KEEPING TRACK OF SAFETY IN THE GLOBAL PHARMACEUTICAL MARKET
Product Inspection Challenges for Multinational Pharmaceutical Organisations
Marketing Communications Manager,
Mettler-Toledo Product Inspection, UK
The global pharmaceutical industry is booming. While North America still leads production with 41% of world pharmaceutical sales, Europe is catching up with 26.7%. According to the European Federation of Pharmaceutical Industries and Associations, the European market alone generated more than 205 billion Euros in 2011, with Italy contributing about 25 billion. The worldwide healthcare industry is further boosted by growing market and research efforts in emerging economies such as Brazil, China and India, leading to a gradual migration of economic and research activities from Europe to these fast-growing markets.
In order to sustain this growth, multinational organisations (MNOs) manufacturing pharmaceuticals have to find effective ways to tackle a number of issues, most importantly the increasing threat of counterfeit medicine, which is estimated to damage the drugs market by $75 billion a year. In addition, there is also mounting pressure for pharmaceutical companies to ensure product safety and quality. A single incident of a substandard product, or a product that is contaminated with foreign bodies, such as glass or metal fragments, could not only cause irreparable damage to a manufacturer’s reputation, it can cost lives.
To minimize this threat and ensure product safety, regulatory bodies such as the US Food and Drug Administration (FDA) and the Pharmaceutical Inspection Co-operation Scheme (PICS) are working hard to enforce common Good Manufacturing Practice (GMP) guidelines. While to date there is no single regulatory body for the global pharmaceutical industry, increasing efforts are being made to establish a comprehensive traceability network.
Globalisation has made pharmaceutical manufacturing more diverse than ever before. Companies navigating the supply chain not only have to adhere to a range of global and local GMP standards to retain access to markets, but also have to take into consideration carbon footprint reduction and price pressures on raw ingredients. Product inspection technology and traceability are therefore of critical importance to maintain competitiveness.
Navigating the Supply Chain
Pharmaceutical manufacturing supply chains are becoming more complex, with raw ingredients increasingly sourced from one part of the world, processed into a final product in a second region, before being exported to a third. This globalisation means that MNOs must comply with more and more regional regulations, particularly regarding the elimination of physical contamination from end products through the use of product inspection technology. They also must adhere to international supply chain standards and guidelines set down by individual retailers and local health authorities. The balancing act is therefore to have a global presence, while retaining the ability to act locally to meet regional safety requirements.
In order to comply with the increasingly strict regulations, any potential issues and hazards must be identified and eliminated from the outset. Manufacturers need to pinpoint the most likely forms of contamination, such as metal, glass shards or plastic through the investigation of the origin of raw ingredients, the manufacturing process, and the packaging format. Equally, they should identify the most likely points of contamination on a production line – for example, broken sieve wires – and implement inspection technologies at the point where they will be most effective, limiting the risk of foreign body contamination.
Requirements are only set to become stricter – advanced product inspection technology such as track and trace systems, precision metal detectors and x-ray inspection systems capable of identifying foreign bodies and removing rejected packs are increasingly becoming the norm. In addition, standards regarding ingredient declaration and labelling on packaging have become rigorous, leading manufacturers to invest in vision inspection systems to automate the label inspection process. In fact, the European Union Directive on Falsified Medicine, which came into force in July 2013, requires all pharmaceutical substances manufactured outside the EU, and imported into the EU, to be accompanied by a written statement from the regulatory in the exporting country. This ensures that GMP standards have been adhered to. This directive aims to facilitate traceability and protect consumers from substandard products.
In such an environment, strict control over production becomes ever-more important. Added to this, the rising costs of raw ingredients and increasing labour costs help to bring the whole area of cost efficiency under the microscope for global manufacturers. In response, they are searching for solutions, such as checkweighers or x-ray inspection systems, to monitor quality parameters such as fill-level, shape and size to reduce wasteful and potentially harmful product under- and overfill.
There are pressing economic needs behind the drive for greater manufacturing efficiency. Uptime of production lines is critical in meeting customer demands, and equipment needs to be fast, reliable, and easy to set up and changeover between jobs. Under the glare of scrutiny from multinational and regional bodies such as the US Food and Drug Administration (FDA) or Italian regulator Agenzia Italiana del Farmaco (AIFA), pharmaceutical manufacturers also need access to data to provide an audit trail, which proves that due diligence has been exercised throughout.
