Current good manufacturing practices

for liquid oral herbal preparations

SUBMITTED BY:-
MEENAKSHI SHRIPAT
REG. NO. 090506016
 GMP is that part of quality assurance which ensures
that products are consistently produced and
controlled to the quality standards appropriate to
their intended use and as required by the marketing
authorization.

 The F D & C Act states that a drug is determined to

be adulterated unless the methods used in its
manufacturing, processing, packaging and holding as
well as the facilities in which it was prepared and the
controls used during its production, confirm to the
GMPs so that it has the correct identity and strength
to meet the quality and purity characteristics that it is
represented to possess.
Maintenance of GMP is essential right from
the cultivation of herbal medicine to the
preparation of its different formulations.
 Thus strict control on each and every step of

the different aspects of herbal medicine

production viz. cultivation, collection,
storage, extraction, formulations, processing,
quality control and packaging, etc. must be
implemented so as to obtain herbal drugs of
uniform quality
I. Suspensions are biphasic liquid dosage forms where particulate matter is
dispersed throughout the dispersion media. 
II. Syrups are viscous preparations containing sucrose as base. Syrups are widely
used for the cough preparations
III. Elixirs are alcoholic or hydro- alcoholic clear liquid oral preparation of potent
drugs.
IV. Linctuses are the viscous liquid preparations having high concentration of
sucrose.
V. Emulsion is a dispersed system in which two immiscible phases are made miscible
with the help of emulsifying agent. Emulsions an be either anionic, cationic or
non-ionic type.

Following points are worthy considering in liquid orals

A. Liquid orals are mostly unstable

B. Chances of cross contamination are more compared to solid dosage forms

C. mix-up confusions due to false labeling during manufacturing

D. heavy metals in liquid orals may cause toxicity of herbal formulations

1. Organization & personnel
2. Building & facilities
3. Equipments
4. Control of components and drug product
containers and closures
5. Production and process controls
6. Packaging and labeling control
7. Drug product container and closures
8. Laboratory controls
9. Records and reports
10. Returned and salvaged drug products
Personnel qualification
 must be educated, trained and experienced.
 Specific requirements for jobs must be fulfilled by the workers such
as higher qualifications in pharmacy, microbiology, chemistry etc.
through recognized institute or university.
 Employees should be provided with initial training before assigning
them to work.
 Additional training sessions are provided time to time as per the
requirement for the upraisal of skills of the employees.

Personnel responsibility
 must have neat and clean clothes, good sanitation and health habits.
 Any person suffering from disease shall be excluded from direct
contact with the components.
 Various medical tests such as chest x- ray, wasser man test (for
syphilis), tuberculosis test etc. must be performed to ensure the
health status of workers.
 While working personnel must wear gloves, aprons, mask, safety
glasses to avoid contamination of product.
Design and construction:
 Environment surrounding the building facilities must

be free of pollution, objectionable odour, and insects.

 adequate lighting system must be there

Buildings must have separate departments such as:

 Storage department

 Production department

 Packaging department

 Finished product department

 QC / QA department

 Research and development department. 

Ventilation and air filteration system:
 should be there to avoid cross contamination. Air filteration systems

such as prefilters and particulate air filters must be present in

appropriate areas.
 A totally enclosed room with HEPA filtered air is desirable. HEPA

filters having high efficiency of removing 0.3 micron particulate

matter are used for filtering the air.
Sanitation and maintenance:
 A high level of sanitation and hygiene should be practiced in every

aspect of manufacturing and it includes hygiene of personnel,

equipment, production materials and containers.
 Buildings used for manufacturing should be kept clean by using

various disinfectants. The walls are usually covered with epoxy

coating and floors with tetrazo coating.
 Control on in process production is necessary to avoid wastage of materials.
 Components for drug product manufacturing shall be weighed, measured or
sub-divided as appropriate.
 If a component is removed from original container to another, the new
container should be identified with the following information:
I. Component name or item code
II. Receiving or control number
III. Weight or measure in new container
IV. Batch for which component was dispensed, including its product name,
strength and lot number. 
 Calculation of yield – actual yield and percentages of theoretical yield shall be
determined at the conclusion of each appropriate phase.
 For manufacturing of liquid oral herbal drugs water is very essential,
therefore water used must be of high purity. Purified water can be prepared
either by:
A. Distillation method
B. Ion exchange method
C. Reverse osmosis
Each component should be tested for conforming its purity, strength and
quality as per the written specifications.
 According to USP , drug product should be tested for freedom of

salmonella species.
 Oral suspensions and solutions must be tested for freedom from E.coli

 In case of emulsions which are prone to microbial degradation, it is

necessary to have specification of total viable microorganisms.

