Drug Regulations: Compare US and Indian GMP Standards

This presentation is compiled by ― Drug Regulations‖ a
non profit organization which provides free online
resource to the Pharmaceutical Professional.
Visit http://www.drugregulations.org for latest
information from the world of Pharmaceuticals.
3/13/2014 1

 This presentation is compiled from freely
available resources like the websites of
FDA, EMA, WHO.
 ―Drug Regulations‖ is a non profit
organization which provides free online
resource to the Pharmaceutical Professional.
 Visit http://www.drugregulations.org for
latest information from the world of
Pharmaceuticals.
3/13/2014 2Drug Regulations : Online Resource for Latest Information

3Drug Regulations : Online Resource for Latest Information

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 The recent ban on Ranbaxy‘s 4th plant in India & the visit
of US FDA commissioner created a debate about US &
Indian GMP‘s standards.
 This presentation compares & highlights the differences.
 The GMP‘s in the Indian Act is specified under Schedule
M I Part I for Drug products.
 The number referred in the comparison for US GMP‘s are
from 21 CFR part 210 and 211 ; those for the Indian
GMP‘s are from Schedule M Part I
Drug Regulations : Online Resource for Latest Information

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 PART 210—CURRENT GOOD MANUFACTURING PRACTICE
IN MANUFACTURING, PROCESSING, PACKING, OR
HOLDING OF DRUGS; GENERAL
1. Product is not classified as Adulterated if GMP‘s are not followed.
( 210.1 c )
2. No separate license or GMP‘s for biological products (210.2 a )
3. Investigational drug has not been defined ( 210.2 c )
4. There are no specific requirements for Investigational drugs.
( 210.2 c )
5. Experimental drugs are completely exempted from GMP‘s

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6. Following terms are not defined ( 210.3 b )
◦ Component
◦ Non fiber
◦ Fiber
◦ In process material
◦ Manufacture, processing , Holding Packing
◦ Medical Feed , Medical premix
◦ Quality Control Unit
◦ Strength
◦ Theoretical Yield , Actual Yield ,Percentage Theoretical Yield
◦ Acceptance Criteria
◦ Representative Sample
◦ Gang Printed Labeling

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 Subpart A—General Provisions
1. No separate classification for OTC drugs ( 211.1 c)
2. Drugs marketed as OTC drugs follow all requirements of Drugs
( 211. 1 c)
 Subpart B—ORGANIZATION AND PERSONNEL
1. Requirement that the authority of QC to review production records other
than manufacturing records to assure that no errors have occurred or, if
errors have occurred, that they have been fully investigated is not
specified. ( 211.22 a)
2. Requirement that the responsibility of the quality control unit for
approving or rejecting all procedures impacting on the identity, strength,
quality, and purity of the drug product not specified. ( 211.22 c).
Specified only for specifications and manufacturing records.
3. Requirement of training in GMP‘s is not specified. ( 211.25 a).

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4. Use of protective apparel, such as head, face, hand, and arm coverings,
shall be worn as necessary to protect drug products from contamination
is not specified. ( 211.28 a)
5. Requirement that only personnel authorized by supervisory personnel
shall enter those areas of the buildings and facilities designated as
limited-access areas is not specified. ( 211.28 c )
6. Requirement that consultants advising on the manufacture, processing,
packing, or holding of drug products shall have sufficient education,
training, and experience, or any combination thereof, to advise on the
subject for which they are retained; Records shall be maintained stating
the name, address, and qualifications of any consultants and the type of
service they provide has not been specified ( 211.34)

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 Subpart C—BUILDINGS AND FACILITIES
1. Requirement that equipment for adequate control over air pressure,
micro-organisms, dust, humidity, and temperature shall be provided
when appropriate for the manufacture, processing, packing, or holding of
a drug product is not specified. ( 211.44 b)
2. Requirement that if air is recirculated to production areas, measures shall
be taken to control recirculation of dust from production is not specified.
( 211.46 c)
3. Requirement that potable water to be supplied under continuous positive
pressure is not specified. ( 211. 48 a)
4. Requirement that written procedures for use of suitable rodenticides,
insecticides, fungicides, fumigating agents is not specified. Specified for
cleaning & sanitizing agents and for warehouse only. ( 211. 56 c).

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 Subpart C—BUILDINGS AND FACILITIES
 Requirement that such written procedures (see 4 above) shall be designed to
prevent the contamination of equipment, components, drug product
containers, closures, packaging, labeling materials, or drug products and
shall be followed is not specified . (211. 56 c )
 Requirement that rodenticides, insecticides, and fungicides shall not be
used unless registered and used in accordance with the Federal Insecticide,
Fungicide, and Rodenticide Act (corresponding Indian Act) is not specified. (
211.56 c)
5. Requirement that sanitation procedures shall apply to work performed by
contractors or temporary employees as well as work performed by full-
time employees during the ordinary course of operations is not specified.
( 211.56 d)

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 Subpart D—Equipment
1. Requirement that equipment and utensils shall be cleaned,
maintained, and, as appropriate for the nature of the drug,
sanitized and/or sterilized at appropriate intervals to prevent
malfunctions or contamination that would alter the safety,
identity, strength, quality, or purity of the drug product beyond
the official or other established requirements is not specified.
( 211.67 (a) )
 Mentioned in a confused way at different place under Blood bank ,
Equipment, Batch Packing & Processing Records and under different
dosage forms.

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2. Requirement that written procedures shall be established and followed
for cleaning and maintenance of equipment, including utensils, used in
the manufacture, processing, packing, or holding of a drug product is
specified in a very confusing way under Part I General requirements and under
Part 1 F for API‘s . ( 211.67 (b) )
3. Requirement that records shall be kept of maintenance, cleaning, sanitizing,
and inspection as specified in §§211.180 and 211.182 is not clearly specified.
( 211.67 (c) )
4. Requirement that automatic, mechanical, or electronic equipment or other
types of equipment, including computers, or related systems that will perform
a function satisfactorily, may be used in the manufacture, processing, packing,
and holding of a drug product is not specified for automatic & Electronic
equipment. ( 211.68 (a) ).

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 Requirement that if such equipment is so used, it shall
be routinely calibrated, inspected, or checked according
to a written program designed to assure proper
performance is not specified for automatic & electronic
equipment.. ( 211.68 (a) ).
 Requirement that written records of those calibration
checks and inspections shall be maintained is not
specified for automatic & electronic equipment. ( 211.68
(a) )

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5. Requirement that input to and output from the
computer or related system of formulas or other
records or data shall be checked for accuracy is
not specified. ( 211.68 (b) )
 Requirement that the degree and frequency of
input/output verification shall be based on the
complexity and reliability of the computer or related
system is not specified. ( 211.68 (b) )

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 Requirement that a backup file of data entered into the computer or related
system shall be maintained except where certain data, such as calculations
performed in connection with laboratory analysis, are eliminated by
computerization or other automated processes is not specified except for
batch records. (211.68 (b) )
 Requirement that in such instances a written record of the program shall be
maintained along with appropriate validation data is not specified.
(211.68 (b) )
 Requirement that hard copy or alternative systems, such as duplicates,
tapes, or microfilm, designed to assure that backup data are exact and
complete and that it is secure from alteration, inadvertent erasures, or loss
shall be maintained is not specified. (211.68 (b) )

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6. Requirement that fiber-releasing filters may be used when it is
not possible to manufacture such products without the use of
these filters is not specified. ( 211.72)
 Requirement that if use of a fiber-releasing filter is necessary, an
additional nonfiber-releasing filter having a maximum nominal pore
size rating of 0.2 micron (0.45 micron if the manufacturing conditions
so dictate) shall subsequently be used to reduce the content of
particles in the injectable drug product is not specified. ( 211.72)
 Prohibition of asbestos containing filter is not specified. ( 211.72)

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 Subpart E—Control of Components and Drug Product
Containers and Closures
1. Handling of components and drug product
containers and closures to prevent cross
contamination is not specified. ( 211.80 (b) )
2. Coding of grouping of containers is not
permitted. ( 211.80 (d) )

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 Subpart E—Control of Components and Drug Product Containers
and Closures
3. Requirement of checking appropriate labeling as to
contents and contaminations as well checking of
grouping of containers is not specified. Checking is
specified for the integrity of the package and seal only
and that too for individual containers only. (211.82 ( a)
4. The finished product shelf life can not exceed the shelf
life of the starting or input materials ( Both Active &
Inactive) is specified. ( 211.84 (a) )

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 Subpart E—Control of Components and Drug Product Containers and Closures
6. Requirement that the number of containers to be sampled, and the
amount of material to be taken from each container, shall be based upon
appropriate criteria such as statistical criteria for component variability,
confidence levels, and degree of precision desired, the past quality
history of the supplier, and the quantity needed for analysis and reserve
where required is not specified. ( 211.84 ( b) ).
7. Requirement that samples shall be collected in accordance with the
following procedures is not specified: ( 211.84 ( c) )
◦ (1) The containers of components selected shall be cleaned when
necessary in a manner to prevent introduction of contaminants into the
component is not specified.

