Drug Schedules By Dr Sonali More.

JR-2, Dept. of Pharmacology

Guide-Dr B.B. Ghongane.

History POSITIN TILL 1930 : India was largely dependent on import of modern medicines

until after first word war. In August 1930 the government of India appointed a drug Enquiry Committee

under the chairmanship of R.N. Chopra, to go in to the question of adulterated & substandard drugs sold in country & to recommend steps by which this menace could be control.

The Drug Enquiry Committee submitted its report in 1931,the government of India could not give effect to its recommendation till 1937.

After passing of the Government of India Act,1935, drug became provincial subject & therefore center could pass law in respect of only imports.

The Drug Import Bill was prepared & placed for consideration before the assembly in 1939. This was not acceptable to the public & provinces for uniform & comprehensive legislation. This led to the introduction of the Indian Drug Bill in the Central Legislative assembly. It was passed & received assent of Governor General in Council & became Drug And Cosmetic Act in 1940.

Drug and Cosmetic Act,1940• The quality of the drugs imported, manufactured and sold in the country

is regulated under the provisions of Drugs and Cosmetics Act, 1940 and Rules made there under.

• The Act visualizes the regulatory control over the drugs imported in to the country by the Central Government while the manufacture, sale and distribution of drugs is primarily regulated by the State Drug Control Authorities appointed by the State Governments.

• The manufacture and sale of the drugs is regulated through a system of licensing and inspection by the Licensing Authorities.

• The Central Drugs Standard Control Organization (CDSCO), headed by the Drugs Controller General (India) is concerned with the regulatory control over the quality of drugs &cosmetics.

• The organization has its head quarters at New Delhi and has six zonal offices, two sub zonal offices, seven seaports/Airports offices and six laboratories under its control.

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OBJECTIVES

To prevent substandard in drugs, maintaining high standards of medical

To regulate the import, manufacture, distribution and sale of drugs & cosmetics through licensing.

Manufacture, distribution and sale of drugs and cosmetics by qualified persons only.

To regulate the manufacture and sale of Ayurvedic, Siddha and Unani drugs.

To establish Drugs Technical Advisory Board(DTAB) and Drugs Consultative Committees(DCC) for Allopathic and allied drugs and cosmetics.

• CHAPTER IINTRODUCTION Short title, extent and commencement and Definitions

• CHAPTER IITHE DRUGS TECHNICAL ADVISORY BOARD, THE CENTRAL DRUGS LABORTORY AND THE

DRUGS CONSULTATIVE COMMITTEE

• CHAPTER IIIIMPORT OF DRUGS AND COSMETICS, Standards of quality, Misbranded drugs,

Adulterated drugs ,Spurious drugs., Misbranded cosmetics., Spurious cosmetics etc.

• CHAPTER IV MANUFACTURE, SALE AND DISTRIBUTION OF DRUGS AND COSMETICS

Chapters in the “Drugs and Cosmetics Act and Rules”

• CHAPTER IVAPROVISIONS RELATING TO AYURVEDIC SIDDHA AND UNANI DRUGS

• CHAPTER VMISCELLANEOUS like Publication of sentences passed under this Act,

Magistrate’s power to impose enhanced penalties

Provisions of Act

Import Manufacturing Sales Labeling & Packaging

Drug & Cosmetics Act,1945

The Repealing and Amending Act, 1949. The Adoption of Laws Order, 1950 The part B States (Laws) Act, 1951. The Drugs (Amendment) Act, 1955 . The Drugs (Amendment) Act, 1960. The Drugs (Amendment) Act, 1962 . The Drugs and Cosmetics (Amendment) Act, 1964 . The Drugs and Cosmetics (Amendment) Act, 1972 . The Drugs and Cosmetics (Amendment) Act, 1982 . The Drugs and Cosmetics (Amendment) Act, 1986. The Drugs and Cosmetics (Amendment) Act, 1995 The Drugs and Cosmetics (Amendment) Act,2003 The Drugs and Cosmetics (Amendment) Act,2008 The drugs and cosmetics (Amendment) Act,2013

List Of Amending Acts And Adaptation Orders

• According to the Drug & Cosmetic Act 1940 (along with the Drugs and Cosmetic Rules 1945) the schedules for the drugs are as follows

Schedule A Gives the specimens of prescribed forms necessary for obtaining

licenses, permits, certificates, intimations and so on.( about 50 in no)

• Form 2-Certificate of test or analysis by the Central Drugs Laboratory

• Form 8- Application for license to import drugs (excluding those specified in Schedule X) to the Drugs and Cosmetics Rules 1945.

