Nearly 20 years ago, when phar­ma­cist Dr. Karl­heinz Sey­fang founded the Pharma Ser­vices depart­ment at Harro Höfliger and set up the first clean­rooms, he made the com­pany a pio­neer among machine man­u­fac­turers. Since then, this area has seen con­tin­uous growth and has become an inte­gral part of the ALL YOU NEED ser­vice idea. When designing machines and devel­oping processes, risk min­i­miza­tion is a top pri­ority. With the range of ser­vices offered by the Process Ser­vices Divi­sion, Harro Höfliger guides cus­tomers every step of the way from the ini­tial idea to pro­duc­tion. The expan­sion of the clean­rooms and the new lab­o­ra­tory were imper­a­tive in order to fur­ther increase this ser­vice port­folio. The expan­sion is part of the ongoing com­mit­ment to improve­ments that moti­vates Harro Höfliger: Pro­viding more ser­vice to our cus­tomers, the best pos­sible pro­tec­tion for our employees and the envi­ron­ment, plus the oppor­tu­nity to con­tin­u­ously opti­mize our machines.

Marcus Hild, Project Leader Clean­room Expansion

We started to plan the expan­sion of our four clean­rooms three years ago. It was already clear at that time that we were reaching our limits with the avail­able capac­i­ties. During fac­tory accep­tance tests (FAT), for example, a room may be occu­pied by a machine for up to sev­eral weeks. In addi­tion, many of our cus­tomers wish to out­source trials because they do not have the nec­es­sary facil­i­ties in-house. There­fore, the deci­sion to expand our capac­i­ties was made quickly. We now have a total of ten clean­rooms with a total area of more than 500 square meters, and an addi­tional 60 square meters of lab­o­ra­tory space available.

The largest room mea­sures about 10 x 5 meters. Three of the clean­rooms are defined as High Potent areas. An addi­tional air lock with an air shower makes it pos­sible to work safely with highly potent active sub­stances up to OEB 5. Four of the ten clean­rooms can be oper­ated at a rel­a­tive humidity of ten per­cent using addi­tional dryers.

“The expan­sion of our clean­room capac­i­ties enables us to con­tinue to meet the high demands of our customers.”

A ring line sup­plies all clean­rooms with dem­iner­al­ized water. The air humidity, the air flow and the tem­per­a­ture can be con­trolled in every room as required. The mea­sured values are shown on a dis­play and saved for mon­i­toring. In order to pro­tect the envi­ron­ment, we not only filter the exhaust air, but also sep­a­rate the waste­water: Con­t­a­m­i­nated water is chan­neled into a spe­cial tank for incin­er­a­tion by a dis­posal company.

How­ever, pro­tecting our employees and cus­tomers was also very impor­tant to us: The air shower, descending door seals and a slight neg­a­tive pres­sure in all rooms pre­vent con­t­a­m­i­na­tion of the sur­rounding areas when pro­cessing active sub­stances in the clean­rooms. Spe­cial air extrac­tion sys­tems at the lab­o­ra­tory work­sta­tions also ensure a more com­fort­able work environment.

Click here to explore the clean­rooms in detail

Click here and dis­cover the clean­rooms and the high potent area in more detail

Dr. Elke Stern­berger-Rützel, Head of Pharma Services

Most employees in Pharma Ser­vices come from the phar­ma­ceu­tical industry. We know our cus­tomers, speak their lan­guage and under­stand what they need. These are impor­tant pre­req­ui­sites for exchanging ideas in a true spirit of part­ner­ship. Our cus­tomers already ben­efit from the fact that we work with a wide range of prod­ucts and for­mu­la­tions every day. Based on the expe­ri­ence of each indi­vidual employee, we have an eye for what will work and what might cause problems.

This enables us to pro­vide cus­tomers with con­crete solu­tions, such as a spe­cific dosing system for their prod­ucts, while always keeping in mind a pos­sible scale-up. The dia­logue between Pharma Ser­vices, the Design Depart­ment and the cus­tomer is the recipe for suc­cess when it comes to machines that are opti­mally tai­lored to the product. Thanks to the increased oppor­tu­ni­ties offered by the new clean­rooms and lab­o­ra­tory space, we can develop and verify filling processes in close coop­er­a­tion with our col­leagues in machine development.

