E m i l F. F R E Y (Galves ton, U.S.A.)

D 1 3

THE REGULATION OF PATENT MEDICINES IN THE UNITED STATES AND FRANCE

B o t h the Un i t ed S t a t e s a n d F r a n c e h a v e developed sa f egua rds aga ins t t h e d i s t r i b u t i o n of u n r e g u l a t e d m e d i c a l r e m e d i e s . The p rocess by w h i c h these safe­g u a r d s have been pu t in to effect h a s been very di f ferent in t h e t w o coun t r i e s , a n d ref lects a difference in a t t i t u d e t o w a r d t h e s t a t e ' s role in social r egu la t ion . The effect of t hese r egu la t ions on the l icensing of n e w d r u g s h a s also led t o a di f ferent a p p r o a c h to d r u g deve lopmen t a n d t e s t ing in t h e Uni ted S t a t e s a n d F r a n c e .

The regu la t ion of pa t en t med ic ines , o r sec re t p rop r i e t a ry r e m e d i e s , w a s begun in F r a n c e in 1728 w h e n t w o dec rees w e r e i ssued . One de lega ted « power s of surve i l lance over p ropr i e t a ry m e d i c a t i o n s »(1) , t o t h e L i e u t e n a n t Genera l of Police of P a r i s ; a n o t h e r c r e a t e d a c o m m i s s i o n to look in to t h e p rob l em of secre t r e m e d i e s . T h r o u g h o u t t h e 18th cen tu ry , phys ic ians a n d sc ien t i s t s ana lyzed the w ide var ie ty of sec re t r e m e d i e s t h a t w e r e u s e d by p r iva te phys ic ians a n d in mi l i t a ry hospi ta l s , a n d some a t t e m p t s w e r e m a d e to d e t e r m i n e the i r efficacy t h r o u g h cl inical t r i a l s . In 1778, King Louis XVI g r a n t e d the newly founded Royal Socie ty of Medic ine t h e sole p o w e r to approve sec re t r e m e d i e s for public u se . Al though m a n y of these n o s t r u m s w e r e found to be w o r t h l e s s , s o m e — s u c h as the an t i syph i l an t rob Boyveau-Laffecteur — w e r e accep ted by the m e d i c a l profess ion (2).

The m a n u f a c t u r e a n d sale of sec re t r e m e d i e s , however , c o n t i n u e d to f lour ish . After t h e Revolut ion, r e p o r t s on t h e p rob lem w e r e p r e s e n t e d to va r ious legislat ive bodies by such lead ing phys ic ians a n d sc ien t i s t s as Guil lot in, Bra i l lon , a n d Four-croy (3). Final ly, t h e law of Germina l , e n a c t e d in 1803, r e g u l a t e d t h e p rac t i ce of p h a r m a c y a n d au tho r i zed only p h a r m a c i s t s to fill p resc r ip t ions w r i t t e n by l icenced phys ic ians . P h a r m a c i s t s w e r e p e r m i t t e d to s tock only t h o s e m e d i c a t i o n s approved by t h e schools of med ic ine ; all o t h e r r e m e d i e s w e r e cons ide red secre t a n d illegal. The adver t i s ing , d i s t r ibu t ion , a n d sale of sec re t r e m e d i e s w e r e p u n i s h a b l e by f ines a n d i m p r i s o n m e n t (4). Unfor tuna te ly , t h e g o v e r n m e n t w a s unab le to f o r m u l a t e a p rac t i ca l def ini t ion of w h a t c o n s t i t u t e d a sec re t r e m e d y . Also, m a n y pa t en t m e d i c i n e s w e r e extol led for t he i r n o n m e d i c i n a l p roper t i e s , so t h a t t h e penal t ies la id d o w n by t h e l aw could be c i r c u m v e n t e d .

