The Quality Imperative in API Manufacturing

Four Steps to Ensure Quality Even When Problems Occur

From quality issues with Johnson & Johnsons’ infant pain reliever to contaminated high blood pressure medication, we all know too well the problems that can occur when mistakes happen in API manufacturing.  The role of quality is paramount, since the implications of poor quality are too big to ignore.  

Quality is so important in biopharma that it is falls under several different departments and programs at most firms, and there is a clear distinction between Quality Assurance (QA) and Quality Control (QC). To generalize them, Quality Assurance refers to the processes implemented and actions taken to proactively design and manufacture safe and effective drug ingredients. Quality Control is the more reactive program, which inspects and tests to verify that the API is safe and effective after it has been produced and it also is responsible for all of the documentation. According to current Good Manufacturing Practices (cGMP), QC is required, yet it is more vague about requirements for QA.

Yet regardless of the protocols implemented and rules followed in QA and QC, issues arise that can compromise the quality of projects and plants. There can be excess impurities in the API manufactured, standard operating procedures (SOPs) for handling equipment or maintaining clean rooms can be compromised, or documentation can contain errors.  Regardless of the problem, every situation can be a lesson learned.  

In fact, in addition to raw materials testing, in-process monitoring, release and stability testing and process validation, investigation of deviations from quality are required by the FDA as part of cGMP compliance.

According to FDA guidelines, meaningful investigations should be thorough, timely, unbiased, well-documented, and scientifically sound. The first phase of a quality investigation should include an initial assessment of the accuracy of the laboratory’s data. If this initial assessment indicates that no meaningful errors were made in the analytical method used to arrive at the data, a full-scale Out-of-Specification (OOS) investigation should be conducted.

Conducting an Effective Quality Investigation

Regardless of whether it’s required by the FDA or an internal issue, the key to learning from the mistake is to conduct a quality investigation. At Seqens CDMO NA, quality investigations are performed in response to any deviation from our SOPs or product specifications.  As part of the investigation, we review and analyze the circumstances in which the deviation occurred to get to the root cause and its impact on products, processes, systems or staff.


We have a specially assigned Quality Assurance Group, responsible for initiating a quality investigation immediately upon notification of an issue. All pertinent facts from the investigation, notes and documentation are included to provide a comprehensive narrative and to ultimately assign a root cause.  A thorough impact assessment also is performed to identify all corrective and preventative actions that should be taken, to not only rectify the situation but prevent it from happening again in the future. 

When conducting a quality investigation, the following four steps ensure that the issues are rectified and continuous improvement occurs:

  1. Gather the data. When first initiating an investigation, make sure all aspects of the event are understood, including what happened, where it happened, who was involved and what materials were involved. You also should review the Standard Operating Procedures (SOPs) that were used in the process, and what was done to immediately address the problem, such as isolating any products that were involved.
  2. Interview all people involved. As objectively as possible, conduct thorough interviews with all team members involved with the incident who can provide valuable information. These discussions might include individual meetings with project managers, QA and QC teams, lab technicians, supervisors and others. They can describe protocols and SOPs followed to help get to the root cause of the problem, but also to help inform new protocols that can prevent the problem form recurring in the future, since often, problems arise not from human error, but from inefficient processes.
  3. Take corrective action. Once the quality investigation is completed, acorrective action plan should be developed to define and document the situation, identify its root cause and provide a detailed roadmap for correcting the issue.
  4. Communicate findings and strive for continuous improvement.  The corrective action program should not be the end of the story. It’s important to share findings and train pertinent staff on the new protocols and procedures that will be implemented as a result of the incident. In addition, these protocols and procedures should be consistently re-evaluated to reflect changing situations and needs.

CDMOs that strive for quality in every aspect of their operations are rewarded with successful projects, happy sponsors and safer staff. And, while issues will always arise that could jeopardize quality despite the best efforts, those CDMOs that have a plan in place and act quickly and honestly to rectify and learn from them, can minimize the severity and frequency of such issues and grow from them.

For other articles about quality control-related issues, check out Successful Audits in API Manufacturing Begin and End with Ongoing Quality Processes; or Incomplete Documentation Can Make or Break API Manufacturing Projects.