The Hungarian Pharmaceutical Industry
The Hungarian Pharmaceutical Industry
The Hungarian Pharmaceutical Industry
ln Hungary, inifiatíves for the starting of pharmaceutical mical industry in the country, the organotherapeutical and
production on industrici seele had been token relatively phytochemical products played the decisive part, and synthe-
early. tic preparetiens have come inte prominence gradually only
ln 1867 was founded the first pharmaceutical enterprise later.
under the name of Hungerion Pharmaceutical and Technical- ln 1927 the Alkaloida Works were found ed, based on the
Chemical Company. At that time, in Europe, only in London, licence of /ános Kabay, which started with the processing of
Paris, Milan and Brussels were fundioning associations of dry poppy-heads, and this permitted-for the first time in the
similor tasks. world-the starting of the produciion of morphine alkaloids
The first Hungerion pharmaceutical campany mentioned on industrici scale without needing opium further on as
werked for 45 years, it was liquidated in 1912. ln the· mean- a raw material. Sincethat time the balance of the Hungarian
time however, in particulor afte_r the turn of the century, drug foreign trade has beceme permanently pasilive and
new industrici enterprises were established mainly out of remained favourable even during the world econernic crisis
chemist's laboratories. Tothemost successful ones belonged in 1929-1933. Th us, the development of the pharmaceutical
the firm of Gedeon Richter, incorporated in 1901, then the industry, by overcoming many difficulties, could be made
company of Dr. Emil Wolf, the Alko Chemical Works continuous. At the end of the thirties, that is in the period
founded in 1910, adopting in 1913 the name Chinoin, further immediately before the outbreak of the Second World War,
the subsidiary company of the Swiss firm Dr. A. Wander 36 drug manufacturing firms were werking in Hungary,
found ed in 1912 in Budapest, the aim of which was to su pp ly some of them had subsidiaries abroad, too. Drug imports
Austria-Hungary, the ·Balkon states and Russia wit:, the constituted 60 percent of the exports. Forty-two countries
weil proved preparoliens of the parent compon y in Bern. were supplied with drugs produced in Hungary.
The rapidly increasing internal demand on human and The Second World War has broken the progress of the
veterinary preparations and the export possibilities focussed Hungarian pharmaceutical industry. The ravages by war
on the countries of South and Eastern Europe arcused have caused- immense material and personal damages to the
the interest of enterpreneurs in pharmaceutical produc- country, included the pharmaceutical industry, too. The
tion. ln this field they could rely upon the home raw efforts made follawing the first post-war years were con-
materials necessary for the production of preparetiens of centroted on the liquidation of damages and on the recon-
vegetal and animal ori gin. Sincethere was no ergonic che- struction. The factories, plants and laboratcries have been
5
nationalized, and after reasonable amalgamations and reign Trade. The home distribution is- carried out through
reorganizations the Hungarian state drug industry has one wholesa/er (Company for the Markeling of Pharma-
reach ed in 1949 ils pre-war level (that of 1938). ceulica/ Products) and through pharmacy cenlers, of which
The production was centralized in eight large enterprises, 19 are to be found in the province and 1 in the capitaL
their production range was established and the necessary
modernizafions effected by means of a resolute policy of
development and investment.
Six of the enterprises ore fundioning under the direction Some data about the production of
of the Ministry of Industri es. The coordinalion of their aclivity the Hungarian pharmaceutical industry
is provided by the Union of the Hungarian Pharmaceutical
lndustry. The Phylaxia Veterinary Biologicals and Feedstuffs The number of employees is at presenl near/y 24,000.
Ltd. is controlled by the Ministry of Agriculture and Food, The magnitude, number of staff, produciion line and produci
the Institute HUMAN for Serobacteriologica/ Produciion and structure (assortment) of each enlerprise are different, Ih us
Research by the Ministry of Health. The registrali on, autho- they represent a differenl proportion both in the produciion
rizalion and control of the products for human therapy of al/ and ex ports (Fi g. 1).
producers is effected, of course, by the competent organs More !han 80 percent of the produciion consists of the
of the Ministry of Hea/th. As to the veterinary products this manufacturing of actíve substances and finished pharma-
Iask is provid ed by the Ministry of Agriculture and Food. ceutical preparations for human and veterinary use. These
The right of drug export and import was assigned to one represenl the majorily of exports, too, although the propor-
enlerprise, MEDIMPEX (Hungarian Trading Company for tion of plant-protecting agenis shows a rising trend both in
Pharmaceulical Products), controlled by the Minislry of Fo- produciion and exports (Fig. 2-3).
6
l
l
l
!
Fig. 1.
Fig. 2
Fig. 3
Production units of the Hungarian
pharmaceutical industry
(in order of their foundation)
13
The Pharmaceutical The modern oral controceptives play a prominent port in
Factory of Kőbánya
(Budapest) is one of family planning.
the largest and mosl Among the synthetic preparations, representing a lower
up-to-date confeciion ing order, the produciion of peptid e hormones is significant.
plan t of Central
Europe - packing RICHTER produce about 150 active principles, a great
and preparing planf of part of which is marketed in form of proprietary drugs.
the Chemica/ Works Several hundred millions, of ampoules, several thousand
of Gedeon Richter,
Lld. millions, of tablets and coated pilis, as weil as other dosage
forms are produced yearly .in the finishing and packing
plants of the compon y.