MATERIAL TYPE MICROBIAL YEAST AND INDICATOR

ALERT MOULD/g ORGANISM
Natural (plant, 1000 500 Salmonella, E.coli,
animal & staphylococcus
mineral origin) aureus,
pseudomonas
aeruginosa.
 Should not be reactive.
 Should provide adequate protection against foreign factors during storage.
 Containers must be clean, sterilized and processed to remove the pyrogenic
properties.

Depending on the intended use & type of container, among the qualities tested are
following-
1. Qualities of container that are checked

2. Physiochemical properties

3. Light transmission for glass or plastic

4. Drug compatibility

5. Moisture barrier

6. Toxicity for plastics

7. Sterility and permeation for parental containers

8. Drug stability for all packaging

Following are the objectives of packaging and labeling
 Prevention of mixing up & cross contamination
 Identification of drug product with lot or batch number
 Drug product inspection
 Expiration dating – these are stated on label and are essential part of any label that the
drug bears.
 Protection from light, moisture, oxygen, mechanical damage.
a. packaging material must be protected from environmental conditions.
b. they must not be reactive with the product.
c. they must be non- toxic.
 
Types of packaging: the packaging can be either of two types
 Primary packaging- these are in direct contact with formulation eg. Bottles made of
glass and plastic
 Secondary packaging- these are not in direct contact with formulations eg. Cartoons,
label etc.

Advantages of glass as primary packaging material-

1. glass have superior protective qualities
2. glass do not deteriorate with age
3. available in variety of sizes
Following factors must be considered for closures and containers:
 Leaching: means the release of container constituents into the drug product
thereby leading to contamination.
 Chemical reactivity :certain constituents of container or closure may react with
drug product. It must be avoided to maintain safety and efficacy of the drug
product.
 Sorption : it is the removal of constituents from the drug product by the
packaging material.
 Light transmission: certain drugs are photosensitive. Such products
formulations must be stored in amber colored glass containers.
 Labeling instructions: Must be proper. They shall possess following information:

I. Information about formulation (weight, volume, dosage unit, type of dosage

form)
II. Suspensions & emulsions must bear the instructions “ shake well before use”
III. As per various formulations following cautions must be mentioned “store in well
closed container” , “store in cool and dry place” etc.
IV. Labels must bear the batch number & license number and also manufacturer
name.
 
 Laboratory controls shall include the establishment of
scientifically sound and appropriate specifications,
standards, sampling plans and the test procedures
designed to assure that components, drug product
containers, closures, labeling conform to appropriate
standard of purity, identity, strength and quality.
Laboratory control shall include:
 Sampling and testing procedures for in-process
materials
 Calibration of instruments, apparatus.
 Sampling procedures for the drug products.
 Appropriate written specifications for acceptance of
each lot within each shipment.
 In the stability testing of formulations storage
condition is very necessary.
 An adequate number of batches of each drug
product shall be tested to determine the
appropriate expiration dating.

 ACCELERATED STUDY 400 C/ambient humidity

 INTERMEDIATE STUDY 300C/ambient humidity
 LONG TERM 250C/ambient humidity
 It comes under schedule U of drug & cosmetic
act 1945
 Records shall be maintained for all

components, drug product containers &

closures for at least one year after the
expiration date.
 Following records must be maintained

◦ Master production records

◦ Batch manufacturing records
 
 To assure uniformity from batch to batch
master production records & control records
for each drug shall be prepared.
It includes following :
I. Name and strength of drug product and
description of dosage form
II. Name and weight of each active ingredient
III.Statement of theoretical yield
IV.Description of product containers and
closures
V. Complete sampling and testing procedure
Batch production record shall be prepared for each batch of
drug product.
It should include following-
 Production dates
 Identity of each individuals used
 In process materials used
 Weights and measures of components
 In process and laboratory control unit
 Packaging and labeling control
 Statement of theoretical yield
 Description of product containers and closures
 Complete sampling and testing procedures
 Any sampling performed
 Identification of the persons performing & direct supervising
or checking each step in the operations.
1. Returned and salvaged products from
wholesalers must be identified by the lot
number & product quality is determined through
appropriate testing
2. drug products that do not met specifications
may be salvaged or reprocessed
3. records for all returned products must be
maintained, and must include the date and
reasons for return, quality and lot number of
product, procedures employed for holding,
testing and reprocessing the product and the
product disposition