Excellence in API Manufacturing Begins and Ends with Quality Assurance

Given the growing number of drug recalls, defects and other issues that can have the opposite effect in treating disease, the role of quality could very well be the most critical function of a Contract Development & Manufacturing Organization (CDMO).

For that reason, various types of quality teams can be found throughout CDMOs. There is the Quality Control (QC) team, which performs the actual testing on raw materials, as well as final products. It analyzes chemical batches, tests samples  and compiles the performance data.

Here at Seqens NA, we have more than 30 QC scientists, performing close to 2,000 analyses/tests per month to assess physical, chemical and biological components. It is comprised of three sub-groups, addressing method development & validation, analysis and stability programs.

The other quality function central to drug manufacturing is the Quality Assurance (QA) group.  This group has the ultimate responsibility for ensuring quality manufacturing. It controls the quality of raw materials and chemical batches, ensuring that Standard Operating Procedures (SOPs) are followed and documenting all steps – from compiling and storing batch records, to signing off on all certificates of analysis and final shipment. The group also manages 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.  Seqens NA includes a group of nine QA professionals, led by a QA manager. 

Quality Begins with Sound SOPs

One of the most critical functions of a QA team is to ensure that the documents that are needed (and there are plenty) are accurate and available. In addition to batch records, quality specification sheets and analytical methods, documenting and ensuring compliance to SOPs ensures that operations are consistently conducted in an unwavering, standard manner that has been proven to protect the quality of chemicals manufactured.   

An example of one of these SOPs in action at Seqens NA involves raw materials – receiving, storing, identifying and tracing them. Thanks to the SOP, no raw material out of specification is used, ensuring that when a material is used it produces the high quality product for which it was intended. Following are the steps involved, as developed by the QA manager:

• Prior to a raw material arriving on site, the materials management personnel receives a completed copy of the Bill of Materials from production after the purchase order for the raw material(s) has been issued. This document will inform receiving personnel of the material ordered, the quantity, the vendor, the purchase order number, and the expected delivery date.
• Once a raw material is delivered, the materials management staff checks to make sure the material has a completed and signed Certificate of Analysis (C of A) from the vendor. Release to manufacturing cannot occur without an appropriate C of A.
• Materials management inspects the material to make sure that all containers or packaging are clearly and accurately labeled and that the lot number on each package matches the Lot Number on the accompanying C of A. They also check that the condition of the containers or packaging is satisfactory and that all containers are adequately sealed.
• Materials are transferred from the warehouse to the manufacturing plant on an as-needed basis only. Upon completion of manufacturing, the warehouse personnel transfers any unused raw materials back to the warehouse. All partial containers are reweighed and restocked. The material consumption is then entered into the inventory management database by production personnel upon completion of the manufactured batch.
• Once these steps are completed, Seqens NA has a product ready for testing or an out-of-specification raw material is sent back to the supplier or destroyed.

Best Practices in Quality Assurance

Establishing SOPs, documenting all analyses and findings and managing audits makes the job of the QA manager quite intense. It takes years of experience, many lessons learned and a committed focus to putting quality above everything else.  Below are five best practices that can help you reach your QA goals:

1. Understand the regulatory strategy. Encourage sponsors to develop and share regulatory strategy early on, so that it can inform project timelines and costs, and identify any potential challenges that could be proactively addressed. 
2. Bring QA in at the earliest stages. You shouldn’t wait for raw materials to be delivered before you involve the QA team.  It’s important that they are familiar with the project at the outset and also understand the regulatory strategy. 
3. Keep QA independent.  While the development, manufacturing and marketing of products may involve more than one unit or department, the QA group should be independent of production processes so that they can remain objective.
4. Have sponsor counterpart to QA. The sponsor should also have someone dedicated to quality assurance who can communicate with the CDMO’s team and understand the quality requirements and collaborate to ensure quality across the project’s lifecycle.
5. 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.

Quality Assurance just may have more moving parts than any other area in API manufacturing, but the consequences of less than diligent attention to it can be devastating. Aristotle once said, “Quality is not an act. It is a habit.” CDMOs that habitually put quality front and center not only more easily meet regulatory requirements, but they also gain the trust and respect of the industry.

For more related articles regarding quality in API manufacturing, check out The Art of Reducing API Failures, An Ounce of Prevention Ensures Reliable Utility Systems, and API Quality Risk Management.

About the Author

Ed is President & CEO of SEQENS North America (formerly PCI Synthesis). He serves as a co-chair of the New England CRO/CMO Council and sits on the Industrial Advisory Board for the Department of Chemical Engineering at UMass, Amherst. Ed is also a long standing member of the American Chemical Society and advises the Bulk Pharmaceutical Task Force of the Society of Chemical Manufacturer’s and Affiliates (SOCMA)...

Do you have questions? Talk to Ed.