From the beginning of the year 1970, for a better exploi-
tation of experience, acquired in the field of drug produciion
ond research, in oddition to human and veterinary medicines,
the company has extended its activity both in Budapest and
in its provinciai workshops to the manufacturing of other
related products, too, li ke the production of biocosmetics, e. g.
the Fabulon family of products, rother popular since that
time, as weil as of agricultural chemicals, primari ly of plant-
protecting agents and feed additives.
14
CHINOIN PHARMACEUTICAL
AND CHEMICAL WORKS
1045 Budapest, Tó u. 1-5 (central establishment)
1325 Budapest, P.O.B. 110 (postai address)
Chinain (Budapest)
- Fermehfafion
plan l - Faclory un il
preparing culture
medium
15
pace in the recent_ period, that of the antitumcur sugar
derivatives and of prostaglandins.
The large~scale production of antibiotics wasstarted first
by CHINO/N in Hungary. Although in 1950 a separate
plan! functioning under the name of BIOGAL was erected
for this purpose, manufacJure of antibiotics ls still going on
in the CHINO/N Works. The main products are nystatine,
gentamycine, fumagliline and sisomycine.
ln addilion to the human preparalions CHINO/N attach
great importance to the development and production of
veterinary ones, disposing similarly of considerable tradition
and experience in this field.
CHINO/N are producing in their factory unils about 100
Chinain (Budapest) -different active substances serving the manufacturing of
- Fermenlalian
most of their pharmaceutical specialities in their finishing
planl - Factory unit
sleri/izing culture and packing pianis of high capacity. More !han hundred
medium million arnpoules and severo[ thousand million solid
drug forms (tablets, capsules, coated pilis) are supplled
by the factory yearly, part/y for covering the home demand,
part/y for foreign markets.
ln order to meet the increased demand of the agriculture,
at the beginning of the 1970's CHINO/N introduced the pro-
duciion of feed additives and particular/y of plant-proJecting
agents, being available already for exporfs. Amon g the plant-
protecting agenis they produce primari/y rungicides and
insecticides.
Chinain (Budapest)
- Fermenlalion
planl - Feed-lanks
16
EGYT PHARMACOCHEMICAL WORKS
1106 Budapest, Keresztúri út 30-38 (central establishment)
1475 Budapest, P.O.B. 100 (postai address)
17
PHYLAXIA VETERINARY BIOLOGICALS
AND FEEDSTUFFS, Ltd.
1107 Budapest, Szállás u. 5/7 (central establishment)
1486 Budapest, P.O.B. 23 (postai address)
Phylaxia (Budapest)-
Production of vaccines
agai nst aphthous fever
18
ALKALOIDA CHEMICAL FACTORV
4440 Tiszavasvári, Kabay jános u. 16 (central establishment)
4441 Tiszavasvári, P.O.B. 1 (postai address)
19
BIOGAL PHARMACEUTICAL WORKS
4042 Debrecen, Paliagi út 13 (central establishment)
4001 Debrecen, P.O.B. 197 (postai address)
Biogal (Debrecen) -
Powder-ampoule filling
machine
20
INSTITUTE HUMAN FOR
SEROBACTERIOLOGICAL PRODUCTION
AND RESEARCH
2101 Gödöllő, Táncsics Mihály u. 82 (central establishment)
2101 Gödöllő, P.O.B. 69 (postai address)
Human (Gödöllő) -
in Hungary was token over by the Department which be-
Freeze-drying come independentin 1954 under the name of Institute HU-
(liophylization) MAN for Serobacteriological Produciion and Research.
of human blood
The production range of the Institute inclucles vaccines,
plasma albumin
therapeutic ~nd diagnostic sera, blood derivatives, plasma
expanders, infusion solutiens and modern diagnostics for
immunology ·and immuno-chemistry.
The Institute possesses actually 207 registered prepara-
tiens and, besides th ese, it has on the market about 140 sorts
of immuno-chemical reagents and culture media. Owing to
íts potent vaccines, the most important bacterial epidemies
could be fought off in Hungary, like typhoid fever,
pertussis, diphtheria, tetanus.
A bau t 850 persons a re kept employed in the Budapest and
Gödöllő plants who carry out an important research and
development activity besides their productive work.
21
REANAL FACTORY OF LABORATORY
CHEMICALS
1147 Budapest, Telepes u. 53 (central establishment)
1141 Budapest, P.O.B. 54 (postai address)
Reana/ (Budapest)-
Fermentation of
antibiolica
(Mythramycin,
0/Jgoniycin)
22
BCR WORKS
2943 Bábolna, P.O.B. 30
BCR (Bábolna) -
Automatic cónlrol
of manufacturing
processes
23
Foreign and Hungarian joint enterprises engaged
in pharmaceutical production
One of the forms, becarning more and· more important duction of som~ important pharmaceutical fine chemicals
of the presence of the Hungerion pharmaceutical industry (e.g. ethambutol, vitamin B12 ) on the basis of Hungerion
on foreign marketsis the participatien in foreign producing know-how. The produci obtained in this way is partly
companies. The firms operating with Hungorian and local subjected to further processing, partly marketed. lts main
capital~apart from the concentration of material forces- pharmaceutical specialities ore: Themibutol, Oxyrin, The-
have elso the advantage of uniting the local contractors' mineuron,. Sumetrol, Peritol, Dopagyt. As a resulf of the
experience ond relatíens on the market with the technical consisfent developmental actiVity the enterprise has obtained
knowledge of the developed Hungerion pharmaceutical recognition within the Indion pharmaceutical industry.
