1.Pharma Regulatory Affairs

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    Need of regulatory affairs in Clinical research

    To discover a

    New drug



    Device which is Safe & Effective for human beingsRegulatory affairs in Pharmaceutical industry----------------

    Aim - Protection of human health

    Ensures - Safety, efficacy, quality of drugs, Accurate drug information

    Regulates Production, import, export, storage, distribution, sale, supply ofdrugs

    Applied National, international level

    Effective in few developed countries

    Needs support government, professional associations, consumer groups,other public interest groups

    Need of harmonization----------------------

    Prevents the compromisation in the standards of safety and effectiveness ofdrug.

    Helps in optimizing the quality of domestic and international markets whilefacilitating the expansion of international market

    Prevents in market circulation of sub-standard drugsHistory-----------------

    Countries like Egypt, Europe, UK faced the problems of drug adulterations inmedieval period and in first century A.D. which lead to death of humans

    This lead to raise of drug control and many countries introduced laws

    Next came the need of new drug development

    Drugs with serious side effects started appearing in international marketeg., Thalidomide tragedy

    Outcomes from the history----------------

    Countries began to make a stringent demands for substantial evidence ofsafety and efficacy

    For new drugs, results of animal tests & research protocols for human testshad to be now provided before any test on humans could be initiated.

    Medicines Act-------------------------

    1971, UK, medicines act came into force leading the pharmaceuticalcompanies to acquire license from the licensing authority.

    This further ensured safety, efficacy, quality of medicines

    The act also gave the country the legislative power to monitor adverseevents, control promotion and advertising, and inspect pharmaceuticalmanufacturing facilities


    After the establishment of WHO in 1948, the pharmaceutical trade concernreceived international recognition.

    WHO taken part in improving quality of drugs in its member states

    It also promoted global mechanisms for regulating the quality ofpharmaceutical products in international market

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    Initiatives taken by WHO------------------------

    Selection of international proprietary names for pharmaceutical products

    Publication of international pharmacopoeia

    Establishment of WHO GMP guidelines for pharmaceuticals

    Creation of WHO certificate scheme to ensure the quality of pharmaceutical

    products sold on international market Creation of national & regional quality control laboratories

    Guidelines dealing with regulatory & QA issues were developed and madeavailable to countries

    Provided support in setting up & strengthening of drug regulatory & QAissues

    Helped around 70 countries to enact either new drug legislation, or to amendexisting drug legislation

    Efforts were made to have common system of regulations for all countriesthereby having a better hold over regulatory requirements of the drugs

    This was first put into practice by European union (EU)COMMON TECHNICAL DOCUMENT-----------------------

    The Common Technical Document (CTD) is a set of specification forapplication dossier for the registration of Medicines and designed to be usedacross Europe, Japan & US.

    It was developed by the European Medicines Agency (EMEA, Europe), theFood and Drug Administration (FDA, U.S) and the Ministry of Health, Labour &Welfare (MHW, Japan).

    The CTD is maintained by the International conference on harmonization oftechnical requirements for the registration of pharmaceuticals for human use(ICH)

    The Common Technical Document is divided into five modules:

    Administrative and prescribing information

    Overview and summary of modules 3 to 5

    Quality (pharmaceutical documentation)

    Safety (toxicology studies)

    Efficacy (clinical studies)

    The contents of Module 1 and certain subheadings of other Modules willdiffer, based on national requirements.

    After the United States, European Union and Japan, the CTD has beenadopted by several other countries including Canada and Switzerland.


    The creation of drug regulatory authority networks, such as

    International conference of drug regulatory agencies

    African drug regulatory Agencies conference

    African drug regulatory authorities networkhelped in promoting cooperation between national drug regulatory

    authorities to discuss issues of mutual interest and to facilitate timely exchangeof technical information

    Geopolitical groups in Asia, Europe, Latin America have promotedHarmonization & mutual recognition of drug regulation at regional, sub-regional, global level facilitating trade in pharmaceuticals

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    NEED FOR DRUG REGULATIONS------------------------

    Importance of drug in human life made the drug regulations mandatory.

    Other reasons, which favor the need for regulation of drugs are

    Presence of third parties like researchers, manufacturers, distributors,promoters, dispensers etc in between Prescriber and Patient.

    Good relation between physician and pharmaceutical industries or salesrepresentatives which attracts the physician to gifts offered rather thanhaving interest on prescribing good medicines to patient

    If a physician acts both as prescriber and dispenser the potential conflictarises between financial gain to be made from sale of more drugs andprofessional obligation to advice what is best for patient

    Misuse of drugs & drug shortages can have serious effects on health ofindividual patients

    Pharmaceutical products have limited shelf life even when stored underspecific storage conditions. Thus if they are stored under adverse or improperconditions they can deteriorate very rapidly, losing their therapeutic value.

    PRESENT SCENERIO OF DRUG REGULATION--------------------------

    Since early 1960s, there has been an increasing in public & governmentinterest in safety and efficacy of pharmaceutical products and medicaldevices.

    This increase in regulatory requirements for pharmaceutical products hasdictated that companies in these industries establish a distinct department,staffed with professionals to assure in meeting regulatory requirements.

    These individuals are known as Regulatory Affairs Professionals

    Medicines exported from industrialized countries are not regulated to thesame level as those domestically consumed

    Relabelling of products to mask details of their origin is also known to occur.

    The problem of distributing of drugs via internet also increased.

    Hence the major concern here would be how to protect consumers fromsubstandard & dangerous drugs moving on international markets

    According to recent working group sponsored by World Bank & attended byrepresentatives of WHO, United Nations childrens fund & otherorganizations, the main barriers to effective drug regulation are

    Absence of policy, regulation

    Lack of political support

    Lack of finance


    Insufficient human resources

    Absence of priorities

    Weak professional association etcHOW TO MAKE DRUG REGULATION MOREEFFECTIVE?---------------------------

    The scope, nature & practice of drug regulation including priorities,standards, resources available vary from country to country.

