n designing the specific spray dry plant for small scale production (≤ 1 MT/yr) for VitaSquare Wolvega Netherlands, Kropman Contamination Control looked at many design considerations

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VitaSquare Wolvega produces nutritional premixes. In the Netherlands, the company enriches dry or ‘instant’ food with vitamins, amino acids, minerals, trace elements, and many more components.

For this to work, the nutrients need to be added in powdered form.

For the design of the specific spray dry plant for small scale production (≤ 1 MT/yr), many design considerations are implemented.

First of all process steps are identified and assessed for: product susceptibility, the risk of spilling, the method to clean in place as well as the exterior, including the room. Logistics of materials, product, staff and waste are also planned for.

Dosing and fine ingredients mixing

Logistics are set up to handle most raw material in bulk containers, positioned outside the process rooms, are hooked up to the process lines (Image 1). This all is done in a non-classified but controlled area of basic hygiene level.

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Spilling is not expected as all raw materials here are in containers or per piping such as feed water. Also, the CIP and waste flows are run as fixed piping. Specific additives are added in the processing room via a tank lid. (Image 2)

The tank itself is at the other side of the wall, with all its pumps, valves, sensors, actuators, wiring and supports. This leaves the processing room quite easy to clean. The various connections for the process and transfer steps can be made by transfer panels. The fine ingredients come to this processing room by an elevator from the ground floor. The elevator acts as an airlock as it is interlocked and flushed by overflow air maintaining the pressure flow cascade.

As shown in images on p55, the logistics are well separated as well as the majority of the process equipment is located in a non-classified hygienic zone. The area of exposure is very limited and in a controlled; ISO Class 9 environment.

The doors have opened for the largest Cleanroom Technology Conference to date! Co-located with Manufacturing Chemist LIVE, this event will welcome over 400 attendees for two days of talks and networking in Birmingham, UK

The doors have officially opened for this year’s Cleanroom Technology Conference at the NCC in Birmingham, and what a lovely sunny day for it!

Over the next two days, more than 400 attendees will walk through the National Conference Centre doors for two days of talks and networking with the best of the best in the cleanroom sector.

Companies such as Ecolab, AstraZeneca, Pfizer and many more, will be represented at the conference. So delegates will have the opportunity to converse with industry powerhouses.

The multi-sector, international event will cover a wide breadth of the industry through case studies and lectures from a panel of global experts, shedding light on the latest industry developments over the past year, as well as future projections for all sectors.

Topics covered include Annex 1, containment, sterility testing, regulations and standards, operation and validation, clothing & PPE, data integrity, HVAC and energy, cleanroom design & build, cleanroom operations, garments & consumables.

Univercells Technologies’ Head of Manufacturing & Supply Chain talks about his approach to building a scalable pharmaceutical manufacturing facility in Belgium. Gareth Crothers from Univercells explains

Belgium is currently positioning itself as a Biotech valley, with a mixture of established “Big Pharma” companies and cutting-edge startups. Given the ready access to highly educated and experienced biotech professionals (including engineering firms) within a relatively small area, it is fertile ground for establishing new biotech activities.

Within this context, Univercells Technologies was founded in May 2020 as a spin-off of the company Univercells. Its mission is to focus on the commercialisation of its novel biomanufacturing technologies product portfolio – the scale-X (trademarked) bioreactor range and the NevoLine (trademarked) Upstream platform. Located in Nivelles, the manufacturing activities for the scale-X (trademarked) bioreactor range and associated Single Use Technology (SUT) such as manifolds, require the use of a cleanroom environment in order to control particulate levels.

Considerations for cleanroom design, construction, and operation

The first consideration for building a cleanroom is which level you need to attain and maintain for your operations. There are well established international standards for this, including ISO 14644-11 (particle count limits only) and EU GMP grades (particle and microbiological). The standard that you target should always be based on the products that you manufacture, as well as your customers.

Final drug products destined for injection into patients require more stringent conditions in terms of both particles and microbiological levels than SUT that will be irradiated before use in upstream processes. Licensed drug products are subject to regulatory requirements whereas biotechnology equipment must meet customer expectations.

Choosing the cleanroom level is important as targeting a more stringent grade than strictly necessary “because it is better” will engender significant incremental cost increase in terms of room construction, qualification, energy consumption, cleaning, gowning, and routine environmental monitoring. On the other hand, targeting too low will engender significant re-engineering costs and potential business disruption if the classification does not meet product, regulatory, or customer needs.