industry. The governm·ents of the countries, where joint ven- Labatec Pharma in Switzerland is one of the oldest joint
tures ar~ functioning, appreciate this form of co-operation, companies of the Hungerion pharmaceutical industry. The
particularly in the developing world, knowing that this pharmaceutical specialities produced (out of which the most
would open new employment opportunities and promotes important ore: Dopatec, Mydocalm, Frenolon, Labamicol,
the growth of the technicallevel in the respective country. Rheumycalm) ore marketed both in Switzerlarid and other
When establishing common enterprises, ·the Hungerion · countries. They ore catrying on an extended commercial
pharmaceutical industry is not.confined only to the transfer activity, too.
of finishing and packing technologies, but a Iso is not averse The sphere of action of the Nigerion firm /marse/ can be
to cede the man\.lfacturing processes of active substances characterized ·in the some way. This campany is marketing
to the party ei ther. A good example for this is the Indion firm i ts products, however, exclusively on the territory of Nigeri a.
Thernis Chemica/s, engeged for a long time past in the pro- The ende~vour to extend the network of productive com-
panies of co-ownership is showed by the foundation of a
Bangladesh company in 1980, werking under the name of
Ambe~ Pharmaceuticals. Their aim is to improve the provision
of Bangladesh consumers wi th modern d ru gs (e. g. Kl ion,
Ampicillin, Trofurit, Verospiron, Prednisolon, Sura!).
TH EM IS
Pharmaceutical
Facfory - India
24
~1
!,
! 25
l
l
l
Historical retrospection, traditions
The pharmaceutical research in modern sense is going traditions, poten_tialities and requirements of the country,
on in Hungary for about 90 years. This activity was in a particulor importance is attached to the research of bio-
progress lill the end of the First World War mcsily in the logicaily active compounds serving the health protection
chemical and pharmacological departments of the univer- and the curing of living beings (humans, animals, plants),
sities. A steadily increasi.ng number of results and sciéntific further to the research of biologically active compounds,
recognitions originated from this research work. ai me d at the_ increcse of agricultural (p lant cultivation, ani-
Between the two World Wars the bigger manufacturing mal breeding) yields. ·
componles had erganized their own research units in close The co-ordination of the research work going on i~ the
co-oper~tion with the university institutions. ln connection pharmaceutical industry is carried out with the enterprises
with drugs of vegetal base, the indtJslrial produciion of (ALKALOIDA, BIOGAL, CHINOIN, EGYT, RICHTER, REA-
morphine alkaloids out of dry poppy-heads, the isolation of NAL) united in the Union of the Hérngarian Pharmaceutical
vitamin C out of paprika, the eiaboralion of the cuitivali on lndustry, by the Research Council of the Union. The members
of er gat by means of artifieia l contami nati on, the. isolation of the latter are, apart from the reseprch directors of the
of ergo! alkaloids, etc., in the line of drugs of animal ori gin, enterprises, the directors of the two indepenclent research
the preparatien of estrone out of pregnant mare Urine, as institutes, the Research Institute for Pharmaceutical Chemis-
weil as th~ introduction of the manufacturing of variaus try and the Research Institute for Medicinal Plants. The Pre-
hermone products were of great importance. Also at this siclent of the Research Council is the deputy director of the
time was laid the foundation of the Hungarian synthetic drug Union, who takes simultaneously part in the work of the
industry, through the implementation of the produciion of National Co-ordinating Corporation engeged in the research
many important active principles (papaverine, sulfonámides) of biologically active compounds.
by means of developed technology. ln 1960 the number .of research workers was 'more th an
After 1945, besides the growing activity of the university 900 in the Hungarian drug industry (see table).
institutes, the institutions of the Hungarian Academy of
Sciences have increasingly token part in drug research. The 1960 1965 1970 1975 1980
res~arch !abo-ratories of the pharmaceutical compani es have
also.developed considerably. ln eddilion to these, the central Number of research
research orgon of the Hungarian pharmaceutical industry, workers 902 1,270 2,200 2,660 2,800
the Research Institute for Pharmaceutical Chemistry, was
Ofthese: graduated
found ed, later the Research Institute for Medicinal Pianis was
research workers, 250 320 590 775 950
likewise incorporCtted orgonicaily info the pharmaceutical
industry.
The more important achievements of the Hungerion drug During the past 20 years the expenditure for research
research ore shown in a se.parate table. represented 4 to 5 percent of theyearly turnover: whereas in
At present the supreme direction of research work is 1981-1985, during the next Five-Year Plan, this ratio will rise
provid ed by the Board of Scientific Policy. Considering the to 7-8 percen!.
29
. ------..<
The pharmaceutical factaries utilize one part of the avail- More important results of the Hungorian
able amount for financing their own research, the other part pharmaceutical research
will be remitted on the basis of research contracts, partly
to the two independent industrici research institutes, partly Yeor Result of research Research
to the more than 100 research laboratories, fundioning workers
independently from the indusiriai branch.