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7. (c) Samples shall be collected in accordance with the following
procedures is not specified: ( 211.84 ( c) )
◦ (2) The containers shall be opened, sampled, and resealed in a
manner designed to prevent contamination of their contents and
contamination of other components, drug product containers, or
closures is not specifed.
◦ (3) If it is necessary to sample a component from the top,
middle, and bottom of its container, such sample subdivisions
shall not be composited for testing is not specified.

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and Closures
7. (c) Samples shall be collected in accordance with the
following procedures is not specified:
◦ (4) Sample containers shall be identified so that the
following information can be determined: name of the
material sampled, the lot number, the container from
which the sample was taken, the date on which the
sample was taken, and the name of the person who
collected the sample is not specified.

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8. In lieu of testing of components by the manufacturer, a report of analysis
may be accepted from the supplier of a component, provided that at least
one specific identity test is conducted on such component by the
manufacturer, and provided that the manufacturer establishes the
reliability of the supplier's analyses through appropriate validation of the
supplier's test results at appropriate intervals is not specified. ( 211.84
(d) (2))
9. In lieu of such testing by the manufacturer, a certificate of testing may be
accepted from the supplier, provided that at least a visual identification is
conducted on such containers/closures by the manufacturer and provided
that the manufacturer establishes the reliability of the supplier's test
results through appropriate validation of the supplier's test results at
appropriate intervals is not specified. ( 211.84 (d) (3))

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and Closures
10. When appropriate, components shall be
microscopically examined is not specified
( 211.84 (d) (4))
11. Each lot of a component, drug product container, or
closure that is liable to contamination with filth, insect
infestation, or other extraneous adulterant shall be
examined against established specifications for such
contamination is not specified. ( 211.84 (d) (5))

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and Closures
12. Retesting or re examination of components, drug
product containers, and closures as appropriate, for
identity, strength, quality, and purity and approved or
rejected by the quality control unit in accordance with
§211.84 as necessary, e.g., after storage for long
periods or after exposure to air, heat or other
conditions that might adversely affect the component,
drug product container, or closure is not
specified.(211.87)

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13. Rejected components, drug product containers, and closures
shall be identified and controlled under a quarantine system
designed to prevent their use in manufacturing or processing
operations for which they are unsuitable is not specified though
a separate rejected area has been specified. (211.89)
14. Drug product containers and closures shall not be reactive,
additive, or absorptive so as to alter the safety, identity,
strength, quality, or purity of the drug beyond the official or
established requirements is specified only for Sterile products &
API‘s and for no other products. ( 211.94 ( a) )

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 Subpart E—Control of Components and Drug Product
Containers and Closures
15. Requirement that container closure systems
shall provide adequate protection against
foreseeable external factors in storage and
use that can cause deterioration or
contamination of the drug product is not
specified.( 211.94 (b) )

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 Subpart F—Production and Process Controls
1. Requirement that there shall be written procedures for
production and process control designed to assure that
the drug products have the identity, strength, quality, and
purity they purport or are represented to possess is not
specified. ( 211.100 (a) )
 Requirement that these written procedures, including any
changes, shall be drafted, reviewed, and approved by the
appropriate organizational units and reviewed and approved
by the quality control unit is not specified.

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2. Requirement that written production and process control
procedures shall be followed in the execution of the
various production and process control functions and
shall be documented at the time of performance and any
deviation from the written procedures shall be recorded
and justified is not specified. ( 211.100 (b) ).
3. Requirement that the batch shall be formulated with the
intent to provide not less than 100 percent of the labelled
or established amount of active ingredient is not
specified.( 211.101 (a) )

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4. Requirement that the components for drug product
manufacturing shall be weighed, measured, or subdivided
as appropriate and that if a component is removed from
the original container to another, the new container shall
be identified with the following information is not
specified: ( 211.101 (b) )
(1) Component name or item code;
(2) Receiving or control number;
(3) Weight or measure in new container;
(4) Batch for which component was dispensed, including its product name,
strength, and lot number.

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5. Requirement that weighing, measuring, or subdividing
operations for components shall be adequately supervised and
that each container of component dispensed to manufacturing
shall be examined by a second person to assure following is not
specified for followig . (211.101 (c ) ):
 (1) The component was released by the quality control unit;
 (2) The weight or measure is correct as stated in the batch production
records;
 (3) The containers are properly identified. If the weighing, measuring, or
subdividing operations are performed by automated equipment under
§211.68, only one person is needed to assure paragraphs (c)(1), (c)(2),
and (c)(3) of this section.

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6. Requirement that such calculations shall either be performed by one
person and independently verified by a second person, or, if the yield is
calculated by automated equipment under §211.68, be independently
verified by one person is not specified (211.103)
7. Requirement of proper identification of processing lines is not specified.
( 211.105 (a)).
8. Requirement of major equipment to be identified by a distinctive
identification number or code that shall be recorded in the batch
production record to show the specific equipment used in the
manufacture of each batch of a drug product; and in cases where only
one of a particular type of equipment exists in a manufacturing
facility, the name of the equipment may be used in lieu of a distinctive
identification number or code is not specified. ( 211.105 (b) )

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9. Requirement of demonstrating adequacy of
mixing to assure uniformity and homogeneity is
not specified unambiguously but mentioned
indirectly under requirement of batch records.
( 211.110 (a) (3) )
10. Requirement of bioburden testing as an
in-process test is not specified. ( 211.110 (a) (5) )

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11. Requirement of valid in-process specifications for such
characteristics to be consistent with drug product final
specifications and shall be derived from previous acceptable
process average and process variability estimates where possible
and determined by the application of suitable statistical
procedures where appropriate is not specified. ( 211.110 (b))
12. Requirement of rejected in-process materials to be identified
and controlled under a quarantine system designed to prevent
their use in manufacturing or processing operations for which
they are unsuitable is not specified except for tablets.

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13. Requirement of time limits, when appropriate ,
for the completion of each phase of production
shall be established to assure the quality of the
drug products is not specified except for sterile &
Liquid orals. ( 211.111)
 Requirement of justifying & documenting deviations
from established time limits may be acceptable if
such deviation does not compromise the quality of
the drug product is not specified.

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14. Requirement to establish & follow
appropriate written procedures, designed to
prevent objectionable microorganisms in drug
products not required to be sterile is not
specified. ( 211.113 (a) )

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 Subpart G—Packaging and Labeling Control
1. Requirement of destroying obsolete and
outdated labels, labeling, and other
packaging materials is not specified. (
211.122 ( e ).

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2. Prohibition of gang-printed labeling for different drug products, or
different strengths or net contents of the same drug product unless the
labeling from gang-printed sheets is adequately differentiated by size,
shape, or color is not specified. ( 211.122 (f) ).
3. Requirement of special control procedures for packaging and labeling
operations if cut labeling is used for immediate container labels,
individual unit cartons, or multiunit cartons containing immediate
containers that are not packaged in individual unit cartons is not
specified. ( 211.122 (g) )
◦ (1) Requirement of dedication of labeling and packaging lines to each
different strength of each different drug product is not specified;

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◦ (2) Use of appropriate electronic or electromechanical equipment to
conduct a 100-percent examination for correct labeling during or after
completion of finishing operations is not specified; or
◦ (3) Use of visual inspection to conduct a 100-percent examination for
correct labeling during or after completion of finishing operations for
hand-applied labeling and that such examination shall be performed by
one person and independently verified by a second person is not
specified.
◦ (4) Use of any automated technique, including differentiation by labeling
size and shape, that physically prevents incorrect labeling from being
processed by labeling and packaging equipment is not specified.

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4. Printing devices on, or associated with, manufacturing
lines used to imprint labeling upon the drug product
unit label or case shall be monitored to assure that all
imprinting conforms to the print specified in the batch
production record is not specified. ( 211.122 (h))
5. Requirement of strict control to be exercised over
labeling issued for use in drug product labeling
operations is not specified. ( 211.125 (a) )

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6. Careful examination of labeling materials issued for
a batch for identity and conformity to the labeling
specified in the master or batch production records
is not specified. ( 211.125 (b) )
7. Waving of labeling reconciliation for cut or roll
labeling if a 100-percent examination for correct
labeling is performed is not specified.
( 211.125 ( c ) )

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8. Requirement of destroying all excess labeling
bearing lot or control numbers is not specified.
( 211.125 (d)).
9. Requirement of written procedures describing in
sufficient detail the control procedures employed
for the issuance of labeling and the requirement to
follow such written procedures is not specified.
( 211.125 ( f ) ).

