Regulatory aspects of Pharmaceuticals and Bulk drug Manufacturing, Regulation of drugs and

pharmaceuticals.

By K. Sampath Kumar,

Y11MPH18060,I/II M.Pharm,

2nd Semester,Pharmaceutical Analysis,

Sims college of Pharmacy.

Under the guidance of

Sri B. Thangabalan Sir, M. Pharm

(Ph.D)

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Drugs play an important role in the health of both people and the

economy of a country.

Pharmaceutical drugs are available from a large number of sources.

People and Governments willing to spend money on drugs for many

reasons so, it must be safe, effective and good quality and used

appropriately.

This means, in turn, that development, production, importation,

exportation and subsequent distribution of drugs must be regulated

to ensure that they meet prescribed standards.

Therefore, effective drug regulation is required to ensure the safety,

efficacy and quality of drugs as well as accuracy and appropriateness

of the drug information available to the public

Introduction:

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►In an ideal world, the need for analysis should be driven by the

desire to assure the quality of a drug product.

►However, in the real world the need for pharmaceutical drug

analysis is driven largely by regulatory requirements.

►A team consisting of R&D, QC, and QA unit members develops

these quality and compliance systems.

►It should be one of the highest priorities of top management and

QA units to develop and monitor these systems to comply with the

cGMP and GLP expectations.

►Compliance documents are needed, in addition to the regulatory

and research documents, to demonstrate the integrity of the data.

►Compliance documents refer to those reports required by GMP

and/or utilized during the course of inspection by a health

authority.

Regulatory requirements

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Product registration (drug evaluation and authorization, and

monitoring of drug efficacy and safety);

Regulation of drug manufacturing, importation, and

distribution;

Regulation & Control of drug promotion and information.

Adverse drug reaction (ADR) monitoring.

Licensing of premises, persons and practices.

Key function of regulatory agencies

Goal of regulatory agency

Main goal of drug regulation is to guarantee the safety, efficacy

and quality of drugs available to public.

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Drug Laws

Drug Regulatory Agencies

Drug Regulatory Boards

Quality Control

Drug Information Centres etc.

The drug regulation

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Drug regulatory system in India

Drugs and Health is in concurrent list of Indian Constitution It is

governed by both Centre and State Governments under the Drugs &

Cosmetics Act, 1940.

MAIN BODIES

Central Drug Standard Control Organization (CDSCO)

Ministry Of Health & Family Welfare (MHFW)

Indian Council Of Medical Research (ICMR)

Indian Pharmaceutical Association (IPA)

Drug Technical Advisory Board (DTAB)

Central Drug Testing Laboratory (CDTL)

Indian Pharmacopoeia Commission (IPC)

National Pharmaceutical Pricing Authority (NPPA)6

WELL DEFINED DRUG REGULATORY SYSTEM(Govt.

of India)

Ministry of health and family welfare

Enforcement & GMP audit Division

Quality Control Division – CDTL

Registration Division

New Drug Division

Pharmacovigilance

Trainings

DCGIDTAB

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Approval of Investigational New Drug (IND)

IND Applicant

CDSCO

Examination

by new drug

division

Recommendation

to DCG (I)

Approval

Detailed review

by IND

committee

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ManufacturerState licensing

authority

Joint inspection

by state and

central inspectors

Examination of

report

License prepared

by state licensing

authority

CLAA approval

and grant of

license

Central licensing

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Head quarters New Delhi

North Zone Ghaziabad

West Zone Mumbai

South Zone Chennai

East Zone Kolkata.

Other zonal offices Ahmedabad and Hyderabad.

Sub-Zonal Office 2

Port offices/Airports 7

Laboratories 6

CDSCO

Central Drug Standard Control Organization

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CDSCO Drug Controller General (I)

Head

QuarterZonal & sub

Zonal office

Port

OfficeLaboratory

New Drugs

CLAA

Imports

DTAB/DCC

GMP Audits

Coordinates

with states

Import

ExportTesting of drug

samples

Validation of

Test Protocol

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Functions undertaken by Central Government

Statutory function:

Laying down standards of drugs, cosmetics, diagnostics and devices.