J-86'6 Discovery of the d iuretic effect of
The research laborotaries of the factaries have developed -<li)i"o!:J.- Calamel and its combinalion with
wide r'elations wi th the research institutes of the Hungerion opium Jendrossik
Academy of Sciences, variaus university institutes, medical 1897 Local anesfheflc effect of chiorabutanol V ámossy
research units and, Iasi but not least, with the Clinical Phar- 1900 Discovery of the laxative eff€cf of.
macological Network, operaling under the control of the phenolphta!eine (this wos the first
National lnsti~ute for Pharmacy. A co-operation in o number synthetic laxative) Vámossy
of scientiflc subjectsis going on within the industrici branch, 1916-17 Recog'hifion of the decrensed effect of
e. g. the development of operalion technics, protection of the quaternary fropeins on the central
environment, instrumentation, automatization, etc. nervous system. Developme.nf of homo-
tropine methylbromide. lntroduction
of the combinatlan of fropeins ond
papaveri ne Földi, lssekutz
1927 Discovery of the diuretic Novurit
(mercurophylfine) Földi, lssekutz,
Végh
30
Ye ar Resulf of research Research Yeo r Resulf of research Research
workers workers
1940 Discovery of Salvoseptyl 1961 Development of No-Spo (drotaverine) Mészáros,
(sulphathiourea) Földi, König, Szentmiklósi
Gerecs, Wolf
1961 Discovery of Pirazocilli''~ (antibiofic) Fehér, Koczka
1948-61 Microbiological transformofion
1961-65 Development of the neuroleptic
of steroids Krámli,
Frenólone (mefofenazafe) Toldy, BorSy
Horváth, Wix
1954 Isolation of primycine Vályi-Nagy, Uri, 1961-77 Development of the coronary d ilotor
Szi'lágyi Sensit (fendiline) Korbonics, Har-
sányi, Tardos
1955-69 Psychophysiological and psycho-
pharmacological methodological 1962 Discovery of the antitussive Libexine
research works J. Knoll, B. Knoll, (prednoxdiazine)) Harsányi,
Kelemen Tardos
1955-70 Analysis of the interconnection between 1962-68 Research of the antlcoagulant, anti-
the e ffed and structure of tropeins. inf!ammatory action of rare earth
Development of G astropi ne (xeny- metals. Development of the local anti-
trapium bromide), Gastrixon (tranfeli- inflammafory Phlogosam (samarium
ni um bromide) and central cholinoly- com pl ex salt of sedium disulfo-
ti cs Nádor, Gyer- salicylate) Jancsó, J. Gábor
mek, György
1962-71 Analysis of the radioprotective effect
l, 1955-73 Development of new cytosfatic sugar of Cysfeine Hernádi
derivotíves [Degranol (mannomusfine),
ji Myelobromol (mitobromitol), Zitosfop 1963 Discovery of Depersolone (mazipre-
(mannusulfan), Lycurim (rifrosulfan),. done) a water-soluble glucocorticoid Tuba, Komen,
Elobromol (mitolactol)] Vargha, Dumbo- Bor, Görög
vich, Horváth, 1963 Discovery of the vasospasmolytic
Mrs. Horváth, Holidor (bencyclane) Komlós, Pallos
lnstitoris
1965-79 Warking out of Jumex (seligiline)
1955-75 Analysis of the interconnection between
of antiparkinson effect, the first
the effect and structure of aminoketones.
selectíve inhibitor of the B-type
Development of Mydocalm (tolperisone)
monoaminooxydase J. Knoll, B. KilOII,
and Karion (pimeclone) Pórszász, Nádor
Ecseri, Magyar
1959-62 Development ofTrioxazine (tri metozine),
a minor tranquillize r Vargha, Dumbo- 1966 Werking out of the anfiseptic
vich, Borsy Resepfyl (Chloroseptyl) Lugossy, Zsol-
nai, Jenei
1959-79 Research of the cerebral vasodilofing
Vinca alkaloids, Devincan (vincamine), 1966-72 Synthesis of human ACTH Bajusz, Med-
Cavinton (vinpocetine) Szász, Szporny, zihradszky, Kis-
Szánta y faludy, Gráf
31
Ye ar Resulf of research Research
workers
1966-74 Development of Grandaxin (tofizopam),
a minor tranquillizer Kőrösi, Láng,
Komlós, Petőcz
32
Organization of the Hungarian pharmaceutical research
33
lnstilute for Drug laboratories-the elaboralion of the indusiriai process for
Research (Budapest) -
Evaluation of a !hinw the total synthesis of oxytocine, as weil as the synthetical
layer chrornatagram production of the human adrenocorticotropic hermone
(in UV-lighl) (ACTH) ore the most prominent.
The activity of the Institute in the field of steroid research
is ralher outstanding, among which the implementation of
the home production of estroné, metandienone, prednisclone
and d-norgestrel (Ovidon®) a re worth to be mentioned. The
fermentation department has done a significant work in the
production and isolation of oxytetracycline, streptomycine,
neomycine, nyStatine, 6-aminopenicjllanic acid and vitamin
B12 , further in the microbiolog.tcal transformatien of steroids.
ln 1952 the number of the lnstitute's staff was 315, today
this number exceeds 700. Out of the 560 persons engaged
tumoral sugar alcohol derivotíves (mannomustine1, ritrow in research work 227 ore graduated. The most important
sulfan'), as weil as that of metofenazate3 (an antipsycholie research subjects ore:
agent), trimetozine 4 (minor tranquillizer), tofizopam 5 (de- agenis acting on the heart and circulation;
veloped in common with EGYT) and cloranolol 6 (a B-blocker). - agentsacting on the central nervous system;
A fruitful field of research of the Institute is the pepiide che- - antibiotics and chemotherapeutics (anti-cancer drugs
mistry, where-in close co-operation with other research included).
