Academic Sciences
`
`Asian Journal of Pharmaceutical and Clinical Research
`
`Vol 5, Issue 3, 2012
`
` ISSN - 0974-2441
`
`Research Article
`
`Vol. 4, Issue 3, 2011
`CONTEMPLATION ON APPROVED DRUGS IN INDIA FROM 1999 THROUGH 2011
`ISSN - 0974-2441
`
`BHAVEN C. KATARIA1,*, VINAYAK H. BHAVSAR2, BHAVESH N. DONGA3
`
`1Department of Pharmacology, C.U. Shah Medical College, Surendranagar, India,2Department of Pharmacology, Chirayu Medical College
`and Hospital, Bhopal, India,3Department of Pharmacology, K. J. Mehta General Hospital and College of Medical Sciences, Amargadh, India.
`Email: drbkataria@gmail.com
`
`Received: 10 may 2012, Revised and Accepted: 4 June 2012
`
`ABSTRACT
`
`Objective: There is a change in the regulatory environment after a system of product patents in India since 2005. The objective of this study was to
`analyse the trends of drug approval in India during the period of 1999 to 2011.
`Materials and Methods: The information about drug approvals was primarily obtained from the Indian regulatory agency website. For the drug
`products identified, the drugs were classified into fourteen main Anatomical Therapeutic Chemical (ATC) groups, single or combination products,
`types of dosage form, approvals for additional strength, approvals for additional indication and approvals for new dosage form.
`Results: We identified 1506 approvals by the DCGI from 1999 to 2011, with a mean of 115.84±83.24 (SD) approvals per year (Median approvals per
`year: 79; Range: 23-264). The ATC groups containing over 10% of total approvals were N (nervous system), with 232 (15.4%); J (antiinfective for
`systemic use), with 204 (13.54%); A (alimentary tract and metabolism), with 192 (12.74%) and C (cardiovascular system), with 186 (12.35%).
`Since 2004, there is a rising trend for approval of products having drugs in combination. Total 448 new drugs were approved during the period of
`1999 to 2011, with a mean of 34.46±8.14 (SD) new drug approvals per year (Median new drug approvals per year: 36; Range: 22-53).
`Conclusions: These results show that there is a rising trend of approval for fixed dose combinations. The pattern of ‘new drug’ approval was
`flattened around the years when patent policy change was introduced.
`
`Key words: Drug approval, ATC group, new drug, regulatory, fixed dose combination
`
`INTRODUCTION
`
`The approval of a drug product by the regulatory authorities is a
`lengthy process. Research and development of new drugs is an
`ongoing process and it often takes more than a decade to launch a
`new drug in the market1. The control of government regulatory
`agencies over the introduction of new drug products is an absolute
`necessity to assure the effectiveness and safety of new drugs.
`
`The main regulatory body for the Indian pharmaceutical industry is
`the Central Drugs Standard Control Organization (CDSCO), which
`falls under the Ministry of Health and Family Welfare. The Drug
`Controller General of India (DCGI) is the controlling body for the
`CDSCO. The office of the Drug Controller General of India is
`responsible for the approval of new drug products and clinical trials.
`The DCGI office also monitors state drug-authorities, which are
`mainly responsible for granting drug manufacturing and retailing
`licenses.
`
`Over the last 40 years, India’s pharmaceutical industry has evolved
`from almost non-existent before 1970 to a world leader in the
`production of high quality drugs2. India has garnered a worldwide
`reputation for producing high quality, low cost generic drugs. The
`Indian pharmaceutical industry is a success-story ensuring that
`essential drugs are available at affordable prices to the vast
`population. The availability of drugs in the country has improved
`tremendously. From the level of being a major importer at the time
`of Independence, the country has become supplier to the World.
`
`When only process patents were granted, the Indian drug houses
`had an advantage to lead the role as a world leader in the production
`of affordable generics. As per World Trade Organisation (WTO),
`from the year 2005, India granted product patent recognition to all
`new chemical entities (NCEs)2. It effectively ended over 35 years of
`protection for Indian companies and terminated legal reverse
`engineering or copying of patented foreign pharmaceuticals drugs.
`Since 2005, many multinational corporations (MNCs) began re-
`entering the Indian pharmaceutical market by setting up their own
`manufacturing, research and development (R&D) facilities.
`
`As there is a tremendous change in the regulatory environment after
`a system of product patents in India, we considered it worthwhile to
`analyse the drug approval trends in India during the period 1999 to
`2011.