Laying down regulatory measures, amendments to Acts and rules.

To regulate market authorization of new drugs.

To regulate clinical research in India

To approve licenses to manufacture certain categories of drugs as

Central License Approving Authority(CLAA) i.e. for Blood Banks, Large

Volume Parenterals and Vaccines & Sera.

To regulate the standards of imported drugs.

Work relating to the Drugs Technical Advisory Board ( DTAB ) and

Drugs Consultative Committee (DCC).

Testing of drugs by Central Drugs Labs.

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National Institute of Health and Family Welfare

NIHFW is an Apex Technical Institute, funded by Ministry of

Health and Family Welfare, for promotion of health and family

welfare programmers in the country through education, training,

research, evaluation, consultancy and specialized services.

The NIHFW was established on March 9, 1977 by a merger of the

National Institute of Health Administration and Education (NIHAE)

with the National Institute of Family Planning (NIFP)

NIHFW

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• 18 members

List of Governing Body Members of NIHFW

NIHFW

1 Chairman

(ex-officio)

1 Vice

Chairman

(ex-officio)

1 Member

Secretary

(ex-officio)

9 Member

(ex-officio)6 Member

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Measuring weight of children to assess the nutritional

status.

Assessment of diseases like level of anemia.

Testing of food material like cooking salt for level iodine.

To release fund on the advice of the Ministry.

It is responsible for all governmental programs relating to

family planning in India.

ACTIVITIES AND RESPONSIBILITIES

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Structure and organization

Union Health Minister

Governing body

Scientific Advisory

Board

Task forces

Scientific advisory

groups

Scientific advisory

committee

Expert groups

Steering

Committee

ICMR

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Extramural research is promoted by ICMR by establishing

Centers for Advanced Research in different research areas.

Open-ended research is conducted on the basis of applications

for grants-in-aid received from scientists in non-ICMR Research

Institutes, Medical colleges and Universities located in different

parts of the country.

Balancing of research efforts between different competing

fields, especially when resources are severely limited, is a typical

problem encountered in the management of medical research,

particularly in developing countries

ACTIVITIES AND RESPONSIBILITIES

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The Indian Pharmaceutical Association (IPA) has demanded to

amend the Drugs &Cosmetics Act and Rules 1945 to make only the

pharmacy graduates eligible to become expert staffs in the pharma

manufacturing units.

In the resolutions passed during the just concluded IPA

Convention, the IPA also urged the government to expedite action to

amend the Rules in such way that all regulatory positions in the

country must be an exclusive area for experienced and qualified

pharmacists.

Indian Pharmaceutical Association (IPA) is the premier professional

association of pharmacists in India.

The association has more than 10,000 members from various

parts of the country and it operates in India through 17 state

branches & more than 33 local branches.

The association represents various facts of pharmaceutical

profession and in managing several academic programmes.

IPA

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DRUG TECHNICAL ADVISORY BOARD

The Central Government constitute a Board (to be called the

Drugs Technical Advisory Board) to advise the Central

Government and the State Governments on technical matters

arising out of the administration of D&C, Act 1940

The Board shall consist of the following members,

– 20 Members

DTAB

DTAB5

Nominated

Members

5 Elected

Members

10 ex-officio

Members

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It advices matter related to Drugs.

The nominated and elected members of the Board shall hold

office for three years, but shall be eligible for re-nomination and

re-election.

The Board may, subject to the previous approval of the Central

Government, regulating its own procedure.

ACTIVITIES AND RESPONSIBILITIES

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CENTRAL DRUG TESTING LABORATORY

The central drug laboratory, Kolkata is national statutory

laboratory of the government of India for quality control of drug

and cosmetic and established under the D&C act ,1940.

Oldest quality control laboratory of the drug control

authorities in India.

Function under the director general of Health Services in the

Ministry of Health and Family Welfare.

CDTL

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► Statutory Function :

To Act as an Appellate authority.

