality risk management in early stage development, yet, the opposite almost always occurs. By not identifying problems early on when they are easier to resolve, companies can actually not only incur additional costs later in the process, but their investment in the drug substance may be for nothing if it’s not able to meet FDA approval.

Improved quality risk management provides the following key benefits:

  • An increase in the quality of chemical data.
  • An earlier halt to ineffective or unsafe drugs.
  • A reduction in development and manufacturing costs.
  • An accelerated time to market.

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So What Exactly is QRM?

Quality risk management (QRM) is an essential element in every aspect of drug product and substance development and manufacturing throughout a product’s life cycle.  According to ICH Q9, 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.

Companies use QRM to understand changes in drug product formulation, analytical methods and manufacturing process operations. Doing so helps to ensure successful FDA approvals and patient safety.

But what exactly is the risk that CMOs are concerned with?

Risk is the probability of harm occurring in a molecule that is used by patients. But in drug development, it’s also the risk that the chemical will not meet FDA approval because of many factors, such as high levels of impurities, incomplete data collection, not following standard operation procedures, etc.

How to Measure Risk Assessment

Risk assessment should be based on scientific knowledge associated with the product and processes; and the level of effort and detail associated with risk assessment should be on par with the level of risk being identified and evaluated.

There are basic elements of a Quality Risk Management program that companies should strive for:

Identify methods suitable for their intended purpose. Method validation is the process of demonstrating that analytical procedures are suitable for their intended use.

From the earliest stages of development, your CMO should share with you the methods it will use to get a molecule ready for scale-up.

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.  Additionally, they lead to implementation of continual improvement in equipment and manufacturing processes and increased process knowledge.

Qualification and validation are key elements of any pharmaceutical development program. Often considered routine, too little attention is paid to them with regards to their potential to contribute to overall developmental time and cost efficiency.

Develop a sound regulatory strategy. Sponsors should work closely with their CMOs, consultants and internal team to develop a sound regulatory strategy that will guide the complete chemical development process. This is the single most important thing you can do and cost-control will follow. Without a clear understanding of goals and processes to reach them, projects can easily get off-track.

Ben Franklin once said that an ounce of prevention is worth a pound of cure. Ensuring sound quality risk management from the earliest stages of drug substance development can go a long way to actually saving costs in the long-run and ensuring your drug candidate can meet any regulatory hurdles.

What are other ways quality risk management can be routinely implemented in the drug manufacturing process?  We’d love to hear from you. Contact us at 978-462-5555. You can also check out:  “Why the FDA and EMA want you to implement QbD Quality by Design – 9 basics and what’s in it for sponsors.”