`
`MATERIALS AND METHODS
`
`This report is based on the information available on the CDSCO
`website. The list of approved drug products was available from 1999
`through 31st December 2011 at the time of analysis of these data.
`The information about the name of approved drug product, the
`indication/s and the date of issue of marketing approval was
`retrieved from the CDSCO website3.
`
`This information from the CDSCO website was entered and analysed
`using a Microsoft Excel worksheet (Microsoft Office 2010). For the
`drug products identified the following features were recorded: the
`ATC code as per WHO Anatomical Therapeutic Chemical (ATC)
`classification4, single or combination product, dosage
`form,
`additional strength, additional indication/s and new dosage form/s.
`As per ATC classification system, the drugs were classified into
`fourteen main groups.
`
`The complete information was not available for the biological
`products on the CDSCO website. Therefore it was decided to exclude
`biological products from the current analysis. We also excluded 20
`veterinary drug products from the current analysis, which were
`approved by the DCGI during 1999-2011.
`
`The approvals included drug products for additional indications,
`additional dosage forms, additional higher or lower strengths, new
`salts and combinations of previously approved drugs besides the
`products having a new molecule as a ‘drug’ (‘new drug’). This aspect
`is considered while analysing the approved drug products and
`attention is paid to the analysis of approved ‘new drug’.
`
`RESULTS
`
`The study identified total 1506 approvals by the DCGI from 1999 to
`2011, with a mean of 115.84±83.24 (SD) approvals per year (Median
`approvals per year: 79; Range: 23-264). The year-wise distribution
`of total number of approvals is shown the table 1. Out of these 1506
`approvals, 95 (6.3%) drug products were approved for additional
`indications, 34 (2.25%) drug products were approved for additional
`dosage forms, 165 (10.95%) drug products were approved for
`additional lower or higher strengths, four (0.26%) drug products
`were approved for additional pack size and 568 (37.71%) drugs
`were approved as fixed dose combination. The mean, median and
`range of drug product approvals are shown in table 2.
`
`Exhibit 1119
`IPR2017-00807
`ARGENTUM
`
`000001
`
`

`

`
`
` Kataria et al.
`
`Asian J Pharm Clin Res, Vol 5, Issue 3, 2012, 25-29
`
`Table 1: Total Number of drug approvals in India, 1999-2011
`(n=1506)
`
`Year
`1999
`2000
`2001
`2002
`2003
`2004
`2005
`2006
`2007
`2008
`2009
`2010
`2011
`Total
`
`Number of Approvals (in %)
`23 (1.52)
`28 (1.85)
`41 (2.72)
`56 (3.71)
`39 (2.58)
`76 (5.04)
`122 (8.1)
`161 (10.69)
`188 (12.48)
`264 (17.52)
`208 (13.81)
`221 (14.67)
`79 (5.24)
`1506
`
`Table 2: Drug products approved per year in terms of mean,
`median and range; in various categories analysed
`
`
`Total number of approvals
`(n=1506)
`Single drug product
`approvals (n=938)
`Combination drug product
`approvals (n=568)
`‘New drug’ approvals
`(n=448)
`
`Mean±SD
`115.84±83.24
`
`72.15±41.56
`
`43.69±43.94
`
`Median Range
`79
`23-
`264
`22-
`141
`0-123
`
`56
`
`41
`
`34.46±8.14
`
`36
`
`22-53
`
`When these 1506 approvals are analysed in terms of dosage forms, it
`is observed that 1026 (67.94%) approvals were for oral dosage
`forms, 197 (13.04%) were for parenteral dosage forms, 28 (1.85%)
`were for inhalation dosage forms, 226 (14.96%) were for topical
`dosage forms, 12 (0.79%) were for transdermal dosage forms and
`
`21 (1.39%) were for other types of dosage forms. Other types of
`dosage forms included nasal spray for systemic use, lozenges,
`intranasal solution, plaster, implant, sublingual tablets, dialysis
`solution and contraceptive rings.