    But, the main goal is promotion & protection of public health by ensuringsafety, efficacy & quality of drugs.

    A drug regulatory body should

    Base its decisions on scientific evidences

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    Provide efficient & timely services

    Apply sound management principles

    Reach its objectives

    Operate to safeguard against corruption

    Countries desiring to make their drug regulation effective need to take

    measures described below- Assess Drug Regulation Performance

    Identify & Develop Priority Functions

    Provide a Clear Mission & Purpose

    Create a Supportive environment

    Formulate Adequate Drug Legislation

    Create Appropriate Organizational Structure

    Allocate Adequate Human & Financial Resources

    Minimize Corruption1. Assess Drug Regulation Performance

    Poor drug regulation leads to prevalence of substandard, harmful, ineffectivedrugs on national & international market resulting in serious harm to healthof consumers.

    Therefore countries must strengthen their drug regulatory authority to ensuresafety, efficacy, quality of drugs & accurate product information.

    Countries must assess their drug regulation performance, using indicatorsthat focus on structures & inputs, processes & outcomes

    They must identify strengths & weaknesses of their regulatory system &reason for them

    Consider alternative options & make the most appropriate & practicablechoices

    2. Identify & develop priority functions

    The development of regulatory capacity occurs in phases Developing countries will need to start with limited priority activities

    Attempt made to introduce all regulatory measures & processes at once willlead to failure

    Government have to set priorities

    For setting priorities, a regulatory agency must first decide what exactly itwants to regulate, what activities it wants regulatees to perform, & how it canensure they perform them

    3.Provide clear mission & purpose

    A clear written mission, based on priorities & functions, should be provided

    for drug regulation, indicating what it intends to achieve & methodology toachieve it.

    The core mission of drug regulation for all countries is to promote publichealth by ensuring the quality, safety & efficacy of dugs, & accurate productinformation, the mission may also include

    Ensuring timely availability of drugs

    Encouraging domestic production of drug products

    4. Create a supportive environment

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    Effective drug regulation is promoted if political system assures basicdemocratic rights by allowing professional associations, consumer unions,public interest groups etc

    Countries with strong consumer unions, public interest groups generally havestronger consumer protection

    The history of drug regulation in developed countries shows thatimprovements in quality of drug regulation have often occurred in responseto a drug incidents & resulting pressure exerted by public groups

    5. Formulate adequate drug legislation

    Drug legislation forms the basis of drug regulation

    Drug legislation must

    Define areas & activities to be regulated

    State the roles, responsibilities, rights & functions of all partiesinvolved with drug regulation

    Create administrative bodies necessary for the implementationof drug regulation, and define their structural & functional

    relationships Set the qualifications & standards for those handling drugs

    Establish the administrative measures & legal sanctions that willapply when provisions of drug legislations are violated

    6. Create appropriate organizational structure

    In almost all countries, the responsibility for regulating drugs belongs togovernment

    However depending on national circumstances, the government maydelegate certain regulatory activities to the private sectors like consumergroups, professional associations etc

    Care should be taken to ensure appropriate distribution of duties,responsibilities, functions between different bodies

    There should be well written terms of reference that describe the linkagesbetween the various bodies

    7. Allocate adequate human & financial resources

    Governments must employ people with specialized knowledge & skills if theywish to promote effective drug regulation.

    Moreover, they must employ individuals of great integrity & pay them well,particularly since drug regulation involves various stakeholders withcommercial interests who will often apply pressure to secure favourabledecisions.

    In promoting effective drug regulation, adequate budgeting is essential

    8. Minimize corruption

    Corruption is often seen at the intersection of public & private sectors

    Some approaches to minimize corruption

    Making rules

    Punishing those who take or offer bribes etcTHE DRUG REGULATORY SYSTEM IN INDIA-----------------------

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    In India approval or ban of drugs are taken care by CDSCO

    It also acts as CLAA (central license approving authority) for Drugs

    CDSCO officers are participating in 3 areas of work with state DrugRegulatory Authorities officers. They are

    Inspection of CLAA category units

    Drawing samples for analysis

    Inspection of manufacturing units for issuing WHO GMPcertificates

    Role of state drug regulatory authority

    There are 3 aspects which are observed by state DRA

    Regulate the manufacture of drugs in their area to meet thespecifications & guidelines laid down by Drugs & Cosmetics Act, 1940& Rules, 1945

    To regulate the standards of drugs in the inter & intra state levels

    To prevent, control & take steps to punish the offenders

    Disposal of detected cases Suspension/cancellation of license if offence is detected

    There are state amendments in Act, which differentiate same crime from 1state to another leading to disposal of offence

    The suggested modifications

    There should be one Act for entire country to control quality of drugs

    The act & rules should be implemented by 1 organization

    Upgrading all state drugs testing laboratories & setting up electronic networkfor effective functioning under the control of CDL (central drugs laboratories)

    Designated courts in each region of state may be established

    Central drug authority (CDA)

    Looks after the overall control of drugs moving in the country & directlyreports to PM or President of India

    Their decisions affect the health of Nation

    CDA approves new drugs & directly supervises the ADR reported

    They should submit annual report of the quality of drugs moving into theIndian market

    Zonal drug authority (ZDA)

    Reports to CDA

    They also acts as licensing authority

    State drug authority

    Directly reports to NDA under intimation to RDA

    They are the licensing authority for manufacture of drugs in their state

    State vigilance officer

    S.P in CBI with support staff & facilities to carry criminal investigations

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    District drug authority

    I.Ph.S (Indian pharmaceutical services) or assistant director

    Supervises the performance of the drug officers working in his area

    Directly reports to SDA

    Licensing authority of all distribution outlets of drugs in the area

    Officer of drugs/ drugs officer

    In charge of the area allocated & responsible for the affairs of that area

    He can register FIR in all criminal cases arising out of the implementation ofacts on drugs in the concerned police station

