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PHARMA REGULATORY AFFAIRS

1.Introduction

Need of regulatory affairs in Clinical research

To discover a

New drug

Treatment

Diagnosis

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

WHO-------------------------

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.

DRUG REGULATORY AUTHORITY NETWORKS-----------------------

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

Corruption

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

Myanmar

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)

Responsibilities

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

3.REGULATIONS ON ALTERNATIVE SYSTEM OF MEDICINE

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NEED FOR REGULATIONS ON ALTERNATIVE SYSTEM OFMEDICINE--------------

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

INDIAN MEDICINE CENTRAL COUNCIL ACT, 1970---------------

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)------------------------

FACTORY PREMISES

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

Functions

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

executive

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