S4.E9. 人與動物同樣面臨呼吸問題

百靈佳殷格翰位於德國多特蒙德（Dortmund）的製造廠，每年能產出數以百萬隻的吸入器供呼吸疾病患者使用，而Respimat^®舒沛噴是百靈佳殷格翰的重點產品之一。

關鍵技術的掌握及大量投入

2011年後，百靈佳殷格翰確實掌握了吸入器的各零件：「支撐環」、「閥體」，以及「uniblock 噴嘴系統」各項技術，這些放在手上幾乎隱形的26個零件便是組成Respimat^®舒沛噴（用於治療特定呼吸系統疾病的吸入器）最重要的關鍵。百靈佳殷格翰除了投入製作Respimat^®舒沛噴，並開始量產吸入器，且在促進倡議、規劃、調整進度…等每一個步驟，都扮演極關鍵的角色。

經年累月蓄積下來的專業知識、過程與經驗，是成功的關鍵

Matthias Hausmann，Respimat^®舒沛噴的開發元老之一，認為吸入器的核心成分是uniblock 通氣系統，它以氣霧形式釋放活性物質。Uniblock通氣系統在第一代設計就出現，即便後期再開發出可重複裝填藥劑的吸入器，依然保有這項設計。同一個吸入器最多可裝填六次藥罐（視各國批准數目而定），吸入器因此更添環保性。在開發新產品的過程中，我們不只接受醫療專家們的建議，也考量使用者所回饋的意見。

3600萬支吸入器，遍佈在世界各地供患者使用

1998年，在Respimat^®舒沛噴即將進入全球市場之際，美國食品藥品監督管理局（FDA）突然改變了吸入器的上市要求。經過數次檢測後，我們很快就確認了原本預計上市的吸入器規格不符合新標準的殘酷事實。Hausmann說：「我們只有兩條路：找到解決方法或放棄。」終究，我們的堅持和努力有所回報，研發團隊成功的調整了吸入器的功能與規格，並按照預定計畫的時間上市。Hausmann與研發團隊的最終目標從頭到尾都沒有改變：改善患者的生活品質；他說：「這是一個值得我們每天奮鬥的目標。」Hausmann表示，噴嘴的製造技術與專業知識，以及與經驗豐富的團隊協力合作，是讓Respimat^®舒沛噴成功開發的兩個關鍵。如他的座右銘所言：「在不違反物理定律的前提下，每個問題都有解決的方法。」

身為產品經理，Hausmann持續推進醫療設備的研發，並全程監督產品的生命週期。

你知道馬也可能需要使用吸入器嗎？

馬也會咳嗽，體能表現也會隨時間流逝而逐漸衰退。馬氣喘的原因可能與過敏原（antigens）有關，例如說：馬匹在呼吸時，將馬廄乾草中的灰塵與空氣吸入肺部。這種污染、傷害，可能會逐漸地發展為馬匹的健康問題。

百靈佳殷格翰在今年年初擴展了產品組合，Aservo^®EquiHaler^®於2020年開始在歐洲市場上進行銷售；Aservo^®EquiHaler^®是馬用吸入器，以人類製藥領域的Respimat^®舒沛噴為基礎。這項產品的開發靈感來自於Nicole Mohren博士，以及百靈佳殷格翰集團德國業務健康事業部的同事們。

從不相信吸入療法到成功治療

從不相信會有藥物或者吸入療法，到能確實對應並且治療馬匹的慢性呼吸道疾病，這中間有個很大的鴻溝。最初的想法是比照Respimat^®舒沛噴的使用原理，製作一個與鼻孔相連的裝置；但為了確保馬匹使用上的易用性，必須以不同的方式裝置藥物；這之後我們才開始思考藥物的適用性。我們需要可以提供馬匹安全的抗炎性物質，跳脫藥片式的給藥形式，而成功治療呼吸道疾病的關鍵，在於藥物是否能在肺部直接起作用，Aservo^®EquiHaler^®所生成的細微、緩慢擴散的噴霧，能讓微顆粒到達肺部，因此成為成功的關鍵。

隻手就能操作

過去很長一段時間裡，馬匹所使用的吸入性藥劑必須透過口罩才能投藥，這個操作程序很複雜，馬匹也不會感覺很舒服。Aservo^®EquiHaler^®在使用上非常方便，可以用一隻手操作，在這裡提供了相當可觀的附加價值。

由人類到動物緊密相連的解決方案

Aservo^®EquiHaler^®吸入器的主要零件，microParts，這個零件的專利技術完全源自於百靈佳殷格翰在多特蒙德的研發計畫。由於團隊已經進行相當多年的研發工作，而我們的同事因此具備令人難以置信的深厚專業知識，讓人類藥物和動物保健，這兩個看似不相關的領域，藉由一個共同的思想—為我們的患者提供全新的解決方案—而緊密相連。

Out of the ruhr region and into the world

Boehringer Ingelheim manufactures millions of inhalers for patients with respiratory diseases each year at its location in Dortmund, Germany. Matthias Hausmann is one of the people who developed the RESPIMAT^®, which ranks among the most important elements in the Boehringer Ingelheim product portfolio. Matthias Hausmann holds his hand out towards his visitors. He points to parts so small they almost disappear in the palm of his hand and names each of them: the support ring, the valve body – and the uniblock. These are three of the 26 individual parts that make up the RESPIMAT^®, an inhaler for treating specific respiratory diseases.

