Christa Hartmann, Director, Corporate Quality, Genentech Inc., USA, argues for a holistic approach

Whenever we carry out audits of sterile products manufacturers we invariably ask questions regarding approaches to steam sterilisation, which leads inexorably to discussions on steam quality.

If you are not yet aware of what is keeping key pharmaceutical industry personnel and regulators awake at night, then read this article by our Neil Wilkinson!

Not so long ago, a microbiologist working for a producer of non-sterile medicines had a relatively easy life – a few total viable counts on some incoming materials here, an occasional test on the water system there – all very relaxed and low key.

The ICH Q10 Guideline ‘Pharmaceutical Quality System’ was signed off as a Step 4 document at the ICH meeting in Portland, Oregon, in June 2008.

Ten years ago, there was a general belief in the global pharmaceutical industry that US GMPs were the most stringent in the world and, thus, if you could satisfy FDA expectations, you could satisfy anyone. At that time most major companies focused their efforts on achieving strict compliance with FDA expectations to avoid the strict penalties seen for non-compliance.

Every year, the pharmaceutical industry wastes huge sums of money as a result of mistakes in the workplace – so-called ”human error.” Human error is often cited as the cause of product recalls, customer complaints, batch rejects, deviations and adverse audit findings. In most cases, however, human error is not the root cause, just a convenient excuse. The good news is that such costly and risky mistakes can be prevented if you follow some very simple and practical rules.

There are many examples of differences in detail between EU and US GMP expectations, but one of the biggest and most important concerns air removal in steam sterilisation. Why is it that some EU regulatory agencies regard this as such a big issue, whilst others fail to see the importance?

A carpenter friend once offered some very sound advice. “Martin, always remember to measure twice and cut once”. Roughly translated this means make sure you have accurate and reliable performance data before making important decisions!With your company facing a level of unparalleled change, the drive to improve every aspect of your business will be unrelenting. The need for making the right decisions at the right time has never been more important.

Increasingly, we are being encouraged by consultants and regulators to identify environmental isolates beyond the genus level and down to the species level. This involves additional time, resource and expense – and to what end?What additional value does speciation provide to us, to the patient or indeed to the regulators?

Risk is a familiar concept. We take risks all the time. Even the act of driving to work carries some risk. It is important to understand that in life no activity can ever be totally risk free. Some individuals want to experience high risk (exhilaration?) so they take up pastimes such as rock-climbing, free fall parachuting, or even bungee jumping. Whatever we do we are constantly assessing the risks associated with our activity and controlling them. If we deem them too high we take risk reduction measures to reduce the overall risk. For example, in free-fall parachuting we carry an emergency ‘chute just in case the main one fails to open. So none of us are strangers to the process of risk management, we have done it from an early age and before that our parents did it for us. If we did not behave in this way, our lives could be considerably shorter!

QP Discretion and Batch Release

The legal duties of the QP are laid down in Directives 2001/82/EC and 2001/83/EC. Amongst these is the requirement to ensure that each batch of medicinal product has been manufactured in accordance with the requirements of the Marketing Authorisation. However, we all know that, from time to time, deviations to manufacturing processes occur. Some of these have significant implications for the quality and safety of the batch, which must not be released. Others, however, have no patient safety implications. Can these batches therefore be certified and released by the QP even though they are not in compliance with the Marketing Authorisation?

DBA has provided auditing, consultancy and training services to the pharmaceutical industry for over 20 years. Over this period we have seen a lot of documentation system, both good and bad! As we all know, documents exist for some very good reasons:

• To reduce the likelihood of errors, particularly with the spoken word
• To improve consistency in all activities; that is to describe who must do what, how, when and why
• To provide traceability and a full history of activities and events

Documentation systems come with a huge price tag which our industry has previously accepted without question. As a consequence, the volume of paperwork has grown and grown, adding massive cost and complexity with very little obvious "payback" to either the patient or the company.

Any pharmaceutical company manufacturing sterile products for the EU and the USA faces a challenge in understanding the different requirements and expectations for clean rooms in these two very important markets and in integrating these expectations into a single, coherent operating standard that is scientifically sound and compliant. This article is intended to help you to achieve both these objectives by comparing and contrasting EU and FDA expectations.