Meeting the Challenges
Virtually all pharmaceutical manufacturing lines have unique requirements, and so it is important to select the most suitable product inspection solutions for each individual line. Regulatory bodies worldwide are making efforts to observe, streamline and enforce GMP guidelines. To this end, they carry out product-related inspections of the manufacturers’ operations to detect any deficiencies that might be harmful to patients or don’t comply with marketing authorisation. The GMP guidelines follow a few basic principles – and central to these are the prevention of contamination, validation and records of manufacture (including distribution) to enable traceability.
Offering solutions for these tasks, advances in product inspection technology break new ground in terms of intelligence and sophistication. The latest developments in metal detection, for instance, ensure that manufacturers can now overcome the “orientation effect” – the phenomenon whereby metal fragments, such as swarf or wire, are easier to identify in one orientation relative to the metal detector search head than another. As a result, pharmaceutical metal detectors reliably reject any contaminated product in tablets, capsules and pharmaceutical powders, facilitating drug safety for consumers and preventing substandard medicines from leaving the production site. Pharmaceutical companies are well-advised to also consider x-ray inspection systems for their production lines, as the latest innovations in this field can identify contamination from foreign bodies including metal and glass fragments, high-density plastics and rubber, while also examining products for seal integrity, identifying broken components and checking fill levels.
To ensure patient safety, in 1992 the European Commission issued a directive on the labelling of medicinal products and on package leaflets. This formed the basis for the introduction of patient information leaflets (PIL), wherein all information has to be set out in a particular order and written in terms that patients can understand. In Europe, the European Medicines Agency (EMA) is responsible for the protection and promotion of public health, through the evaluation of medicines including coordinating inspections within pharmaceutical production facilities. As such, this can include GMP inspections. To comply with these requirements, manufacturers can integrate checkweighing or x-ray technology to detect if a PIL is missing and/or vision inspection technology to ensure that the information label is intact and contains the correct patient information needed.
The installation of a product inspection machine does not automatically guarantee compliance with GMP guidelines. The equipment must be maintained correctly to ensure that it continues to perform with optimum performance and detection sensitivity. Manufacturers should also test inspection systems regularly using certified test samples and weights. In the unlikely event of a failed test, all products manufactured since the last successful test should be quarantined for re-inspection. A good equipment partner can assist MNOs with all of these necessities, carrying out such line audits and providing comprehensive documentation systems that demonstrate due diligence and transparency.
With the reduction of production costs in mind, while also aiming to ensure product quality and safety, pharmaceutical manufacturers are looking to harmonize their processing systems by sourcing product inspection equipment from a single supplier. Innovative software then allows them to connect the product inspection technology used on various manufacturing lines to a single data collection network. Thus, pharmaceutical companies can better monitor their performance records and achieve greater control over their products’ quality by providing a full audit trail consequently supporting them to demonstrate due diligence. Storing all data in one central location facilitates tracking of product batches and, in the event of a product recall, streamlines the identification of problem batches and corrective procedures.
Growth in the Global Market
Multinational pharmaceutical manufacturers face stiff challenges in respect of the weight of global awareness of drugs safety. Their production practices are strictly observed by national and international agencies as never before. Operating worldwide and managing complex supply chains, MNOs must ensure compliance with standards relevant in each region they are working in and increasingly bring their entire production in line with evolving global guidelines.
The development of a single internationally-recognised safety standard for manufacturers is a long way off, but harmonisation of international regulations through schemes such as PICS will facilitate the expansion of the industry worldwide, while protecting the consumer. In addition, there is a growing trend towards knowledge sharing through observing and conducting joint inspections as well as participating in discussions to bring global pharmaceutical manufacturing and regulations closer together.
While GMP guidelines are not prescriptive instructions on how to manufacture products, they are a series of general principles that must be observed during manufacturing. There are many ways GMP requirements can be fulfilled and it is the company’s responsibility to determine the most effective and efficient process to achieve this. By working in partnership with product inspection equipment suppliers that have global experience and local account handling expertise, MNOs can be confident they can successfully manage this task. These close relationships with suppliers can help pharmaceutical manufacturers safeguard consumer wellbeing, protect their brand and grow their business.
Neil Giles is Marketing Communications Manager at the Mettler-Toledo Product Inspection Division of Mettler-Toledo, based in the UK. He currently specialises across all four main product inspection technologies, which are x-ray, metal detection, vision inspection, and checkweighing. A member of the Chartered Institute of Marketing, he has over 20 years of experience in the food and pharmaceutical industries and has extensive knowledge of equipment for the packaging, process weighing and inspection sectors.