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10. Requirement of written procedures with features
given below designed to assure that correct labels,
labeling, and packaging materials are used for drug
products and that such written procedures shall be
followed is not specified. ( 211.130)
• Requirement to Prevent mixups and cross-contamination
by physical or spatial separation from operations on
other drug products is not specified . ( 211.130 (a) )

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• Requirement of identification and handling of filled drug product
containers that are set aside and held in unlabeled condition for future
labeling operations to preclude mislabelling of individual
containers, lots, or portions of lots is not specified. ( 211.130 (b) ).
11. The Indian Act , Rules or the GMP‘s do not have separate
classification for OTC drugs. ( 211.132 (a))
12. Requirement of an OTC drug product (except a
dermatological, dentifrice, insulin, or lozenge product) for
retail sale that is not packaged in a tamper-resistant
package or that is not properly labelled under this section is
adulterated is not specified. ( 211.132 (a) )

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13. Features of Tamper Evident packing are not
specified. ( 211.132 (b) )
14. Special labeling to make consumers aware of
tamper evident packing is not specified.
( 211.132 (c ) ).
15. Requirements of exemption from tamper evident
packing and labeling have not been specified.
( 211.132 ( d ) )

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16. Requirement of examining packaged and labelled products
during finishing operations to provide assurance that
containers and packages in the lot have the correct labels is
not specified . ( 211.134 (a) )
17. Requirement of visually examining a representative sample
of units at the completion of finishing operations for correct
labeling is not specified. (211.134 (b) )
18. Requirement of documenting results of these examinations
in the batch production or control records is not specified.
( 211.134 (c ) )

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 Subpart G—Packaging and Labeling
Control
19.Requirement that if the drug product is to be
reconstituted at the time of dispensing, its
labeling shall bear expiration information for
both the reconstituted and unreconstituted
drug products is not specified.
( 211.137 (c ) ).

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20. Requirement that New drug products for investigational use
are exempt from the requirements of Packaging & Labeling
Controls , provided that they meet appropriate standards or
specifications as demonstrated by stability studies during
their use in clinical investigations is not specified.
( 211.137 (g) )
 Requirement that where new drug products for investigational use
are to be reconstituted at the time of dispensing, their labeling
shall bear expiration information for the reconstituted drug
product is not specified.

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 Subpart H—Holding and Distribution
1. Requirement of storage of drug products
under appropriate conditions of temperature,
humidity, and light so that the identity,
strength, quality, and purity of the drug
products are not affected is not specified
clearly & directly. ( 211.142 (b) )

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 Subpart I—Laboratory Controls
1. Requirement of investigating any deviation from the
written specification , standards, sampling plans, test
procedures, or other laboratory control mechanism is
not specified ( 211.160 (a) ).
2. Requirement of determination of conformance to
written specifications and a description of sampling
and testing procedures for in-process materials and
that such samples shall be representative and properly
identified is not specified. ( 211.160 (b) (2) )

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3. Requirement of determination of conformance to written
descriptions of sampling procedures and appropriate
specifications for drug products and that such samples shall
be representative and properly identified is not specified.
(211.160 (b) ( 3))
4. Requirement of having provisions for remedial action in the
event accuracy and/or precision limits are not met during
calibration and the requirement of not using instruments,
apparatus, gauges, and recording devices not meeting
established specifications is not specified. (211.160 (b) (4) )

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5. Where sterility and/or pyrogen testing are conducted on
specific batches of shortlived radiopharmaceuticals, such
batches may be released prior to completion of sterility
and/or pyrogen testing, provided such testing is completed
as soon as possible is not specified. ( 211.165 (a) )
6. Requirement of acceptance criteria for the sampling and
testing conducted by the quality control unit to be adequate
to assure that batches of drug products meet each
appropriate specification and appropriate statistical quality
control criteria as a condition for their approval and release
is not specified.( 211.165 (d) )

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7. Requirement of establishing and documenting
the accuracy, sensitivity, specificity, and
reproducibility of test methods employed by the
firm is not specified. ( 211.165 ( e ) ).
8. Requirement of Sample size and test intervals
based on statistical criteria for each attribute
examined to assure valid estimates of stability is
not specified. ( 211.166 (a) (1) )

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9. Requirement of a written testing program designed to
assess the stability characteristics of drug products is
specified only for New Drugs under Schedule Y to the
Act. Similarly the requirement that results of such
stability testing shall be used in determining
appropriate storage conditions and expiration dates
and that the written program shall be followed and
shall include requirements given below is specified for
New Drugs Only.: ( 211.166 (a) (1) to (5) )

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• Sample size and test intervals based on statistical criteria for each
attribute examined to assure valid estimates of stability is not specified
at all. ( 211.166 (a) (1) )
• Storage conditions for samples retained for testing is specified for New
products only; ( 211.166 (a) (2) )
• Reliable, meaningful, and specific test methods is specified for new
products only. ( 211.166 (a) (3) )
• Testing of the drug product in the same container-closure system as that
in which the drug product is marketed is specified for new products only;
( 211.166 (a) (4) )
• Testing of drug products for reconstitution at the time of dispensing (as
directed in the labeling) as well as after they are reconstituted is
specified for new products only. ( 211.166 (a) (5))

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10. Requirement of adequate number of batches of each drug
product shall be tested to determine an appropriate
expiration date and a record of such data shall be
maintained is not specified.( 211.166 (b) )
◦ Requirement of accelerated studies, combined with basic
stability information on the components, drug products, and
container-closure system, may be used to support tentative
expiration dates provided full shelf life studies are not
available and are being conducted is not specified.
( 211.166 (b) )

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◦ Requirement that where data from accelerated studies
are used to project a tentative expiration date that is
beyond a date supported by actual shelf life studies,
there must be stability studies conducted, including
drug product testing at appropriate intervals, until the
tentative expiration date is verified or the appropriate
expiration date determined is not specified
( 211.166 (b) )

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11. Requirement that for each batch of controlled-release dosage form, there shall be
appropriate laboratory testing to determine conformance to the specifications for
the rate of release of each active ingredient and that the test procedures shall be in
writing and shall be followed is not specified. ( 211.167 ( C ) )
12. Requirement that for an active ingredient in a radioactive drug product, except for
nonradioactive reagent kits, the reserve sample shall be retained for:
◦ (i) Three months after the expiration date of the last lot of the drug product
containing the active ingredient if the expiration dating period of the drug product
is 30 days or less; or
◦ (ii) Six months after the expiration date of the last lot of the drug product
containing the active ingredient if the expiration dating period of the drug product
is more than 30 days is not specified ( 211.170 ( a) (2) )

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13. Requirement of storing the reserve sample under conditions
consistent with product labeling is not specified. ( 211.170
(b) )
14. Except for those for drug products described in paragraph
(b)(2) of this section, reserve samples from representative
sample lots or batches selected by acceptable statistical
procedures shall be examined visually at least once a year
for evidence of deterioration unless visual examination
would affect the integrity of the reserve sample is not
specified. (211.170 (b) )

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15. Requirement of performing investigations on evidence of reserve sample
deterioration is not specified. ( 211.170 (b) )
16. Requirement that if a reasonable possibility exists that a non-penicillin
drug product has been exposed to cross-contamination with
penicillin, the non-penicillin drug product shall be tested for the
presence of penicillin is not specified. ( 211.176 )
◦ Further such drug product shall not be marketed if detectable levels are
found when tested according to procedures specified in ‗Procedures for
Detecting and Measuring Penicillin Contamination in Drugs,‘ which is
incorporated by reference is not specified..

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 Subpart J—Records and Reports
1. Requirement that all records required under this part, or
copies of such records, shall be readily available for
authorized inspection during the retention period at the
establishment where the activities described in such records
occurred is not specified. ( 211.180 (c ) )
 Requirement that these records or copies thereof shall be subject
to photocopying or other means of reproduction as part of such
inspection is not specified
 Requirement that records that can be immediately retrieved from
another location by computer or other electronic means shall be
considered as meeting the requirements of this paragraph is not
specified.

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2. Requirement that records required under this part may
be retained either as original records or as true copies
such as photocopies, microfilm, microfiche, or other
accurate reproductions of the original records is not
specified. ( 211.180 (d) ).
 Where reduction techniques, such as microfilming, are
used, suitable reader and photocopying equipment shall
be readily available is not specified. ( 211.180 (d) ).

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3. Requirement that written records required by this part shall
be maintained so that data therein can be used for
evaluating, at least annually, the quality standards of each
drug product to determine the need for changes in drug
product specifications or manufacturing or control
procedures is not specified. ( 211.180 (e) )
 Requirement of establishing written procedures which shall be
followed for such evaluations and shall include following
provisions is not specified.

