It’s hard to imagine a doctor’s office or clinic any­where in the world without infu­sion bags. As with any product admin­is­tered intra­venously, the need to min­i­mize patient risks means that quality require­ments for the bag con­tent are espe­cially high. Fre­quently, after being filled with liquid, infu­sion bags are ter­mi­nally ster­il­ized to ensure the vitally impor­tant sterility. How­ever, this method is not suit­able for active ingre­di­ents that are sen­si­tive to heat or gamma radi­a­tion, as is the case with the prod­ucts of the Hong Kong biotech­nology com­pany New β Innovation.

“The line takes every nec­es­sary hygiene and safety guide­line into account.” Chris­tian Kol­lecker, Director Aseptic Tech­nology at Harro Höfliger

That’s why Harro Höfliger went in a dif­ferent direc­tion with its first aseptic filling and sealing machine for IV bags. Our ­experts focused on com­pletely sterile processes and an active open restricted access bar­rier system (RABS).In the sterile con­di­tions of the line (EU/GMP Clean­room Grade A/ISO 5), New β Inno­va­tion man­u­fac­tures IV prod­ucts at a mid-scale level in its Cana­dian facility. 

“We spe­cialize in vet­eri­nary prod­ucts that are used around the world, and which we fill and seal at up to ten bags per minute,” says Endre Szi­lagyi, Senior Man­ager, Pro­duc­tion from New β Inno­vation. “Of course, the machine can also be used for filling oxygen-sen­si­tive IV prod­ucts for human use,” notes Chris­tian Kol­lecker, Director Aseptic Tech­nology at Harro Höfliger. “The line takes every nec­es­sary hygiene and safety guide­line into account. It is suit­able for bags with fill vol­umes of 20 to 250 mil­li­liters, and is a par­tic­u­larly good fit for the ‘low volume-high margin’ sector.”

“One-time docking”: a global first

The machine is loaded man­u­ally. “The no-touch method proved itself to be the best solu­tion for the con­tin­uous transfer of our flex­ible bags, which can easily stick together,” says Endre Szi­lagyi. Oper­a­tors use glove ports to open the pre-ster­il­ized, bagged com­po­nents, as well as to sep­a­rate them. A camera records the posi­tion of the bag on the transfer belt so that the Stäubli Ster­i­clean robotic arms can pre­cisely place the IV bags on the rotary plat­form and con­nect the filling tube to the aseptic triple filling head.

The spe­cial fea­ture is that the con­nec­tion to the filling nozzle remains in place through all of the fol­lowing gas purging, evac­u­a­tion and filling processes until the transfer from the machine. Harro Höfliger uses this one-time docking prin­ciple to min­i­mize the risk of par­ticle entry and keep the residual oxygen con­tent in the bag low.

The amount of nitrogen flushing and the sub­se­quent evac­u­a­tion of the bag using vacuum can be flex­ibly adjusted. An inte­grated, laser-based Wilco HSA (head space analysis) module pro­vides an in-line mea­sure­ment of the oxygen con­tent, making the quality con­trol results avail­able imme­di­ately. If the residual oxygen level is over one per­cent, the bag is removed and not filled. A high-pre­ci­sion mea­sure­ment of mass flow using the ­Cori­olis effect is per­formed by a sensor, which ensures that each infu­sion bag has been filled to exactly the right amount. An aseptic rotary dis­tri­b­u­tion is used to supply all fill media in a sterile manner.

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Learn more about “One time docking” in the video: 

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The video gives you a panoramic view of the semi-auto­matic line: 

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Quality down to the very last detail

In the next step, pad­dles “mas­sage” the filled bags so that any trapped gas from the infu­sion solu­tion rise upwards to the filling tube. The opening is tightly sealed by radio fre­quency welding to min­i­mize the heat transfer to the active sub­stance. Then, the filling tube is cut off and removed.

An impor­tant com­po­nent of quality-­ori­ented pro­duc­tion is per­fect cleaning after each batch using an inte­grated CIP/SIP (cleaning in place/sterilization in place) system. “The machine’s hygienic design meets the highest phar­ma­ceu­tical stan­dards,” explains Chris­tian Kol­lecker. “The com­plete pipeline system is con­nected to an auto­matic CIP/SIP system, making dis­as­sembly unnec­es­sary for cleaning. Fur­ther­more, the entire line is opti­mized for decon­t­a­m­i­na­tion using hydrogen per­oxide based dry fog.”

“The filling system is one of a kind, only the team at Harro Höfliger can make it happen.” Ben­jamin Wai, Director of New B Inno­va­tion Limited

Ben­jamin Wai, Director of New β Inno­va­tion, is very sat­is­fied with the filling machine – a second line for the Chi­nese pro­duc­tion facility was ordered quickly. “When we first con­tacted Harro Höfliger, we were looking for lab­o­ra­tory equip­ment for aseptic liquid filling,” says Ben­jamin Wai. “Because the processes have worked per­fectly, Harro Höfliger has scaled from tabletop devices to the semi-auto­matic pro­duc­tion line. In close coor­di­na­tion, we have jointly devel­oped a com­pact machine layout that meets all of our require­ments and takes into con­sid­er­a­tion the spa­tial con­di­tions in the clean­room of our pro­duc­tion facility down to the smallest detail.”

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Photos: Helmar Lünig, New β Inno­va­tion, stock.adobe.com/Sherry Young