At Univercells Technologies, our product range and customer expectations led us to target an ISO Class 8 classification.

Targeting a more stringent grade than strictly necessary ‘because it is better’ will engender significant incremental cost increase

The second consideration is the surface area you need for your operations. Here again, there is a balance to be found. A cleanroom that is under-dimensioned will restrict capacity and could cause operator discomfort; it could even become an EHS problem in terms of personnel/material flows or workstation human-factor design. Also, an over-dimensioned cleanroom will again engender significant incremental cost increase in terms of room construction, qualification, energy consumption, cleaning, and routine environmental monitoring. In a small but rapidly growing company, it is possible to have a modular approach where the basic personnel and material airlocks are in place, and additional cleanroom space can be added in extension as needed.

This is the approach that was adopted at Univercells Technologies: the cleanroom capacity initially installed in 2019 (before the spin-off) was doubled to 1830 sqm in 2022 as product volumes and product range complexity increased. The additional surface area was added in a cost-effective way by leveraging the original infrastructure, positioning Univercells Technologies for the next few years of growth (product range and volumes) without having to move to costly shift operations

It has also given the company a greater flexibility in the organisation of the cleanrooms, an important enabler for creating leaner manufacturing processes.

As a third consideration, the choice of engineering partner for the cleanroom design and construction is important. For smaller companies with a lower level of cleanroom needs, such as Univercells Technologies, a cost-effective approach can be to work with smaller local engineering companies as opposed to larger international groups.

The trade-off here is that larger international groups are more likely to have experience of working in a regulated pharmaceutical environment with the associated documentation requirements; where smaller local companies can sometimes struggle with providing the needed level of documentation in a timely manner without multiple iterations.

Finally, a company also needs to consider the operating parameters for the cleanroom at the targeted classification. These include gowning, cleaning practices, and HVAC optimisation. Each of these parameters require a balance to be struck: too little and the classification will not be maintained; more than necessary, and costs can rapidly rise.

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A good example of this is cleaning: monthly cleaning of all surfaces on an ISO-8 area with a sporicidal agent is arguably over-kill, especially since such an agent requires neutralisation if corrosion of metallic components is to be avoided. Setting this at the right level before initial qualification is important as reducing the cleaning, gowning, or HVAC regimes after this will certainly require requalification (with the associated costs).

There are several ways to sensibly target the parameters for a given classification; these include use of engineering guides (such as the ISPE) and benchmarking with companies having similar product lines. Nevertheless, periodic review of actual operating conditions as the business evolves is essential e.g. given the significant increase in energy costs throughout 2022, the business case for creating a reduced HVAC regime for non-manufacturing periods such as nights and weekends has become much stronger.

The Chinese currency renminbi (RMB), or the yuan, saw its share in global payments rise in March, a report has said.

The RMB’s global share was up from 2.19 percent in February to 2.26 percent last month, according to the Society for Worldwide Interbank Financial Telecommunication, a global provider of financial messaging services. The currency remained the fifth most active currency.

In March, the RMB payments value gained 25.04 percent from a month ago, higher than the 21.46 percent increase in that of all payments currencies.

In terms of international payments excluding the Eurozone, the RMB ranked 7th with a share of 1.67 percent.

Managing Director of the International Monetary Fund (IMF) Kristalina Georgieva on Thursday said the world economy is expected to grow less than 3 percent this year, with India and China projected to account for half of global growth in 2023.

“Growth remains weak by historical comparison, both in the near and medium term,” Georgieva said in a speech in Washington, D.C., ahead of the IMF-World Bank spring meetings next week.

The IMF chief said some momentum comes from emerging economies, with Asia a bright spot.

“India and China are expected to account for half of global growth in 2023. But others face a steeper climb,” she said.

The IMF sees economic activity in the United States and the Euro Area slowing, where higher interest rates weigh on demand.

About 90 percent of advanced economies are projected to see a decline in their growth rate this year, Georgieva said.

“With rising geopolitical tensions and still-high inflation, a robust recovery remains elusive,” she warned.

The IMF projects global growth to remain around 3 percent over the next five years, the lowest medium-term growth forecast since 1990 and well below the average of 3.8 percent from the past two decades.

“This makes it even harder to reduce poverty, heal the economic scars of the COVID crisis and provide new and better opportunities for all,” Georgieva said.

The IMF will release more details about its growth outlook when it publishes its updated World Economic Outlook next week.