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 Requirement that a review of a representative
number of batches, whether approved or
rejected, and, where applicable, records associated
with the batch is not specified. ( 211.180 (e) (1 ) )
 Requirement that a review of
complaints, recalls, returned or salvaged drug
products, and investigations conducted under
§211.192 for each drug product is not specified. (
211.180 (e) (1 ) )

64
4. Requirement that procedures shall be established to assure
that the responsible officials of the firm, if they are not
personally involved in or immediately aware of such actions,
are notified in writing of any investigations conducted under
§§211.198, 211.204, or 211.208 of these regulations, any
recalls, reports of inspectional observations issued by the
Food and Drug Administration, or any regulatory actions
relating to good manufacturing practices brought by the
Food and Drug Administration is not specified.
(211.180 ( f ) )

65
5. Requirement that a written record of major equipment cleaning,
maintenance (except routine maintenance such as lubrication and
adjustments), and use shall be included in individual equipment logs that
show the date, time, product, and lot number of each batch processed is
not specified . ( 211.182)
 Requirement that if equipment is dedicated to manufacture of one product,
then individual equipment logs are not required, provided that lots or
batches of such product follow in numerical order and are manufactured in
numerical sequence. In cases where dedicated equipment is employed, the
records of cleaning, maintenance, and use shall be part of the batch record
is not specified.

66
 Requirement that the persons performing and
double-checking the cleaning and maintenance (or,
if the cleaning and maintenance is performed using
automated equipment under §211.68, just the
person verifying the cleaning and maintenance done
by the automated equipment) shall date and sign or
initial the log indicating that the work was
performed and entries in the log shall be in
chronological order is not specified.

67
6. Requirement of permitting reasonable
variations, however, in the amount of components
necessary for the preparation in the dosage
form, provided they are justified in the master
production and control records is not specified ;(
211.186 (b) (4) )
7. Requirement of a statement of theoretical
yield, including the maximum and minimum
percentages of theoretical yield beyond which
investigation is required is not specified; ( 211.186 (b)

68
8. Requirement that if a significant step in the
operation is performed by automated
equipment under §211.68, the identification
of the person checking the significant step
performed by the automated equipment be
recorded is not specified. ( 211.188 (b) (11)
9. Requirement of any investigation made be
recorded is not specified. ( 211.188 (b) (12)

69
10. Requirement of thoroughly investigating any unexplained
discrepancy (including a percentage of theoretical yield
exceeding the maximum or minimum percentages
established in master production and control records) or the
failure of a batch or any of its components to meet any of its
specifications, whether or not the batch has already been
distributed is not specified. ( 211.192)
 Requirement that the investigation shall extend to other batches
of the same drug product and other drug products that may have
been associated with the specific failure or discrepancy and the
requirement of making a written record of the investigation with
the conclusions and follow-up is not specified. ( 211.192)

70
11. Requirement that the records shall indicate the location of
data that establish that the methods used in the testing of
the sample meet proper standards of accuracy and reliability
as applied to the product tested is not specified. ( 211.194)
12. Requirement to keep complete records of any modification of an
established method employed in testing; and the requirement that
such records shall include the reason for the modification and data
to verify that the modification produced results that are at least as
accurate and reliable for the material being tested as the established
method is not specified. ( 211.194 (b ) )

71
13. Requirement of maintaining complete records of any testing and
standardization of laboratory reference standards, reagents, and
standard solutions is not specified. (211.194 (c ) )
14. Requirement of Complaint handling procedures to include provisions for
review by the quality control unit, of any complaint involving the possible
failure of a drug product to meet any of its specifications and, for such drug
products, a determination as to the need for an investigation is not specified (
211.198 (a) )
 Requirement that such procedures include provisions for review to determine
whether the complaint represents a serious and unexpected adverse drug
experience which is required to be reported to the Food and Drug Administration
is not specified.

72
15. Following requirement of complaint file is not
specified. ( 211.198 (b))
◦ A written record of each complaint shall be maintained
in a file designated for drug product complaints. The
file regarding such drug product complaints shall be
maintained at the establishment where the drug
product involved was manufactured, processed, or
packed, or such file may be maintained at another
facility if the written records in such files are readily
available for inspection at that other facility.

73
15. Following requirement of complaint file is not specified.
( 211.198 (b))
◦ Written records involving a drug product shall be maintained
until at least 1 year after the expiration date of the drug
product, or 1 year after the date that the complaint was
received, whichever is longer. In the case of certain OTC
drug products lacking expiration dating because they meet
the criteria for exemption under §211.137, such written
records shall be maintained for 3 years after distribution of
the drug product.

74
15. Following requirement of complaint file is not specified. (
211.198 (b))
◦ ((1) The written record shall include the following information, where
known: the name and strength of the drug product, lot number, name of
complainant, nature of complaint, and reply to complainant.
◦ (2) Where an investigation under §211.192 is conducted, the written
record shall include the findings of the investigation and followup. The
record or copy of the record of the investigation shall be maintained at
the establishment where the investigation occurred in accordance with
§211.180(c).
◦ (3) Where an investigation under §211.192 is not conducted, the written
record shall include the reason that an investigation was found not to be
necessary and the name of the responsible person making such a
determination.

75
 Subpart K—Returned and Salvaged Drug Products
15. Following requirements of returned products is not specified.
( 211.204 )
◦ Returned drug products shall be identified as such and held. If the
conditions under which returned drug products have been
held, stored, or shipped before or during their return, or if the condition
of the drug product, its container, carton, or labeling, as a result of
storage or shipping, casts doubt on the safety, identity, strength, quality
or purity of the drug product, the returned drug product shall be
destroyed unless examination, testing, or other investigations prove the
drug product meets appropriate standards of
safety, identity, strength, quality, or purity.

76
15. Following requirements of returned products is not specified.
( 211.204 )
◦ A drug product may be reprocessed provided the subsequent drug
product meets appropriate standards, specifications, and characteristics.
Records of returned drug products shall be maintained and shall include
the name and label potency of the drug product dosage form, lot
number (or control number or batch number), reason for the return,
quantity returned, date of disposition, and ultimate disposition of the
returned drug product. If the reason for a drug product being returned
implicates associated batches, an appropriate investigation shall be
conducted in accordance with the requirements of §211.192. Procedures
for the holding, testing, and reprocessing of returned drug products
shall be in writing and shall be followed.

77
15. Following requirements of returned products is not specified. (
211.204 )
◦ Drug products that have been subjected to improper storage conditions including
extremes in temperature, humidity, smoke, fumes, pressure, age, or radiation due
to natural disasters, fires, accidents, or equipment failures shall not be salvaged and
returned to the marketplace. Whenever there is a question whether drug products
have been subjected to such conditions, salvaging operations may be conducted
only if there is (a) evidence from laboratory tests and assays (including animal
feeding studies where applicable) that the drug products meet all applicable
standards of identity, strength, quality, and purity and(b) evidence from inspection
of the premises that the drug products and their associated packaging were not
subjected to improper storage conditions as a result of the disaster or accident.
Organoleptic examinations shall be acceptable only as supplemental evidence that
the drug products meet appropriate standards of identity, strength, quality, and
purity. Records including name, lot number, and disposition shall be maintained for
drug products subject to this section.

79
FDA GMP‘s Indian GMP‘s
• §210.1 Status of current good
manufacturing practice regulations.
• (a) The regulations set forth in this part and
in parts 211, 225, and 226 of this chapter
contain the minimum current good
manufacturing practice for methods to be
used in, and the facilities or controls to be
used for, the manufacture, processing,
packing, or holding of a drug to assure that
such drug meets the requirements of the act
as to safety, and has the identity and
strength and meets the quality and purity
characteristics that it purports or is
represented to possess.
• Schedule M does not specify the requirement
of following GMP‘s . However this is specified
in the ― The Drugs & Cosmetics Rules‖ under
the requirement of ― Conditions of Licence as
―The factory premises shall comply with the
conditions prescribed in Schedule M.‖

80
• (b) The failure to comply with any regulation
set forth in this part and in parts 211, 225,
and 226 of this chapter in the manufacture,
processing, packing, or holding of a drug
shall render such drug to be adulterated
under section 501(a)(2)(B) of the act and such
drug, as well as the person who is responsible
for the failure to comply, shall be subject to
regulatory action.
• Not following GMP;s does not render the
product to be classified as ― Adulterated‖.
• However rule 85 specifies that if conditions of
licence are not followed the manufacturing
license can be cancelled.

81
• (c) Owners and operators of establishments engaged
in the recovery, donor screening, testing (including
donor testing), processing, storage, labeling,
packaging, or distribution of human cells, tissues,
and cellular and tissue-based products (HCT/Ps), as
defined in §1271.3(d) of this chapter, that are drugs
(subject to review under an application submitted
under section 505 of the act or under a biological
product license application under section 351 of the
Public Health Service Act), are subject to the donor-
eligibility and applicable current good tissue
practice procedures set forth in part 1271 subparts
C and D of this chapter, in addition to the
regulations in this part and in parts 211, 225, and
226 of this chapter
• Biological products do not have a separate
licence.
• Nothing is specified for human cells, tissues,
and cellular and tissue-based products in
schedule M.
• Schedule F specifies requirements for Blood
banks and blood components; requirements
for manufacture of blood products,
requirements for umbilical cord blood and
derived stem cells.
• Schedule F 1 specifies requirements for
vaccines.