`
`Table 3: The approved drugs (n=1506) in India categorised in
`Anatomical Therapeutic Chemical (ATC) groups
`
`ATC Group
`
`Number of
`Approvals (in
`%)
`A - Alimentary tract and metabolism 192 (12.74)
`B - Blood and blood forming organs
`39 (2.58)
`C - Cardiovascular system
`186 (12.35)
`D - Dermatologicals
`108 (7.17)
`G - Genito urinary system and sex hormones
`56 (3.71)
`H - Systemic hormonal preparations
`10 (0.66)
`(excluding sex hormones and insulins)
`204 (13.54)
`J - Antiinfectives for systemic use
`
`L - Antineoplastic and immunomodulating 102 (6.77)
`agents
`145 (9.62)
`M - Musculo-skeletal system
`232 (15.4)
`N - Nervous system
`
`P - Antiparasitic products, insecticides and 20 (1.32)
`repellents
`R - Respiratory system
`S - Sensory organs
`V – Various
`
`115 (7.63)
`74 (4.91)
`23 (1.52)
`
`The approvals are categorized in terms of ATC groups. The analysis
`is shown in the table 3. Classification of the approved drug products
`from point of view of therapeutic utility showed some interesting
`aspects. The ATC groups containing over 10% of total approvals
`were N (nervous system), with 232 (15.4%); J (antiinfective for
`systemic use), with 204 (13.54%); A (alimentary tract and
`metabolism), with 192 (12.74%) and C (cardiovascular system),
`with 186 (12.35%).
`
`1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
`22
`28
`41
`56
`38
`55
`71
`94
`97
`141 139 118
`38
`
`1
`
`23
`
`0
`
`28
`
`0
`
`41
`
`0
`
`56
`
`1
`
`39
`
`21
`
`76
`
`51
`
`67
`
`91
`
`123
`
`69
`
`103
`
`122 161 188 264 208 221
`
`41
`
`79
`
`Year
`
`Single
`
`Combination
`
`Total
`
`
`
`300
`
`250
`
`200
`
`150
`
`100
`
`50
`
`0
`
`No. of approvals
`
`Single
`
`Combination
`
`Total
`
`Figure 1: Time trends of drug approvals in India during 1999-2011 (n=1506)
`
`The time-trend curve for all the approved drug products during the
`period from 1999 to 2011 is presented in figure 1. It also shows the
`drug products containing both, single or combination of drugs,
`which are plotted separately. The plot shows an overall rising trend,
`with the highest approvals in 2008 (n=264); in subsequent years the
`number of approvals are less. Since 2004 a rising trend is seen for
`approval of products having drugs in combination. This trend also
`peaks up during 2008 (n=123). Then it recedes in the subsequent
`
`years; with lowest number being in 2011 (n=41). The gap is being
`narrowed down between the approvals of single drug product and
`combination drug product in 2010 and 2011. Actually there are
`more number of approvals for combination products in 2011 (n=41)
`as compared to the approvals of single drug products (n=38). In
`other words, half of the approvals in year 2010 and 2011 are in the
`form combinations of the drugs.
`
`
`
`26
`
`000002
`
`

`

`
`
` Kataria et al.
`
`Asian J Pharm Clin Res, Vol 5, Issue 3, 2012, 25-29
`
`Data is further analysed in terms of approved drug products
`containing single or combination of drugs, for different therapeutic
`categories. Figure 2 shows the drug products approved for each
`group of ATC classification. There are more number of combination
`drug products approved in Cardiovascular system (C) ATC group
`(n=106 for combination and n=80 for single). For Dermatologicals
`(D) ATC group and Antiparasitic, insecticides and repellents (P) ATC
`
`group also the combination drug product approvals are more in
`number as compared to the single drug product approvals. For
`Antineoplastic and immunomodulating agents (L) ATC group, there
`are more number of single drug product approvals as compared to
`the combination drug products (n=100 for single and n=2 for
`combination).
`
`
`
`Single
`
`Combination
`
`182
`
`200
`
`180
`
`160
`
`140
`
`
`
`111
`
`100
`
`93
`
`86
`
`59
`
`68
`
`50
`
`47
`
`46
`
`10
`0
`
`2
`
`13
`7
`
`28
`
`21
`
`2
`
`120
`
`112
`
`106
`
`80
`
`80
`
`58
`50
`
`40
`
`16
`
`25
`14
`
`100
`
`80
`
`60
`
`40
`
`20
`
`0
`
`No. of approvals
`
`A
`
`B
`
`C
`
`D
`
`G
`
`H
`
`J
`
`L
`
`M
`
`N
`
`P
`
`R
`
`S
`
`V
`
`ATC Group*
`
`Figure 2: Drug approvals as single and combination products for fourteen ATC groups (n=1506)
`
`*ATC Group: A (Alimentary tract and metabolism), B (Blood and blood forming organs), C (Cardiovascular system), D (Dermatologicals), G
`(Genito urinary system and sex hormones), H (Systemic hormonal preparations, excluding sex hormones and insulins), J (Antiinfectives
`for systemic use), L (Antineoplastic and immunomodulating agents), M (Musculo-skeletal system), N (Nervous system), P (Antiparasitic
`products, insecticides and repellents), R (Respiratory system), S (Sensory organs), V (Various).