    2. DRUG REGULATORY AUTHORITIESThe Role of Drug Regulatory Authorities-----------------

    Before new medicines reach the prescription pad, the appropriate regulatoryauthorities, who assess their safety & efficacy, must approve them first

    Because of following incidents GMP Guidelines came into existence andbecame mandatory

    Elixir of Sulfanilamide Tragedy (1937)

    Thalidomide Tragedy (1961) Devonport Hospital Tragedy (1972, 5 people died at Devonport

    hospital because a batch of infusion solution had not been fullysterilized by the producer, due to poor GMP)

    GMP guidelines were 1st given by statutory authority in USA, 1962 & in UK,1971

    Now EU Guide received statutory authority, through an EU directive, in 1991

    It defines GMP as that part of quality assurance which ensures that productsare consistently produced & controlled to the quality standards appropriate totheir intended use & as required by their marketing authorization or product

    specification It contains 9 chapters, designed to be applicable to all pharmaceuticalmanufacturing

    The 9 chapters are1. Quality management2. Personnel premises & equipment3. Documentation4. Production5. Quality control6. Contract manufacture & analysis7. Complaints8. Product recall

    9. Self inspectionSome Drug Regulatory Authorities World Wide---------------------Agencies of United States of America------------------------------1. The World Health Organization

    WHO is the United Nations specialized agency for Health established on 7 thApril, 1948

    WHO main objective attain highest possible level of Health.

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    WHOs constitution defined Health as a state of complete physical, mental &social wellbeing & not merely the absence of disease

    Quality assurance & safety of medicines (QSM) team is responsible fordevelopment, harmonization & promotion of international standards, & forthe exchange of information

    The drug regulatory program supports Member states in their regulatory workwith WHO guidelines

    All European countries face new regulatory changes that require internationalcollaboration

    Drug regulation in countries of EU is covered under the CADREAC(collaboration agreement of drug regulatory authorities in European Unionassociated countries) agreement to discuss progressive harmonization withEuropean union Regulation

    2. Food and Drug Administration (FDA)

    Oldest & most respected consumer protection agencies

    Aim- to promote & protect public health by allowing only safe & effectiveproducts reach the market

    It monitors the products for continued safety even after they have beenbrought into use

    It helps the public to get accurate, scientific information needed to improvetheir health

    FDA protects the public from unnecessary exposure to radiation fromelectronic products (microwave ovens, cell phones, x-ray equipment, lasersetc)

    FDA regulates drugs & devices used for animals

    Manufacturers can market animal drugs after getting approval from FDA byproviding proof of their safety & effectiveness

    3. The PAN American Health Organization (PAHO)

    International public agency with 100 yrs of experience

    Work to improve health & living standards of Americans

    Serves as specialized organization for health of Inter-American system

    Serves as regional office for American WHOAgencies of U.K-----------------------------1. National institute for biological standards & control (NIBSC)

    Multi-disciplinary scientific establishment

    Purpose is to safeguard & enhance public health by standardizing &controlling biological substances used in medicine

    International role in preparing, evaluating, distributing international biologicalstandards

    It is also a WHO international laboratory for biological standards

    2. Medicines & healthcare products regulatory agency (MHRA) Executive agency of department of health

    Protects & promotes public health & patient safety by ensuring thatmedicines, healthcare products & medical equipment meet appropriatestandards of safety, quality, performance & effectiveness & are used safely

    Main objectives

    Minimize the cost of regulation

    Provide authoritative & accessible information

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    Make an effective contribution to public health

    Support industry & scientific innovation

    Influence international regulationAustralian Regulatory AgenciesTherapeutic Goods Administration (TGA)

    Unit of Australian Government Department of Health Performs assessment & monitoring activities to ensure therapeutic goodsavailable in Australia are of an acceptable standard

    Objective of TGA, 1989 is to provide national framework for regulation oftherapeutic goods in Australia & ensure their quality, safety & efficacy

    Any product for which therapeutic claims are made must be entered in theAustralian register of Therapeutic goods (ARTG) before the product can besupplied in Australia

    TGA regulations are on a number of factors including advertising, labeling,product appearance & appeal

    Pre-market assessment

    Products assessed as having higher/lower level of risk are evaluated for

    safety, efficacy, quality Once approved for marketing, products are included in ARTG as registered

    products & are identified by AUST R/L number

    Licensing of manufacturers

    Australian manufacturers of therapeutic goods must be licensed

    Their manufacturing processes must comply with GMP principles

    Post marketing vigilance

    Includes investigating reports of problems, laboratory testing of products,monitoring to ensure compliance with legislation

    Irish policiesIrish Medicines Board (IMB)

    To ensure current medical & scientific knowledge, quality, safety, efficacy ofmedicines available in Ireland

    IMB provides the approval for use of medicine, monitors the type & frequencyof any reported side effects

    IMB monitors the quality of medicines by conducting inspections at sites ofmanufacture & distribution of medicines

    In case of veterinary medicines also there must be assurance of quality,safety, efficacy

    IMB carries out the following services within Ireland

    Licensing of medicinal products for human use

    Licensing of veterinary products

    Licensing of manufacturers of human & veterinarymedicines

    Pharmacovigilance & drug safety monitoring

    Clinical trial licensing

    Inspection of wholesale & manufacturing sitesRegulatory Authority in JapanPharmaceuticals & medical devices evaluation center

    Established in 1997 to strengthen governments evaluation capacity forsecuring safety & preventing harmful side effects of pharmaceuticals

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    Evaluates quality, safety, efficacy of each prescription drugs & medicaldevices as well as proprietary drugs, cosmetics that are purchased directly bypublic

    Process for the approval of newly developed drug

    Applicant must apply to ministry of health, labour & welfare (MHW) with thedata

    MHW leaves the data reliability survey to external institution

    after evaluation by different officials with different back ground

    The report is submitted to pharmaceutical affairs & food sanction council(PAFSC), which is a consultative body of minister

    Based on this report the ministry finalizes the whether they should approvethe drug or not.