82
• (c) Failure to comply with any applicable regulation
set forth in this part, in parts 211, 225, and 226 of
this chapter, in part 1271 subpart C of this chapter,
or in part 1271 subpart D of this chapter with
respect to the manufacture, processing, packing or
holding of a drug, renders an HCT/P adulterated
under section 501(a)(2)(B) of the act. Such HCT/P, as
well as the person who is responsible for the failure
to comply, is subject to regulatory action.
• [43 FR 45076, Sept. 29, 1978, as amended at 69 FR
29828, May 25, 2004; 74 FR 65431, Dec. 10, 2009]
• Not following GMP;s does not render the
product to be classified as ― Adulterated‖.
• However the rule 85 specifies that if
conditions of licence are not followed the
manufacturing license can be cancelled.

83
• §210.2 Applicability of current good manufacturing
practice regulations.
• (a) The regulations in this part and in parts 211, 225,
and 226 of this chapter as they may pertain to a
drug; in parts 600 through 680 of this chapter as
they may pertain to a biological product for human
use; and in part 1271 of this chapter as they are
applicable to a human cell, tissue, or cellular or
tissue-based product (HCT/P) that is a drug (subject
to review under an application submitted under
section 505 of the act or under a biological product
license application under section 351 of the Public
Health Service Act); shall be considered to
supplement, not supersede, each other, unless the
regulations explicitly provide otherwise. In the event
of a conflict between applicable regulations in this
part and in other parts of this chapter, the regulation
specifically applicable to the drug product in question
shall supersede the more general.
• Applicability of GMP requirements is specified in rules
for conditions of grant of a manufacturing licence.
• Biological products do not have a separate licence
nor separate GMP requirements.

84
• §210.2 Applicability of current good
• (b) If a person engages in only some
operations subject to the regulations in this
part, in parts 211, 225, and 226 of this
chapter, in parts 600 through 680 of this
chapter, and in part 1271 of this chapter,
and not in others, that person need only
comply with those regulations applicable to
the operations in which he or she is engaged.
• Biological products do not have a separate
licence nor separate GMP requirements.

85
• §210.2 Applicability of current good
• (c) An investigational drug for use in a phase 1
study, as described in §312.21(a) of this chapter, is
subject to the statutory requirements set forth in 21
U.S.C. 351(a)(2)(B). The production of such drug is
exempt from compliance with the regulations in part
211 of this chapter. However, this exemption does
not apply to an investigational drug for use in a
phase 1 study once the investigational drug has
been made available for use by or for the sponsor in
a phase 2 or phase 3 study, as described in
§312.21(b) and (c) of this chapter, or the drug has
been lawfully marketed. If the investigational drug
has been made available in a phase 2 or phase 3
study or the drug has been lawfully marketed, the
drug for use in the phase 1 study must comply with
part 211.
• [69 FR 29828, May 25, 2004, as amended at 73 FR
40462, July 15, 2008; 74 FR 65431, Dec. 10, 2009]
• Investigational drug has not been defined and there
are no specific requirements for Investigational
drugs.
• Rules 86 to 93 define requirements for manufacture
of products for experimental purposes. These rules
define the labeling and storage of such material and
the procedure to apply for a test licence.
• Rule 86 defines that the exemption for such
products from the requirements of Section 18 of the
Drugs and Cosmetics Act. Section 18 specifies the
Quality standards for products. Therefore most of
the requirements of the act , rules and schedules do
not apply to such materials.

86
• §210.3 Definitions.
• (a) The definitions and interpretations contained in
section 201 of the act shall be applicable to such
terms when used in this part and in parts 211, 225,
and 226 of this chapter.
• (b) The following definitions of terms apply to this
part and to parts 211, 225, and 226 of this chapter.
• (1) Act means the Federal Food, Drug, and Cosmetic
Act, as amended (21 U.S.C. 301 et seq.).
• (2) Batch means a specific quantity of a drug or
other material that is intended to have uniform
character and quality, within specified limits, and is
produced according to a single manufacturing order
during the same cycle of manufacture.
• (3) Component means any ingredient intended for
use in the manufacture of a drug product, including
those that may not appear in such drug product.
• Defined in the Act : Section 3
• Not defined. However explanation given in rules
under labeling and packing provisions as to how a
batch number is to be given for different products
like parenteral products , crams liquids etc. Slide
157 , Slide 158
• Though the term ― Component‖ has been used
several times in the Act , Rules and GMP‘s several
times it has not been defined.

87
• (6) Nonfiber releasing filter means any filter, which
after appropriate pretreatment such as washing or
flushing, will not release fibers into the component
or drug product that is being filtered.
• (7) Active ingredient means any component that is
intended to furnish pharmacological activity or other
direct effect in the diagnosis, cure, mitigation,
treatment, or prevention of disease, or to affect the
structure or any function of the body of man or other
animals. The term includes those components that
may undergo chemical change in the manufacture of
the drug product and be present in the drug product
in a modified form intended to furnish the specified
activity or effect.
• (8) Inactive ingredient means any component other
than an active ingredient.
• Not defined
• Though the term ― Active Ingredient‖ has been used
several times in the Act , Rules and GMP‘s it has not
been defined.
• The definition of ― Drug‖ in the Act includes amongst
several other things active ingredient.
• Though the term ―In active Ingredient‖ has been used
several times in the Act , Rules and GMP‘s it has not
been defined.
• The definition of ― Drug‖ in the Act includes amongst
several other things inactive ingredient.

88
• (9) In-process material means any material
fabricated, compounded, blended, or derived by
chemical reaction that is produced for, and used in,
the preparation of the drug product.
• (10) Lot means a batch, or a specific identified
portion of a batch, having uniform character and
quality within specified limits; or, in the case of a
drug product produced by continuous process, it is a
specific identified amount produced in a unit of time
or quantity in a manner that assures its having
uniform character and quality within specified limits.
• (11) Lot number, control number, or batch number
means any distinctive combination of letters,
numbers, or symbols, or any combination of them,
from which the complete history of the manufacture,
processing, packing, holding, and distribution of a
batch or lot of drug product or other material can be
determined.
• Though the term ― In process material ‖ has been
used a few times in the Act , Rules and GMP‘s , it has
not been defined.
• The term lot has been used several times in the Act ,
the rules and the GMP‘s .However the term has not
been defined.
• The term lot number has been used several times in
the Act , the rules and the GMP‘s .However the term
has not been defined.

89
• 12) Manufacture, processing, packing, or holding of
a drug product includes packaging and labeling
operations, testing, and quality control of drug
products.
• (13) The term medicated feed means any Type B or
Type C medicated feed as defined in §558.3 of this
chapter. The feed contains one or more drugs as
defined in section 201(g) of the act. The
manufacture of medicated feeds is subject to the
requirements of part 225 of this chapter.
• (14) The term medicated premix means a Type A
medicated article as defined in §558.3 of this
chapter. The article contains one or more drugs as
defined in section 201(g) of the act. The
manufacture of medicated premixes is subject to the
requirements of part 226 of this chapter.
• (15) Quality control unit means any person or
organizational element designated by the firm to be
responsible for the duties relating to quality control.
• There is no definition in the Act , the rules or the
GMP‘s
GMP‘s
GMP‘s
GMP‘s

90
• (16) Strength means:
• (i) The concentration of the drug substance (for
example, weight/weight, weight/volume, or unit
dose/volume basis), and/or
• (ii) The potency, that is, the therapeutic activity of
the drug product as indicated by appropriate
laboratory tests or by adequately developed and
controlled clinical data (expressed, for example, in
terms of units by reference to a standard).
• (17) Theoretical yield means the quantity that would
be produced at any appropriate phase of
manufacture, processing, or packing of a particular
drug product, based upon the quantity of
components to be used, in the absence of any loss
or error in actual production.
• (18) Actual yield means the quantity that is actually
produced at any appropriate phase of manufacture,
processing, or packing of a particular drug product.
GMP‘s
GMP‘s
GMP‘s

91
• (19) Percentage of theoretical yield means the ratio
of the actual yield (at any appropriate phase of
manufacture, processing, or packing of a particular
drug product) to the theoretical yield (at the same
phase), stated as a percentage.
• (20) Acceptance criteria means the product
specifications and acceptance/rejection criteria, such
as acceptable quality level and unacceptable quality
level, with an associated sampling plan, that are
necessary for making a decision to accept or reject a
lot or batch (or any other convenient subgroups of
manufactured units).
GMP‘s
GMP‘s

