Manual Visual Inspection

FDA’s take on manual visual inspection 

Manual visual inspection occurs purely in pharmaceutical manufacturing, blending the risk aspects during manual inspections. Global regulatory agencies, including the US FDA, insist that 100% of pharmaceutical products must be inspected.  There are three different ways to perform these inspections: using a fully automated system, 100% manual system or a hybrid system. 

Last year, the FDA released guidance documents which further emphasized the movement of manual visual inspection into a more risk-based approach. The manual visual inspection process continues to receive criticism because it relies on the manufacturer, which must understand its processes, manufacturing systems, plant and employees, to develop a system that properly identifies the risk and a plan to mitigate those risk.  

What about risk mitigation? 

Risk mitigation goes all the way back to at least 1860, when “Prohibited Acts” began to be established to regulate the sales of pharmaceutical products and provided the FDA the constitutional right to oversee food and drug manufacturing; in the US, this falls under what is known as “strict liability.”  Therefore, if a company has a manual visual inspection that the regulator deems as insufficient, the FDA can legally pursue the manufacturer without having to prove intent. Therefore, if a manufacturer’s system is not robust, their product may be taken off the market and they can be prosecuted. 

Even with 100% of vials or capsules being inspected, the success rate for these products is still very low. Depending on what source you follow, you could see anywhere from a 20% to a 40% percent failure rate, depending on the manufacturer. Therefore, PQE utilizes our over two decades of experience supporting clients in this space to ensure that best industry practices and updated guidance’s are followed in developing their inspection planning and execution. And we not only train these manufacturers on manual visual inspection, which is an FDA requirement; we build robust programs for them.  

Proper inspection is critical 

We emphasize the importance of understanding how important the inspection process is, and how essential it is to proactively examine it. Even if the process is not failing the manufacturer today, it is critical to prevent the issue from becoming out of control and having to fix and revise the company’s procedures. As the manufacturing process continues to rapidly become much faster and more efficient, the industry must keep in mind that human error remains the largest cause of patient death.  

Manual visual inspection training 

Manual visual inspection training is a long and arduous process. Training inspectors to successfully complete manual visual inspections typically occurs in phases. The first phase of the process teaches the proper technique of manual visual inspection. That is, literally, how to pick up a vial, how to swirl it, how to invert it, what to look for, what defects - cosmetic or particulate - exist.  This phase typically takes one to two days and pertains to generic vials or IV bags.  

The next step is done with smaller groups which are trained with respect to specific product families, so inspectors are being trained on the exact product they will be examining every day. When defects are identified, they are tested. Inspectors must pass tests to show they are proficient in testing these imperfections because defects in particulates in these products can kill patients, so it is critical that the manual visual inspection is done properly and any defects, some of which are critical, are identified. 

What are manual visual inspections? 

Manual visual inspections include everything from filling the product, inspecting it, and acceptance sampling (AQL), which means a certain amount of product is scrutinized at a higher level. If a certain percentage of the total amount being tested shows defects, the entire batch must be addressed. Continuing education following training is important; industry trends are moving so quickly, and adapting so dramatically, it is challenging to keep up with these regulatory guidances, which are revised and updated periodically. The responsibility is on the manufacturer. Just a few examples of FDA’s guidance with respect to manual visual inspections include: 

• Manufacturers must create a "holistic, risk-based approach to visible particulate control that incorporates product development, manufacturing controls, visual inspection techniques, particulate identification, investigation, and corrective actions designed to assess, correct and prevent the risk of visible particulate contamination"; 
• Views on Clinical Risk of Visible Particles (route of administration, patient population, nature or class of particles); 
• The incorporation of quality risk assessment in the development phase of the product vs. just post market;
• Further input on defect libraries and how they should be built and managed. 

Conclusion 

The FDA's new guidance has raised the bar in expectations as a result, they've already issued more warning letters than ever before. These warning letters can be a consequence of insufficient manual visual inspections, for example, if extrinsic particles are identified within batches and insufficient time was taken to investigate the cause and assess the drug product impact. And if warning letters are not addressed and the issue corrected, companies can be fined, production can be paused, and even some manufacturers have been shut down. 

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PQE Group is an ISO 9001-certified technology solutions and compliance consulting services company for the life sciences industry, providing global capabilities deliverable throughout the entire product quality life cycle. Established in 1998, PQE has 30 offices worldwide and more than 1500 industry subject matter professionals. PQE specializes in areas including Data Integrity Assurance, Digital Governance and Cybersecurity, Medical Devices, Qualification and Engineering, Laboratory Excellence, Quality Compliance, Regulatory Affairs, and Third-Party Audits. It also has a proven track record managing large multi-site projects as well as small, medium, and start-up pharmaceutical, biotech, and medical device clients.  

PQE Group's highly professional subject matter experts can help ensure your inspectors are thoroughly and appropriately trained on manual visual inspections. By partnering with PQE Group, you can be confident that your company will maintain FDA (and other regulatory agency) compliance and that your product can be safely developed and manufactured.