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Because of the nature of these types of products, which may be applied to or ingested by humans, the purity of ingredients used in their production is critical. A case of product contamination or mix-up could have serious consequences. This has led to the introduction of increasingly stringent measures to safeguard the integrity of production processes and supply chains in these industry sectors.

GMP (Good Manufacturing Practice) guidelines have been developed in order to guarantee the quality of finished pharmaceutical as well as both the active and non-active chemicals used in their manufacture (see 'What is GMP?' section below). GMP compliance has been a legal requirement in Europe since 2005 for active ingredients and although not yet mandatory for non-active ingredients (excipients) this is expected to change in future.

'We expect to see GMP compliance eventually extended to chemicals in a wide range of pharmaceutical applications, as well in the production of food and cosmetics,' explains Sigrid Verstegen, regional IPA Product Manager. 'As we are among the world's largest IPA producers we wanted to demonstrate leadership in developing this capability in Europe.

'This is both a response to the growth of interest in GMP-compliant material we have seen from customers and our own desire to continually raise the quality of products we are able to offer.'

IPA is a versatile, cost effective solvent that can be used in the preparation of a number of pharmaceutical products such as medicinal tablets and also disinfectants, sterilisers and skin creams. GMP regulations require the implementation of a quality control system that covers the manufacturing, storage, supply and distribution of product destined for these applications.

'By implementing GMP you are effectively creating a closed production system in which the purity of the product can be controlled and traced from the intake of the feedstocks to the point of delivery to the customer,' says Ilse Dullens, a solvent specialist from Shell Global Solutions who helped with the introduction of IPA-GMP¹ production at Pernis in The Netherlands.

'The main emphasis of these measures is to ensure the integrity of IPA by preventing it from coming into contact with contaminants such as other chemicals, cleaning agents, dust and moisture. You have to demonstrate that you have taken the necessary measures to ensure the product has been handled properly throughout the supply chain and that you have the necessary tests and documentation in place to track that.'

The first customer to trial the IPA-GMP¹ from Pernis was Hedinger of Stuttgart, Germany, a specialist chemical distributor serving the European pharmaceutical industry.

Frank Milek, Hedinger's Head of Quality Assurance, Quality Control and GMP, says: 'Pharmaceutical producers have very specific needs in terms of quality, purity and certification and we act as a link between their requirements and the production processes commonly used in the chemical industry.

New standards

'GMP compliance is an opportunity to set new standards in the European excipients market and may increasingly become a differentiator for suppliers to the European pharmaceutical industry.'

Milek is chairman of the GDP (Good Distribution Practice) Committee of IPEC, the International Pharmaceutical Excipients Council Europe, which serves the interests of producers, distributors and users of pharmaceutical excipients.

He says that because pharmaceutical producers are subject to a range of mandatory pharmacopoeia standards, they place a lot of emphasis on supply chain and distribution standards.

'Anything that contributes to a higher degree of safety in their supply chains is regarded as proactive risk management. As a result, GMP compliance is becoming a key element of supplier qualification programmes.'

One of the challenges of implementing GMP compliance at Pernis was defining exactly what measures had to be in place to achieve the required quality standards. 'Because they cover food and cosmetics as well as pharmaceutical they are a very broad set of guidelines, and even within the pharmaceutical sector there are different levels of compliance,' says Dullens.

'As IPA is rarely used as an active ingredient, and based on customer interest, we focused our efforts on meeting the excipient level requirements.'

Physical measures introduced at Pernis include the use of a dedicated storage tank and pipelines for the IPA-GMP¹ grade to help to eliminate the risk of contamination from other products or grades, and special loading and transport procedures. Road tankers used to deliver the product are also dedicated to IPA-GMP¹ so there is no potential for product mix-ups and no need for cleaning between deliveries, which further reduces risk of contamination.

Product analysis

Additional product analysis procedures have also been put in place in the onsite analytical laboratory at Pernis. 'Samples are taken from every production batch of IPA-GMP¹ to check for traces of undesirable components,' explains Arjen Koppert, Solvents Quality Assurance Manager for Europe and Africa.

'Test results are checked against the GMP specifications and results have to be validated by a second person before product is released for sale,' he says. The extensive quality data is included in additional documentation that can be provided with each delivery while the product's GMP status is also identified on the certificate of analysis.

To maintain the integrity and traceability of IPA-GMP¹, similar measures also have to be in place while the product is en route to and at the customer's premises. 'We have to establish robust relationships with both contract hauliers and customers. The system has to provide assurance that no contamination can take place while road tankers are on the way to the customer.'

The implementation of GMP has required a major competency and training programme for plant, laboratory, sales and customer service staff, as well hauliers. Similar training will be provided to customers to ensure they fully understand the GMP requirements and have the appropriate measures for product reception in place.

The GMP implementation at Pernis is part of a developing global capability. Coen Wilms, Business Manager Solvents Europe, Africa and Middle East, says: 'GMP compliance is already in place for Shell IPA from plants in Canada and the US, and the measures put in place at Pernis means Shell companies are the first producers in Europe currently offering this. The introduction of the IPA-GMP¹ grade provides our customers in Europe with the assurance of product quality they require and is in line with our global leadership in Solvents and the principles of Responsible Care that we adhere to.'

What is GMP?

Good Manufacturing Practice (GMP) regulations were initially developed by the US Food and Drug Administration and require manufacturers, processors, and packagers of pharmaceutical, medical devices and some foodstuffs to take proactive steps to ensure that their products are safe, pure, and effective.

GMP is a system for ensuring that raw materials and finished products are consistently produced and controlled according to quality standards. The system requires detailed procedures for each process that could affect the quality of a finished product, and documented proof that correct procedures have been followed.

This ensures that products are consistently produced and to the quality standard appropriate to their intended use. This in turn protects the consumer from purchasing a product that may be ineffective or even dangerous.

¹meets excipient level of GMP

IPA-GMP web content
Pernis manufacturing facility profile

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