The recent recall of some products due to metal contamination has caused concern among consumers and pharmaceutical manufacturers alike about the safety of the products. And this is also a pointer to the fact that the problem of metal contamination in pharmaceutical products should be addressed before a product goes to market to prevent warning letters and recalls.
The pharmaceutical giant Johnson & Johnson Inc voluntarily recalled their popular drug Rolaids, brand of antacid when they discovered specks of both wood as well as metal inside the drug. The recall consisted of 13 million parcels of the said product. Johnson & Johnson-Merck Consumer Pharmaceuticals Company (JJMCP) voluntarily recalled approximately 12,000 units of Infants' Mylicon(R) Gas Relief Dye Free Drops (simethicone-antigas) non-staining due to possible metal fragments. Though small in size, repeated ingestion of metal-contaminated pharmaceuticals can lead to adverse health effects ranging form slight stomach pain to metal poisoning.
The most common source of metal contamination is processing equipment but it can also originate form contaminated raw materials. Currently available detectors not only detect minute contamination but also can locate contaminants in products packaged in foil or metal film.
A number of detection techniques are available in the market though pharmaceutical manufacturers have not yet mastered the art of tackling the metal contamination problem completely. Clearly there is some element of negligence. “Good metal detection is fairly easy to achieve” says Bill Leonard, engineering manager at contract manufacturer and packager Pharma Tech Industries (Royston, Georgia). But sometimes it can be cost prohibitive; requiring additional capital or you can be tight on space to fit an extra piece of equipment in. In addition Leonard says, that some companies may receive certification from supplier that materials are metal-free and thus assume that packaged product is metal-free as well.
Metal contaminants are classified as ferrous (magnetic), nonferrous (highly conductive non-magnetic metals such as copper, aluminium, and brass), and non-magnetic stainless steel. Ferrous contaminants are the easiest to detect and 300 series stainless steel contaminants (such as those commonly used in pharmaceutical processing and packaging machinery) are the most difficult to locate because the material is not particularly conductive or magnetic.
Detecting and measuring metal elements in pharmaceutical products is an important consideration in finished-product pharmaceutical manufacturing. The FDA insists that contamination problems are fully investigated in a time- bound manner. The problem of metal contamination can be minimized through the use of metal detectors at critical points in the pharmaceutical manufacturing and packaging process. The pharmaceutical industry has used metal-detection systems for more than a decade to detect metallic contaminants and the systems are evolving to offer improved performance and ease of use.
Several metal detectors are on the market specifically for the examination of pharmaceutical products, e.g. tablets, capsules, powders etc. These detectors typically are positioned to check product either pre- or post filling, but sometimes a unit is installed to inspect the product before filling and another unit is used to double check filled containers. In some cases, metal detectors may be integrated with check-weighers to provide another quality control function.
A metal detector features an aperture or tunnel through which the product passes and a user interface–control system, which generally is housed separately but may be integrated in some models. Typical designs configure the unit around a conveyor or a pipe carrying a product or ingredient. The aperture is sealed to protect the components inside and is lined with a non-metallic material.
Within the aperture, a transmitter coil emits a radio frequency signal and generates an electromagnetic field. Receiver coils on either side of the unit detect disturbances in the field caused by magnetic or electrically conductive material. This configuration often is described as a “balanced coil” system. The size, shape, and orientation of the particle and type of material determine the strength of the signal. New technology with inclusion of multicoil in metal detectors to get better signal as compared with a single transmitter with two receivers, multicoil arrangements can improve detection performance of the instrument by up to 20 per cent.
There are a number of criteria which has to be taken into account while selecting and evaluating metal-detection systems for pharmaceuticals. However the most important criteria is the sensitivity and susceptibility to external influences such as vibration and electromagnetic noise, which can cause false rejects. When selecting the size of the system's aperture, one should consider performance as well as throughput and size to avoid product jams during production.
Metal detectors designed to be integrated with tablet presses and dedusters are built to the strict hygiene standards of the pharmaceutical industry. These designs can detect very small particles of metal, including stainless steel–sieve wire and metal flakes from the punch and die sets of tablet presses.
Metal detectors can easily detect and identify spherical particles while wire-shaped contaminants can be difficult to detect because the signal varies depending on the orientation of the metal piece. Many units today can detect contaminants as small as one mm. Detection becomes complicated when the product creates a magnetic or conductive signal for which the unit must compensate. As a result, products typically are classified as dry (nonconductive) or wet (conductive) and units are designed for automatic calibration, which is sometimes called phasing, to differentiate between signals generated by the product and any contaminants. Wet products are more challenging to scan than dry products.
Currently available metal detectors utilize latest digital signal processing technology to detect and reject ferrous and non-ferrous metals, including stainless steel. Latest pharmaceutical detectors have advantages like highest processing power, superior speed, accuracy and ease-of-use with additional features like current GMP design and construction suited for FDA compliance and meet the demanding quality standards and regulations required by the industry. It detects the tiniest of metal contaminants in high speed product lines with a throughput of 10,000-30,000 tablets per minute.
Further, integrated software enables metal detectors to meet 21 CFR Part 11 requirements and provides full batch traceability. The software may include security access controls, user identification, and audit trails. The data can be accessed by a remote personal computer (PC) or a PC panel integrated into the metal detector itself. The latter replaces the standard operator interface so that 21 CFR Part 11 compliance, tests, diagnostics and equipment set-up and operation are handled from one location. The remote PC configuration accommodates operations with multiple metal detectors.
Although the installation of a metal detector is a well-established method to identify and reject metal contamination, it is not the only way to accomplish quality control. X-ray technology offers to detect metal with its ability to multitask like to check product count, product size, product mass, container fill level, product–package condition, and package insert presence. Some metal detector suppliers, like Mettler Toledo, Safeline, Eriez, Thermo Fisher Scientific and others offer this type of equipment also, with variety of shapes and sizes for various applications and from hand-held to cabinets for larger packages, but the installation cost and maintenance expenses are greater as compared to conventional metal detector.
Foreign-metal-object detection systems can help to prevent product contamination. Selecting a system requires a trial-and-error approach that takes into consideration the system's sensitivity, ease of use, and audit ability. Once implemented on a production scale, a metal-detection system can help to maximize product volume and quality. Since the natural wear and tear of the equipment cannot be prevented, pharmaceutical manufacturers must continue to diligently monitor not only quality of product but also the condition of manufacturing machineries which will surely help to prevent metal contaminated pharmaceuticals from reaching store shelves and the consumers.
- Dr. Rashmin B. Patel is Asst. Prof.A.R. College of Pharmacy & G. H. Patel Institute of Pharmacy,Vallabh Vidyanagar. Mrunali R. Patel is Asst. Prof.,Indukaka Ipcowala College of Pharmacy, New Vallabh Vidyanagar and Dr. (Prof). B. G. Patel is Director, ISTAR,Vallabh Vidyanagar