Moving to stricter supplier controls
January 13, 2011
In the past five years, several contaminated products have led to patient and end-user injuries and deaths globally. In 2007, there was diethylene-glycol contaminated toothpaste, and millions of toys were recalled due to lead contamination. In 2008, contaminated heparin was recalled by the US FDA, and melamine-contaminated milk caused thousands of adverse events and several infant deaths. In 2009, peanut-flavoured foods containing contaminated peanut butter products made several people sick.
Investigations into the causes of these adverse events found that, among other reasons, inadequate or poor supplier controls were a factor. US FDA observations and warning letters for medical device manufacturers increased from 19 in 2006 to 25 in 2007 and 35 in 2008.1
These incidents have triggered US and European regulatory bodies to increase their vigilance on supplier controls for the pharmaceutical and medical device industries. In December 2008, the Global Harmonization Task Force issued a guidance document that outlines the steps medical device manufacturers should include in their supplier control process.<sup>2</sup> A second document issued in November 2009 (in draft form) describes the techniques for inspecting a medical device manufacturer’s supplier controls.<sup>3</sup> At an AdvaMed Conference in 2009, Kim Trautman from the US FDA said: ‘Supplier control is a much bigger issue now than it was in 2007. Even though issues with toothpaste and nuts are not directly in the device sector, these events still greatly affect FDA thinking and controls. The emphasis on the linkage between supplier control and risk management will continue to increase.’
The level and extent of controls should be based on the criticality and risk of the products or services that could affect the safety, effectiveness and quality of the final product. It is the responsibility of the manufacturers of the finished product or device to determine and communicate those requirements to their suppliers. The benefits of good supplier controls translates to effective quality management systems and risk management processes, high quality and consistent products, lower scrap, improved productivity, and fewer adverse events, complaints and recalls.
more rigorous controls
Component, part and material suppliers to pharmaceutical and medical device manufacturers must be prepared to expect much more rigour and control from their customers. The level and extent of controls on suppliers will not only depend on the criticality and risk of the product they supply, but also on their position in the supply chain. Tier 1 suppliers will see more controls than Tier 2 and Tier 3 suppliers (Figure 1). Wherever material suppliers fall in the value chain, they must still ensure that their products meet all the performance and regulatory requirements needed for the specific application.
Many companies in the supply chain do not fully understand where risks and changes to their products can come from. In some cases, they see the pharmaceutical and medical device market as high risk and of low business interest. A few suppliers have developed a dedicated approach to supplying their products and services to this market. Clariant and LyondellBasell work closely with each part of their supply chains to mitigate risks posed not only to themselves and their direct customers, but ultimately to the pharmaceutical and medical device companies.
Clariant is a supplier of masterbatches and compounds, and LyondellBasell is a supplier of polyolefin resins to a diverse industrial base including the healthcare industry. Each company has served the industry for decades, and has adopted similar approaches to ensure that their business processes and healthcare products are well positioned to meet the challenges associated with more stringent controls.
The pharmaceutical and medical device industries continue to use plastics with high-performance properties and aesthetics in ever-increasing amounts. These materials must meet specific properties such as sterilisation resistance, chemical and lipid resistance, and biocompatibility. Slight differences in impurities, extractables or leachables could potentially affect the biocompatibility and toxicity of the final formulated product.
The United States Pharmacopoeia (USP) and the European Pharmacopoeia (Eur.Ph) require detailed information on the material components and formulation, manufacturing processes, and extensive supporting data with respect to physical and mechanical properties, chemical resistance, biocompatibility and toxicity tests. The results must be maintained in specific files, or the material must meet required properties set in standards.<sup>5,6</sup> The advantage of this system is that manufacturers of finished products could use these materials in their designs and products with the confidence that they would meet regulatory and application requirements.
The disadvantage, however, is that this file or record is a point-of-time submission and is material-specific and formulation-specific. Managing any material or formulation change over time is, thus, not easy and becomes a formidable task both from regulatory and business perspectives.
To meet the ever changing requirements and needs of their customers, Clariant and LyondellBasell have implemented strategic business processes that involve working with them (developers and manufacturers of healthcare products, converters and processors, trade associations etc.) and their suppliers (resins, pigments, additives, catalysts etc.) to manage, control and mitigate the risks associated with the products they supply
Clariant is an international and publicly traded speciality chemical company headquartered in Switzerland. Several business units (BU) supply the pharmaceutical and medical device industry with products such as intermediates, excipients and masterbatches. BU Masterbatches is a leading player in colour and additive concentrates and compounds for the plastics processing industry across diverse applications.
The company’s focused strategy to the healthcare industry includes a risk-based approach that aims for controlled, consistent, and compliant products. The business unit is concentrating the know-how at three dedicated centres of competence across the globe with the possibility of offering complete manufacturing line-segregation capabilities for medical grade materials.
These centres have a global quality management system that is based on current good manufacturing practices and uses the ISO 13485 standard for medical devices. External certification has been completed at all three sites, with the final site later in 2010. Processes and procedures instituted for medical products include fully traceable production lots, an “open to audit” policy (a policy that encourages both direct customers and the brand owner to carry out audits) and rigorous change control processes.