1 Degranol® 4 Trioxazine<~~>
2 Lycurim® 5
Grandaxi n®
3 Frenolon® 6
Tobanum®
34
development of the home volatile oil production, the cuiti-
vation of ergot, as weil as in exploration and enrichment of
the home medicinal herb flora (revival of mint cultures,
acclimatation of ricinus, the starting of the cu!tivation of
Digitalis lanata). The Institute belonging since 1967 orgoni-
caily to the drug industry, has today a staff comprising 150
persons of which 35 ore quaiifled researchers.
The research work of the Institute is extended to the Sludy
of the propogoti on, compositi on, utilization, biology, genetic
properties, putting info cultivation, improvement, as weil
as to the implementation of the modern large-scale egro-
lechnics and cullivalion systems of pianis used in the phar-
maceutical, volatile oil industries, as weil as in drug com-
merce.
The Institute, in co·operation with the agricultural institu-
tions, has worked out and introduced the system of poppy
and ergo! cultivation on an indusiriailevel in Hungary.
lts Iask comprises the produciion of the improved seed-
grains of the more important medicinal herbs, the main-
fenonce of the co-operation in the exchange of grains on an
internalional level, the propagation of results obtained in
RESEARCH INSTITUTE FOR MEDICINAL research of medicinal herbs by means of publications (Herba
PLAN TS
Hungarica) and advisi n g, as weil as the sup p ly of expertise for
2011 Budakalász, józsef Attila u. 68 (central establishment) ali problems concerning the malter of medicinal herbs.
2011 Budakalász, P.O.B. 11 (postai address) ln addition to the field experiments, the modern phytotron
technics ore also used during the research work in the well-
The legal predecesser of the Institute was established in equipped laboratories.
1915 by the Ministry of Agriculture of that time. The Institute The Iask of the Institute is the official qualification and
of a great past acquired considerab\e results in the research control work in connection wi th the ingathering and cuitivat-
of morphine alkaloids, poppy improvement, the starting and ing of mediCinal herbs.
35
Institute for Drug-plant Drug research in the factaries
Research (Budakalász)
- C/imate room (in afphabetic order)
phl(ir;fsc1n
J
36
Biogat (Debrecen) - but the instrumentally well-equipped pi lot plan! provicles an
Isolation of penicillin-
produdng strains
opportunity to the opti malizalion and automation of techno-
logies, too. Besides antibiotics they ore carrying on experi-
ments o iso wi th other fermentotion products, li ke enzymes.
A considerable branch of research is the warking out of
manufacturing procedures for new ontibiotics and semi-
synthetic derivotives. ln the research of anti bacterial, anti-
rungal and antiviral agenis the company displays similarly
on important activity.
The further development of galenie preparalions, the
development of modern human and veterinary drug dosage
forms is the aim of the pharmaco-technological research,
already traditional with BIOGAL.
37
----J
Chinain (Budapest) (Uitraseptyl). After the Second World War they have started
- Pifot plant -
preparatory laboratory the microbiological research in Hungary first, making pos-
sible the produciion of penicilline, streptomycine and oxy-
tetraeyeline by fermentation. Since 1955, they have achieved
success in the research of sugar oleahol derivotíves of anti-
tumoraus effect (mannomustine, mifobronitol, mitolactol).
Amon g the more important results of the sixties the develop-
ment of drotaverine (No-Spa), a spasmolytic, various di-
phenylalkylamine derivatives, like the antitussive pred-
noxdiazine (Libexine) and the calcium-antagonist fendiline
(Sensit) may be listed. An original new anaigesic and anti-
inflammatory preparalion is rimazolium (Probon).
ln addition to the synthetic compounds, CHINOIN are
engeged i n the research of semi-synthetic derivotíves of fer-
mentation products and other natural substances. This work
resulted in the implementation ofthe manufacturing of severo l
penicilline derivotíves (meticilli.n, oxacillin, ampicillin) on
industrici scale and, recently, in successes in the fleld of
prostaglandins.
LATI (Gödöllő) The works iniliated v i gorously the development of modern,
Housing of experimen~
lal animals original plant-protecting agen ts, amon g !hem that of synthetic ·
pi retroids.
Well-equipped pilot pianis serve the speeding up and
opti malizatien of laboratory proced u res.
ln the line of research CHINOIN are relying not only on
their own research work, but they mainfain co~operative
relatíens with a number of outside research organizations.
too. Their collaboratien extends to foreign institutions and
big industrici companies notable even on a world scale.
ln order to cover their need in experimental animals for
preclinical research, they mainfain a laboratory animal-
breeding institute (LATI) in common with RICHTER.
ln the domain of research CHINOIN keep employed
approx. 700 persons, nearly onethird ofthese are graduated.