    Regulatory Authority in Republic of Latvia

    Non profit state joint stock company state agency of medicines ( SAM )

    Founded on 9th Oct, 1996

    SAM acts in accordance with

    Pharmacy law

    Law of joint stock companies Law of non profit organizations

    Other regulatoriesRegulatory Authority in CanadaHealth Products & Food Branch (HPFB)

    Integrated approach to the management of risks & benefits related to healthproducts & food by

    Minimizing health risk factors to Canadians while maximizing thesafety

    Promoting conditions that enable Canadians to make healthy choices &providing information so that they can make informed decisions about

    their health HPFB inspectorate is responsible for management of inspection,

    investigation, monitoring activities related to fabrication, packing, labeling,testing, import, distribution of regulated health products for human & animaluse

    Marketed Health Products Directorate (MHPD)

    Responsible for coordination of consistency of post approval surveillance &assessment of safety trends concerning all marketed health products

    Works in collaboration with other directorates in Health Products & FoodBranch & with other involved branches

    MHPD Activities

    Monitors & collects ADR data

    Conducts risks / benefit assessment

    Communicates product related risks to healthcare professionals& public

    Conducts active surveillance & drug effective projects

    Natural Health Products

    SEQ of Health products

    Office of Nutrition policy & planning

    promotion & protection of activities related to nutrition

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    Office of Assistant Deputy Minister

    to improve efficiency & effectiveness of functions

    Regional operations

    HPFB activities are carried out through offices in thenational capital region & regional offices (Atlantic region,

    Quebec, etc)Regulatory Agency in SlovakiaState institute for drug control (SIDC)

    In Bratislava

    Is the institution of Ministry of Health of Slovak republic responsible forensuring surveillance of quality, efficacy, safety of medicinal products forhuman use

    SIDC Responsibilities

    Controls, standardizes, evaluates the process of assessing Q,E,Sof drugs

    Performs inspections of GMP, GLP, GCP, Good Pharmacy practice

    Keeps database of registered drugs & medical devices

    Performs vigilance in the field of medical devices Acts in field of training & education

    Status of Drug Regulation in some Countries--------------------------WHO African Region

    A survey conducted during 1992-93 using a questionnaire to assess existenceof QA systems in WHO African Region found that

    Out of 26 countries

    11 has QA system (including QC lab)but it was not functioning well

    9 had some kind QA system without QC lab

    6 did not have any QA system

    19 countries mentioned illegal importation as a serious problem

    Of 21 countries with domestic pharmaceutical manufacturing, 6 did not haveQC lab & 4 are without an inspectorate

    Lao peoples democratic republic

    Before 1988 all drugs were distributed by public sector

    At present, there are 6 manufacturing plants, 32 private importers & 2018private pharmacists

    Food & Drug Department (FDD) is responsible for registration of drugs,inspection & licensing of manufacturers

    It is also responsible for public sector drug supply, control of narcotic drugs &psychotropic substances

    Food & Drug Quality Control Center (FDQCC), 1995. undertakes

    chemical analysis of drugsKenya

    Kenya has 1 public sector drug procurement agency, 135 private importers &wholesalers, 40 pharmaceutical companies

    The legal instructions for regulating drugs are Pharmacy & Poisons Act,1957

    Pharmacy & Poisons Rules, 1981 apply to registration of Drugs

    Pharmacy & Poisons Board established under Pharmacy & Medicines Act, isresponsible for registration of pharmacy professionals, market authorizationof drugs, issuing licenses to manufacturer, wholesaler, retail pharmacies

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    A national drug control laboratory was established in 1995 under pharmacy &poisons Board. It carries out limited pre & post marketing QC of drugs

    The inspectorate, under the director of medical services/ ministry of health,undertakes surveillance of wholesale & retail outlets

    Drugs are being smuggled into country

    WHO certificate scheme is not applied as recommended by WHO whenassessing status of drugs

    Kenya exports drugs to other African countries by issuing free salecertificates even though it has no inspectorate to assess GMP compliance


    3 authorities are responsible for drug regulation1. The Myanmar Food & Drug Board Authority2. Food & Drug Supervisory Committee (FDSC)3. FDA

    FDSC issues licenses & inspects drug wholesalers, retailers

    FDA issues marketing authorization, inspects manufacturing plants & teststhe quality of drugs

    Drug Advisory Committee (DAC)- applications are reviewed for marketauthorization, post marketing surveillance

    VietnamVietnams Ministry of Health

    Acts as Drug regulatory authority and manages state owned Drugmanufactures, imports & exports

    FDA responsible for formulation, drug legislation, registering drugs, issuinglicenses etc

    Drugs are being smuggled in & out of vietnamColombiaColombias Drug Regulatory Agency (DRA)


    Controlling quality & safety of medicines, biological products,foods, cosmetics, medical devices

    Issuing licenses concerning manufacture of medicines

    Issuing marketing authorizationsPakistanPakistans drug act, 1976

    Licensing of manufacturing plants, importing & exporting & registration ofmedicines to federal government

    At federal level, Central licensing & registration body consists of

    Federal director general

    Drug controller provincial director general of health

    Central board of revenue & justice division, medical & pharmaceuticalexperts

    All are responsible for regulating, manufacturing, registering, imports,exports of drugs


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    India is a land of different origin for a number of systems of medicine likeAyurveda & Unani

    As there are no special rules enforced on manufacture of Ayurvedamedicines, it resulted in spoiling the quality of medicines

