Whe­re do our acti­ve ingre­di­ents come from?

Gene­ric medi­ci­nes make up the vast majo­ri­ty of medi­ci­nes that are nee­ded every day in Ger­ma­ny. The pro­duc­tion of the acti­ve ingre­di­ents of the­se medi­ci­nes (APIs = acti­ve phar­maceu­ti­cal ingre­di­ents) no lon­ger takes place in Europe.

This is the result of a stu­dy con­duc­ted by the con­sul­tancy Mun­di­Ca­re on behalf of Pro Gene­ri­ka. It shows for the first time on the basis of facts: Euro­pe has lost its for­mer lea­ding position.

Around two thirds of the appr­ovals (=CEPs, Cer­ti­fi­ca­te of Sui­ta­bi­li­ty of Mono­graphs of the Euro­pean Phar­ma­co­poeia) requi­red for the pro­duc­tion of acti­ve sub­s­tances are now held in Asia, and more than half of the manu­fac­tu­r­ers are also based the­re. Important to know: An acti­ve sub­s­tance can be pro­du­ced by dif­fe­rent manu­fac­tu­r­ers. So the­re can be seve­ral CEPs from dif­fe­rent manu­fac­tu­r­ers for one API.

% in Asia
% in Europe

The main fin­dings of the study:

Dyna­mic growth and mas­si­ve shifts in the mar­ket over the past 20 years: In con­trast to the year 2000, around two-thirds of the acti­ve sub­s­tance cer­ti­fi­ca­tes (CEPs) are now held in Asia.

  • The num­ber of acti­ve ingre­di­ent cer­ti­fi­ca­tes has increased fiv­e­fold bet­ween 2000 and 2020. Much of the growth is attri­bu­ta­ble to Asi­an mar­ket par­ti­ci­pan­ts. The share of CEPs held the­re increased by more than 1,200 percent.
  • For the year 2000, the data­ba­se lists 589 CEPs, of which 59 per cent were held in Euro­pe and 31 per cent in Asia.
  • In 2020, the ratio will be rever­sed: 63 per cent will be held in Asia, only 33 per cent in Europe.

India and Chi­na play a spe­cial role

More than 80 per cent of all acti­ve sub­s­tance appr­ovals (CEPs) in Asia are held here.

  • For exam­p­le, almost 90 per cent of CEPs in India are loca­ted in just four sta­tes: Telanga­na, Maha­rash­tra, Guja­rat and Karnataka. 
  • The pic­tu­re is simi­lar in Chi­na. Here, almost three quar­ters of the CEPs are found in just five pro­vin­ces in the east of the People’s Repu­blic (Zhe­jiang, Shan­dong, Jiangsu, Hebei and Hubei).

Not only in the num­ber of CEPs, but also in the num­ber of manu­fac­tu­r­ers that have CEPs for the EU, the­re is a clear shift in the indi­vi­du­al world regi­ons: Whe­re­as in 2000, 132 out of 248 manu­fac­tu­r­ers (around 53%) were based in Euro­pe, in 2020 this figu­re is only 236 out of 717 (around 33%). In Asia, the num­ber of manu­fac­tu­r­ers has risen from 91 to 421 in the same period.

The detail­ed ana­ly­sis of the data also pro­ves that pro­duc­tion is not only regio­nal­ly con­cen­tra­ted, but for many acti­ve phar­maceu­ti­cal ingre­di­ents (APIs) also limi­t­ed to a few manufacturers.

For more than half of the APIs, only five or fewer cer­ti­fi­ca­tes are lis­ted in the EDQM data­ba­se. This means that for a lar­ge part of the APIs nee­ded in Euro­pe, only about a handful of manu­fac­tu­r­ers world­wi­de even have an API certificate.

The stu­dy shows three dependencies

The­se rela­te to the pro­duc­tion of acti­ve ingre­di­ents and pose con­sidera­ble risks to the sup­p­ly of medicines:

  1. from non-Euro­pean producers,
  2. from a few regi­ons of the world,
  3. from a few manu­fac­tu­r­ers for the majo­ri­ty of the acti­ve ingre­di­ents needed.