To function as Government Analyst for such states who do not have

their own testing facilities.

Analytical quality control of majority of the imported drugs.

Analytical quality control of drug formulations manufactured

within the country on behalf of the Central & State Drug standard

control organization

►Other Functions:

Procurement, establishment, maintenance, Storage and distribution

of I.P & International Reference standards.

Preparation and standardization of I.P. reference standards against

USP, BP primary standards.

To undertake analytical research in standardization and

methodology development of drug.

FUNCTIONS UNDER TAKEN

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Indian Pharmacopoeia Commission

IPC

General body

(19 Members)

CIPL lab Governing body

(10members)

IPC

secretariat

Scientific body

23 experts

IPC

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Development of comprehensive monographs.

Accord priority to monographs of drugs included in the

national Essential Drug List and their dosage forms.

Preparation of monograph for products that have normally

been in the market for not less than 2 years.

Collaborate with pharmacopoeias like the BP, USP, JP and

International Pharmacopoeia with a view to harmonizing with

global standards.

ACTIVITIES AND RESPONSIBILITIES

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National Pharmaceutical Pricing Authority

• For the purpose of implementing provisions of DPCO, powers of

the Government have been vested in the National Pharmaceutical

Pricing Authority (NPPA).

• Drugs have been declared as essential and accordingly put under

the Essential Commodities Act.

• Only 74 out of 500 commonly used bulk drugs are kept under

statutory price control.

• However, the prices of other drugs can be regulated, if warranted

in public interest.

• The NPPA was established on 29th August 1997 as an

independent body of experts following the Cabinet Committee’s

decision in September 1994 while reviewing the Drug Policy.

NPPA

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The Authority, inter alia, has been entrusted with the task of

fixation/revision of prices of pharmaceutical products (bulk

drugs and formulations),

enforcement of provisions of the Drugs (Prices Control) Order

monitoring the prices of controlled and decontrolled drugs in

the country.

NPPA

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Ceiling and Non Ceiling Prices of drugs and medicines in the

controlled category regulated .

Ceiling Price is the single maximum selling price fixed that is

applicable throughout the country in the case of each bulk drug,

which is under price control.

Non-Ceiling Price fixed by NPPA are specific to a particular

pack size of scheduled formulation of a particular company.

Features

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Good Manufacturing Pratices

GMP guidelines are not prescriptive instructions on how to

manufacture products.

They are a series of general principles that must be observed

during manufacturing.

When a company is setting up its quality program and

manufacturing process, there may be many ways it can fulfill

GMP requirements.

It is the company's responsibility to determine the most effective

and efficient quality process.

GMP

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To ensure that their products are safe, pure, and effective.

To minimize or eliminate contamination, mix up and errors.

Issues including recordkeeping, personnel

qualifications, sanitation, cleanliness, equipment verification, process

validation, and complaint Handling.

GMP is also sometimes referred to as "cGMP”.

Failure of firms to comply with GMP regulations can result in very

serious consequences including recall, fines, and even

imprisonment.

REQUIREMENTS

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WHO GUIDELINES (World Health Organization):

Who is an agency of United Nations. It is a specialised agency and its

primary responsibility includes international health matters so that

the goal, health for all, can be achieved.

The WHO GMP and the certification scheme was accepted by WHA

(world health assembly) in solution no WHA 28.65, as the revised

version in 1975.

With appearance of ISO (International Organization For

Standardization) the WHO GMP needed next revision. The revised text

contains 3 parts.

Part I: out lines the general concepts of quality assurance and salient

components of GMP’s.

Part II: outlines on actions to be taken by production & quality control

personnel separately for implementing general principles of quality

assurance.

Part III: supporting and supplementary guidelines.

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The revised text of GMP appears as annex.

