API manufacturing, you can never be too concerned about quality. After all, unclean equipment, sloppy
procedures or unkempt facilities, can have a serious impact on the drugs that
are produced from your Active Pharmaceutical Ingredient (API). For this reason,
conducting an audit of your Contract Development & Manufacturing
Organization (CDMO) is a good way to be assured that it is living up to your
standards. It’s also a good way to make sure that when FDA inspections come
along, your CDMO will pass with flying colors without holding up your critical
good rule of thumb for sponsor audits is to conduct one-to-two per year,
usually when you first begin working with a CDMO and then about half way
through a project. Unless you have a QA specialist in house that can be freed
up, it’s a good idea to hire an experienced consultant to conduct the audits
for you. In terms of the planning, it’s important to give your CDMO a few
weeks’ notice before arriving for an audit so that the appropriate
professionals will be available to address your questions and host you through
an inspection tour.
addition to these general guidelines for conducting a sponsor audit, below are
eight considerations to think about before conducting your audit:
- It’s all in the prep. Before planning an audit of your CDMO, it’s important to do a little research on your own. Look at the CDMO’s past regulatory history, and read up on current FDA guidelines and their thinking so that you go into the inspection with the same mindset.
- Develop a realistic audit plan. Be thoughtful about your audit plan and make sure it’s flexible, providing enough detail and action items to be thorough, but leaving room to follow different plans if different needs arise. Also ask for the CDMO’s quality manual and index of Standard Operating Procedures (SOPs). Following this, you should pursue any areas of concern you uncover.
- Share your passion for the project. While you should steer away from presenting a lengthy corporate slide deck during the visit, it’s always a good idea to have a few slides or a leave-behind available that provides appropriate background and context for the visit. You should also share your ultimate goal and your enthusiasm about the project and the benefits it will provide patients. CDMOs often feel isolated from the actual impact of the work they do, so this can help everyone see the end-goal.
- Tour the facilities. Guided by the CDMO’s QA manager, this tour should allow you take the time to review key areas and tasks and ask questions along the way. You can note some of the material lot numbers, ask for identification of equipment and the names of staff members performing key tasks.
- Consider the suppliers. In addition to key areas, such as the production controls, quality system, packaging & labeling and others, you should also examine the CDMO’s oversight of its suppliers and any subcontractors it uses. Ask if and how it evaluates its suppliers to make sure they’re meeting the same high standards as its own.
- Follow the FDA Approach. You should follow the FDA’s systems-based inspection approach, spending time reviewing the foundational quality systems, such as change control deviations and investigations. Ask to see any Corrective and Preventive Actions (CAPA) or Out of Specifications (OOS) reports, as well as documentation for completed training programs for staff. Also ask to see original qualifications, calibrations and preventative maintenance records.
- Don’t go overboard with documentation. While you should do a thorough review of documentation, don’t spend most of your time reviewing SOPs. You should pick a few, focusing on higher-level procedures so you can see that the CDMO is writing effective SOPs that comply with regulatory requirements and more importantly, that they are adhering to them.
- Share your assessment. In your closing meeting, you should share meaningful observations, sticking to the facts without disclosing too much of your own opinion. Hopefully this is one of many meetings and discussions you will have with the CDMO and you want to make sure it is a relationship of honesty and trust.
Following these steps should help you learn a
lot of what you need to know about your CDMO and its operations. But, sometimes
there are also warning signs that can guide you as well. If the CDMO does not allow you in certain
areas, if it prohibits you from speaking to certain employees, if it’s
reluctant to share certain documents, you have the right to be suspicious. A
good CDMO should be an open book with nothing to hide.
This article is the third in a series of articles on audits in API manufacturing. For additional insights, please read: Paving the Way for a Smooth FDA Inspections; and Internal Auditing – The Belt and Suspenders Approach to Quality in API Manufacturing.
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.