92
• (21) Representative sample means a sample that
consists of a number of units that are drawn based
on rational criteria such as random sampling and
intended to assure that the sample accurately
portrays the material being sampled.
• (22) Gang-printed labeling means labeling derived
from a sheet of material on which more than one
item of labeling is printed.
7389, Mar. 3, 1986; 58 FR 41353, Aug. 3, 1993; 73
FR 51931, Sept. 8, 2008; 74 FR 65431, Dec. 10,
2009]
GMP‘s
GMP‘s

93
• Subpart A—General Provisions
• §211.1 Scope.
• (a) The regulations in this part contain the minimum
current good manufacturing practice for preparation
of drug products (excluding positron emission
tomography drugs) for administration to humans or
animals.
• (b) The current good manufacturing practice
regulations in this chapter as they pertain to drug
products; in parts 600 through 680 of this chapter,
as they pertain to drugs that are also biological
products for human use; and in part 1271 of this
chapter, as they are applicable to drugs that are also
human cells, tissues, and cellular and tissue-based
products (HCT/Ps) and that are drugs (subject to
review under an application submitted under section
505 of the act or under a biological product license
application under section 351 of the Public Health
Service Act);
• Requirement specified under rules for
manufacturing licence: 69, 69A,70, 71, 71A, 74, 75,
75A,75B, 79.
• GMP‘s for Drug products are specified in Schedule M
• GMP‘s Biological Products are not specified.
Assumed that Drug GMP‖s are applicable for
Biological Products.

94
• §211.1 Scope.
• ( b ) supplement and do not supersede the
regulations in this part unless the regulations
explicitly provide otherwise. In the event of a conflict
between applicable regulations in this part and in
other parts of this chapter, or in parts 600 through
680 of this chapter, or in part 1271 of this chapter,
the regulation specifically applicable to the drug
product in question shall supersede the more
general.
• (c) Pending consideration of a proposed exemption,
published in the Federal Register of September 29,
1978, the requirements in this part shall not be
enforced for OTC drug products if the products and
all their ingredients are ordinarily marketed and
consumed as human foods, and which products may
also fall within the legal definition of drugs by virtue
of their intended use.
• GMP‘s for Drug products are specified in Schedule M
• GMP‘s Biological Products are not specified. Assumed
that Drug GMP‖s are applicable for Biological
Products.
• The Act does not have a separate classification for
OTC products.
• Therefore OTC products need to follow Drug GMP‖s

95
• §211.1 Scope.
• ( c ) Therefore, until further notice, regulations
under part 110 of this chapter, and where applicable,
parts 113 to 129 of this chapter, shall be applied in
determining whether these OTC drug products that
are also foods are manufactured, processed, packed,
or held under current good manufacturing practice.
66522, Dec. 19, 1997; 69 FR 29828, May 25, 2004;
74 FR 65431, Dec. 10, 2009]
• The Act does not have a separate classification for
OTC products.
• Therefore OTC products need to follow Drug GMP‖s

96
• Subpart B—Organization and Personnel
• §211.22 Responsibilities of quality control unit.
• (a) There shall be a quality control unit that shall have the
responsibility and authority to approve or reject all
components, drug product containers, closures, in-
process materials, packaging material, labeling, and drug
products,
• and the authority to review production records to assure
that no errors have occurred or, if errors have occurred,
that they have been fully investigated.
• The quality control unit shall be responsible for
approving or rejecting drug products manufactured,
processed, packed, or held under contract by another
company.
• Part 1 . Clause : 16.0 : Quality control shall be concerned
with sampling, specifications, testing, documentation,
release procedures which ensure that the necessary and
relevant tests are actually carried and that the materials
are not released for use, nor products released for sale or
supply until their quality has been judged to be
satisfactory.
• Not specified except for Manufacturing records.
( Schedule U ) 21.
• Counter-signature of the head of the testing units or
other approved person-in-charge of testing for having
verified the batch records and for having released and
batch for sale and distribution, the quantity released and
date of release.
• Specified

97
• §211.22 Responsibilities of quality control
unit.
• (b) Adequate laboratory facilities for the testing
and approval (or rejection) of components, drug
product containers, closures, packaging
materials, in-process materials, and drug
products shall be available to the quality control
unit.
• (c) The quality control unit shall have the
responsibility for approving or rejecting all
procedures or specifications impacting on the
identity, strength, quality, and purity of the drug
product.
• (d) The responsibilities and procedures
applicable to the quality control unit shall be in
writing; such written procedures shall be
followed.
• Facility Requirements specified in Part 1 ,clause
5 .
• Slide 159
• Slide 160
• Not specified
• Specified in Part 1, Clause 16.4 as Standard
operating procedures shall be available for
sampling, inspecting and testing of raw materials,
intermediate bulk finished products and packing
materials and, wherever necessary, for monitoring
environmental conditions.

98
• §211.25 Personnel qualifications.
• a) Each person engaged in the manufacture,
processing, packing, or holding of a drug product
shall have education, training, and experience, or
any combination thereof, to enable that person to
perform the assigned functions.
• Training shall be in the particular operations that
the employee performs and in current good
manufacturing practice (including the current good
manufacturing practice regulations in this chapter
and written procedures required by these
regulations) as they relate to the employee's
functions.
• Training in current good manufacturing practice
shall be conducted by qualified individuals on a
continuing basis and with sufficient frequency to
assure that employees remain familiar with CGMP
requirements applicable to them.
• Part 1, 6.1. The manufacture shall be conducted
under the direct supervision of competent technical
staff with prescribed qualifications and practical
experience in the relevant dosage and / or active
pharmaceutical products.
• Necessity of GMP training not specified.
• Part 1 ,6.6. The licensee shall ensure in accordance
with a written instruction that all personnel in
production area or into Quality Control Laboratories
shall receive training appropriate to the duties and
responsibility assigned to them. They shall be
provided with regular in-service training.
• Necessity of GMP training not specified.

99
• §211.25 Personnel qualifications.
• (b) Each person responsible for supervising the
manufacture, processing, packing, or holding of a
drug product shall have the education, training, and
experience, or any combination thereof, to perform
assigned functions in such a manner as to provide
assurance that the drug product has the safety,
identity, strength, quality, and purity that it purports
or is represented to possess.
• (c) There shall be an adequate number of qualified
personnel to perform and supervise the
manufacture, processing, packing, or holding of
each drug product.
• Part 1, 6.6. The licensee shall ensure in accordance
with a written instruction that all personnel in
production area or into Quality Control Laboratories
shall receive training appropriate to the duties and
responsibility assigned to them. They shall be
provided with regular in-service training.
• Part 1, 6.5. Number of personnel employed shall be
adequate and in direct proportion to the workload.

100
• (§211.28 Personnel responsibilities
• (a) Personnel engaged in the manufacture,
product shall wear clean clothing appropriate
for the duties they perform.
• Protective apparel, such as head, face, hand,
and arm coverings, shall be worn as
necessary to protect drug products from
contamination.
• (b) Personnel shall practice good sanitation
and health habits.
• Part 1, 7.7 All personnel shall wear clean
body coverings appropriate to their duties
• Not Specified.
• Part 1, 7.3 All persons prior to and during
employment shall be trained in practices
which ensure personnel hygiene. A high level
of personal hygiene shall be observed by all
those engaged in the manufacturing
processes. Instructions to this effect shall be
displayed in change rooms and other
strategic locations.

101
• (c) Only personnel authorized by supervisory
personnel shall enter those areas of the
buildings and facilities designated as
limited-access areas.
• Not specified.

102
• Subpart B—Organization and
Personnel
• (d) Any person shown at any time (either by
medical examination or supervisory
observation) to have an apparent illness or
open lesions that may adversely affect the
safety or quality of drug products shall be
excluded from direct contact with components,
drug product containers, closures, in-process
materials, and drug products until the condition
is corrected or determined by competent
medical personnel not to jeopardize the safety
or quality of drug products.
• All personnel shall be instructed to report to
supervisory personnel any health conditions
that may have an adverse effect on drug
products.
• Part 1, 7.4 No person showing, at any time,
apparent illness or open lesions which may
adversely affect the quality of products, shall be
allowed to handle starting materials, packing
materials, in-process materials, and drug
products until his condition is no longer judged
to be a risk.
• Part 1, 7.5 All employees shall be instructed to
report about their illness or abnormal health
condition to their immediate supervisor so that
appropriate action can be taken.

103
• §211.34 Consultants.
• Consultants advising on the manufacture,
processing, packing, or holding of drug
products shall have sufficient education,
training, and experience, or any combination
thereof, to advise on the subject for which
they are retained. Records shall be maintained
stating the name, address, and qualifications
of any consultants and the type of service they
provide.
• Nothing mentioned or specified for
consultants.

