There’s a great deal at stake for pharmaceutical manufacturers and CMOs when filling expensive liquid pharmaceuticals into vials. Errors during the fill-finish process can cause costly product loss. Visual inline inspection technology counteracts this scenario. Integrated cameras and sensors monitor and document every step of the process – from empty vial inspection to print verification of filled vials.
Reliability is key in fill-finish processes. It not only involves manufacturing high-value products according to the highest quality standards, but also doing it economically. The production of liquid pharmaceuticals, including highly specialized biotech drugs for small and very small patient groups, is a cost-intensive task. Pharmaceutical manufacturers must reduce product loss to a minimum. Visual inline inspection technology, which is directly integrated into the production process, plays an important role in helping manufacturers proactively reduce rejects.
Increased quality thanks to proactive inline inspection
According to GMP Annex 1, pharmaceutical manufacturers and contract manufacturing organizations (CMOs) must subject filled vials to a stopper seat verification before crimping. The goal is to prevent microbiological contamination and to ensure product quality. Many manufacturers add further inline inspection steps to this mandatory procedure. They enable them to intervene in the capping process at an early stage, if necessary. This precaution makes perfect sense: once the drug has been filled into the container, the vials can only be sorted out at the end of the manufacturing process – even if the inspection systems identify them as faulty beforehand. This might lead to financial losses and a waste of resources. Moreover, CMOs and pharmaceutical manufacturers can no longer determine which processing step caused the defect.
Inline inspection technologies check empty vials, the stopper’s seat, crimp quality, cap roundness, and pressure, and continuously monitor the quality of both the filling process and the packaging materials. They also detect deviations from defined standards and provide data for subsequent process optimization. The centerpiece of these systems consists of special cameras or optical sensors and precisely matching lighting.
First step: empty vial inspection
A central lever for reducing product loss can be found right at the beginning of the process when cameras check the integrity of the empty containers before filling them. They inspect the opening, base, and side walls of the vials for foreign bodies such as glass fragments or impurities to rule out contamination. They also examine the integrity of the vial itself, which should not show any chipping or cosmetic defects such as scratches or cracks. Defective vials are marked as faulty and are rejected. This inspection step before filling plays an important role, especially for lyophilized drugs, since foreign bodies such as splinters or impurities in the product are much more difficult to identify after freeze-drying.
zInspecting sealed vials
Good vials are filled and fitted with a stopper in the next process step. Visual inspection systems then check the stopper presence and positioning, i.e. whether the stoppers are positioned at an angle inside the vial or are missing altogether. According to GMP Annex 1, the stopper gap must not exceed one millimeter at an output of 30,000 containers per hour and a transport speed of about 40 meters per minute. A larger gap indicates that the stopper has not been placed correctly; the vial is thus considered unsealed and is rejected.
In the next step, cameras thoroughly check the crimping process. They take images of the containers to detect cosmetic defects or crimping errors, as well as missing or uncrimped caps. Even before the caps are applied to the vial, faulty caps can be sorted out thanks to integrity checks. Subsequent rejection, for example, due to deformation or incorrect color, should be prevented, even more so in the case of high-priced drugs.
Visual inspection systems can also be used for print verification of the container, cap, or label. If required, they perform a presence and quality check of the coding number. This data allows manufacturers to draw conclusions about the drug itself, the manufacturing company, and the batch number and serves to improve traceability.
Data is the key to better quality
Inline inspection has many more advantages. In case of process discrepancies, it allows manufacturers to perform effective, data-supported troubleshooting. The second the system identifies a process error, it documents the corresponding time window, batch number, and production parameters. Operators can use this inspection data stored in the HMI to determine where the error occurred during the fill-finish process. They can also rectify errors quickly, knowing whether it was a single incident or a chain of irregularities. This not only ensures significantly lower downtimes and less product loss; it also makes a decisive contribution to increasing the overall equipment effectiveness (OEE) and profitability of production.
In addition, data-based inline inspection supports the required consistent documentation, especially for GMP-relevant interventions. If, for example, a glove intervention is mandatory in the sterile process, operators can document this via digital images. In the event of legal claims, this documentation can prevent pharmaceutical companies from completely discarding affected batches. The data enables the creation of digital protocols that document the complete audit trail of production. This evidence is a crucial prerequisite to validate the filling line and to receive market approval for the filled drug.
Inline and end-of-line: it’s the combination that counts
Experienced partners such as Syntegon have been supporting pharmaceutical manufacturers in finding application-specific solutions for many years – for both existing and new filling lines. The new development Versynta microBatch is a good example: the flexible platform for very small batches inspects the entire filling process via cameras and coordinates packaging supply and processing. Defective containers are already sorted out during the filling process.
In addition, Syntegon also offers mandatory end-of-line inspection equipment. Innovative and high-precision technologies identify cosmetic and attributive defects as well as visible particles in liquids, lyophilized solutions, or powders in syringes, vials, cartridges, or ampoules. Thanks to many years of inspection experience, the broad portfolio includes state-of-the-art visual inspection technologies for fully automated processes as well as semi-automated and manual solutions. With a sophisticated combination of inline and end-of-line inspection solutions, pharmaceutical manufacturers are approaching zero-defect production, which minimizes product loss of costly drugs and ensures maximum product safety.
Author: Daniel Sturm, Global Product Manager Inline-Inspection, Syntegon Technology, [email protected]
This article was published in Packaging South Asia’s April 2023 issue.