• Form 8 A- Application for license to import drugs specified in Schedule X to the Drugs and Cosmetic Rules 1945.

• Form no 46-Permission / Approval for manufacture of new drug formulation.

FORM 8(See Rule 24)Application for licence to import drugs (excluding those specified in Schedule X) to the Drugsand Cosmetics Rules 1945.I/We* ………………………………………….. (full address with telephone number, faxnumber and e-mail address) hereby apply for a licence to import drugs specified belowmanufactured by M/s ………………………………(full address with telephone no, fax and emailno.).2. Names of the drugs to be imported:(1)(2)(3)3. I/We* …………………………………. enclose herewith an undertaking in Form 9dated………. signed by the manufacturer as required by rule 24 of the Drugs and CosmeticsRules, 1945.4. I/We …………………………………. enclose herewith a copy of RegistrationCertificate concerning the drugs to be imported in India, issued under Form 41 of the rules,vide Registration Certificate No. …………dated ………….. issued through M/s..………………….(name and full address)……………………valid up to …………………..I/We* ……………………………….. hold a valid wholesale licence for sale ordistribution of drugs or valid licence to manufacture drugs, under the provisions of the Act andrules made thereunder. A copy of the said licence is enclosed.6. A fee of ………….. has been credited to Government under the Head of Account “0210– Medical and Public Health, 04-Public Health, 104-Fees and Fines” under the Drugs andCosmetics Rules 1945 – Central vide Challan No. ……………… dated ……….. (attached inoriginal)Signature ………………..Name ………………..Designation …………Seal/Stamp of Manufacturer’s agent in IndiaPlace ……..Date ………..___________________________________________________________________________

FORM 8-AApplication for licence to import drugs specified in Schedule X to the Drugs and CosmeticRules 1945.I/We* ……………………………(full address with telephone number, fax number and e-mailaddress) hereby apply for a licence to import drugs specified below manufactured byM/s………………………… (full address with telephone No, fax and e-mail No.).2. Name of the drugs to be imported.(1)(2)(3)3. I/We* ………………………… enclose herewith an undertaking in Form 9 dated………… signed by the manufacturer as required by rule 24 of the Drugs andCosmetics Rules, 1945.4. I/We* ………………………….. enclose herewith a copy of Registration Certificateconcerning the drugs to be imported in India, issued under Form 41 of the rules, videRegistration Certificate No. …………. dated ………………. issued through M/s.……………………….(name and full address) ………..……….. valid upto ……5 I/We* ………………. Hold a valid wholesale licence for sale or distribution of drugsor licence to manufacture drugs, under the provisions of the Act and rules madethereunder. A copy of the said licence is enclosed.6. A fee of ……………….. has been credited to Government under the Head of Account“0210 – Medical and Public Health, 04- Public Health, 104- Fees and Fines” under theDrugs and Cosmetics Rules 1945 – Central vide Challan No. ……. dated ……….. (attached in original).Signature ………………..Name ………………..Designation …………Seal/Stamp of Manufacturer’s agent in IndiaPlace ……..Date ………..

Schedule B States fees for test or analysis by the Central Drug

Laboratory or the Government Analyst.Under this schedule fees of for tests are mentioned :• 1. Test and assay of Drugs requiring use of animals

• 2. Microbiological tests and assays

• 3. Identification tests like chemical,microscopical, UV spectroscopy, Chromatography, Electrophoresis

• 4. Physical tests- Optical rotation, Specific gravity, Solubility,pH, Refractive index, Disintegration and dissolution test.

Schedule C & C1

C: Deals with biological products such as sera antigens, toxin, antitoxin, Vaccines for parenteral injections, solution of serum proteins intended for injection, Insulin etc

C1: Special products such as fish liver oil, ergot preparations, drugs belonging to digitalis groups, adrenaline, Liver extract,vitamines, hormones

Labelling specialClass of drugs

Nature of medicines Specific particulars appeared on label

Schedule C/C1

In original form 1) Proper name in addition to patent name2) Potency in units3) Name & address of manufacturer4) Licence No. under which manufacturer5) Date of manufacture6) Date of expiry7) Precaution for preparation

Schedule D Devoted to exemption regarding import of drugs. Substances

not intended for medicinal use According to provisions of Chapter III of this Act and Rules ,if

the substance is imported in bulk, the importer should certify that the substance is imported for non-medicinal uses, and if imported otherwise than in bulk, each container should bear a label indicating that the substance is not intended for medicinal use or is intended for some purposes other than medicinal use.