104
• Subpart C—Buildings and Facilities
• §211.42 Design and construction features.
• (a) Any building or buildings used in the
a drug product shall be of suitable size,
construction and location to facilitate cleaning,
maintenance, and proper operations.
• (b) Any such building shall have adequate space
for the orderly placement of equipment and
materials to prevent mixups between different
components, drug product containers, closures,
labeling, in-process materials, or drug
products, and to prevent contamination.
• The flow of components, drug product
containers, closures, labeling, in-process
materials, and drug products through the
building or buildings shall be designed to
prevent contamination.
• Part 1.2 Building and premises.- The building(s)
used for the factory shall be designed, constructed,
adapted and maintained to suit the manufacturing
operations so as to permit production of drugs
under hygienic conditions.
• The premises used for manufacturing, processing,
warehousing, packaging labeling and testing
purposes shall be – (i) compatible with other drug
manufacturing operations that may be carried out in
the same or adjacent area / section; (ii) adequately
provided with working space to allow orderly and
logical placement of equipment, materials and
movement of personnel so as to: (a) avoid the risk
of mix-up between different categories of drugs or
with raw materials, intermediates and in-process
material; (b) avoid the possibilities of contamination
and cross- contamination by providing suitable
mechanism;

105
• (c) Operations shall be performed within specifically
defined areas of adequate size. There shall be
separate or defined areas or such other control
systems for the firm's operations as are necessary
to prevent contamination or mixups during the
course of the following procedures:
• (1) Receipt, identification, storage, and withholding
from use of components, drug product containers,
closures, and labeling, pending the appropriate
sampling, testing, or examination by the quality
control unit before release for manufacturing or
packaging;
• (2) Holding rejected components, drug product
containers, closures, and labeling before
disposition;
• See last slide Last Slide
• Part 2.1 Adequate areas shall be designed to allow
sufficient and orderly warehousing of various
categories of materials and products like starting
and packaging materials, intermediates, bulk and
finished products, products in quarantine, released,
rejected, returned or recalled, machine and
equipment spare parts and change items.
• Part 2.5.Segregation shall be provided for the
storage of rejected, recalled or returned materials
or products. Such areas, materials or products shall
be suitably marked and secured. Access to these
areas and materials shall be restricted.

106
• (3) Storage of released components, drug product
containers, closures, and labeling;
• (4) Storage of in-process materials;
• (5) Manufacturing and processing operations;
• (6) Packaging and labeling operations;
• (7) Quarantine storage before release of drug
products;
• (8) Storage of drug products after release;
• (9) Control and laboratory operations;
• Specified : see last slide
• Specified : See last slide
• Specified : See this slide

107
• (10) Aseptic processing, which includes as
appropriate:
• (i) Floors, walls, and ceilings of smooth, hard
surfaces that are easily cleanable;
• (ii) Temperature and humidity controls;
• (iii) An air supply filtered through high-
efficiency particulate air filters under positive
pressure, regardless of whether flow is laminar
or nonlaminar;
• (iv) A system for monitoring environmental
conditions;
• (v) A system for cleaning and disinfecting the
room and equipment to produce aseptic
conditions;
• Specified under Part I A : Specific requirements for
sterile products

108
• (vi) A system for maintaining any equipment
used to control the aseptic conditions.
• (d) Operations relating to the manufacture,
processing, and packing of penicillin shall be
performed in facilities separate from those
used for other drug products for human use.
• [43 FR 45077, Sept. 29, 1978, as amended at
60 FR 4091, Jan. 20, 1995]
• Specified under Part I A : Specific requirements for
sterile products
• Part 1, 3.2. In order to avoid the risk of cross-
contamination, separate dedicated and self
contained facilities shall be made available for the
production of sensitive pharmaceutical products
like penicillin or biological preparations with live
micro-organisms. Separate dedicated facilities
shall be provided for the manufacture of
contamination causing and potent products such
as Beta-Lactum, sex hormones and cytotoxic
substances.

109
• §211.44 Lighting.
• Adequate lighting shall be provided in all
areas.
• Part 1, 1.2 ( iv) The production and dispensing areas
shall be well lighted…….. Also mentioned at several
other places under different headings.
• §211.46 Ventilation, air filtration, air
heating and cooling.
• Part 1, 1.2 (iv) air-conditioned, where prescribed for
the operations and dosage forms under production.
The production and dispensing areas shall be well
lighted, effectively ventilated, with air control facilities
and may have proper Air Handling Units (wherever
applicable) to maintain conditions including
temperature and, wherever necessary, humidity, as
defined for the relevant product. These conditions
shall be appropriate to the category of drugs and
nature of the operation. These shall also be suitable to
the comforts of the personnel working with protective
clothing, products handled, operations undertaken
within them in relation to the external environment.
These areas shall be regularly monitored for
compliance with required specifications;

110
• §211.46 Ventilation, air filtration, air heating
and cooling.
• (a) Adequate ventilation shall be provided.
• (b) Equipment for adequate control over air
pressure, micro-organisms, dust, humidity,
and temperature shall be provided when
appropriate for the manufacture, processing,
packing, or holding of a drug product.
• Part 1, 8.2.1. The licensee shall prevent mix-up
and cross-contamination of drug material and drug
product (from environmental dust) by proper air-
handling system, pressure differential, segregation,
status labeling and cleaning. Proper records and
Standard Operating Procedures thereof shall be
maintained.
• Nothing specified for adequate control over,
microorganisms

111
and cooling.
• (b) Equipment for adequate control over air
pressure, micro-organisms, dust, humidity,
and temperature shall be provided when
appropriate for the manufacture, processing,
packing, or holding of a drug product.
• Part 1 B : : Oral Solid Dosage Forms:
• 1.5 : Where the facilities are designed to provide
special environmental conditions of pressure
differentials between rooms, these conditions shall
be regularly monitored and any specification
results brought to the immediate attention of the
Production and quality Assurance Department
which shall be immediately attended to.
• Part I E Metered Dose Inhalers
• 3.1. Where products or clean components are
exposed, the area shall be supplied with filtered air
of Grade C.
• 3.3 There shall be a difference in room pressure
between the manufacturing area and the support
areas and the differential pressure shall be not less
than 15 Pascals (0.06 inches or 1.5mm water
gauge).

112
and cooling.
• (c) Air filtration systems, including prefilters and
particulate matter air filters, shall be used when
appropriate on air supplies to production areas.
• If air is recirculated to production areas, measures
shall be taken to control recirculation of dust from
production.
• In areas where air contamination occurs during
production, there shall be adequate exhaust
systems or other systems adequate to control
contaminants.
• Part 1, 8.2.1. The licensee shall prevent mix-up
and cross-contamination of drug material and drug
product (from environmental dust) by proper air-
handling system, pressure differential, segregation,
status labeling and cleaning. Proper records and
Standard Operating Procedures thereof shall be
maintained.
• Not specified.
• Specified

113
and cooling.
• (d) Air-handling systems for the manufacture,
processing, and packing of penicillin shall be
completely separate from those for other drug
products for human use.
• Part 1, 3.2. In order to avoid the risk of cross-
contamination, separate dedicated and self-
contained facilities shall be made available for the
production of sensitive pharmaceutical products
like penicillin or biological preparations with live
micro-organisms. Separate dedicated facilities shall
be provided for the manufacture of contamination
causing and potent products such as Beta-Lactum,
sex hormones and cytotoxic substances.
• Part 1, 8.2.2 The licensee shall ensure processing
of sensitive drugs like Beta-Lactum antibiotics, sex
hormones and cytotoxic substances in segregated
areas or isolated production areas within the
building with independent air-handling unit and
proper pressure differential. The effective
segregation of these areas shall be demonstrated
with adequate records of maintenance and services.

114
• §211.48 Plumbing.
• (a) Potable water shall be supplied under
continuous positive pressure in a plumbing system
free of defects that could contribute contamination
to any drug product. Potable water shall meet the
standards prescribed in the Environmental
Protection Agency's Primary Drinking Water
Regulations set forth in 40 CFR part 141. Water not
meeting such standards shall not be permitted in
the potable water system.
• (b) Drains shall be of adequate size and, where
connected directly to a sewer, shall be provided
with an air break or other mechanical device to
prevent back-siphonage.
11426, Mar. 18, 1983]
• Potable water to be supplied under continuous
positive pressure not specified.
• Specified that potable water should meet Indian
specifications.
• Part 1, 1.2 , (v) Provided with drainage system, as
specified for the various categories of products,
which shall be of adequate size and so designed as
to prevent back flow and/or prevent insets and
rodents entering the premises. Open channels shall
be avoided in manufacturing areas and, where
provided, these shall be shallow to facilitate
cleaning and disinfection;

115
• §211.50 Sewage and refuse.
• Sewage, trash, and other refuse in and from the
building and immediate premises shall be
disposed of in a safe and sanitary manner.
• Part 1, 1.4 (i) The disposal of sewage and effluents
(solid, liquid and gas) from the manufactory shall
be in conformity with the requirements of
Environment Pollution Control Board.
• §211.52 Washing and toilet facilities.
• Adequate washing facilities shall be provided,
including hot and cold water, soap or
detergent, air driers or single-service towels,
and clean toilet facilities easily accessible to
working areas.
• Part 1, 4.2 Facilities for changing, storing clothes
and for washing and toilet purposes shall be easily
accessible and adequate for the number of users.
Toilets, separate for males and females, shall not be
directly connected with production or storage areas.
There shall be written instructions for cleaning and
disinfection of such areas.