    Drugs & Cosmetics Act, 1940 was valid only to Allopathic medicines

    But later in 1976 Ayurvedic medicines were also included

    With the announcement of GMP norms for alternative medicine, theAyurvedic medicines manufacturers are now liable to follow QC measureswhich were intended only for Allopathic medicines till now


    To provide for the establishment of a Central Council of Indian Medicine

    Maintenance of a Central Register of Indian Medicine

    Indian Medicine the system of Indian medicine commonly known as AshtangAyurveda, Siddha or Unani Tibb

    1. The central council & its committees :-

    Members not exceeding 5 from each state. President, vice president electedamong them selves. Meets at least once per year. Holds office for a term of 5yrs. Decisions regarding Ayurveda, siddha, unani system of medicines.2. Recognition of medical qualification :-

    Medical qualifications granted by any university etc are recognized. Medicalqualifications granted by institutions outside India are also recognized. Acquiresinformation about university etc which provides medical qualification. Appointsvisitors for inspection of medical colleges, hospitals etc. council withdrawsrecognition if the institute does not meet standards.3. Central register of Indian medicine :-

    Practitioners Register maintained by central council in separate parts for eachsystem of medicine. It contains names of candidates enrolled in state register of

    Indian medicine. Registrar of central council maintains the central registrar &updates it by receiving copies of state register of Indian medicine. Persons whoare enrolled on central register of Indian medicine are eligible to practicemedicine in any part of IndiaRegulations in regard to Indian medicine central council Act,1970------------------

    Manner of election of president, vice-president, their powers; resignation ofmembers

    Appointment, powers, duties & procedures of inspectors & visitors

    Standards of staff, equipment, accommodation, training & other facilities foreducation in Indian medicine

    Conduct of professional examination, qualifications of examiners etc

    Particulars to be stated & proof of qualifications to be given in applications forregistration

    Fees to be paid on applications & appealsGMP FOR AYURVEDA, SIDDHA, UNANI MEDICINE------------------------

    GMP are prescribed to ensure that

    Raw materials used in manufacture of drugs are authentic ofprescribed quality. Free from contamination

    Manufacturing process is as prescribed, to maintain standards

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    Adequate QC measures are adopted

    Manufactured drug, which is released for sale, is of acceptable qualityGMP (schedule- M)------------------------


    The manufacturing plant should have adequate space for

    Receiving raw material

    Storing raw material

    Manufacturing process area

    QC section

    Finished goods store

    Rejected goods/ drugs store

    officeGeneral requirements-------------------------

    Location & surroundings avoid contamination from open sewage, drain etcwhich produces disagreeable odor, fumes, smoke etc

    Buildings premises used for manufacturing, processing, packaging, labelingwill be in conformity with provisions of Factory Act

    Water supply pure water must be used.

    Disposal of waste waste water & residues are disposed off after suitabletreatment as per guidelines of pollution control authorities to render themharmless

    Containers cleaning adequate arrangements separated from manufacturingoperations for washing, cleaning, drying of containers

    Stores adequate space for storage of different types of material, such asraw material, packaging material & finished products

    Raw materials care must be taken to handle different kinds of rawmaterials. Each container used for raw material storage shall be properlyidentified with label clearly stating the status (approved. Under test,

    rejected). Raw materials shall be sampled & tested either by in house orlaboratories by government. Records of receipt, testing, approval, rejectionshall be maintained

    Packaging materials containers, closures shall be cleaned & dried beforepacking products

    Finished goods stores finished goods are stored within an area markedquarantine. Only approved finished goods after QC tests will be dispatched.Distribution records shall be maintained.

    Working space adequate place to facilitate easy& safe working and tominimize risk of mix-up, cross contamination etc

    Health, clothing, sanitation & hygiene of workers

    Medical services adequate facilities for first aid. Medical examination ofworkers periodically

    Equipment based on size of operation, nature of product manufacturedsuitable equipment shall be made available. SOP for cleaning, maintainingetc of machine shall be laid down

    Batch manufacturing records (BMR) the licensee shall maintain BMR toprovide an account of list of raw materials, quantities obtained, chemicaltests performed etc. it is essential to maintain records for each & everyprocess

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    Distribution of records records of sale & distribution of drugs shall bemaintained in order to facilitate prompt & complete recall of batch

    Record of market complaints once in 6 months manufacturer shall submitrecord of complaints to licensing authority. The register shall also beavailable for inspection. Adverse reactions reported on the product shall alsobe recoded

    The quality control section shall carry out the following functions

    The section should be provided with an area of 150 sq. feet

    Samples should be maintained for identification of raw drugs & for reference

    Manufacturing record should be maintained for the various processes carriedout during manufacturing

    Supervise & monitor adequacy of conditions under which raw materials, semifinished products & finished products are stored

    Keep records of shelf life &storage requirements for drugs

    All raw materials will be monitored for fungal, bacterial contamination with aview to minimize such contamination

    The standards for identity, purity & strength as given in respective

    pharmacopoeias of Ayurveda, Siddha & Unani systems of medicinespublished by government of India shall be complied

    Requirement for sterile products--------------------1. Manufacturing area

    For manufacture of sterile ayurvedic, siddha, unani drugs separateenclosed area (dust free, properly ventilated) shall be provided. HEPAfilters are to be used. Manufacturing areas shall be restricted tominimum number of authorized personnel

    2. Precautions against contamination and mix

    Provide a suitable exhaust system

    Carry out manufacturing operations in a separate block of adequatelyisolated building

    Expert technical staff approved by licensing authority shall check theyield

    Room relative humidity, volume filled, leakage & clarity should bechecked & recorded

    THE GLOBAL AYURVEDIC PRODUCT MARKET------ The global Ayurvedic market is booming. The reported growth rate is 9-10 %

    per annum The herbal drugs in India is presently estimated to be around 2,300 crores

    with a 15% growth/annum Since, the rise of Ayurvedic medicines Kerala is fast becoming a unique

    selling proposition (USP) to earn for exchange for the country An Indian system of Medicine & Homeopathy drug policy is currently

    establishing A medicinal plant board & GMP authority is reportedly being constituted to

    implement good manufacturing practices

    Regulation relating to Homeopathic medicine--------------------

    Since early 1990s, number of changes in status of homeopathic remedieshave taken place.