`
`The approved drug products in all fourteen ATC groups were
`analysed from the point of view of year wise trends. There are more
`number of approvals for Nervous system (N) ATC group as
`compared
`to other groups
`in
`last 3 years (2009-2011);
`Antiinfectives for systemic use (J) ATC group had highest number of
`approvals in year 2006 and 2008. Similar higher numbers of
`approvals are exhibited in categories of Cardiovascular (C) and
`Musculo-skeletal system (M) during period 2005 to 2010 and 2006
`to 2010 respectively. In case of about half of the categories (namely,
`A, C, D, J, M, N, R and S), there are more number of approvals from
`year 2005 to 2010. Categories B, G, H, L, P and V do not exhibit a
`trend of this kind.
`
`The data is also screened from point of view of approved products
`having ‘new drug’. The study identified total of 448 ‘new drug’
`approvals during 1999-2011; the year wise distribution being as
`follows: 22 (4.91 %) in 1999; 28 (6.25%) in 2000; 39 (8.7%) in
`2001; 53 (11.83%) in 2002; 37 (8.25%) in 2003; 33 (7.36%) in
`2004; 36 (8.03%) in 2005; 37 (8.25%) in 2006; 31 (6.91%) in 2007;
`38 (8.48%) in 2008; 32 (7.14%) in 2009; 40 (8.92%) in 2010 and 22
`(4.91%) in 2011. The DCGI has approved an average 34.46 ‘new
`drugs’ per year during the period of 1999 to 2011 (Median ‘new
`drug’ approvals per year: 36; Range: 22-53). It is also noted that the
`number of ‘new drug’ approvals shows a rising trend from 1999 to
`2002. However, after 2002 the pattern is almost flat; ranging 31-40
`per annum during the past few years. The number of new drug
`approvals in 2011 (n=22) is the lowest in the last 12 years.
`
`A list of selected ‘new drugs’ approved during 1999-2011 is
`presented in table 4. The list is categorized in terms of ATC
`classification. Some stereoisomers of existing molecules were also
`
`
`
`approved during 1999-2011. These stereoisomers included: R-
`sibutramine, S-amlodipine, S-metoprolol, R-ondansetron, S-
`pantoprazole, S-atenolol, S-etodolac and S-bupivacaine. It is worth
`noting that subsequent to their approval, some of the drugs were
`banned by the Indian drug regulatory authority. These banned drugs
`were Rimonabant, Rosiglitazone, Sibutramine, R-Sibutramine,
`Gatifloxacin
`(for systemic use), Tegaserod, Rofecoxib and
`Valdecoxib5.
`
`Table 4: A list of selected ‘new drugs’ approved during 1999-
`2011
`
`A: Alimentary tract and metabolism
`Irsogladine, Sitagliptin,
`Fosaprepitant,
`Ilaprazole, Troxipide,
`Exenatide, Ademetionine, Clebopride, Ondansetron, Rabeprazole,
`Palonosetron, Saxagliptin, Lafutidine, Ramosetron, Cinitapride,
`Voglibose, Vildagliptin, Cimetropium, Lansoprazole, Pantoprazole,
`Esomeprazole, Aprepitant, Rimonabant, Mebeverine,
`Itopride,
`Tiropramide, Caroverine, Racecadotril, Trimebutine, Rebamipide,
`Miglitol,
`Orlistat,
`Fenoverine, Metadoxine,
`Nateglinide,
`Paromomycin, Tegaserod, Balsalazide, Mosapride, Repaglinide,
`Rosiglitazone, Rifaximin, Levocarnitine, Granisetron, Pioglitazone,
`Octylonium, Glimepiride
`B: Blood and blood forming organs
`Dabigatran Etexilate, Cilostazol, Rivaroxaban, Prasugrel, Tranexamic,
`Enoxaparin, Fondaparinux, Dalteparin, Eltrombopag, Clopidogrel,
`Bemiparin, Camostat, Bivalirudin, Tirofiban, Triflusal, Eptifibatide
`C: Cardiovascular system
`Aliskiren, Ivabradine, Dronedarone, Ranolazine, Levosimendan,
`Telmisartan, Ambrisentan, Rosuvastatin, Ramipril, Nadolol,
`Perindopril, Bosentan, Chlorthalidone, Acipimox, Carvedilol,
`
`27
`
`000003
`
`

`

`
`
` Kataria et al.