E.g. Skimmed milk, powdered milk fortified with vitamins, farex, oats, ginger, pepper, cummins etc

Schedule D(I)

• Following information and undertaking required to be submitted by the manufacturer or his authorized agent with the Application Form for a Registration Certificate.

1. Particulars of the manufacturer and manufacturing premises 2. Particulars of the manufactured drugs to be registered under Registration Certificate 3. Undertaking to declare that manufacturer should comply with all the conditions imposed on the Registration Certificate.

SCHEDULE D (II)• Following information required to be submitted by the

manufacturer or his authorized agent with the Application Form for the registration of a bulk drug/formulation/special product for its import into India.

General Chemical and pharmaceutical information of drugs. Biological and biopharmaceutical information Pharmacological and toxicological information of

Drugs.Clinical documentation

Labelling and packing information of drug Specified information required for special products

SCHEDULE E & E1[Omitted as per GOI Notification No.G.S.R. 462(E) dt 22-6-1982] SCHEDULE E (I)-Gives the list of

poisonous substances under Ayurvedic, Siddha & Unani systems

of medicine. Ex- Snake poison,

arsenic,mercury,CuSo4 Dhatura, Bhang, Gunj etc

Schedule F and F (I)F states requirements for functioning of blood

bank & preparation of blood component.

F (I) : Give details of the standards of bacterial vaccines made from any microorganism pathogenic to man or other animals and also the vaccines made from other microorganisms which have any antigenic value.

Schedule FF Gives details of standards for ophthalmic preparations. Part A Ophthalmic Solutions and Suspensions a)should be sterile when dispensed or when sold in the unopened container of the

manufacturer.

b)contain one or more of the following suitable substances to prevent the growth of micro -organisms.

• Benzalkonium Chloride, 0.01 per cent • Phenyl mercuric nitrate, 0.001 per cent.• Chlorbutanol 0.5 per cent.• Phenyl ethyl alcohol 0.5 per cent

(c) free from foreign matter.

d) contained in bottles made of either neutral glass or soda glass specially treated to reduce the amount of alkali released when in contact of aqueous liquids, or in suitable plastic containers which would not in any way be incompatible with the solutions.

e)following particulars should also be shown on the label:-(1) containers(i) The statement ‘Use the solution within one month after opening the container’.(ii) Name and concentration of the preservative, if used.(iii) The words ‘NOT FOR INJECTION’.

(2) carton or package leaflet(i) Special instructions regarding storage, wherever applicable.(iii) WARNING.“ Do not touch the dropper tip or other dispensing tip to anysurface since this may contaminate solutions”.

Part-B. Ophthalmic OintmentsOphthalmic Ointments should-(a) be sterile when dispensed or when sold in the unopened

container of the manufacturer.

(b) be free from foreign matter.

(c) following particulars should be shown on the container or carton or package leaflet-(i) Special instructions regarding storage wherever applicable.(ii) “Warning :- If irritation persists or increases discontinue the use and consult physicians”

Schedule F (II)• Gives details of standards for Surgical dressings and bandage cloth.

Schedule F (III)

Gives standard for umbilical tapes.

Schedule G Medicines listed as schedule G medicines carry on the label a

caution• Caution – “it is dangerous to take this preparation except

under medical supervision”. conspicuously printed and surrounded by a line within which there should be no other words.

It is necessary to make proper bill of sale. Records of purchase and sale of these medicines must be maintained for a period of 2 yearsEg: L asperginase,Bleomycin, Busulphan, chlorambucil, chlorthiazide, chlorpropamide, doxorubicin, ethosuximide, Metformin, Insilin all types,Hydroxyurea, Mercaptopurines etc

Schedule H ((Drugs & cosmetics (2nd amendment) Rules 2006)

• Deals with drugs and medicines which must be sold by retail only when a prescription by Registered Medical Practitioner is produced.

• Drugs come under Schedule H should be labelled with the symbol Rx and conspicuously displayed on the left top corner of the label.

• Drugs specified in Schedule H, and comes within [Narcotic Drugs and Psychotropic Substances Act, 1985 labelled with the symbol NRx which shall be in red and conspicuously displayed on the left top corner of the label.

• Examples-Alprazolam, Allopurinol, Amikacin, Atenolol ,Acyclovir, Buspirone, Azathioprine, Captopril, Carbidopa, Clindamycin, Cimetidine, Ciprofloxacin,Cefuroxime,DiclofenaC,

• Glimepiride, diazepam etc.

For monitoring use and misuse of antibiotics

• Schedule H of the drug and cosmetics act contains a list of 536 drugs which are required to be dispensed on the prescriptions of a registered medical practitioner.

