Addressing Quality From All Angles in API Manufacturing

Best Practices in Quality Assurance and Quality Control

A relentless focus on quality has to be paramount to all activities undertaken by Contract Development and Manufacturing Organizations (CDMOs) developing Active Pharmaceutical Ingredients (APIs) and other chemicals. It’s not only required to meet current Good Manufacturing Practices (cGMP) standards and regulatory requirements, but it’s also what sets the most successful CDMOs apart.

From clean room operations, to calibration of instruments and preventative maintenance in utilities systems, processes and controls must be effective and strictly enforced. Here at SEQENS (formerly Seqens), we maintain cGMP quality systems compliant with ICH Q7, and our class 100,000 finishing and packaging areas ensure high quality manufacturing, but it’s even more than that – it’s a mindset that puts quality above all else.

Quality Control and Quality Assurance are both key areas where CDMOs should invest significantly. But what exactly are the differences between the two?

Quality Control and Quality Assurance are both key areas where CDMOs should invest significantly. But what exactly are the differences between the two?

Quality Control (QC) is the group that performs the actual testing on raw materials, as well as final products.  They execute the analysis of chemical batches or medical devices, testing samples  and compiling the performance data. Here at SEQENS we have approximately 30 people responsible for QC.

Our QC group performs close to 2,000 analyses/tests per month to assess physical, chemical and biological components. It is comprised of three key sub-groups:

  • Method development and validation group
  • Quality control analysts (the technicians who execute the tests using the methods developed)
  • Stability program group

Quality Assurance (QA), however, is the final authority, providing the ultimate checks and balances. The QA group has final say over raw materials quality, batch quality, and then for writing and compiling all batch records, and signing off on all certificates of analysis. The QA team reviews every aspect of the manufacture of a product – from receipt of raw materials to final shipment – and makes sure that Standard Operating Procedures (SOPs) have been followed. QA also is responsible for hosting FDA inspections, customer audits and supplier inspections.  It also must write responses to any noted deficiencies, as well as issue, track and store every document and batch record. At SEQENS we have a group of nine people in Newburyport, reporting directly to the unit’s senior management. 

Both Quality Control and Quality Assurance play related and integral roles,  but it can be difficult to develop and ensure compliance to strict SOPs.  Below are some best practices that can help to inject quality across the organization:

  1. Conduct rigorous training.  At a minimum, QC teams should undergo training for at least six months to ensure proficiency in all SOPs, including method development, clean room operations, equipment calibration and everything in between.
  2. Documentation is key. Complete documentation that anyone can follow should be part of every project deliverable. As part of its QA process, quality assurance should check for documentation—and turn back any work if it is incompletely documented. Again, it is up to QA to enforce this quality control checkpoint.
  3. Perform annual reviews of SOPs.  The use of new equipment and processes change over time, so it’s important to evaluate SOPs in place to assure quality operations and quality products. A good way to do this is for QA managers to perform internal audits and periodical reviews to identify any gaps in the system.
  4. Keep QA independent.  While the development, manufacturing and marketing of products may involve more than one unit or department, the quality assurance group should be independent of production processes so that they can remain objective.

Adherence to quality standards is crucial for chemical manufacturing because the implications of less-than-stellar quality control are too big to ignore. Yet, effective Quality Assurance and Quality Control can help CDMOs not only maintain adherence to FDA  and other industry regulations, but it can improve production efficiency and processes as well.