ANNEX I: Quality Management in the Drug Industry

– Philosophy & Essential Elements

Quality Assurance

Good Manufacturing Practice

Quality Control

Sanitation & Hygiene

Validation

Complaints

Product recalls

Contract Production & Analysis

Self inspection and quality audits

Personnel

Premises

Material

Documentation

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ANNEX II:Good Practices – Production & Quality Control

Good Practices in Production

Good Practices in Quality Control

ANNEX III:Supporting and Supplementary Guidelines

Sterile pharmaceutical Products

Good Manufacturing Practice for Active

Pharmaceutical Ingredients

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WHO GMP CertificationOriginally established in 1969 and revised in 1975.

Main objectives were :

To inspect drug manufacturing facilities

To assess compliance of GMP

This would facilitate implementation of the scheme.

WHO GMP ensures the following:

Avoidance of Cross- Contamination

Prevention of Mix-ups

Provide Traceability

Accountability of actions

Responsibility

Product Performance Guarantee

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DEFINITIONThe U.S. Food and drug administration is an agency of the

United States Department of Health and Human services and is

responsible for the safety regulation of most type of foods

dietary supplements

Drug

Vaccines

Biological medical products

blood products

medical devices

radiation – emitting devices

veterinary products and

Cosmetics

The agency of the U.S. Department of Health and Human Services.

Established in 1927.

FDA

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How does ICH work?

ICH operates through the ICH Steering Committee with

administrative support from the ICH Secretariat and ICH

Coordinators.

The Steering Committee meets at least twice a year . During these

meetings, new topics will be considered for adoption, reports are

received on the progress of existing topics, and maintenance and

implementation of the guidelines are discussed.

The topics identified for harmonization by the Steering Committee

are selected from Safety, Quality, Efficacy, and Multidisciplinary

matters.

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1. Before searching any person, explain him that he has a right to be

searched before a gazetted officer or a magistrate. If he so

requires, take him to a gazetted officer or a magistrate before whom

he can be searched. (Section 50.) without giving him a chance to

part with the drug, controlled substance, etc. you can search him

under Section 100 of the Cr. P. C. (Section 50(5) and 50 (6)).

2. Take down any information given by any person in writing before

authorizing a search (Section 41). If the search is under Section

42, also send a copy of the information taken in writing or the

grounds of belief for search within 72 hours to your immediate

superior officer.

3. Inform the arrested person, as soon as may be, the grounds of his

arrest (Section 52 (1)).

Your Responsibilities Under The Law

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4. If a person is arrested or an article has been seized under a

warrant issued by a magistrate, forward the person/seized article

to that magistrate (Section 52 (2)).

5. If the person has been arrested or the article has been seized

otherwise than under a warrant , forward it to the nearest police

station or any other officer empowered under section 53 (Section

52 (3)).

6. If the person has been arrested or the article has been seized

otherwise than under a warrant , forward it to the nearest police

station or any other officer empowered under section 53 (Section

52 (3)).

7. Whenever you arrest any person, make a full report to your

superior within 48 hours ( Section 57)37

1. Officers Officers acting in discharge of their duties in good faith

under the Act are immune from suits, prosecution and other

legal proceedings ( Section 69).

2. Addicts Addicts charged with consumption of drugs (section 27)

or with offences involving small quantities will be immune from

prosecution if they volunteer for de addiction. This immunity

may be withdrawn if the addict does not undergo complete

treatment (Section 64 A ).

3. Offenders Central or state governments can tender immunity to

an offender in order to obtain his evidence in the case. This

immunity is granted by the government and not by the court

(Section 64).

4. Minors All offences committed under any law by persons under

the age of 18 will be covered by the Juvenile Persons (Care and

protection) Act. This Act seeks to reform such juveniles rather

than punish them under the respective Acts. It prevails over any

other Act in respect of persons below the age of 18.

IMMUNITIES IN DRUG CASES

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1. DRUG REGULATORY AFFAIRS by sachin itkar, Dr.S.wyavahare

2. www.fda.gov/cder/guidance/index.htm

3. www.fda.gov/cber/cberftp.html.

References

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End of 2nd semester

Thank you all for your cooperation and appreciation. All the best for the exams & your future

Ur’s K. Sampath Kumar

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