• In order to have separate regulation to check unauthorized sale of antibiotics, a separate schedule as Schedule H1 may be introduced under the Drugs and Cosmetics (4th amendment ) rules 2013 to regulate sale of antibiotics exclusively.

• Under schedule H1, drug formulations should be labelled with symbol Rx in red and conspicuously displayed on left corner of the label with the following words in box with red border

• Warning-It is dangerous to take this preparation except in accordance with the medical advice.Not to be sold by retail without the prescription of a RMP.

Drugs under schedule H are omitted

Drugs under Schedule H1

Alprazolam Thiacetazone Alprazolam Diazepam

Cefdinir zolpidem Cefdinir Codein

Cefepime Ethambutol HCl Cefepime Cycloserine

Clofazamine Meropenem Cefixime Ertapenem

Codein Ethionamide Cefoperazone Doripenem

Diazepam Nitrazepam Imipenem Ethambutol HCl

Cefpirone Pentazocine Midazolam Gemifloxacin

Midazolam Sparfloxacine Cefpirome Rifampicin

Tramadol Chlordaizepoxide Ceftriaxone Tramadol

Schedule IParticulars as to proportion of poison in

certain cases.(Omitted by GOI Notification No. G.S.R 462(E)

dt 22.6.1982

Schedule J Schedule J specifies the disease and ailments, for which no

drug should claim prevention or cure. Some of the diseases and ailments under this schedule are

1. AIDS2. Angina Pectoris3. Appendicitis4. Arteriosclerosis5. Baldness6. Blindness7. Bronchial Asthma8. Cancer and Benign tumour9. Cataract10. Change in colour of the hair and growth of new hair.11. Change of Foetal sex by drugs.(almost 51 ailments mentioned on Schedule J)

Schedule K Schedule K specifies the extent and conditions of exemption for

certain class of drugs from the provisions of the Chapter IV of this act.

Class of Drugs is not sold for medicinal use and that each container is labelled conspicuously with the words “NOT FOR MEDICINAL USE”.

The medicines that continue to be under the 'household remedy' category include Paracetamol tablets, Analgesic Balms, Antacid Preparations, Calcium preparations with or without Vitamin D, Gripe Water for use of infants, Inhalers (containing drugs for treatment of cold and nasal congestion), Syrups lozenges, pills and tablets for cough, cold or sore throat.

However, these drugs should not contain any substance specified in Schedules G, H or X of D&C Act and Rules. The shopkeepers are also to ensure that the drugs are sold in the original unopened containers of the licensed manufacturers.

Note- Aspirin and Quinine Sulphate have been removed from this schedule

Mashelkar Committee recommendations• The Committee on Drug Regulatory System headed by the Chief Dr

Mashelkar.• suggested to expand the scope of Schedule K to include OTC

drugs.• The ultimate objective is to enhance public access to commonly

required medicines but at the same time ensuring quality of delivery.

OTC Drugs • The phrase “OTC” has no legal recognition in India, all the drugs not

included in the list of prescription-only drugs” are considered to be non-prescription drugs (or OTC drugs).

• OTC Drugs ‟ means drugs legally allowed to be sold “Over The Counter” by pharmacists, i.e. without the prescription of a Registered Medical Practitioner.

• Prescription-only drugs are those medicines that are listed in Schedule H and X and Schedule G

Ayurvedic (OTC) Medicines • OTC drugs registered as “Ayurvedic Medicines”

containing natural / herbal ingredients• Ayurvedic drugs are manufactured under a

manufacturing license issued by the Ayurvedic State Licensing Authorities. However, they do not require a drug sale license and can be sold freely by non-chemists.

• Largest OTC brands in India are registered as “Ayurvedic Medicines‟ because of their plant-based natural active ingredients

Categories with OTC potential • Vitamins and minerals; • Health tonics, • Cough suppressants likes vicks 44• Gastrointestinal drugs like Gas X• Analgesics • Dermatological preparations• Herbal / Ayurvedic medicines

Schedule L Omitted

Schedule L-I ( Drugs and cosmetics (3rd amendment) Rules 2008) “Good Laboratory Practices and requirement of

premises and equipments as laid down in Schedule L-I

Schedule M Deals with the Good Manufacturing Practices (GMP)

and requirements of premises , plant and equipment.

Part I deals with GMP & Factory premises. Part II deals with plant and equipment.

