Staying ahead of the game

Increasingly, contract manufacturers are assuming a vital quality assurance role throughout the product life cycle. Continuous updating is the way to make sure equipment and technology are up to the job, says Edward Prady

Changing customer demands have precipitated a major shift in the provision of quality services by contract manufacturers. One of the key drivers is the need for a "one stop shop" service provider. 'Typically, customers are demanding a complete, comprehensive service. In fact, the term customer is out, we're partners now,' says Edward Prady, head of quality for Ashton under Lyne-based Celltech Manufacturing Services.

Manufacturing product as a partner differs significantly from the outmoded customer/supplier relationship. Although the quality that is built into the product is the same operationally, the way of working alongside the customer has changed. Rather than the traditional method of leaving feedback to the annual audit, Celltech Manufacturing Services now operates a system that incorporates regular review meetings and updates, including quality plans and metrics that clearly display the company's effectiveness.

There are drawbacks to this new 'glasnost' in the system, though. Previously, good practice meant that customers were not necessarily bothered with every blip in the process, provided the contract manufacturer adhered to GMP, remained within the licence parameters and did not compromise compliance in any way. Now, the intimacy of the relationship means that every issue is examined. 'It's not always a time-efficient process, but it does mean there are no skeletons in the locker or surprises in store,' Prady emphasises.

Increasingly, contract manufacturing service suppliers have to take responsibility for all areas of a product's life cycle. The quality role may now include both pre- and post- manufacture activities, such as artwork, analytical validation and stability testing.

In some instances, particularly for those companies with an FDA slant, this stretches to include areas such as annual product quality reviews covering complaints, deviations and statistical analysis.

At Celltech, the flexibility required to produce such a comprehensive service has resulted in a sustained investment programme over the last 12 months, upgrading and re-equipping various areas of its quality control function, including stability testing and the special projects laboratory. To ensure that working practices, techniques and instrumentation are the same across the whole site, one main supplier was chosen for all the equipment. An additional benefit is that there is often an excellent synergy with customers' own in-house resources.

working environment

The ongoing £100,000 (US$147,000) laboratory upgrade places great emphasis on the impact an efficient working environment has on the fundamentals of staff productivity. The new laboratories include new work areas, benches, storage areas and lighting. 'There's no point in investing in the right people and training them to the highest standards if you then give them a working environment which effectively works against them,' Prady says. Since the first laboratory came on stream, he believes there has been a marked improvement in performance.

Celltech Group, which acquired the site as part of the merger with Medeva in 2000, has maintained a five-year rolling programme of investment that now exceeds £10m (US$15m). The spend has included a new stability studies facility, within the special projects department. In-house stability testing cuts out the method transfer requirement and the attendant risk. 'It's one less supplier a customer has to regularly audit,' says Prady.

'Stability testing is performed to the International Conference on Harmonisation (ICH) standards requiring analysis at a frequency of one to four times a year,' Prady explains. 'By comparison, batch analysis is much more regular, therefore stability testing is not an unknown quantity to our analysts.'

customer requirements

Stability studies requirements in terms of marketing authorisation variations have also been tightened up in recent years. From an ad-hoc, unstructured approach, conditions are now far more formalised and more detailed guidance is available.

On-site stability testing is becoming more important to customers as it provides the necessary back-up to product licence applications and variations. Celltech's current capabilities include 25°C, 60% RH, and 30°C, 60% RH for standard storage conditions, 40°C, 75% RH for accelerated and 25°C, 60% RH specifically for controlled drugs.

Together with many in the industry, Prady believes that the regulatory authorities will become more didactic and the only way to remain compliant is to ensure that investment is continuously one step ahead of the requirements. 'The industry is being forced by health and safety and regulatory authorities to take on more and more responsibility, with new initiatives and regulations being introduced all the time,' he says.

'Technology and equipment have to be bang up to date. Couple this with customers' requirements broadening out right across the production process and those service providers not offering a comprehensive, confident service will drop further and further behind.'

All the new equipment incorporates continuous monitoring, enabling the functioning of the incubators to be monitored 24 hours a day. Prady believes this is now essential in terms of current GMP and customer expectations.

'The industry standard has moved from mechanical monitoring morning and afternoon, through hourly to continuous monitoring,' he states.

'We are now in the business of predicting the future. We try and give our customers what they want before they realise they need it, and make even greater demands on ourselves than the authorities place upon us. This is what it takes to stay ahead in the game.'

e-Calibration includes FDA site

e-Calibration.com, a web-site dedicated to gathering the latest information about changes in calibration regulations has added Calibration and the FDA" to its site. These pages are designed to provide FDA information, including web-links, regulations, standards and electronic signatures. There are pages where the user can read about actual real life scenarios about non-compliance, and how to remedy them. The site can be found at www.e-Calibration.com

Invitrogen weighs up POMS and Mettler Toledo balances

Biotechnology specialist Invitrogen, of Paisley in Scotland, has installed a Honeywell POMS computerised weighing system. Integral to this are precision balances from Mettler Toledeo, which were chosen for their ability to interface with the complex software system. Invitrogen manufactures and markets a range of products for life science discovery, development and production. These include robots that synthesise lengths of DNA to order and genetic engineering tools. Marketing director Jim Greaves explains: Our weighing system demands balances that are extremely accurate and reliable and they must have excellent interface capabilities." There are four booths in the company's dispensary capable of weighing out orders, and two balances from Mettler Toledo are installed in each, connected to the computerised weigh system. As the work order is selected, the system shows all the chemicals required. The operator selects each chemical to be weighed and its barcode is scanned to confirm that it is correct. The system prompts the operator throughout the weighing process and allows the weighing to be completed only when the weight is within acceptable tolerance. T +44 116 235 7070
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