`
`Asian J Pharm Clin Res, Vol 5, Issue 3, 2012, 25-29
`
`Temozolamide, Nicardipine, Ivabradine, Eprosartan, Moxonidine,
`Nicorandil, Cholestyramine, Pitavastatin, Eplerenone, Olmesartan,
`Doxazosin, Imidapril, Metolazone, Bendrofluazide, Trandolapril,
`Fluvastatin, Ezetimibe, Fosinopril, Lercanidine, Nebivolol, Quinapril,
`Valsartan, Trapidil, Irbesartan, Candesartan, Pravastatin, Milrinone,
`Atorvastatin, Fenofibrate
`D: Dermatologicals
`Tacalcitol, Retapamulin, Luliconazole, Sertaconazole, Methoxsalen,
`Halometasone, Eberconazole, Sodium Hyaluronate, Eflornithine,
`Diflorasone, Acitretin, Trolamine, Pimecrolimus,
`Isotretinoin,
`Imiquimod, Azelaic Acid, Amorolfine, Tazarotene, Butenafine,
`Oxiconazole
`G: Genito urinary system and sex hormones
`Silodosin, Udenafil, Pentosan polysulfate Sodium, Naftopidil,
`Oxybutynin, Dapoxetine, Trospium, Darifenacin, Cabergoline,
`Apomorphine,
`Solifenacin, Dutasteride, Alfuzosin, Tadalafil,
`Mifepristone, Tamsulosin, Cyproterone, Raloxifene, Alprostadil,
`Sildenafil, Tolterodine
`H: Systemic hormonal preparations, excl. Sex hormones and
`insulins
`Deflazacort, Cinacalcet, Desmopressin, Ganirelix, Teriparatide,
`Nafarelin, Doxercalciferol
`J: Antiinfectives for systemic use
`Imipenem+Cilastatin,
`Raltegravir, Azithromycin, Oseltamivir,
`Doripenem, Fluconazole, Clindamycin, Caspofungin, Micafungin,
`Anidulafungin, Darunavir, Tenofovir Disoproxil, Nevirapine,
`Posaconazole, Amphotericin B, Abacavir, Valganciclovir, Maraviroc,
`Balofloxacin, Ribavirin, Atazanavir, Ertapenem, Zanamavir,
`Daptomycin, Cefditoren, Cefdinir, Pazufloxacin, Cefepime, Rifabutin,
`Prulifloxacin, Cefprozil, Cefetamet,
`Saquinavir, Tobramycin,
`Atazanavir, Tigecycline, Stavudine, Telbivudine, Gemifloxacin,
`Levofloxacin, Cefixime, Nelfinavir, Emtricitabine, Faropenem,
`Efavirenz, Didanosine, Entecavir, Adefovir, Linezolid, Voriconazole,
`Cefuroxime, Meropenem, Famciclovir, Valacyclovir, Aztreonam,
`Indinavir, Moxifloxacin, Gatifloxacin, Ganciclovir
`L: Antineoplastic and immunomodulating agents
`Crizotinib, Abiraterone, Fludarabine, Topotecan, Basiliximab,
`Daclizumab, Capecitabine, Trastuzumab, Rituximab, Temozolomide,
`Imatinib, Exemestane, Vinorelbin, Gemtuzumab, Thalidomide,
`Sirolimus, Bicalutamide, Cladribine, Anastrozole, Gemcitabine,
`Tacrolimus,
`Everolimus,
`Gefitinib,
`Erlotinib,
`Bortezomib,
`Fulvestrant, Paclitaxel, Pemetrexed, Sorafenib, Lapatinib, Sunitinib,
`Docetaxel, Glatiramer,
`Ixabepilone, Carmustine, Doxifluridine,
`Bendamustine, Decitabine, Trabectedin, Dasatinib, Temsirolimus,
`Miltefosine, Pazopanib, Nilotinib,
`Irinotecan, Temozolomide,
`Pirfenidone, Cytarabine, Cabazitaxel
`M: Musculo-skeletal system
`Nabumetone, Meloxicam, Rofecoxib, Celecoxib, Zoledronic Acid,
`Parecoxib, Valdecoxib, Risedronate, Aceclofenac, Ibandronic Acid,
`Diacerein, Etoricoxib, Strontium Ranelate, Eperisone, Lumiracoxib,
`Dexibuprofen, Lornoxicam, Oxaprozin, Etodolac, Cyclobenzaprine,
`Phenyramidol, Tizanidine, Tolperisone, Loxoprofen, Dexketoprofen,
`Amtolmetin Guacil, Febuxostat, Zaltoprofen
`N: Nervous system
`Sulpiride, Topiramate, Zuclopenthixol, Zolpidem, Tetrabenazine,
`Paroxetine, Venlafaxine, Moclobemide, Fluvoxamine, Olanzapine,