• GENERAL REQUIREMENTS Location and surroundings.- The factory building(s) for manufacture of

drugs should be so situated and should have such measures as to avoid risk of contamination from external environmental including open sewage, drain, public lavatory or any factory which product disagreeable or obnoxious odour, fumes, excessive soot, dust, smoke, chemical or biological emissions.

Building and premises.- The building(s) used for the factory should be designed, constructed, adapted and maintained to suit the manufacturing operations so as to permit production of drugs under hygienic conditions. They should conform to the conditions laid down in the Factories Act, 1948

Water Supply. – There should be validated system for treatment of water drawn from own or any other source to render it potable in accordance with standards specified by the Bureau of Indian Standards or Local Municipality.Purified Water conforming to Pharmacopoeial specification. Purified Water so produced should only be used for all operations except washing and cleaning operations where potable water may be used. Water should be stored in tanks, which do not adversely affect quality of water and ensure freedom from microbiological growth. The tank should be cleaned periodically and records maintained by the licensee in this behalf.

GOOD MANUFACTURING PRACTICES FOR PREMISES AND MATERIALS.

• Disposal of waste. - The disposal of sewage and effluents (solid, liquid and gas) from the

factory should be in conformity with the requirements of Environment Pollution Control Board.

All bio-medical waste should be destroyed as per the provisions of the Bio-Medical Waste (Management and Handling) Rules, 1996.

Additional precautions should be taken for the storage and disposal of rejected drugs. Records should be maintained for all disposal of waste.

Provisions should be made for the proper and safe storage of waste materials awaiting disposal. Hazardous, toxic substances and flammable materials should be stored in suitably designed and segregated, enclosed areas in conformity with Central and State Legislations.

• Personnel.- The manufacture should be conducted under the direct supervision of

competent technical staff with prescribed qualifications and practical experience in the relevant dosage and / or active pharmaceutical products.

Schedule M1 Prescribes in detail requirements of factory premises for the

manufacture of Homeopathic drugs.

Schedule M- II Prescribes requirements of factory premises for manufacture of cosmetics.

Schedule M- III Prescribes requirements of factory premises for manufacture of medical devices.

Schedule N Deals with the minimum equipment of a pharmacy & gives

directions regardinga) Entrance of Pharmacyb) Premisesc) Furniture & Apparatusd) General Provisions.

Schedule O (Drugs & Cosmetics (8th amendment) Rules 2005)

Deals with the provisions applicable to disinfectant fluids.

Schedule P It deals with life period of drug. Period in months (unless otherwise specified)between date of manufacture and date of expiry which the labelled potency period of the drug should not exceed under the conditions of storageSpecified. The schedule includes antibiotics,vitamins,insulin preparation, normal

human plasma, sera toxins, toxoids , other toxins , anti-toxins, miscellaneous drugs

Schedule P Life period of drugs

Name of Drug Period in Month Conditions of storage

Adriamycin 30 In a cool place

Ampicillin Na 36 In cool place

Carbenicillin Sodium Powder

24 At temperature notexceeding 5°C

Schedule P 1 Schedule P I – specifies the pack size of certain drugs. It gives the

names of drugs, along with the dosage form and the pack size. No other pack size than the one listed is allowed to be marketed. Examples of a few drugs under this schedule:

Schedule P- I pack size of the drug

Name of Drug Dosage form Pack size

Albendazole suspension 10ml

Atenolol Tablet 14 tabs

Piperazine Granules 5 gm

Schedule Q Gives the list of dyes, colors and pigments permitted to be used in cosmetics and soaps.

• No drug should contain a colours other than specified below :

(1) Natural Colours

Carotene, Chlorophyll, Red Oxide of Iron, Yellow Oxide of Iron, Titanium Di-oxide, Black Oxide of iron

(2) Artificial Colours Caramel

(3) Coal Tar Colours

Schedule R Describes the standards for mechanical contraceptive. Eg. Condom, Cu- T

Schedule R-1 Prescribes standards for medical devices. The following medical device shall conform to the Indian Standards specification laiddown from time to time by the Bureau of Indian Standards: -1. Sterile Disposable Perfusion sets for single use only 2. Sterile Disposable Hypodermic Syringes for single use only 3. Sterile Disposable Hypodermic Needles for single use only

Schedule S – Prescribes standard for cosmeticsThe following cosmetics in finished form should conform to the Indian Standards specifications laid down from time to time by the Bureau of Indian Standards (BIS)].