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    Numerous remedies that were once sold as OTC drugs have been moved intoprescription status

    This is due to publication of FDA, Homeopathic pharmacopoeias of Unitedstates (HPUS)

    The Homeopathy central council act,1973

    Maintenance of a central register of Homeopathy

    The central council & its committees

    Recognition of medical qualifications

    Central register of HomeopathyThe central council & its committees :-

    Members not exceeding 5 from each state. President, vice president elected among them selves. Meets at least once per

    year. Holds office for a term of 5 yrs. Decisions regarding Homeopathic system of

    medicines.Recognition of medical qualification :-

    Qualifications granted by any university etc are recognized.

    Qualifications granted by institutions outside India are also recognized. Acquires information about university etc which provides medical

    qualification. Appoints visitors for inspection of medical colleges,hospitals etc. council withdraws recognition if the institute does notmeet standards.

    Central register of Homeopathy:- Practitioners Register maintained by central council for Homeopathic

    system It contains names of candidates enrolled in state register of Indian

    medicine. Registrar of central council maintains the central registrar & updates it

    by receiving copies of state register of Indian medicine.

    Persons who are enrolled on central register of Indian medicine areeligible to practice medicine in any part of India

    4.DRUG POLICY IN INDIAMain objectives of Drug Policy, 1986----------------------

    To ensure abundant availability, at reasonable prices of essential & lifesaving medicines of good quality

    To strengthen the system of quality control over drug production & promotingrational use of drugs in country

    To create an environment for new investment into pharmaceutical industry

    To encourage cost effective production & to introduce new technologies &new drugs

    To strengthen the production of drugs

    The policy was implemented through Industries act and Drugs pricecontrol order

    Implementation of the drug policy provisions has been throughIndustries(development & regulation) act [I(D&R)Act] on industrial licensingaspects & through Drugs price control order (DPCO) act

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    Enforcement of quality & standards in medicines is done through theprovisions contained in Drugs & Cosmetics Act, which is administered byMinistry of Health & Family Welfare, Government of India

    The drug policy has also given the policy framework with regard to QualityControl & rational use of drugs

    Present status & approach adopted Over last 7 yrs, policy have been directed towards promoting growth of

    industry. As on date there 250 large units & 8000 small units in operation, which form

    the core of the country These units produce the complete range of formulations i.e., medicines ready

    for consumption by patients, 350 bulk drugs etc It is estimated that 70% of demand for bulk drugs & almost the entire

    demand for formulations are being met through domestic production In India, during the last decade the production of bulk drugs has grown from

    Rs.240 crores in 1980-81 to Rs.1320 crores in 1993-94 & correspondenceincrease in production of formulations i.e., Rs 1200 crores to Rs6900 crores

    Since 1986, the drug industry has grown significantly, in terms of productionof bulk drugs & formulations

    It is estimated that in case of bulk drug production the contribution of smallscale is approximately 30% of the total production in India

    Industrial licensing Import & economic policies have undergone major changes like pruning of

    negative list for imports, doing away with the Actual user condition & fullconvertibility of Rupee on trade market

    In this changed scenario, it is felt that there is no need to be more restrictivethan before in granting industrial approvals, provided the 2 main concernsi.e.,

    Achieving basic stage manufacturing Discouraging undue imports It is also felt that, like in other sectors of economy, production would get

    necessary importance to meet any future demands as well as of ensuringadequate availability of drugs at reasonable prices with more liberalization ingranting industrial approval

    R & D, Investment & Pricing------------------

    The drug industry is highly R & D oriented which needs to ensure thattechnologies used in country are cost effective & efficient.

    Investment is necessary in order to update the existing technologies

    Basic research in drug sector has assumed greater importance

    In order to meet the growing needs of country, to promote exports, it is

    proposed to treat entire drugs & pharmaceutical sector as a high priorityindustry for the purpose of permitting foreign investment in terms ofNewIndustry Policy.

    The high turn over of a drug is an index of its extent of usage

    To encourage the production & availability of the drugs, it is considered toallow a uniform MAPE (Maximum allowable post-manufacturing expenses) inall cases of drugs

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    The government has set up an independent body of experts, called NationalPharmaceutical Pricing Authority, to do the work of price fixation fordrugs.

    This body would also monitor the prices of decontrolled drugs & formulations& oversee the implementation of provisions ofDrugs Price Control Order

    Government will keep a close watch on prices of medicines, which are takenout of price control.

    In case, the prices of the medicines rise unreasonably, the government wouldtake necessary actions

    Quality control & rational use of drug----------------

    Quality control & rational use of drugs are important aspects ofpharmaceutical industry

    Steps have been taken in strengthening the Drug Control Organization byestablishing Sub-Zonal offices at Hyderabad, Ahmedabad, Patna.