`Ropinirole, Oxcarbazepine, Citalopram, Bupropion, Donepezil,
`Mirtazapine, Reboxetine, Acamprosate, Fosphenytoin, Butorphanol,
`Quetiapine, Vinpocetine, Ziprasidone, Zaleplon, Divalproex,
`Sufentanil, Modafinil, Vinpocetin, Aripiprazole, Rizatriptan,
`Escitalopram, Entacapone, Atomoxetine, Duloxetine, Ziprasidone,
`Lamotrigine, Citicoline, Memantine, Tiagabine, Cabergoline,
`Zonisamide, Pregabalin, Levetiracetam, Pramipexole, Midazolam,
`Amisulpride, Desflurane, Etizolam, Edaravone, Varenicline,
`Eplerstat, Eszopiclone, Paliperidone, Milnacipran, Betahistine,
`Naratriptan, Desvenlafaxine, Dexmedetomidine, Methadone,
`Ropivacaine, Nicotine Polacrilex,
`Levosulpiride, Rasagiline,
`Ramelteon, Opipramol,
`Lacosamide, Armodafinil,
`Zotepine,
`Flupirtine, Tofisopam, Dosulepin, Eletriptan, Tiapride, Tapentadol,
`Asenapine, Eslicarbazepine, Iloperidone
`P: Antiparasitic products, insecticides and repellents
`Bulaquine, β-arteether, Nitazoxanide, Arterolane+Piperaquine,
`Artemether+Lumefantrine
`
`
`
`R: Respiratory system
`Bambuterol, Zafirlukast, Desloratadine, Ebastine, Poractant Alfa,
`Levocetirizine,
`Mizolastine,
`Montelukast,
`Tiotropium,
`Levosalbutamol,
`Rupatadine,
`Erdosteine,
`Levodropropizine,
`Ciclesonide,
`Doxophylline,
`Olopatadine,
`Fexofenadine,
`Acebrophylline, Ozagrel, Arformoterol, Fluticasone, Zileuton,
`Levocloperastine, Indacaterol, Acrivastine
`S: Sensory organs
`Trifluridine, Brimonidine, Apraclonidine, Loteprednol Etabonate,
`Bimatoprost, Unoprostone, Dorzolamide, Ibopamine, Travoprost,
`Epinastine, Pegaptanib, Bromfenac, Nepafenac, Flurbiprofen,
`Acetylcysteine,
`Difluprednate,
`Levobetaxolol,
`Tafluprost,
`Besifloxacin, Brinzolamide
`V: Various
`Iobitridol, Meglumine gadoteric, Gadoversetamide,
`Iomeprol,
`Gadobenate, Neotame,
`Lanthanum
`Carbonate,
`Sevelamer,
`Acesulfame Potassium, Deferasirox, Perflutren
`
`DISCUSSION
`
`The study identified total 1506 approvals by the DCGI from 1999 to
`2011, the period under the study. An average rate of approval, per
`annum turns out to be 115.84 (Median approvals per year: 79;
`Range: 23-264). This number looks impressive. Of course one should
`not forget that the approvals included the drug products of the
`existing drugs for additional indications, additional dosage forms,
`additional higher or lower strengths, new salts and combination
`with other drug/s. In terms of dosage forms, about 2/3 of the
`approved drug products are meant for oral administration; about
`1/4 are meant for parenteral administration and topical application.
`It is to be noted that as per ATC classification, the approved drug
`products are maximum in the group N (Nervous system). That is
`followed by group J (Antiinfective for systemic use), group A
`(Alimentary system) and group C (Cardiovascular). Each constitutes
`more than 10 per cent of the approved drug products. Even the ‘new
`drug’ entries are higher in these categories (in each group there are
`more than 10 per cent of approved ‘new drugs’). In Group L
`(Antineoplastic and immunomodulating agents) also there are good
`numbers of ‘new drug’ entries. These approvals in the above groups
`reflect the use of drugs in the society.