An exem­pla­ry detail­ed ana­ly­sis has also shown that the acti­ve ingre­di­ents that are par­ti­cu­lar­ly fre­quent­ly nee­ded come main­ly from Asia. Dr Andre­as Mei­ser, aut­hor of the stu­dy and Mana­ging Direc­tor at Mun­di­Ca­re, sum­ma­ri­ses the results as fol­lows: “Our stu­dy pro­vi­des for the first time a fact-based over­view of whe­re the acti­ve ingre­di­ents nee­ded in Euro­pe come from. It shows why Euro­pe has lost its domi­nant posi­ti­on in the pro­duc­tion of acti­ve ingre­di­ents. And it makes clear that Euro­pean sup­p­ly is high­ly depen­dent — on only a few acti­ve ingre­di­ent manu­fac­tu­r­ers in very small parts of the world. This poses risks to the sup­p­ly of medicines.”

In addi­ti­on to the chan­ges of the past deca­des, the stu­dy also shows poten­ti­als. After all, part of the acti­ve ingre­di­ent pro­duc­tion — curr­ent­ly around 30 per cent — is still loca­ted in Europe.

A detail­ed ana­ly­sis of the Euro­pean demand for 21 exem­pla­ry APIs shows that today main­ly APIs with a com­pa­ra­tively low pro­duc­tion volu­me and/or a com­plex pro­cess are pro­du­ced in Euro­pe. Examp­les are tam­oxi­fen — an acti­ve ingre­di­ent used in the tre­at­ment of breast can­cer — or for­mo­te­rol, an acti­ve ingre­di­ent used in the tre­at­ment of bron­chi­al asth­ma and chro­nic obs­truc­ti­ve pul­mo­na­ry dise­a­se (COPD). Lar­ge-volu­me APIs tend to come from Asia. If the know-how nee­ded for API pro­duc­tion is to be main­tai­ned in Euro­pe, con­sis­tent action is required.

An ana­ly­sis of the indi­vi­du­al acti­ve sub­s­tances shows: The later an acti­ve ingre­di­ent went off patent in the past 20 years, the ear­lier the shift to non-Euro­pean count­ries began. Bork Brett­hau­er, Mana­ging Direc­tor of Pro Gene­ri­ka, empha­si­s­es the poten­ti­al that the stu­dy shows: “The stu­dy also con­ta­ins cle­ar­ly posi­ti­ve news, becau­se it shows us that acti­ve ingre­di­ents are still being pro­du­ced in Euro­pe, and on a signi­fi­cant sca­le. Poli­ti­ci­ans should now focus on streng­thening the (still) exis­ting pro­duc­tion of acti­ve ingre­di­ents and medi­ci­nes and on stop­ping fur­ther migra­ti­on. The best way to do this is to chan­ge the frame­work con­di­ti­ons that led to the relo­ca­ti­on to Asia in the first place. In con­cre­te terms, this means: it must final­ly eli­mi­na­te the extre­me cost pres­su­re on basic sup­pli­es and thus crea­te scope for more resi­li­ence in the sup­p­ly chains again.”

The rese­arch ques­ti­on Metho­do­lo­gy of the study

The Pro Gene­ri­ka Acti­ve Sub­s­tance Stu­dy has inves­ti­ga­ted whe­re in the world the pro­duc­tion sites of around 560 acti­ve sub­s­tances are loca­ted that are in sup­p­ly in Ger­ma­ny. In addi­ti­on, the stu­dy iden­ti­fied 21 important acti­ve ingre­di­ents and deter­mi­ned the ext­ent to which their Euro­pean demand could also be manu­fac­tu­red in Euro­pe. As a point of refe­rence for the ana­ly­sis, it cho­se the so-cal­led CEPs (“Cer­ti­fi­ca­te of Sui­ta­bi­li­ty of Mono­graphs of the Euro­pean Phar­ma­co­poeia”) as the most important form of acti­ve ingre­di­ent appr­ovals. The­se cer­ti­fy a manufacturer’s abili­ty to pro­du­ce an acti­ve sub­s­tance in the requi­red qua­li­ty. The CEPs are recor­ded in the public data­ba­se of the “Euro­pean Direc­to­ra­te for the Qua­li­ty of Medi­ci­nes and Health­ca­re” (EDQM). The stu­dy inves­ti­ga­ted gene­ric acti­ve phar­maceu­ti­cal ingre­di­ents (APIs) for which at least one CEP was available in the EDQM data­ba­se as of 30 April 2020. The stu­dy was con­duc­ted by Mun­di­Ca­re Life Sci­ence Stra­te­gies on behalf of Pro Gene­ri­ka e.V.. It is cal­led “Whe­re do our APIs come from? A world map of API production”.

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