39
Humán (Budapest)- efficieni work of th ei r researchers, both theoretically and
Analysis of
immunochemicaf practically, has greolly enriched the veterinary and livestock-
reagenls breeding skill. (Homologous swine erysipelas serum of high
titre, hyperimmune serum and vaccine against Aujeszky's
disease, goose influenza antiserum, hyperimmune serum
and atfenuated vaccine against viral diarrhoea, vaccine
against infectious bovine rhinolracheilis (IBR), Giberellic
acid, pectinase, aga r gel precipilalion testsfor the demonstra-
fion of swine-fever, foot and mouth disease, etc.).
The number of research workers amounts to 201 persons,
of which 67 a re graduated.
40
stand i ng res u l ts in the synthesis of polypeptides (total synthesis
of oxytocin and synthesis of human ACTH) and in the disco-
very of many new compounds. These include tolperisone
(Mydocalm), being not only a poten! myotonolytic, but proved
to be excellenily useful in the Ireatmeni of peripheral circula-
tory disorders, too, further pimeclone (Karion), compiet-
ing the range of respiratory analeptics. On the basis of a
recent conception of antiinflammatory treatment, the'sama-
rium camplex salt of sedium disulfosalicylate (Phlogosam,
Phlogosol), an efficacicus local antiinflammatory agent was
Chemicaf Works of made. They succeeded in developing a patent-independent
Gedeon Richer, Lld. process for diazepam.
(Budapesl}- A traditional field of RICHTER's research work is the As a resuli of the programmesof operali on-development,
The pharmacologicaf
research laboratory phytochemistry. A number of active principles of Digitalis new machinary was put into use both for the manufacturing
provided with modern lanala were isolated and put on the market, inform of prepa- of active principles and the finishing and packing of dosage
inslruments and own raliens ofhigh purity. Numerous ergo! alkaloid products have fo rrns.
animal colony
constitutes one of
been developed by using artifidal contami nation and special The research team of the works maintains extensive co-
the bases of the technologies. They played a pioneering post in the isolation, operation on the one hand with Hungarian, on the other
high/y organized testing and development info a drug (Devincan) of the aclive hand with ·foreign research organizations, scientific institutes
and deve/oped
research aclfvities agent of Vinca minor, the vincami ne. A semi-synthetic deri- and enterprises. They display recently an increased activity
valive of this is vinpocetine (Cavinton), a specific drug for the in respect ofveterinary products and plant-protecting agents.
cerebral fissue regeneration. Vinblastine and Vincristine
isolated from Calharantus roseus proved to be effective in the
treatment of certein molignant tumours.
The researchers ofthe firm ore efficient in the investigations
of synthetic organic chemistry. They have achieved out-
41
------------J
Co-operation in research
The evaluation system of new products has developed in or taking over of some new products. Co-operation can be
Hungary in su ch a mannerthat the experimental (preci i ni cal) brought about between a Hungerion enterprise ond foreign
studies ore carried out in the first place wilhin the drug eli nics, institutesor between a foreign enterprise and Hunga-
industry (in the Research Institute for Pharmaceutical Che- rian eli nics, institutesfor the carrying out of cerfain special,
mistry and in the enterprises, resp.), in the second place in so-cal led target studies. The respective agreements with the
university, academical and other scientific institutes. The foreign enterprises and institutes, resp. ore concluded in such
fundamental experiments in men, called phases l. and ll. cases (in concertwl th the Hungarian producer) by MEDIMPEX
human trials, ore effected by a Clinical Pharmacological Net- H ungorion Trading Company for Pharmaceutical Products.
work (CPN) consisting of 27 units, created in university A "development" company may be established abroad
elinics and special departments of hospitals with a total by the Hungerion drug industry, in order to ensure the full
number of staff of about 110 persons, of which 65 ore gra- conformity of the fest results of new Hungerion products
duated research workers. The work of CPN is co-ordinated with the drug-evaluation requirements of the given country
and managed by the National Institute of Pharmacy, i ts main- or of an economical community in a relatively fast way li ke
tenance and development is provided jointly by the Ministry e.g. Optifaro, functioning in the FRG.
of Health, the State Committee on Technical Development The Hungarian drug industry takes part in the realizalion
and the drug industry. of co-operation agreements fixed in interstate conventions,
The Hungerion pharmaceutical industry is carrying on as weil as in the work of international organizations (UNO,
research co-operation wi th foreign partners, too. The charac- WHO).
ter ofthis may be mani fold, starting from the wid est, so-cal led The favourable experience acquired so far inspire the
general (frame) agreements to the mutual undertaking of Hungerion pharmaceutical research organizations to extend
strictly determined, concrete tasks. their co-operation in the research and warking out of new
Caneerning the conten ts of the co-operation, it mostly co ver products with any foreign partner who-on mutual basis-
thejointdevelopment (exami nation ), and thereafterthe transfer showsan interest in this.
42
Hungarian drug patents
j•
Patents Applications
granted being under
judgemeni
Alkaloida 18 12
Biogal 63 7
Chinoin 357 148
EGYT 177 43
Reanal 29 18
Richter 234 144
R.lnst. for Pharm. Chem. 144 56
R. lnst. for Med. Plants 21 3
43
Traditions
47
lntroduction of new drugs
State Pharmaceuticaf and Clinical Pharmacology and the Medical Commil/ee on Research
fnslifule (Budapest) -
High-pressure thin- Ethics.
layer chromatographic The control and evaluation of the expert opinions ore
examinations followed by a decision caneerning the authorization for cli-
nico-pharmacological research, i.e. for the so-called phases
l. and il. human trials. It is prohibited to conduct non-author-
ized human experiments with a new drug.
