The trend to increased specialization and higher-potency active ingredients creates the need for hermetically sealed process flows. Government regulations are also becoming stricter. To an increasing extent, the production process will have to be designed as a containment system. Containment (at least in the pharmaceutical industry) is nothing new. It is actually a long-term trend. Nevertheless, expertise in this field is not evenly distributed.
Frankfurt/Germany — No data — no market. This brief dictum from Brussels is a cause for serious concern at many companies in the process industry. It all stems from the EU Reach directive which requires prior registration for every substance produced or imported in volumes of one ton per year or more. As marketing volumes increase, so too does the amount of data which a company must submit. This has a direct impact on the cost of the toxicological testing which is required. Testing costs an estimated $ 15,300 for volumes up to one ton per year, but that figure can rise to more than $ 1,06 million for volumes of 1,000 metric tonnes a year or more. Expensive as it is, registration is not some sort of modern-day sale of indulgences. It is actually only the first step. Echa or a national regulatory authority then reviews the documentation which has been submitted.
The EU would prefer that substitutes are found for hazardous substances. Where this is not possible, plant operators must prove that they can safely handle highly active substances. A look at the statistics shows that more than just a few companies are effected by these policies. More than 50 % of all NCEs (new chemical entities) are considered to be potent compounds (OEL < 10 µg/m3). The magic answer for maintaining smooth production flows despite these developments is containment.
The Need to Fully Understand the Process
In 2004, the Containment Expert Group at Ispe, the International Society for Pharmaceutical Engineering, began putting containment on the agenda by offering training courses and seminars in Germany, Switzerland and Austria. 13 years have passed in the meantime, and Richard Denk, Head of Containment Sales at Skan, still feels that these efforts have only reached the tip of the iceberg. A lot of uncertainty remains. One reason why companies have such different levels of expertise on containment is undoubtedly the fact that the number of new products which are classified as extremely hazardous is increasing faster than the number of engineers and plant operators who are familiar with the issues involved, Denk reports. According to him, the knowledge deficit which has built up over the years was evident at conferences and training courses which are now attracting a large number of registrations and enrollments.
The number of highly active substances has risen over the years, with the result that OEB level 5 is now often the standard. OEB stands for Occupational Exposure Band, and allocation to a band is based on the toxicological potency of a substance. OEB 5 means contamination of less than 1 µg/m3. If this were scaled up to the size of the Empire State Building in New York, not more than one-twentieth of a teaspoon of the substance could be present in the entire building. There is naturally not just the "one solution" for achieving this. Instead, there are a number of different possible approaches. That is why, according to Claude Lefebvre, Director of Business Development at the milling equipment manufacturer Frewitt, one thing above all else is essential, namely a very good understanding of the process.
Human and Product Protection
The difficulties basically begin with the designations and definitions. Acceptance of the OEB classification is now widespread, but many pharmaceutical companies have their own standards which to some extent exceed the requirements of an OEB 5 solution. To cite only one example, the OEB 5 equivalent at Roche is called 3B. These are precisely the companies which are seen as major forces driving the containment solutions market. "In recent years, pharmaceutical mass production has relocated from Europe to Asia. In the industrialized countries, companies have been forced to concentrate more on the development of high-price products, e.g. for oncology," explained Iris Barnstedt, CEO of Brinox Deutschland which specializes in process systems.
Working with these high-potency products has made it necessary to improve occupational safety standards. It soon became apparent that working in full-body protective clothing was a simple but uneconomic solution. People wearing this type of clothing can only work for relatively short periods at a time, and that drives up production costs. Moreover, clothing protects people, which of course always has priority, but not the product. Particularly in the pharmaceutical industry, the monetary value of a few grams of active ingredient can run into the hundreds or thousands of euros.
David Johnson, containment expert at the pharmaceutical equipment manufacturer GEA , also stressed the need for an in-depth understanding of the process when the search for an optimal containment solution gets underway. According to Johnson, it is vital to realize that when determining the level of equipment needed and the containment performance, it is not enough to simply measure the product's Occupational Exposure Limit (OEL). This is a common misconception, and the result is a tendency in the industry for over-specification, he said. If the solution chosen was too complicated, system operation, cleaning and maintenance become more difficult, and the procurement costs are obviously higher. Proving that a given solution is 'good enough' can be problematic but not impossible. If the reason why containment is necessary and the product are well understood and proper consideration is given to the operator and the equipment, it is possible to develop solutions which are more sophisticated and effective.
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