1. Skin Powders2. Skin Powder for infant3. Tooth Powder4. Toothpaste5. Skin Creams6. Hair Oils

Schedule T• Lays down the requirements of factory premises and

hygienic conditions for Ayurvedic and Unani drugs.• The Good Manufacturing Practices (GMP) are

prescribed as follows in Part I and Part II :PART I• GOOD MANUFACTURING PRACTICESPART II• List of machinery, equipment and minimum

manufacturing remises required for the manufacture of various categories of ayurvedic, siddha system of medicines

Schedule T –A ( Drug & Cosmetics (1st amendment) 2008)

• Contains form for record of utilisation of raw material by Ayurveda, Siddha,Unani licensed manufacturing units during the financial year.

Schedule U & U1 Gives the particulars to be shown in manufacturing records.1. Serial number2. Name of the product3. Reference of Master Formula Records.4. Lot/Batch Size.5. Lot/Batch Number6. Date of commencement of manufacture and date of completion of manufacture and7)assigned date of expiry.

Gives the particulars to be recorded of raw materials

Gives the particulars to be recorded in analytical records.

Schedule VGive details of standards for patent and

proprietary medicines.

Schedule W Gives the name of the drugs which shall be marketed under

generic names only. This includes only five drugs that shall be marketed under

generic names only:1. Analgin2. Aspirin and its salt3. Chlorpromazine and its salt4. Ferrous sulfate5. Piperazine and its salts(Schedule W) – Inserted as per G.O.I. Notificiation No. GSR 27(E) dt 17.1.1981 and deleted as per G.O.I. Notification No. GSR 94(E) dt 8.2.2000.

Schedule XSchedule X contains list of drugs which: Need discretion while dispending and pharmacist should ensure that this drugs

are not sold without prescription

Have a waning mentioned on a label ‘Schedule X drug’ – Warning : to be sold on retail on prescription of a registered medical practitioner only. The label will also have a symbol ‘XRx’ in red & conspicuously displayed on the top left corner of the table

After dispending the drug the pharmacist must Stamp & retain the prescription

Maintain & record purchase & sale of the drug and Preserve it for a period of 2 years from the date of transactions

Examples of few drugs under schedule X

1)Amobarbital 2)Amphetamines 3)Dexamphetamines 4) Glutethimide5)Methylphenidate etc.

Schedule Y ( Drugs & Cosmetics ( 2nd amendment) 2005)

Requirement And Guidelines On Clinical Trials For Import And Manufacture Of New Drug or To Undertake Clinical Trials.

The schedule covers details like :– Chemical and pharmaceutical information– Animal tests, toxicology and pharmacology– Clinical Trails • Nature of trails• Permission for trials• Responsibility of sponsor / Investigator

Nature of trials. - The clinical trials required to be carried out in the country before a new drug is approved for marketing depend on the status of the drug in other countries.

If the drug is already approved/marketed, Phase III trials are usually required.

If the drug is not approved / marketed trials are generally allowed to be initiated at one phase earlier to the phase of trials in other countries.

For new drug substances discovered in other countries phase I trials are not usually allowed to be initiated in India unless Phase I from other countries are available.

However, such trials may be permitted even in the absence of Phase I data from other countries if the drug is of special relevance to the health problem of India.

For new drug substances discovered in India, clinical trials are required to be carried out in India right from phase I.

Though Phase III permission to carry out these trials is generally given in stages, considering the data emerging from earlier phase.

Clinical Trials

Permission for trials – Permission to initiate clinical trials with a new drug may be obtained by

applying in Form 12 for a test license (TL) to import or manufacture the drug under the Rules.

In addition, the protocol for proposed trials, case report forms to be used, and the names of investigators and institutions should also be submitted for approval.

The investigators selected should possess appropriate qualifications and experience and should have such investigations facilities as are required to the proposed trials protocol.

It is desirable that protocols for clinical trials be reviewed and approved by the institution’s ethical committee.

For new drugs having potential for use in children, permission for clinical trials in the pediatric age group is normally given after phase III trials in adults are completed.

Responsibilities of Sponsor –

Sponsors are required to submit to the

licensing authority as given under Rule 21 an annual status report on each clinical trial, namely ongoing, completed, or terminated. In case a trial is terminated, reason for this should be stated.

Any unusual, unexpected or serious adverse drug reaction (ADR) detected during a trial should be promptly communicated by the sponsor to the licensing authority and the other investigators.

To implement & maintain quality assurance system.

Investigator In all trials an informal, written consent required to be obtained

from each volunteer/patient in the prescribed Forms which must be signed by the patient/volunteer and the chief investigator.

Conduct of trial according to protocol & Good Clinical Practice.

Standard Operating Procedure (SOP) should be followed.