    The Bio-Laboratory at Madras has been upgraded to level of NationalLaboratory

    Central Drugs Laboratory Mumbai

    Regional Laboratories Guwahati, Chandigarh, Hyderabad For certain Drugs like

    Large volume ParenteralsSera & vaccinesWhole human blood & Blood products

    Which has found to caused Adverse effects due to lack of drug control in orother state, the central government has taken upon itself the responsibility ofgranting license

    GMP has made mandatory

    Screening of irrational & harmful drugs are done

    Definition of new drugs has been widened & guidelines issued on clinical

    trials Adverse Drug Reaction Monitoring Centers Leading hospitals atPondicherry, Chandigarh, New Delhi, Bombay, Lucknow

    National Drug Authority responsibilities

    Develop & define basic standards relating to Manufacture, Import, Supply &Use of drugs

    To approve & register pharmaceutical products for use in the country only if

    It meets real medical need

    It is therapeutically effective

    It is acceptable safe

    To enforce effectively appropriate quality standards of medicines & GMPthroughout the country

    To monitor

    The standard practices in drug promotion

    The prescribing practices

    To ensure that appropriate information about registered pharmaceuticals ismade available for the guidance of consumers in regard to

    Adverse consequences of non-complaince by patients particularly incase of antibiotics, steroids etc

    Dangers of self-medication

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    Need to involve consumers as full partners in the healthcare system &to publish national formularies for the guidance of consumers &doctors


    Special focus on examining the technology of bulk drugs

    Assessing suitability of manpower for bulk drug production Developing testing labs for cosmetics, diagnostics & devices

    Laying down standards for veterinary drugs

    Quality control of herbal medicines

    Updating new drug approval process

    Formation of expert committees for examination of new drugs

    Examination of labelsIn addition, Screening promotional literature Monitoring ongoing clinical trials through IRB Unearthing substandard & spurious drugs with the help of legal cum

    intelligence cells Centralizing all manufacturing licensees Updating GMPs Setting up of new analytical testing labs etc were also performed by National

    Drug Authority There is an imperative need to undertake up gradation of drug testing

    facilities under the central & state organizations Therefore, there is a need for establishing more Zonal & Sub-zonal offices

    under CDSCO as well as regional testing laboratories A coordination committee consisting of secretaries of ministries/ departments

    of commerce, revenue, health, biotechnology, industrial development &chairman, bureau of industrial costs & prices is been set up under thechairmanship of secretary (chemicals & petro chemicals) for monitoring the

    key concerns on time & for taking timely action

    Foreign Investment--------------------

    Foreign investment up to 51% is permitted in the case of all Bulk drugs, theirintermediates & formulations

    Investment of above 51% will be considered on a case by case basis in areaswhere investment is otherwise not forthcoming, particularly in themanufacturing of bulk drugs

    Automatic approval for foreign technology agreements are also given in thecase of all bulk drugs, their intermediates & formulations except thoseproduced by the recombinant DNA technology

    4. REGULATORY AFFAIRS PROFESSION The pharmaceutical industry is the most highly regulated industry demanding

    a high level of information be submitted to government before apharmaceutical product is being brought to the market place

    Regulatory affairs is responsible for obtaining & maintaining licenses to

    market medicinal products in as many countries as necessary

    According to the present laws all organizations involved in the development

    & marketing of medicinal products is legally required to have some form ofregulatory support

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    Many people move into Regulatory Affairs from laboratory research, clinical

    research, regulatory compliance, QC, QA or drug safety

    Qualification required Minimum a life science or pharmacy degreeMany technical companies require post-graduate qualification, pharmacy,

    chemistry, biology degrees

    Experience 1-2 yrs of exp in pharmaceutical industry in a related area

    Regulatory affairs professionals have opportunities to work scientifically or

    commercially, nationally or internationally & many regulatory professionalswill at sometime or another experience travel in their role

    Roles & responsibilities of regulatory affairs professionals vary depending onthe company

    Some of the opportunities in Regulatory affairs are

    Task specialist specializes in 1 area of regulatory affairs

    Eg ; document management, product labeling etc

    Regulatory specialist works as pharmacist or chemist with specialization

    in preparing & managing a specific element of product registration Project manager the professional manages all the regulatory aspects of

    a product development & maintenance

    Therapeutic specialist manages regulatory affairs for products in specific

    therapeutic area from formulation stage to license maintenanceEg ; oncology, cardio vascular

    Line manager professional moves into managing power

    Service provider work with different companies on numerous projects

    Graduates may enter into a role as Regulatory affairs officer or scientist or


    This could be in any number of areas like clinical research, manufacturing,

    sales, marketing Regulatory affairs profession provides in an depth overview of full spectrum

    of drug development, from clinical trials, marketing to post-approval activities

    As members of the drug development team, regulatory affairs professionals

    play a very important role in new drug approvalsDevelopment of the profession Regulatory affairs is a new profession which is developed from the desire of

    government to protect public health, by controlling the safety & efficacy ofproducts

    The regulatory affairs profession developed in almost all countries of theworld

    Governments have responded to public concern over public health & product

    safety in a number of area by placing requirements on manufacturers toconfirm to stringent safety testing procedures & obtain marketingauthorizations before placing a product in the market

    The companies responsible for discovery, testing, manufacture of theproducts also want to ensure that they supply products that are safe

    The Regulatory Affairs professionals job is to keep track of the ever changinglegislation in all regions in which the company wishes to distribute itsproducts

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    In order for a regulatory authority to issue a marketing authorization, it mustcarryout a close scrutiny of all reports generated during development ofproduct, review the manufacturing methods, QC procedures, clinical safety &efficacy

    This activity is known as assessment Regulatory affairs profession is becoming increasingly influential in the

    overall drug development process & increasingly populated by highly trainedscientists & medical professionals

    Responsibilities of Regulatory Affairs Professionals The regulatory affairs department is the first point of contact between

    government authorities & company Regulatory affairs professionals helps to ensure that the product

    development, manufacturing & marketing practices meet or exceedgovernment requirements

    Regulatory affairs program provides graduates with the specializedknowledge required to help biotechnology, medical device, pharmaceutical &food companies manage regulatory processes

    Students will gain knowledge of international healthcare system, healthcare

    legislation, procedures & practices for regulating the development,manufacture, QA & manufacturing of healthcare products