Severa l a t t e m p t s w e r e m a d e to enforce t h e p roh ib i t ion aga ins t u n a u t h o r i z e d sec re t r e m e d i e s . I n 1810, Napoleon p roc l a imed t h a t all secre t r e m e d i e s would h a v e to be au tho r i zed by t h e Min i s t e r of t h e In t e r io r , w h o wou ld be adv ised by a commiss ion . The c o m m i s s i o n « wou ld s t u d y t h e compos i t ion of t h e r e m e d y , d e t e r m i n e i ts safety a n d efficacy, and , if it w a s j u d g e d valuable , r e c o m m e n d p u r c h a s e of t h e fo rmu la f rom t h e inven to r a t a fair p r ice »(5) . I n 1820, t h e b u r d e n of t e s t ing a n d approving secre t r e m e d i e s w a s shif ted to t h e Commiss ion on Sec re t a n d N e w Remed ie s of t h e A c a d e m y of Medic ine . B o t h c o m m i s s i o n s w e r e ine f f ic ien t ; by 1843, they h a d approved fewer t h a n 20 sec re t r e m e d i e s for sale to t h e publ ic .

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The p rob lem of p ropr i e t a ry m e d i c i n e s w a s closely r e l a t e d to t h a t of t h e adu l t e ra ­t ion of d rugs . Many d r u g s w e r e a d u l t e r a t e d in t h e ear ly 1800s b u t no inspect ion s y s t e m exis ted t o a s c e r t a i n t h e qua l i ty of d r u g s i m p o r t e d in to F r a n c e . T h e l a w of Ge rmina l p rov ided for t h e a n n u a l inspect ion of p h a r m a c i e s for t he purpose of conf isca t ing s u b s t a n d a r d d r u g s , b u t t h e p rob lem pe r s i s t ed in to t h e m i d d l e of t h e c e n t u r y , w h e n in 1851, t h e l eg i s la tu re m a d e t h e sale of a d u l t e r a t e d food a n d d r u g s pun i shab le by f ines a n d i m p r i s o n m e n t (6). This legis la t ion r e m a i n e d in force un t i l t he ear ly 20th cen tu ry .

The F r e n c h approach to t h e r egu la t ion of d r u g s in t h e 1800s w a s cont ra ­d ic to ry a n d ineffectual . Al though a n u m b e r of l aws on the books proh ib i ted t h e sa le of sec re t r e m e d i e s a n d a d u l t e r a t e d d rugs , t he se l aws w e r e enforced sporadi ­cally a n d t h u s d id l i t t le to h a l t t h e d i spers ion of p a t e n t med ic ine s .

The s i tua t ion in F r a n c e d u r i n g th is per iod w a s t h u s no t very different f rom t h a t in the Uni ted S t a t e s , w h e r e v i r tua l ly no r egu la t ion of d r u g s w a s done before t h e Civil War . T h e use of p a t e n t med ic ines w a s w i d e s p r e a d in t h e Uni ted S t a t e s in the ear ly 19th c e n t u r y for severa l r ea sons . F i r s t , because of t h e l ack of phys ic ians in the f ron t ie r a r e a s , t h e self-help approach to h e a l t h c a r e w a s a necess i ty . Second , med i c ine w a s stil l in t he ea r ly s t ages of scientif ic r e sea rch , a n d doc to r s re l ied on m a n y r e m e d i e s t h a t h a d been favored in the pas t . F o r example , people fea red the m a l i g n a n t inf luence of t h e « evening d a m p », a n d bleeding w a s stil l r ecom­m e n d e d in m a n y cases (7). Final ly , n o r e s t r i c t i ons w e r e p laced on adver t i s ing by t h e sel lers of n o s t r u m s , w h e r e a s phys ic ians t hemse lves s e ldom adver t i s ed . Ear ly Amer i cans w e r e t h u s u n d e f e n d e d aga ins t t h e inf la ted c l a ims of quacks a n d f add i s t s .

A p rob lem facing p h a r m a c i s t s a n d phys ic ians w h o w i s h e d to s t a n d a r d i z e the m a n u f a c t u r e of d r u g s in Amer ica in the ear ly 1800s w a s t h a t m o s t p h a r m a c o p o e i a s avai lable r e f e r r ed exclusively to E u r o p e a n d rugs a n d h a d l i t t le to do w i t h « t h e consensus of t h e A m e r i c a n m e d i c a l p r ac t i ce »(8) . One of t h e ear l ies t p h a r m a c o ­poeias pub l i shed to r e m e d y th i s s i tua t ion w a s i s sued by t h e M a s s a c h u s e t t s Medica l Society in 1808 I t w a s no t un t i l 1820, however , t h a t a ser ious a t t e m p t w a s m a d e to compi le a list of m e d i c i n e s t h a t wou ld se rve t h e n e e d s of t he m e d i c a l profess ion in the Uni ted S t a t e s as a who le . The r e su l t i ng work , t h e Uni ted S t a t e s P h a r m a c o ­poeia (USP) , h a s b e e n rev ised every d e c a d e s ince .