The inhaler is manufactured at Boehringer Ingelheim microParts GmbH in Dortmund, under Hausmann’s watchful eye. Hausmann is an engineer born in Berlin. 24 years ago, a colleague directed him from the nation’s capital to the Ruhr region, where microParts has developed and produced micro-nozzles since 1990. Eleven years later, Boehringer Ingelheim picked up the technology and started preparing the RESPIMAT^® for series production. Hausmann plays a decisive role in this endeavor, organizing, finetuning, and creating the necessary processes for high-volume series production of the inhaler and cartridges.

He looks down at his hand. The smallest component, the valve body, is as small as the head of a pin and weighs less than a snowflake. “Six of such delicate components are so special that they are only produced by us here onsite,” he explains. In 2019, more than 36 million inhalers were delivered worldwide.

“Expertise and years of process experience are the decisive factors for success,” says Hausmann. The core component of the inhaler is the uniblock, which releases the active substance as a fne mist. It does the same in the reusable version, which has been available in a number of European countries since April 2019. Thanks to its reusability for up to six cartridges – depending on the approval status in the respective country – the inhaler is now more environmentally friendly. Not just physician experience but patient feedback was especially considered in the course of developing new generation products.

MORE THAN 36 MILLION INHALERS WERE DELIVERED WORLD WIDE

As the product manager, Hausmann continuously advances the development of the medical device and oversees the entire lifecycle of the product. Thanks to the varied nature of his work, Hausmann remains dedicated to microParts and the Ruhr region. In recent years, a sum in the high double-digit million euro range has been invested in developing the Dortmund location, where a new building wing was constructed and new machinery purchased.

The road has not always been smooth, however, and there have been setbacks over the years. In 1998, just before the RESPIMAT^® entry into the global market, the US Food and Drug Administration (FDA) changed its requirements for inhalers. After several tests, it quickly became clear that the inhaler did not meet the new criteria. “From then on, it was either find a solution, or the project has failed,” Hausmann recalls. Persistence and drive paid off, and the team success fully modified the inhaler so that the market launch could take place as planned. Improving patients’ quality of life is the ultimate goal for Hausmann and his pioneering team. “This is a goal worth fighting for every day.”

Two factors were decisive in the successful development of the RESPIMAT^®, says Hausmann: expertise in nozzle manufacturing and collaboration with an experienced team. As his personal motto states: “There’s a solution for every problem, as long as it doesn’t violate the laws of physics.”

“There’s a solution for every problem, as long as it doesn’t violate the laws of physics.” –Matthias Hausmann

“HORSES ALSO COUGH ”

Boehringer Ingelheim expanded its product portfolio at the start of the year: The ASERVO^® EQUIHALER^® has been on the market in Europe since the spring of 2020. This is an inhaler for horses, which is based on RESPIMAT^® technology from the field of human pharmaceuticals. The idea originated with Dr. Nicole Mohren and her colleagues in the Group’s German Animal Health business.

Mrs. Mohren, why do horses need an inhaler?

Horses also cough, which gradually reduces their performance over time. The cause for this may include antigens, for instance, which are inhaled together with the dust that is blown up out of the hay in the horse’s stable. Over time, this contamination can become a problem for horses. Before I joined Boehringer Ingelheim, I spent seven years working as a veterinarian in clinical practice. After joining Boehringer Ingelheim, I was asked what therapy horses would urgently require.

And you saw inhalation as the greatest area of need?

Exactly. Back then, there wasn’t any medicine available as an inhalation therapy for treatment of chronic respiratory diseases in horses that I was entirely convinced of. There was a real gap here.

What were your first steps in the development of the ASERVO^®EQUIHALER^®?

The original idea was to take the RESPIMAT^® for humans, and to attach a connector to integrate a nostril adapter. But to ensure ease of use, the entire mechanism needed to be housed differently. And then the question as to the right substance came up.

Which criteria did the substance need to fulfill?

We needed an anti-inflammatory substance that offers a good safety profile for the horse and does not require administration forms such as tablets. The crucial point for the successful treatment of respiratory diseases is that the medication needs to be effective directly in the lung.

Does the ASERVO^® EQUIHALER^® achieve this?

Yes. We have achieved very strong availability of the substance at the site of action, in the lung. The fine and particularly slow spray mist the ASERVO^® EQUIHALER^® delivers plays a key role here. It enables fine particles to penetrate deep into the lung.

What additional strengths does the new inhaler offer?

It is easy to use, since the inhaler can be operated with one hand. For a long time, inhaled substances for horses have mainly been administered via masks. That is complicated and not very comfortable for the horse. Our ASERVO^® EQUIHALER^® provides significant added value here.

The inhaler is based on the key components of RESPIMAT^®, which are produced in Dortmund. What was it like working with Boehringer Ingelheim microParts?

The knowhow for these components has entirely resulted from the Group’s development activities in Dortmund. For that reason, we worked together intensively throughout the development cycle. Our colleagues there have unbelievable expertise thanks to their years of development work. The two fields – Human Pharmaceuticals and Animal Health – are linked by a common idea: to offer innovative solutions for our patients.