`
`It is important to look for the situation with the entry of the new
`molecules as approved
`‘new drug’. The approvals of newer
`molecules as drug during the period under study are comparatively
`lesser in number. Total of 448 ‘new drugs’ are approved during the
`period from 1999 through 2011. Thus an average of 34.46 drugs is
`approved per year (Median new drug approvals per year: 36; Range:
`22-53). This annual rate of approval of ‘new drugs’ in India in the
`present study is higher as compared to the US FDA data for ten year
`period from 2001 through 2010 (Mean: 22.9±5.36; Median: 21.5;
`Range: 17-36)6. However, the data of the past years show that during
`1988-2002, the mean number of ‘new drugs’ approved in India was
`26.4±9.57. This rate appears lesser than what is observed in the
`present study. Of course there is overlapping of data of 4 years
`(1999 to 2002). This simply point outs the better performance of
`Indian pharmaceutical industry in recent past. The revised strategies
`of
`the pharmaceutical
`industry, better
`technical knowhow,
`multinational collaborations, improved economy of the country and
`realization of better marketing avenues in India may be the
`speculative factors for the observed performance. This is probably a
`reflection of the fact that the Indian pharmaceutical companies in
`general took the advantage of process patent law in India and
`introduced copycat drugs developed by the foreign multinational
`corporations (MNCs). The pattern of ‘new drug’ approval looks
`flattened around the years when patent policy change was
`introduced. In year 2011, there is a sharp decline in ‘new drug’
`approvals, which is in line with the ‘new drug’ approvals in the
`developed market (in the United States, Mean 22.9±5.36; Median:
`21.5; Range: 17-36)8.
`
`One of the concerns due to product patent is that the prices of drugs
`would rise. Because patent on a product would give a monopoly for
`the patent holder to decide the price of the product dimmed
`necessary to compensate the R&D expenses. However, to say that
`the market would be totally driven only by the patented products
`
`28
`
`000004
`
`

`

`
`
` Kataria et al.
`
`Asian J Pharm Clin Res, Vol 5, Issue 3, 2012, 25-29
`
`may also not be correct. On an average, only 15 to 20 drugs enter the
`market every year globally and only a few of them are commercially
`successful. At the same time, each year patents for the earlier
`products expire. Hence, at a particular point of time only 5 to 10
`percent of the drugs in the market may be under product patent
`protection and the rest of the market could still be in the generic
`category. Availability of the patent expired therapeutic equivalents
`would, automatically keep the prices of such new entities under
`control.
`
`The new drug approvals data from the US FDA show that there is flat
`approval rate in past few years8. The reason for this flat approval
`rate over the time is that drug companies are not filing as many
`applications with FDA for new drug approval as they had in the
`past8. In Global economic slowdown, MNCs are cutting their R&D
`budget and reducing their employees. All these factors may lead to
`slowing of new drug development and approvals. One may expect
`that the trend of new drug approvals in India will now be similar to
`that
`in the developed markets. Most of the multinational
`pharmaceuticals companies (MNCs) have presence in India and they
`may try to introduce their patented drug products in India,
`simultaneously along with the introduction in the developed
`markets.
`
`Another trend we observed in this study is that there is more
`interest in launching fixed dose combinations, stereoisomers and
`new dosage forms. As development of a ‘new drug’ is a lengthy
`process and very costly affair, the Indian companies are focussing in
`launching of fixed dose combinations, stereoisomers and new
`dosage forms of the existing products. The attempt is to differentiate
`the new product from the existing ones. This may be part of survival
`in the increasing competition amongst the drug-houses. Because of
`process patent in India before 2005, there are so many brands
`available in the Indian market for single drug molecule. It’s not easy
`for the pharmaceutical companies to differentiate their brands from
`the competitors. Thus, to differentiate their product from the
`competitors some innovations are attempted. These attempts are
`resulting into the products mentioned above. Drug development is a
`risky, unpredictable and expensive process involving combination of
`scientific excellence and a thorough understanding of the business
`environment. Many Indian companies are shifting to contract
`manufacturing, outsourcing, contract research or tie-ins with MNCs.
`With the introduction of product patents, Indian companies will
`have to shift the area of focus from process development to
`developing new drug products, if not independently then at least, in
`the collaboration with MNC giants to make a beginning. Of course,
`there are number of confounding factors to take care of.