The result has been the introduction of two new internal classifications of manufacturing for products used in medical and pharmaceutical applications referred to as MedCat 1 and MedCat 2 and the introduction of a new brand to distinguish products and services from the conventional products. The levels of controls with respect to material change notification, process controls, risk management, quality management systems and documentation, are different from the processes used in standard compound and masterbatch production sites
LyondellBasell is a large polyolefin supplier. Purell is a brand of polypropylene and polyethylene developed for use in the healthcare industry. The value of Purell products includes consistency of formulation, continuity of supply, single sourcing, back-up plants and pharmacopoeia compliance. LyondellBasell was the first polyolefin company to launch a dedicated group of products used in healthcare applications, with dedicated internal quality systems and procedures that exemplify the spirit of pharmaceutical and medical device good manufacturing practices. Risk management procedures are an integral part of this process.
Clariant and LyondellBasell work co-operatively to educate medical and pharmaceutical suppliers. They are building awareness of the importance and significance of change controls as they are applied to polymers, masterbatches and compounds. Using risk management to control products used in the healthcare industry is also part of their strategy.
Both companies recognise that risk increases with the complexity of the supply chain, and have developed strategies to mitigate such risks and manage raw material changes, consistency and quality.
Clariant has been working with its suppliers to provide pigments and additives with consistent quality and purity. The less the variation in these chemicals, the better the confidence that the masterbatches will not change their biocompatibility and toxicity properties from lot to lot or batch to batch.
Stephen Duckworth, head of Clariant’s Global Market Segment Consumer Goods and Medical and Pharmaceutical, says: ‘In 2008 we made a conscious decision to remain in, and invest in, this segment, after carrying out independent studies to ask the medical device and pharmaceutical industry what they needed. It required a detailed understanding of the market, including where the risk of change comes from, in an industry where it is very routine to change raw materials and suppliers. To get where we are today needed a change in the culture, processes standardisation across three sites, and the training of our global team. We realised what we needed to do was not possible across our 50 plus masterbatch sites globally. We realised this market is different. Now customers tell us that our approach is contributing to a new level of security. However, we clearly recognise that if we look at the overall supply chain, including our suppliers, there is still more work to do.’
The macroscopic properties of polymers and resins such as viscosity, flow, and physical and mechanical characteristics are well understood, and can be controlled and measured. These physical properties are used in the evaluation and selection of materials used by customers in healthcare applications. Certificates of analysis (CoA) and quality metrics are also based on these macroscopic properties.
LyondellBasell recognises that properties specific and critical for healthcare applications such as leachables and extractables, biocompatibility and toxicity are highly dependent on the resin’s microscopic properties such as impurities, molecular weight distribution and low molecular weight oligomers.
‘Since 2002, LyondellBasell has been developing and marketing products used by customers in the healthcare industry,’ says Jochen Schneider, head of Healthcare Applications and Closure Systems at LyondellBasell. ‘We’ve strengthened our quality standards and have developed a better understanding of how to effectively address the needs of the industry. The information has been distilled and defined in our medical policy – a policy that controls product consistency, quality and availability. This policy is a living concept; it is regularly modified to address growing customer needs, industry standards and requirements established by pharmaceutical GMP. This policy is reflected in our Purell brand and products, enabling our customers to meet their regulatory and application requirements.
‘In addition, we work with customers to understand how our resins are used in healthcare applications by conducting a risk assessment of applications. Based on this data, we can make informed decisions about whether to supply resins for these applications. The risk assessment is based upon the risk classification of the EMEA and the Medical Device Directive (MDD). This partnership is beneficial to both LyondellBasell and its customers in mitigating risks both in the supply chain and ultimately for the end-user.’
Supplier controls are becoming a very important aspect of the quality systems for drug manufacturers. Inspections by regulatory bodies will be placing an increased emphasis on purchasing controls to ensure that these manufacturers exert the appropriate extent and level of controls on their suppliers based on product risk and criticality. Clariant and LyondellBasell have taken a proactive approach to building awareness among their suppliers of the importance of mitigating risk, minimising change and maintaining compliance and consistency of their products supplied to the healthcare industry. In so doing, Clariant and LyondellBasell are well-positioned to serve customers who require preferred suppliers that have understood and implemented risk-based quality systems for the healthcare industry.
- E.C. Wilson Jr, M.S. Heyl, Journal of Medical Device Regulation 2009 6(2), 24 – 39
- Quality Management System – Medical Devices – Guidance on the Control of Products and Services Obtained from Suppliers, GHTF Inspection – Supplier Controls, Dec. 11, 2008
- Guidelines for Regulatory Auditing of Quality Management Systems of Medical Device Manufacturers Part 5: Audits of manufacturer control of suppliers” Nov. 13, 2009
- M.Miller, Medical Product Outsourcing Magazine July/August 2009, 22 – 24
- ISO 10993 Biological Evaluation of Medical Devices
- USP Class VI as defined in United States Pharmacopeia XXII, Part 88
Read the original article published at www.manufacturingchemist.com