“We speak the lan­guage of our cus­tomers and exchange ideas in a true spirit of partnership.“

At a very early stage we can ensure a reli­able, repro­ducible product quality across all scale-up steps. Thus, we can con­tribute, every now and then, to accel­er­ating product approval together with the cus­tomer. By using the ­Design of Exper­i­ment (DoE) method­ology, we per­form exper­i­ments, for example, with dif­ferent machine speeds and vari­able filter inserts, and iden­tify a process window with para­me­ters that work reliably.

Karin Marek, Lab­o­ra­tory Manager

Just two years ago, we restricted our approach to purely phys­ical mea­sure­ment methods. Now we can per­form a much wider range of ana­lyt­ical tests. With the new par­ticle mea­suring sys­tems, ultra-fine par­ti­cles can be mea­sured, which could influ­ence the later pro­cessing of a product.

We now have new capa­bil­i­ties in the wet-chem­ical field. By using high-per­for­mance liquid chro­matog­raphy (HPLC), we can deter­mine if and to what extent active agent par­ti­cles accu­mu­late on machine sur­faces. We aim to ensure, for example, that no uncon­trolled loss of active ingre­di­ents occurs during filling processes. By mea­suring the uni­for­mity of the mix­ture con­tent, we test how a product behaves under dif­ferent man­u­fac­turing con­di­tions and whether this might influ­ence the filling properties.

“With the expan­sion of the lab­o­ra­tory, ana­lyt­ical methods have changed.”

For inhala­tion, we now have the New Gen­er­a­tion Impactor (NGI), a kind of aero­dy­namic flow model of the lung. The NGI gives us the pos­si­bility to deter­mine the fine par­ticle frac­tion (FPF) or the fine par­ticle dose (FPD). This ana­lyt­ical option is one of the most com­plex I know of. Now we have much better overall con­trol of the filling process.

The largest clean­room mea­sures 10 x 5 meters and offers space for entire machines.

Exten­sive ana­lyt­ical tests can be car­ried out with the aid of clas­sical and state-of-the-art mea­suring systems.

The air shower pro­vides a safe working envi­ron­ment when han­dling highly potent substances.

We can ana­lyze the CPP (Crit­ical Process Para­me­ters), the CMA (Crit­ical Mate­rial Attrib­utes) and other sim­ilar rel­e­vant infor­ma­tion for our cus­tomers, or per­form data queries directly via our exten­sive product data­base. All this offers the best pre­req­ui­sites for pro­viding our ­machine designers and devel­opers with the solid data they need for the tar­geted, rapid and suc­cessful design of a machine or for improving existing ones. Now product analysis is actu­ally fun!

Michael Renz, Process Engi­neer Engi­neering & Inno­va­tion Services

Our cus­tomers usu­ally have cer­tain ideas about the type of dosing system they want their product to be processed or filled with.With the help of the ana­lyt­ical facil­i­ties in our lab­o­ra­tory, we can deter­mine at a very early stage whether these ideas indeed can be imple­mented or if we need to influ­ence machine devel­op­ment with insights gained from pre­vious research.
Due to the reg­u­la­tory require­ments in the phar­ma­ceu­tical industry, mod­i­fi­ca­tions to the machine or the product after approval are very costly and time-con­suming. There­fore, cer­tainty about the func­tion­ality of the process at an early stage is par­tic­u­larly valu­able. As process man­agers, we work hand in hand with our lab­o­ra­tory team and the design depart­ment to meet the customer’s spe­cific product require­ments. We never cease to wel­come these insights as a part of our ongoing internal development.

“The expan­sion of the clean­rooms and ana­lyt­ical facil­i­ties gives us ­entirely new oppor­tu­ni­ties to iden­tify and improve processes.”

With the help of our new clean­rooms, we have the unique oppor­tu­nity to recreate the product con­di­tions found on the cus­tomer’s premises, to better under­stand poten­tial issues and to find suit­able process solu­tions. By sim­u­lating real con­di­tions, the com­plex test pro­gram for the qual­i­fi­ca­tion and val­i­da­tion of new machines can be scaled back. Tests for para­meter setups or for spe­cial solu­tions can be trans­ferred to Harro Höfliger. In this case, the cus­tomer prefer­ably pro­vides active phar­ma­ceu­tical ingre­di­ents (API) or a placebo. Training and pro­duc­tion sup­port at the customer’s site can also reduce the costly and time-con­suming start-up phase of the machine.

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Photos: Helmar Lünig, shutterstock.com/Haywiremedia, Harro Höfliger, Andreas Dalferth, Jan Seidl