Clinico-pharmacological tests are carried out by the
units of the Clinical Pharmacological Network and the results
ore assessed by the two aforesaid Committees ofthe Scientitk
Health Council. Auth orizalion for therapeutical experiments
(phase lll. human trials) depends on the evaluation results.
The Clinical Pharmacological Network consists of 27 re-
search uni ts, each unit is fundioning as an integral part of a
specialized health-institution (elinic or hospital) but ils activity
is fixed by a co-ordinated national research project for clini-
cal pharmacology.
The positive evaluation of the results of therapeutical
experiments, as weil as the decision of the National Institute
of Pharmacy in respect of "drug suitability" are equally
precondili ens of the registralion of a new drug. The applica-
tion for registrotion contains the data and expert opinions,
on the basis of which the registrotion proced u re is conducted
ln Hungary one ofthe basic principles of the introduction by the Institute, in exactly regulated and prescribed forms.
of drugs is that the uniimited increase ofthe number ofphar- The data and expert opinions are scrutinized by the ln-
maceutical preparoliens does not serve public health. stitute's sections for Chemistry, Biology and Microbiology,
The preclinical requirements ore regulated by detailed Pharmaceutical Technology and Pharmacopoeia and the
prescriptions. Expert opinions, containing the methods and quality requi remenis and control test methods a re established
results of tests ore controlled by the National Institute of in the Quality Prescriptions.
Pharmacy and evaluated by !wo expert committees of the The text oflabel and package i nse rt (d i rections for use) is a iso
Scienlific Health Council, the Committee on Drug Administration prescribed by the Institute du ring the registralion proced u re.
48
Quality control
49
International
l
co-operations
CMEA
50
EFTA Pharmaceutical lnspection Convention International responsibility of Hungarian
drug control authorities
Hungaryismember ofthe international conventien elabo-
rated by EFTA states (Pharmaceuticallnspeclion Convenlion: The Hungarian health authoriti es ore aware of the inter-
PIC*), which over and above the GMP recommendations of national responsibi li ty ofthe registrotion and control agendes
WHO, regulates and makes compulsory the application of of countries transacting considerable drug export businesses.
safe condiliens in drug manufaciure and the regutar offidol ln Hungary there ore no "two different" registrotion pro-
control ofthe respective prescriptions. cedures. The stipulations of the Hungarian Pharmacopoeia
Hungary is closely co-operating with the other Member and the Quality Prescriptions of the National Institute of
States (Austria, Denmark, Finland, lceland, lreland, Liech- Pharmacy refer to the registered drug preparations, inde-
tenstein, Norway, Portugal, Sweden, Switzerland and the pendenily whether they ore used in the country or abroad.
Uniled Kingdom) in implementing the provisiens of the ln resped of the registered drugs, Hungarian authorities
Convention. The co-operation and the uniformily of inspec- issue certificates on the request of the health authorities of
tions ore usefully serv ed by the jointtraining and continuation importing countries, and both on multilateral or bilateral
courses of inspectors. basis they un9ertake the guarantee-offering part, the fuifil-
meni of which is made possible by the more !han half a
century tradiliens of the active regulatory drug control
United Nations lndustrial Development system and by the central orgonizalion of the pharmaceutical
Organization industry and foreign trade.
51
Historical retrospection
The development at a rapid pace of the Hungarian phar- is representing the foreign trade interest of the Hungarian
maceutical factaries has created early the basis for exports. pharmaceutical factori es.
CHINOIN and the GEDEON RICHTER WORKS had deliv- Though, the export and import of pharmaceutical fine
ered already prior to theFirst World War a considerable chemicals and specialiti es make up a decisive part of MED-
quantily of drugs to foreign countries, main ly to Russia and IMPEX' activity, they achieve a considerable turnover in
the Balkan countries. Later the export activity became more other fields too. Their export range is completed by feed
intensíve and in the thi rties European and ev en overseas additives, medicated feeds, biocosmetics, medicinal her_bs,
subsidiaries were established, the latters first of ali in Latin volatile oils, medicinal waters, laboratory fine chemicals,
America. biochemical products and radieaelive substances. As far as
The Hungarian pharmaceutical industry, rec.onstructed imports ore concerned, they purehose important basic
after the devasta!ions of the Second World War, has beceme substonees-apari from the drug industry-for 45 to 50
relatively fast able to produce-apart from covering the different enterprises.
home needs-aiso for foreign markets. ln the beginning the The development of the pharmaceutical industry has early
state enterprise KELIMPEX was engaged -besides other types made necessary for MEDIMPEX to undertake tasks in the
of articies-in the export of their products, but already in 1949 field ofintellectual export-import. The licence and know-how
the dynamical development has made necessary to establish agreements have contributed considerably to the extension
a company specialized in pharmaceutical foreign trade. ofthe industry's produci range, as weil as to the introduction
At this time MEDIMPEX Hungarian Trading Company for in foreign countries of preparoliens resulti n g from Hungarian
Pharmaceutical Products was founded which sincethat time research (Fig. 4 and 5).