Data required to be submitted with application for permissionto market a New Drug

• 1. INTRODUCTIONA brief description of the drug and the therapeutic class to which it belongs.

• 2.CHEMICAL AND PHARMACEUTICAL INFORMATION.2.1. Chemical name, code name or number, if any, non-proprietary or generic name, if any, structure, physio-chemical proportion.2.2 Dosage form and its composition.2.3 Specifications of active and inactive ingredients.2.4. Tests for identification of the active ingredient and method of its assay.2.5. Outline of the method of manufacture of the active ingredient.2.6 Stability data

3)ANIMAL PHARMACOLOGY3.1) Specific pharmacological actions.3.2) General pharmacological actions.3.3). Pharmacokinetics, absorption, distribution, metabolism, excretion. 4)ANIMAL TOXICOLOGY 4.1 )Acute Toxicity4.2) Long Term Toxicity4.3)Reproduction Studies.4.4) Local Toxicity4.5) Mutagenicity and Carcinogenicity.

5)HUMAN/CLINICAL PHARMACOLOGY (PHASE I).5.1) Specific Pharmacological effects.5.2) General Pharmacological effects.5.3)Pharmacokinetics, absorption, distribution, metabolism, excretion.

6)EXPLANATORY CLINICAL TRIALS (PHASE II).6.1) Investigator wise reports.

7.CONFIRMATORY CLINICAL TRIALS (PHASE III)7.1)Investigator reports

8)SPECIAL STUDIES8.1)Bioavailability and dissolution studies.8.2)Studies in specific population like pediatric age group, pregnant women)

9)REGULATORY STATUS IN OTHER COUNTRIES.• Countries where –

a) Marketedb)Approved.c) Under trial, with phase.d)Withdrawn, if any, with reasons.

• Restrictions on use, if any, in countries where marketed/approved.• Free sale certificate from country of origin.

10)PRESCRIPTION INFORMATION.10.1)Proposed full prescribing information10.2)Drafts of labels and cartons.10.3)Sample of pure drug substance, with testing protocol.

Submission of ReportsThe reports of completed clinical trials shall be submitted by the applicant duly signed by the investigator with a stipulated period of time.

Marketing information.The product monograph should comprise the full prescribing information necessary to enable a physician to use the drug properly. It should include description, actions, indications, dosage precaution, drug interactions, warnings and adverse reactions.

Post-marketing surveillance study.On approval of a new drug, the importer or the manufacturer should conduct post-marketing surveillance study of that new drug after getting the protocols and the names of the investigators approved by the Licensing Authority during the initial period of two years of marketing.

Format for submission of clinical Trial Reports.• ___ Title of the trial• ___ Name of investigator and institution• ___ Objectives of the trial• ___ Design of study: Open, single-blind or double blind, non-comparative or comparative,• parallel group or crossover.• ___ Number of patients, with criteria selection and exclusion, whether written, informed• consent, was obtained.• ___ Treatments given – drugs and dosage forms, dosage regimens, method of allocation

of• patients to treatments, method of verifying compliance, if any• ___ Observations made before, during and at the end of treatment, for efficacy and

safety, with methods used.• ___ Results : exclusions and dropouts, if any, with reasons, description of patients with

initial comparability of groups where appropriate, clinical patients with initial comparability of groups where appropriate, clinical and laboratory observations on efficacy and safety, adverse drug reactions.

• ___ Discussion of results ; relevance to objectives, correlation with other reports/data, if any,

• guidance for further study, if necessary.• ___ Summary and conclusion.

Therapeutic goods in the United States are regulated by the U.S. Food and Drug Administration (FDA), which makes some drugs available over the counter at retail outlets and others by prescription only.

The possession of some substances is prohibited by scheduling under the Controlled Substances Act, under the joint control of FDA and the Drug Enforcement Administration (DEA).

Under the jurisdiction of controlled substance act of the United States of America ,drugs are categorized according to their potential abuse and are divided in 5 schedules.

These schedules have been detailed by United states Pharmacopoeia Vol. XXII and by National Formulary.

In United States

Schedule I category of drugs not considered legitimate for medical use. Included are heroin, lysergic acid diethylamide (LSD), and marijuana.

Schedule II, category of drugs considered to have a strong potential for abuse or addiction but that also have legitimate medical use. Included are opium, morphine, and cocaine.

Schedule III, category of drugs that have less potential for abuse or addiction than Schedule I or II drugs and have a useful medical purpose. Included are short-acting barbiturates and amphetamines.

Schedule IV, medically useful category of drugs that have less potential for abuse or addiction than those of Schedules I, II, and III. Included are diazepam and chloral hydrate.