The in s t i t u t ion of t h e U S P w a s an i m p o r t a n t s tep t o w a r d self-regulat ion by t h e m e d i c a l profess ion. A n o t h e r s tep w a s t h e c rea t ion of t he A m e r i c a n Medica l Associa t ion (AMA) in 1847, w h i c h f rom i ts ea r l ies t yea r s , p r o t e s t e d t h e sa le of quack r e m e d i e s t o an i gno ran t public . T h e pres t ig ious Journal of the American Medical Association, however , c o n t i n u e d to c a r r y a d v e r t i s e m e n t s for n o s t r u m s un t i l t he ear ly 1900s, on the g r o u n d s t h a t such adve r t i s ing w a s essen t ia l to the f inancia l well-being of t he m a g a z i n e (9). A t h i r d s tep w a s t a k e n in 1852 w h e n the A m e r i c a n P h a r m a c e u t i c a l Associa t ion w a s founded , in p a r t to es tab l i sh s t a n d a r d s t h a t could be fol lowed t h r o u g h o u t t he p h a r m a c e u t i c a l profess ion (10).

The sys t em of free en te rp r i s e t h a t c h a r a c t e r i z e d t h e d rug i n d u s t r y before the Civil W a r w a s h a m p e r e d only sl ightly by the in s t i t u t ion of compu l so ry con t ro l s . F o u r s o u t h e r n s t a t e s and severa l local j u r i sd i c t i ons , inc lud ing New Or leans a n d New York, e n a c t e d legis la t ion to r egu la t e t h e p rac t i ce of p h a r m a c y (11). These local a t t e m p t s a t regu la t ion w e r e ineffectual , however , in t h e face of w idesp read a d u l t e r a t i o n of d rugs . I t w a s n o t un t i l 1848 t h a t a n a t i o n a l d rug- impor t law, des igned to h a l t t h e i m p o r t a t i o n of a d u l t e r a t e d d rugs , w a s enac ted . T h e S e c r e t a r y of t he T r e a s u r y w a s d i rec ted t o e x a m i n e t h e pu r i t y a n d s t r e n g t h of all d rugs a t t h e i r po in t of en t ry in to t h e Un i t ed S t a t e s . Approximate ly 90,000 p o u n d s of d r u g s w e r e t u r n e d a w a y w i t h i n t h e f i rs t 10 m o n t h s a f te r t h e passage of t h e l aw (12). Unfor tuna te ly , t h e s t a n d a r d s u s e d to d e t e r m i n e d rug qual i ty w e r e u n c l e a r a n d few inspec tors w e r e qual i f ied to pe r fo rm t h e r equ i r ed e x a m i n a t i o n s .

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D r u g r egu la t i ons a f te r t h e Civil W a r a lso focused on t h e p rob lem of d r u g a d u l t e r a t i o n r a t h e r t h a n on p a t e n t m e d i c i n e s . Before t h e end of t h e 19th cen tu ry , v i r tua l ly anyone cou ld bot t le a n d sell a m i x t u r e of d r u g s a n d chemica l s a n d m a k e c l a ims in good fa i th o r b a d about i t s ef fect iveness in t h e t r e a t m e n t of a w ide r ange of ills. Because phys ic ians usua l ly d i spensed the i r o w n med ic ine s , p h a r m a c i s t s w e r e forced to c o m p e t e for bus iness by bo th d iagnos ing a n d t r e a t i n g d i sease (13). M a n u f a c t u r e r s of n o s t r u m s could p ro t ec t t he i r monopoly over a popu la r m i x t u r e e i t h e r by p a t e n t i n g t h e m e d i c i n e (in w h i c h case t h e ing red ien t s w o u l d b e l i s ted a t t h e P a t e n t Office), o r by sel l ing a sec re t m i x t u r e u n d e r a t r a d e m a r k . The u s e of a t r a d e m a r k p ro t ec t ed t h e m a n u f a c t u r e r a n d a l lowed h i m t o keep t h e fo rmu la a n d t h e m e t h o d of p r e p a r a t i o n a sec re t (14).