    Regulatory affairs program have an international focus for the followingreasons

    Most companies develop products for an international market Current regulatory processes in most countries are based on international

    guidelines Regulatory affairs professionals must ensure that the product information

    submitted to the authorities is as complete as possible & in the correct form They are also responsible for subsequent contacts with the regulatory

    authorities Since authorizations are issued for a specified time, & have to be renewed

    before expiry, a very important part of regulatory affairs function ismaintenance & updating of authorizations

    Regulatory professionals will critically review all the scientific evidencepresented by the company to establish the products quality, safety, efficacy

    Regulatory affairs executive has the responsibility to communicate with allpeople within the pharmaceutical company, external communicants, medicswho have an input to all the data that is put together for the regulatoryauthorities

    The regulatory affairs professionals will then communicate this information tothe government regulatory authorities worldwide in the for of Dossiers

    Regulatory affairs professionals should be involved at initial synthesis stages,preclinical stages, clinical stages & all the way through drug developmentlifecycle & beyond into product marketing cycle

    The whole process of drug discovery & ultimate release into market may takeup to 15yrs & many problems may arise during this period of scientificdevelopment

    It is the job of the regulatory affairs professional to help the company avoiddeficiencies in their data, which may create difficulties in the registration ofthe product

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    Regulatory affairs executive has to collect all the documented data, keep thedocuments in the correct & specified order, summarize where necessary,check the validity & make sure there are no conflicts among the datasupplied

    Regulatory authorities will generally seek clarification & ask specific scientificquestions from regulatory professionals on the areas of Quality, Safety,

    Efficacy & they will require prompt & accurate answer for giving license toproduct

    After the company got license to manufacture & sell new pharmaceuticalproduct in the chosen market there is a need to maintain & renew the licensewhich is the duty of regulatory affairs professional

    Skills, which regulatory affairs professional must have areKey negotiation skillsProject management skillsInformation technology skillsManagement skillsInterpersonal skills

    All these skills are set against a background of ever changing pharmaceutical

    regulations world wideIn clinical trials, Regulatory affairs professionals have the following role to play Provide strategic leadership for the development & execution of regulatory

    plans to support a global drug development plan Provide the company with regulatory intelligence & expertise in translating

    regulatory requirements into practical, workable plans Manage the daily activities of personnel responsible for regulatory

    submissions, train, mentor & coach regulatory personnel Ensure timely preparation of organized & scientifically valid submissions of

    IND etc Represent regulatory affairs to other departments & provide guidance on

    adherence to regulatory guidelines for effective submissions Assure adherence & compliance with all applicable FDA/ICH guidelines & with

    current GLP,GMP & GCP guidelines Set objectives for training sessions, standard practices, SOPS &

    departmental policies Responsible for supporting the GCP compliance program by conducting

    comprehension audits of clinical investigator sites Presentation of GCP training to other staff Provide support to internal & external GCP compliance program Planning, scheduling, conducting, coordinating investigator sites according to

    SOP, applicable regulatory requirements Assisting in performing internal systems audits, reviewing clinical documents As a product goes through the review process, regulatory affairs

    professionals are looking at requirements for manufacturing, packaging &advertising

    Manufacturing is related with QA, QC Packaging, labeling & advertising will also interfere with manufacturing There are stringent regulations everywhere that govern these spheres Regulatory affairs personnel work with distribution & make sure the

    processes meet regulatory requirements

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    Once the product is in use, regulatory affairs professional is also involved inreporting any adverse effects of a drug to FDA

    QUALIFICATIONS, SKILLS & ABILITIES OF REGULATORY AFFAIRSPROFESSIONAL Minimum requirement for an individual to enter into regulatory affairs

    profession is to have a scientific background in order to have the knowledge

    to ask the scientists the right questions in the light of a vast quantity ofproduct data, pharmaceutical legislation & guidelines

    Having some working knowledge of the industry is always preferable The usual requirement is a degree in life science, pharmacy or medical

    degree with some experience in pharmaceutical /biotech industrySkills Required

    Good Written Skills Verbal communication skills Problem solving abilities Critical/analytical thinking skills Ability to plan & manage multiple projects Meeting deadlines Accommodate changing priorities Assignments Proficiency in computer applications Interpersonal skills to interact with other departments effectively

    In the pharmaceutical industry, regulatory affairs professionals should haveexpertise in the legal & regulatory environments, as well as in clinicalresearch protocols

    They are the primary interpreters of the laws & regulations for othermembers of the company like R & D, manufacturing etc

    Regulatory affairs professionals must have a thorough understanding of thecomplex set of regulations

    Keeping up to date on regulations is essential in regulatory affairs; changes inregulations can affect the clinical trials process, regulatory strategy, whatkinds of decisions are needed on trials etc

    According to some critics the field of regulatory affairs has becomeincreasingly more science & issue based

    As the speed of pharmaceutical & biologics development has increasedscience has become more complex

    A regulatory professional now spend more time on substantive scientific &medical issues & planning for experiments & clinical studies to achieveapproval

    A regulatory affairs professional has to be able to provide expert opinions ontechnical & legal matters associated with registration of products

    Regulatory professionals must always exercise considerable integrity &judgment in the practice of their roleTHE RELATIONSHIP OF REGULATORY AFFAIRS PROFESSIONS TO OTHERPROFESSIONS

    Regulatory affairs professional must have capacity to draw upon theinformation provided by specialists (pharmacologists, toxicologists, chemists,pharmacists, doctors etc) & must be able to synthesize the knowledge & useit to impart information & make aware of staff about current regulatoryguidelines

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    As regulatory processes increase in complexity & scope, globalization occurswithin this field, there will be continuing industry demand for people with astrong foundation in regulatory affairs

    Communication & organizational skills are also extremely important indealing with government agencies

    Advantages of certification Regulatory affairs certification enhances employment prospects Many companies, both large & small are now beginning to indicate that

    Regulatory Affairs certificate is a desirable qualification Certified professionals will earn 5-15% more salary than others