Schedule V medically useful category of drugs that have less potential for abuse or addiction than those of Schedules I to IV. Included are antidiarrheal and antitussives with opioid derivatives.

• In U.S. ,drug products are also coded under the National Drug Code (NDC).

• In U.S.,NDC serves as a universal product identifier for drugs used in humans.

• The current edition of the National Drug code Directory is limited to prescription drugs and few selected over-the-counter products.

• Each drug product listed under the Federal Food, Drug and Cosmetic act is assigned a unique 10 digit, 3 segment number.

• This number, known as NDC number identifies the labeller/vendor, product, and package size.

• The labeller/vender code is assigned by FDA.• The second segment, product code identifies specific strength,

dosage form, formulations for particular drug company.• The third segment , package code identifies package size.• Both package and product codes are assigned by manufacturer.

In Canada, regulation of therapeutic goods are governed by the Food and Drug Act and associated regulations.

In addition, the Controlled Drugs and Substance Act

In China The regulation of drugs in China is governed by the State Food

and Drug Administration.

In Canada

Medicines for Human Use in the United Kingdom are regulated by the Medicines and Healthcare products Regulatory Agency (MHRA).

The availability of drugs is regulated by classification by the MHRA

The United Kingdom has a three-tiered classification system:1. General Sale List (GSL)2. Pharmacy medicines (P)3. Prescription Only Medicines (POM)

In United Kingdom

Medicines in Norway are divided into five groups: Class A Narcotics, sedative-hypnotics, and amphetamines in this class

require a special prescription form: morphine and its immediate family, heroin, desomorphine, nicomorphine; codeine and its immediate family, dihydrocodeine, ethylmorphine, nicocodeine;

Class B Restricted substances which easily lead to addiction like diazepam, nitrazepam, and all other benzodiazepines(with the exception of temazepam and flunitrazepam), phentermine;

Class C - All prescription-only substances

Class F - Substances and package-sizes not requiring a prescription

Unclassifieds - Brands and packages not actively marketed in Norway

In Norway

Australia • Therapeutic goods in Australia are regulated by the Therapeutic Goods

Administration (TGA).

• The availability of drugs and poisons is regulated by scheduling under individual state legislation, but is generally under the guidance of the National Standard for the Uniform Scheduling of Drugs and Poisons (SUSDP).

Under the SUSDP, medicinal agents generally belong to one of five categories:• Unscheduled• Schedule 2 (S2) - Pharmacy Medicines• Schedule 3 (S3) - Pharmacist Only Medicines• Schedule 4 (S4) - Prescription Only Medicines• Schedule 8 (S8) - Controlled Drugs

In other countries…………….

References• Drugs and Cosmetics Act. (Internet) 1940[cited 2014 Jun 23]Available from: http

://www.drugscontrol.org/. • Drug and cosmetics rules. (Internet) 1945 corrected on 30th Nov 2004 [cited 2014 Jun 23]

Available from: http://www.drugscontrol.org• Drug and cosmetics (amendment) bill (Internet) 2013 [ Cited 2014 Jun 23] Available from:

http://www.drugscontrol.org• Drug and cosmetics (amendment) act( Internet) 2010 [ Cited 2014 Jun 23] Available from:

http://www.drugscontrol.o• Drug and cosmetics (amendment) act (Internet) 2008 [ Cited 2014 Jun 23] Available from:

http://www.drugscontrol.org• Controlled substance act : Regulatory requirements (Internet) 2012[Cited 2014 Jun 24]

available from:http://fas.org/sgp/crs/misc/RL34635.pdf• New york state controlled substances act (Internet) 2012 [ Cited 2014 Jun 23] Available from:

http://www.health.ny.gov/regulations/public_health_law/article/33/docs/33.pdf• Narcotic bill. (1985). THE NARCOTIC DRUGS AND PSYCHOTROPIC SUBSTANCES ACT,

1985. [cited 2014 jun 23] Available from http://narcoticsindia.nic.in/upload/download/document_id08b2dbdc9ca941d237893bd425af8bfa.pdf.

• Bernard P. Schimmer L., Goodman and Gilman’s The pharmaceutical basis of Therapeutics; Principles of prescription order writing and patient.; chapter 66, 1882-1884; 12th ed., 2011, New York: Mc Graw Hill.

• H.L.Sharma. (2013)General principles of pharmacology:Introduction. In: H.L Sharma, K K Sharma Principles of Medical Pharmacology. 2nd ed.5-6 New Delhi: Paras publisher.

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