By the ear ly 20th cen tu ry , m a n y phys ic ians a n d m e d i c a l w r i t e r s w e r e rebel l ing aga ins t t h e secrecy of n o s t r u m m a n u f a c t u r e r s : « Among t h e ob jec t ions given w e r e t h a t in te l l igent u s e w a s imposs ib le w h e n t h e i ng red i en t s w e r e kep t secre t a n d t h a t secrecy i n d u c e d t h e possible conc lus ion t h a t t h e m a k e r of t h e p roduc t w a s monopol iz ing t h e p r o d u c t for selfish r e a s o n s a n d t h a t t h e a c t u a l cos t of t h e p r o d u c t w a s en t i re ly ou t of p ropo r t i on to i ts sales pr ice »(15). M a n y phys ic ians suspec ted t h a t m a n u f a c t u r e r s u s e d s o m e ing red i en t s secre t ly t h a t wou ld no t b e accep ted if t he i r p resence w e r e ident i f ied, a belief t h a t p layed n o sma l l p a r t in t h e passage of t h e P u r e Food a n d Drugs Act of 1906.

I n the yea r s i m m e d i a t e l y fol lowing t h e passage of t h e 1906 Act, m o s t a c t i ons t a k e n u n d e r t h e n e w regu la t ions involved t h e con t ro l of food add i t ives ; less t h a n a f o u r t h of t h e m involved d rugs . Of these , however , m o s t w e r e a i m e d a t p a t e n t med ic ine s . When s t a t e c h e m i s t s found a « shock ing d i spar i ty » b e t w e e n the c l a ims m a d e on t h e labels of p a t e n t med ic ines a n d t h e t h e r a p e u t i c powers of the i r ingre­d ien t s , t h e provis ions of t h e Act w e r e b r o u g h t t o b e a r on m a n u f a c t u r e r s w h o m i s b r a n d e d the i r p r o d u c t s (16). M a k e r s of h e a d a c h e cu re s con ta in ing ace tan i l id w e r e p rosecu ted , a s w e r e t h e m a k e r s of ton ics t h a t c l a i m e d t o c u r e n a r c o t i c add ic t ion , cancer* a n d o t h e r d r e a d d iseases . The p u n i s h m e n t s in t h e s e cases , however , w e r e of ten l ight , a n d m o s t m a n u f a c t u r e r s w e r e c o n t e n t t o pay t h e i r f ines a n d go b a c k in to bus iness af ter m a k i n g s l ight changes in t he i r p r o d u c t s . As l a t e as 1922, t h e m a k e r of a « c u r e » for t ube rcu los i s w a s p e r m i t t e d u n d e r t h e l aw to c o n t i n u e sel l ing h is p r o d u c t a f te r a f inding t h a t h e h a d n o t i n t e n d e d to de f raud t h e publ ic (17).

T h e l imi ted abil i ty of a s s a y e r s to d e t e r m i n e t h e a m o u n t a n d t h e qual i ty of t h e ing red ien t s u s e d in p a t e n t m e d i c i n e s h a d a lways m a d e en fo rcemen t of p a t e n t m e d i c i n e l aws difficult. P r o g r e s s h a d been m a d e in th i s field by t h e mid-1920s, however , a n d by 1930, t h e Food a n d D r u g A d m i n i s t r a t i o n h a d es tab l i shed t o l e r ance levels for t h e m a n u f a c t u r e of m o s t m a j o r d rugs . E v e n so, r egu la t ion w a s n o t successful b e c a u s e t h e m a j o r conce rn of leg is la tors in th i s per iod s e e m e d to be t h a t of h o w bes t to p ro t ec t t h e public aga ins t quacks (18). T h e p rob lem of un regu­l a t ed p a t e n t med ic ines w a s n o t solved in t h e Un i t ed S t a t e s u n t i l t h e pas sage of t h e 1938 Food, Drug a n d Cosmet ic Act, w h i c h r e q u i r e d t h a t d a n g e r o u s or habit-fo rming d rugs be a d m i n i s t e r e d only by p resc r ip t ion . P h a r m a c i s t s b e c a m e c r imina l ly l i ab le for sel l ing d r u g s over t h e c o u n t e r t h a t shou ld h a v e been sold by p resc r ip t ion only. All m e d i c i n e s t h a t w e r e sold over t h e c o u n t e r w e r e r e q u i r e d t o have a label t h a t l is ted the i r i ng red ien t s a n d p rov ided c lear i n s t ruc t i ons as to t h e proper dosage . T h u s t h e d a n g e r s i n h e r e n t in t h e i n d i s c r i m i n a t e u s e of p a t e n t med ic ines in t h e Un i t ed S t a t e s w e r e effectively al layed.