116
• §211.56 Sanitation.
• (a) Any building used in the manufacture,
processing, packing, or holding of a drug product
shall be maintained in a clean and sanitary
condition.
• Any such building shall be free of infestation by
rodents, birds, insects, and other vermin (other
than laboratory animals).
• Trash and organic waste matter shall be held and
disposed of in a timely and sanitary manner.
• Part 1, 9.1 The manufacturing premises shall be
cleaned and maintained in an orderly manner, so
that it is free from accumulated waste, dust, debris
and other similar material. A validated cleaning
procedure shall be maintained.
• Part 1, 1.2 (iii) designed / constructed / maintained
to prevent entry of insects, pests, birds, vermins,
and rodents.
• Specified in Part 1, 1.4 : Disposal of waste.
• (b) There shall be written procedures assigning
responsibility for sanitation and describing in
sufficient detail the cleaning schedules, methods,
equipment, and materials to be used in cleaning the
buildings and facilities; such written procedures
shall be followed.
• Specified.

117
• (c) There shall be written procedures for use of
suitable rodenticides, insecticides, fungicides,
fumigating agents, and cleaning and sanitizing
agents.
• Such written procedures shall be designed to
prevent the contamination of equipment,
components, drug product containers, closures,
packaging, labeling materials, or drug products and
shall be followed.
• Rodenticides, insecticides, and fungicides shall not
be used unless registered and used in accordance
with the Federal Insecticide, Fungicide, and
Rodenticide Act (7 U.S.C. 135).
• Written procedures for use of suitable rodenticides,
insecticides, fungicides, fumigating agents is not
specified except for warehoue.
• Not specified.
• Not Specified.

118
• (d) Sanitation procedures shall apply to work
performed by contractors or temporary
employees as well as work performed by full-
time employees during the ordinary course of
operations.
• Not Specified.
• §211.58 Maintenance.
• Any building used in the manufacture,
product shall be maintained in a good state of
repair.
• Specified.

119
• Subpart D—Equipment
• §211.63 Equipment design, size, and location.
• Equipment used in the manufacture,
product shall be of appropriate design,
adequate size, and suitably located to facilitate
operations for its intended use and for its
cleaning and maintenance.
• Part 1, 11.1 Equipment shall be located, designed,
constructed, adapted and maintained to suit the
operations to be carried out. The layout and design
of the equipment shall aim to minimise the risk of
errors and permit effective cleaning and
maintenance in order to avoid cross contamination,
build-up of dust or dirt and, in general any adverse
effect on the quality of products. Each equipment
shall be provided with a logbook, wherever
necessary.
• §211.65 Equipment construction.
• a) Equipment shall be constructed so that
surfaces that contact components, in-process
materials, or drug products shall not be
reactive, additive, or absorptive so as to alter
the safety, identity, strength, quality, or purity
of the drug product beyond the official or other
established requirements.
• Part 1,11.3 The parts of the production equipment
that come into contact with the product shall not be
reactive, additive or adsorptive to an extent that
would affect the quality of the product.

120
• §211.65 Equipment construction.
• (b) Any substances required for operation, such
as lubricants or coolants, shall not come into
contact with components, drug product
containers, closures, in-process materials, or
drug products so as to alter the safety, identity,
strength, quality, or purity of the drug product
beyond the official or other established
requirements.
• Part 1, 11.4 To avoid accidental contamination,
wherever possible, non-toxic/edible grade
lubricants shall be used and the equipment shall be
maintained in a way that lubricants do not
contaminate the products being produced.

121
• §211.67 Equipment cleaning and maintenance.
• (a) Equipment and utensils shall be cleaned,
maintained, and, as appropriate for the nature
of the drug, sanitized and/or sterilized at
appropriate intervals to prevent malfunctions or
contamination that would alter the safety,
identity, strength, quality, or purity of the drug
product beyond the official or other established
requirements.
• Mentioned in a confused way in different sections under
Blood bank , Equipment, Batch Packing & Processing
Records and under different dosage forms.
• Blood Banks : Rules Part 12 B ( E ) :Equipment used in
the collection, processing, testing, storage and
sale/distribution of blood and is components shall be
maintained in a clean and proper manner and so placed
as to facilitate cleaning and maintenance.
• Schedule M : Part 1, 11.1 Equipment shall be located,
designed, constructed, adapted and maintained to suit
the operations to be carried out. The layout and design
of the equipment shall aim to minimise the risk of errors
and permit effective cleaning and maintenance in order
to avoid cross contamination, build-up of dust or dirt
and, in general any adverse effect on the quality of
products. Each equipment shall be provided with a
logbook, wherever necessary.

122
requirements.
• Part 1, 20.2 Before any packaging operation begins,
check shall be made and recorded that the
equipment and the work stations are clear of the
previous products, documents or materials not
required for the planned packaging operations, and
that the equipment is clean and suitable for use.
• Part 1, 21.2 Before any processing begins, check
shall be performed and recorded to ensure that the
equipment and work station are clear of previous
products, documents or materials not required for
the planned process are removed and the
equipment is clean and suitable for use.

123
requirements.
• Part I B : ( Oral Solid Dosage Forms) :
• 1.6. Care shall be taken to guard against any
material lodging and remaining undetected in any
processing or packaging equipment. Particular care
shall be taken to ensure that any vacuum,
compressed air or air-extraction nozzles are kept
clean and that there is no evidence lubricants
leaking into the product from any part of the
equipment.
• 7.1. Care shall be taken when using automatic
tablet and capsule counting, strip and blister
packaging equipment to ensure that all ‗rogue‘
tablets, capsules or foils from packaging operation
are removed before a new packaging operation is
commenced.

124
requirements.
• Part I D : ( Topical Dosage Forms) :
• 4. The equipment used shall be designed and
maintained to prevent the product from being
accidentally contaminated with any foreign matter
or lubricant.
• Part 1 F ( API)
• 4.2. If the equipment is used for different
intermediates and active pharmaceutical
ingredients, proper cleaning before switching from
one product to another becomes particularly
important. If cleaning of a specific type of
equipment is difficult, the equipment may need to
be dedicated to a particular intermediate or active
pharmaceutical ingredient.

125
requirements.
• Part 1 F ( API)
• 4.4. Written procedures shall be established and
followed for cleaning and maintenance of
equipment, including utensils used in the
manufacture, processing, packing or holding of
active pharmaceutical ingredients.
• 4.5. Equipment shall be cleaned between successive
batches to prevent contamination and carry-over of
degraded material or contaminants unless
otherwise established by validation.

126
• (b) Written procedures shall be established and
followed for cleaning and maintenance of
equipment, including utensils, used in the
a drug product. These procedures shall include,
but are not necessarily limited to, the following:
• (1) Assignment of responsibility for cleaning
and maintaining equipment;
• (2) Maintenance and cleaning schedules,
including, where appropriate, sanitizing
schedules;
• Mentioned in a very confused way under different parts:
under Part 1 General Requirements and under Part 1 F
for API‘s as follows:
• Part I :
• 22.5.2 There shall be written standard operating
procedures and the associated records of actions taken
for: (c) maintenance, cleaning and sanitation;
• Part 1 F : API
• 4.4. Written procedures shall be established and
followed for cleaning and maintenance of equipment,
including utensils used in the manufacture, processing,
packing or holding of active pharmaceutical ingredients.
These procedures shall include but should not be limited
to the following :
• (a) assignment of responsibility for cleaning and
maintaining equipment;
• (b) maintenance and cleaning program schedules,
including where appropriate

127
• (3) A description in sufficient detail of the
methods, equipment, and materials used in
cleaning and maintenance operations, and the
methods of disassembling and reassembling
equipment as necessary to assure proper
cleaning and maintenance;
• (4) Removal or obliteration of previous batch
identification;
• (5) Protection of clean equipment from
contamination prior to use;
Mentioned in a very confused way under different parts
under Part 1 General Requirements and under Part 1 F
for API‘s. See last slide .

128
• §211.67 Equipment cleaning and
maintenance.
• (6) Inspection of equipment for cleanliness
immediately before use.
• (c) Records shall be kept of maintenance,
cleaning, sanitizing, and inspection as specified
in §§211.180 and 211.182.
• [43 FR 45077, Sept. 29, 1978, as amended at
73 FR 51931, Sept. 8, 2008]
• Specified.
• Not Clearly specified for keeping records of
maintenance, cleaning, sanitizing, and inspection

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