Regulatory aspects of Pharmaceuticals and Bulk Drug Manufacturing

1. Regulatory aspects of
Pharmaceuticals and Bulk
Drug Manufacturing
Dr.Vinod M. Thakare
Nagpur College of Pharmacy
Nagpur

2. 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.
Introduction:

3. 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

4. Regulatory requirements
►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.

5. 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 nd/or utilized during the
course of inspection by a health authority.

6. Product registration(drug evaluation and authorization,
and monitoring of drug efficacy and safety);
Regulation of drug manufacturing, import, 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.

7. Drug Laws
Drug Regulatory Agencies
Drug Regulatory Boards
Quality Control
Drug Information Centres etc.
The drug regulations
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8. • Department of Pharmaceuticals:
The Department of Pharmaceuticals was created on the 1st of July in
the year 2008 in the Ministry of Chemicals & Fertilizers with the
objective to give greater focus and thrust on the development of
pharmaceutical sector in the country and to regulate various complex
issues related to pricing and availability of medicines at affordable
prices, research & development, protection of intellectual property
rights and international commitments related to pharmaceutical
sector which required integration of work with other Ministries.

10. 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)
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11. 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
DCGI
DTA
B
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Drugs Controller General of India (DCGI)
Directorate general of Health Sciences
(DGHS)
Central Drug Standard Control
Organization (CDSCO)
Drug Technical Advisory Board
(DTAB)

12. 12
IND
Applicant
CDSCO
Examination by new
drug division
Recommendation to
DCG (I)
Approval
Detailed review by
IND committee
Approval of Investigational New Drug (IND)

13. Manufacturer
State
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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14. CDSCO
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Central Drug Standard Control Organization
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

15. CDSCO Drug Controller General (I)
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Head
Q uarter
Zonal & sub
Zonal office
Port
Office
Laboratory
New Drugs
CLAA
Imports
DTAB/DCC
GMP Audits
Coordinates
with states
Import
Export
Testing of drug
samples
Validation of
Test Protocol

16. Functions undertaken by Central Government
Statutory function:
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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.

17. 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)
NIHF
W
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18. 18 members
List of Governing Body Members of NIHFW
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NIHFW
1 Chairman
(ex-officio)
1 Vice
Chairman
(ex-officio)
1Member
Secretary
(ex-officio)
9 Member
(ex-officio)
6 Member

19. Measuring weight of children to assess th e 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 governm ental program s relating
to family planning in India.
ACTIVITIES AND RESPONSIBILITIES
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20. Structure and
organization
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Union Health Minister
Governing body
Scientific Advisory
Board
Scientific advisory
groups
Scientific advisory
committee
Expert groups
Steering
Committee
ICMR
Task forces

21. 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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22. IPA
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. 22

23. DTA
B
23
DTAB
5
Nominated
Members
5 Elected
Members
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
10 exofficio Members

24. 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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25. 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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26. FUNCTIONS UNDER TAKEN
► 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
m2
2 ethodology development of drug.

27. Indian Pharmacopoeia Commission
IPC
General body (19
Members)
CIPL
lab
Governing body
(10members)
IPC
secretariat
Scientific body
23 experts
IP
C
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28. Development of comprehensive monographs.
Accord priority to monograph s of drugs included in the
national Essential Drug List and their dosage forms.
Preparation of monograph for products tha t 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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29. NPPA National Pharmaceutical Pricing Authority
 For the purpose of implementing provisions of DPCO, powers of
th e Govern men t have been vested in th e National
Pharm aceutical Pricing Authority (NPPA).
Drugs have been declared as essential and accordingly put unde
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
indepen den t body of experts following th e Cabinet
Committee’s d25ecision in September 1994 while reviewing the Drug
Policy.

30. 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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31. 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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32. GMP
Good Manufacturing Pratices
 GMP guidelines are not prescriptive instruction s on how to
manufacture products.
 They are a series of general principles that m ust be
observed during manufacturing.
 When a com pany is setting u p 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.
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33.  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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34. WHO GUIDELINES (World Health Organization):
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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.

35. The revised text of GMP appears as annex.
ANNEX I: Quality Management in the Drug Industry
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– 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

36. ANNEXURE II:
Good Practices – Production & Quality Control
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Good Practices in Production
Good Practices in Quality Control
ANNEXURE III:
Supporting and Supplementary Guidelines
Sterile pharmaceutical Products
Good Manufacturing Practice for Active
Pharmaceutical Ingredients

37. WHO GMP
Certification
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Originally 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

38. DEFINITION
The 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
38
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

39. How does ICH work?
• 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. 39
th rough th e ICH Steering
operates administrative Com mittee with support
Coordinators.
fromthe ICH Secretariat and ICH

40. Your Responsibilities Under The Law
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
3 6
arrest (Section 52 (1)).

41. 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)

42. 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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43. 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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