S imi l a r s teps w e r e t a k e n in F r a n c e d u r i n g t h e ear ly 20th c e n t u r y to suppress t h e d i s t r i bu t ion of p a t e n t r e m e d i e s a n d h a l t t h e a d u l t e r a t i o n of d rugs . A n a t i o n a l l abora to ry w a s es tab l i shed in 1918 for t h e ana lys i s of med ic ina l p r o d u c t s . Ano the r n a t i o n a l l abo ra to ry w a s e s t ab l i shed in 1922 for t h e u s e of t he Codex Commiss ion ,

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which , l ike t h e USP, a s says d r u g s for the i r pur i ty a n d efficacy. Final ly , in 1926, the p rob lem of secre t r e m e d i e s w a s resolved w h e n a l aw w a s passed t h a t r e q u i r e d t h e full d i sc losu re of t h e q u a n t i t y of ac t ive ing red ien t s , a n d t h e n a m e a n d p lace of t h e m a n u f a c t u r e r , on the label (19). Thus , t h e i n f o r m a t i o n on t h e package of a m e d i c i n e n o w c a n be u s e d to d e t e r m i n e w h e t h e r i t con fo rms to t h e r egu la t ions es tab l i shed by t h e Codex.

R E F E R E N C E S

1. BERMAN Alex. — « Drug Control in Nineteenth-Century France : Antecedents and Directions », in John B. Blake (ed.), Safeguarding the Public (Baltimore, John Hopkins Press, 1970), p. 4.

2. Ibid., p. 5. 3. FLIGOT L, — La question des remèdes secrets sous la Révolution et l'Empire (Paris,

Occitania, 1924), p. 35. 4. Codex medicamentarius Galliens seu pharmacopoea gallica. Pharmacopée Française

rédigée par ordre du gouvernement. 6th ed., 2 vols, vol. 1 (Rennes, Imp. Oberthur, 1937), pp. 11-12.

5. BERMAN. — P. 7. 6. Ibid., p. 9. 7. DYKSTA David L. — « The Medical Profession and Patent and Proprietary Medicines

during the Nineteenth Century», Bulletin of the History of Medicine, 29 (1955), p. 401-419.

8. ROWLING Harry F. — Medicines for Men (New York, Afred A. Knopf, 1970), p. 141. 9. Ibid., p . 155.

10. SONNEDECKER Glenn. — «Contribution of the Pharmaceutical Profession Toward Controlling the Quality of Drugs in the Nineteenth Century», in John B. Blake (ed.), Safeguarding the Public (Baltimore, John Hopkins Press, 1970), p. 100.

11. SONNEDECKER Glenn. — Kremers and Urdang's History of Pharmacy (Philadelphia, Lippincott, 1963), p . 193.

12. SONNEDECKER Glenn. — « Controlling the quality of drugs in the nineteenth century », pp. 101-102.

13. DYKSTRA David L. — P. 403. 14. Ibid. 15. Ibid., p. 414. 16. YOUNG James Harvey. — « Drugs and the 1906 Law », in John B. Blake (ed.),

Safeguarding the Public (Baltimore, Johns Hopkins Press, 1970), p . 148. 17. Ibid., p. 150. 18. CAVERS David F. — «The Evolution of the Contemporary System of Drug Regulation

under the 1938 Act », in John B. Blake (ed.), Safeguarding the Public (Baltimore, Johns Hopkins Press, 1970), p . 158.

19. BERMAN. — P. 133. SLIDES

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