55
Main markets
The commercial relations of MEDlMPEX extend almost The significance of drug consignments destined to the
to the who le world. They se ll and buy n early in 100 countries. socialist countries is shown by the fact that the i r value exceed~
Besides the socialist countries, the mosf developed non-socia- ed 200million rubles already in 1979.
list countries and !hose being on the lowest grade of develop- The exports effected on the basis of bilaterel or multilateral
ment can be found amon g their partners. product specializatien play an important part in the forrnation
of the turnover.
The specializatien is a tool fo increcse both the exporfs and
Distribution of the Hungarian drug export
imports. MEDlMPEX is constanily looking for possibilities
and import aceording to the main country groups
to en large the range of the home drug supply by the must
(1980)
up~to~date preparations ofthe other socialist countries. Th us,
the ratio of finished drugs is steadily increasing wilhin the
Expol"ts lm ports
assortment of pharmaceutical products imporled from the
Million % Million % socialist countries.
Ft Ft
Amon g the socialist countries the highest turnaver is achiev~
1. Socialist counfries 5,656 57.3 967 15.0 ed with the Soviet Union. This is followed by the European
CMEA (Comecon) 5,631 57.0 940 14.5 CMEA countries, at the some time Vietnam, Mongolia, the
Others 25 O.l 27 0.5
Korean Peaple's Republic and Cambodia are catching up
2. Non-socialist more and more (Fig. 6).
countries 4,213 42.7 5,474 85.0
Developed 2,729 27.6 5,144 79.9
EEC 1,610 16.3 2,925 45.5 Distribution of the Hungarian
Other European 696 7.1 1,602 24.8 drug export and import in the year 1980
Outside of Europe 423 4.2 617 9.6 effected with socialist countries
Under development 1,484 15.1 330 5.1 EX PORTS IM PORTS
Total 9,869 100.0 6,441 100.0
Socialist countries
56
Fig. 4.
--
Fig. s.
Developed non-sodalist countries activily-in the development of produciion and research
relations, too. The joint enterprise Optifara was established
ln 1980 about 65 percent of the export turnaver of non- in the German Federal Republic explicitely for the deve-
rouble eleari n g of MEDIMPEX was achieved wi th the develop- lopment of research.
ed non-socialist countries which circumstance accentuates the The developed non-socialist countries represent a market
importance of this area in the Hungarian pharmaceutical not only for sales but are importani for the purchases by
foreign trade. The development of the commercial relations MEDIMPEX. The import volume exceeds yearly US $ 160
shows a firm tenden ey. ln 1980 the average increcse amount- million which meets still the needs of many other indusiriai
ed to 6.2 percent related to 1979, the concrete rate of de- branches.
velopment shows, of Course, o rother different pattern for
each country. For the most dynamical markels e.g. these MEDIMPEX's drug export ond import data
figures are the following: of 1980 in respect of some developed non-socialist
countries (Million Ft)
Denmark 138 percent
Canada 100 percent Exports lm ports
61
Countries under development
62
NETWORK OF MEDIMPEX
(without agencies)
..
63
ADDENDUM
Sin ce puth ng the manuscript to press the realizalion of the targets ri g h! of foreign trade for technical-scientific colloboration (co-opera-
of the pharmaceutical industry has made necessary to carry out some tions, licence agreements, etc.), and also "Medimpex" has been re-
organizational changes. The main point of this change is the efficieni organized into a joint foreign trade enterprise. ln ils Board of Directors
realizalion of theso-called innovation chain (research-development- !here is a seventh member beside the six directors of the ph,armaceuti-
production- marketing-sales), to ens u re the synerglsm between deve- cal companies, namely the director of Pharmatrade Foreign Trading
lopment and marketing. Aceording to the Government's resolution the Company. This orgonizalion was established because foreign trade
manufacturer would control the innovation chain. Thus, the sphere activily of Medimpex covered in the previcus years not only the phar-
of activity and authorily of the six factorles of the pharmaceutical maceutical industry, but also other indusiriai branches (medicinal
industry (Alkaloida, Biogal, Chinoin, EGYT, Richter, Reanal) have herbs, medicinal mud, food industry, agriculture, cosmetics, per-
changed. The enterprises of the pharmaceutical industry possess seve- fumery, etc.).
ro! joint ventures which contribute to the realizatien of the innovation
The imrnedlate superlor aufhorily of Medimpex Hungarian Trad-
chain. The joint ventures ore controlled by the Board of Directors,
Ing Campany is a Board of Directors, consisting of seven members,
consisting of the campany managers. The Union of the Hungarian
out of which every two years a president is elected, controlling the
Pharmaceutical Industry arranges the efficieni sirategical decisiens of
adivili es of the foreign trading compon y.
the Board of Directors of the indusiriai sector and co-operates in the
execution. The Board of Directors of the individual research institutes Medimpex Hungarian Trading Campany for Pharmaceutical Pro-
is the controlling and leading orgon of ali three pharmaceutical re- ducts is thus a so-called ioinf veniure and a joint property of the
search institutes (Institute for Drug Research, Medicinal Plan! Rese- pharmaceutical factories, as weil as of Pharmatrade Trading Com-
arch, Organochemical Development), forming a joint enterprise. pany. Wilh ils marketing network extending to more than 25 coun·
Caneerning the foreign trade, severo! modifications have been !ries, it helps and impreves the steadily developing international
effected, too. The producing componles have obtained the individual relationsof the Hungaria n pharmaceutical industry.