`
`There is additional aspect about the fixed dose combination in
`Indian scenario. The grant of fixed dose combinations by different
`State Licensing Authorities (in India) has been a very contentious
`issue. There has been no uniformity in the different states as regards
`to grant of permission to manufacture such combinations. This has
`led to a situation where another State Licensing Authority grants a
`product not permitted by one State Licensing Authority9. This study
`included the fixed dose combinations approved by the DCGI office
`only. There is a possibility that our list doesn’t include some fixed
`dose combinations available in the Indian market approved by
`different State Licensing Authorities.
`
`There is a great scope for implementing all the rules and regulations,
`which would guide, monitor and control the activities of the
`providers of the healthcare system in the country and to find the
`means to bring the situation up to the international standards.
`Recommendations of Mashelkar committee9 and establishment of
`the Central Drug Authority at the earliest, for control over
`manufacture, quality & supply of drugs are important from this
`angle. Besides approval of drug products there are number of issues
`related
`to healthcare system and availabilities of drugs.
`Comprehensive changes are needed in regulatory system to keep
`abreast with the changing trends in the industry with the objective
`of maintaining uniform parameters to produce quality drugs.
`Regulatory infrastructure needs to be strengthened to ensure good
`quality of products and check the production of spurious drugs.
`
`India’s population is just over 1.2 billion at present and projected to
`rise to 1.7 billion by 2050 and India will become the world’s most
`populous country10. This projection shows that the demand of drugs
`will rise in coming years. There is a need, at national level to acquire
`an expertise in the field of R&D and to develop the technology to
`build up capacity in innovation and production of the drugs to
`ensure that essential drugs at affordable prices are available to the
`vast population. The R&D of new drugs should be in line with the
`country’s healthcare needs. Further analysis on disease pattern and
`it’s comparison with the pattern of new drug introduction would
`guide us to identify the right strategies to improve healthcare needs
`of India.
`
`
`
`CONCLUSIONS
`
`The results of this study confirm that there is a rising trend of
`approval for fixed dose combinations. The pattern of ‘new drug’
`approval was flattened around the years when patent policy change
`was introduced. Nervous system (15.4%), antiinfective for systemic
`use (13.54%), alimentary tract and metabolism (12.74%) and
`cardiovascular system (12.35%) were top four ATC groups which
`received highest number of approvals.
`
`REFERENCES
`1.
`
`Spellberg B, Powers JH, Brass EP, Miller LG, Edwards JE.
`Trends in antimicrobial drug development: implications for
`the future. Clin Infect Dis 2004;38:1279-86.
`2. Report of the working group on drugs and pharmaceuticals for
`the eleventh five-year plan (2007-2012), Planning commission
`of
`India.
`[Internet]
`2012.
`Available
`from:
`http://planningcommission.nic.in/aboutus/committee/wrkgr
`p11/wg11_pharma.pdf [Last accessed on 2012 Feb 25].
`The Central Drugs Standard Control Organization (CDSCO).
`List of drug approved for marketing in India. [Internet] 2012.
`Available
`from:
`http://cdsco.nic.in/listofdrugapprovedmain.html.
`[Last
`accessed on 2012 Feb 25].
`4. WHO Collaborating Centre for Drug Statistics Methodology,
`Guidelines for ATC classification and DDD assignment, 2012.
`Oslo, 2011.
`The Central Drugs Standard Control Organization (CDSCO).
`Drugs banned in India. [Internet] 2012. Available from:
`http://cdsco.nic.in/html/Drugsbanned.html. [Last accessed
`on 2012 Feb 25].
`6. U.S. Food and Drug Administration. Is it true FDA is approving
`fewer new drugs lately? [Internet] 2012. Available from:
`http://www.fda.gov/downloads/AboutFDA/Transparency/B
`asics/UCM247465.pdf. [Last accessed on 2012 Feb 25].
`7. Ghosh A, Hazra A, Mandal SC. New drugs in India over the past
`15 years: Analysis of trends. Natl Med J India 2004;17:10-16.
`8. U.S. Food and Drug Administration. NME Drug and New
`Biologic Approvals.
`[Internet] 2012. Available
`from:
`http://www.fda.gov/downloads/Drugs/DevelopmentApprov
`alProcess/HowDrugsareDevelopedandApproved/DrugandBio
`logicApprovalReports/UCM242695.pdf. [Last accessed on
`2012 Feb 25].
`The Central Drugs Standard Control Organizati