Considerations for Finished Product Inspection Systems

Finished pharma product inspection requires stringent oversight that may be lacking in systems that rely on manual or only semi-automated processes. With the rise of automation technologies applied to biomanufacturing systems, having an automated finished product inspection system in place can make up for gaps where a lack of trained personnel may persist.

Determining a system

Finished product inspection starts with an evaluation of the inspection process to determine if it is able to detect defects in a pharmaceutical presentation. Once that determination is made, it is important that the inspection method is established, whether manual, semi-automatic, or fully automated. There are cases where a semi-automated or automated inspection system is not an option, which leaves manual inspection; however, if semi-automated or automated inspection options are available, then an inspection method should be determined based on lot size. In one example, lot sizes under 5000 are likely to utilize manual inspection, while lot sizes between 5000 and 15,000 would likely require a semi-automatic inspection. Above a 15,000-lot size, a fully automated inspection system is the better choice (1).

Using X-ray

Mike Pipe, head of Global Sales & Product Management at Mettler-Toledo, points to X-ray technology as one solution in product inspection, noting that there are three main quality control issues that X-ray technology can solve in the packaging area: detection of foreign body contaminants, identifying incomplete or missing medicines, and identifying damaged packaging.

“As any responsible manufacturer knows, there can be no trade-offs in quality standards when it comes to the manufacture of pharmaceutical products. Whether the medicine is in liquid or tablet form, it is essential that foreign body contaminants are detected and removed,” Pipe states. He emphasizes that the dosage or fill levels must be correct, and that the integrity of both the packaging and the product must not have been compromised.

Pipe explains that it is now commonplace for product inspection equipment to be used in the pharma sector to overcome these challenges. “Metal detection systems can be used before tablets are pressed or packed to detect ferrous, non-ferrous, and stainless-steel metal contaminants. Vision systems and checkweighers also play a vital role in ensuring that products are complete, labeled correctly, and are at the correct weight,” he says.

Pipe points out, however, that with tablets being increasingly packaged in aluminum foil-based blister packs, metal detection systems may have a difficult time identifying if metal contaminants are present if the pharma products are inspected after packaging. “This is where X-ray technology can help. [X-ray] can detect a wide range of foreign body contaminants, including metal, both before and during packaging. It can also deliver several further quality assurance benefits,” he states.

Pipe highlights five key areas where X-ray inspection can make an important contribution in pharma production and packaging:

• Detect contaminants. As pipe points out, foreign body detection is a critical aspect of any pharma manufacturer’s product inspection operation. While metal detection is a robust inspection technology for detecting metal contaminants, including stainless steel, in the preparation or tableting process, X-ray inspection can complete contamination checks early in the production process. Using X-ray can also allow for inspection of contaminants at the final packaging stage following the blister-packing process. X-ray measures differences in absorption between low and high-density matter and can provide exceptional detection not only metal contaminants, but also glass and certain plastics and rubbers, regardless of the contaminant’s shape, size, or location within the product.
• Help ensure product and packaging integrity. X-ray inspection can carry out a range of additional quality control (QC) tasks while simultaneously detecting foreign body contaminants, including:
  • Product completeness checks, including counting components and identifying damaged components—with comparison to the known number of items that should be in a pack
  • Identifying damaged packaging, inspecting seal quality to detect product trapped in the seal, and identifying missing components such as screw caps
  • Measuring product mass and comparing it to a known mass value for a reference pack
  • Checking fill levels—X-ray inspection images show clear discrepancies in fill levels between packs, where, for example, one pack may be under-filled and another pack may be over-filled, which can make the overall pack weight seemingly correct.
• Avoid product recalls. Product recalls represent a twin-headed peril for pharma manufacturers, says Pipe. On the one hand, a product recall is costly because of wasted products and production time; on the other hand, a recall causes damage to the pharma manufacturer’s good name. “While the costs of the former are often quickly absorbed, the negative effects on brand reputation can be much more long lasting,” he notes. Therefore, implementing a well-designed X-ray inspection program can cut the risks and the costs involved in product recalls. X-ray “run codes” are assigned to each product run and can be compared to checkweigher batch data, which potentially helps isolate smaller contaminated batches that need to be recalled, instead of an entire production run.
• Protect brands. The absence of good product inspection can endanger patient health and safety. Such incidents can lead to major legal action being taken. Even without a worst-case scenario such as major legal action being taken; however, there is still danger posed to a pharma brand. For example, in the United States, says Pipe, pharma producers that fall foul of FDA 21 Code of Federal Regulations (CFR) Part 210 (Current Good Manufacturing Practice in Manufacturing Processing, Packing, or Holding of Drugs) (2) and 21 CFR Part 211 (Current Good Manufacturing Practice for Finished Pharmaceuticals) (3) are issued warning letters that are publicly available. The issuance of a warning letter can impact public trust in the brand and the brand’s reputation in the industry as well as cause extra delays and costs in bringing products to market.
• Comply with regulations. Because the pharmaceutical industry is highly regulated, compliance is critical for both patient safety and the furtherance of responsible drug supply. Quality assurance programs should therefore be robust and comprehensive, with risks identified and mitigated, Pipe says. The requirements specified in FDA’s 21 CFR Parts 210 and 211 include that pharma producers must take steps to protect against contaminants getting into products and protect against damaged or compromised products reaching the market. “X-ray technology can play a key part in helping to ensure compliance, for the reasons already listed above. In addition, modern X-ray inspection systems keep digitalized records of activity, helping producers to meet the demands of 21 CFR Part 11 (i.e., audit trails and digital signatures) (4),” Pipe adds.

Practical considerations

The advantages offered by automated visual inspection include speed, precision, and consistency. An automated system can quickly process large volumes while at the same time detecting small defects, which can be missed in a manual inspection (5).

It is important to note that automated vision inspection systems have their own limitations, namely that the system’s performance is only as good as its programming. For instance, if the system has been programmed to account for every possible variation in inspection conditions, then there is a risk that it may erroneously flag safe products as defective (6). Meanwhile, there are practical considerations that may hinder widespread implementation of automated vision inspection systems across all operational scenarios. Contract development and manufacturing organizations may encounter challenges, for example, when justifying the capital investments needed (significant capital investments) and associated validation processes for implemented automated inspection. Justifying implementation could be particularly difficult when dealing with products manufactured in small batches or products that have infrequent production cycles (7).

References

1. Grand River Aseptic Manufacturing. Finished Product Inspection: Automation, Complex Therapeutics, and Quality Standards. grandriverasepticmfg.com, March 28, 2024.
2. CFR Title 21, Part 210 (Government Printing Office, Washington, DC).
3. CFR Title 21, Part 211 (Government Printing Office, Washington, DC).
4. CFR Title 21, Part 11 (Government Printing Office, Washington, DC).
5. Marsale, T. Balancing Act: Human vs. Machine Inspection in Pharmaceutical Manufacturing. PDA Letter online, Oct. 18, 2023.
6. Yadav, V.; Kennedy, C. Vision Inspection Using Machine Learning/Artificial Intelligence. Pharmaceutical Engineering. ispe.org. November/December 2020.
7. Melchore, J. A. Sound Practices for Consistent Human Visual Inspection. AAPS PharmSciTech 2011, 12 (1), 215–221. DOI: 10.1208/s12249-010-9577-7

About the author

Feliza Mirasol is the science editor for Pharmaceutical Technology.

Article details

Pharmaceutical Technology®
Vol. 48, No. 8
August 2024
Pages: 29–30

Citation

When referring to this article, please cite it has Mirasol, F. Considerations for Finished Product Inspection Systems. Pharmaceutical Technology 2024, 48 (8), 29–30.