gmp of liq

8/8/2019 GMP OF LIQ.

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CURRENT GOOD MANUFACTURING

PRACTICES FOR LIQUID ORAL

HERBAL PREPARATIONS

SUBMITTED BY:-

MEENAKSHI SHRIPAT

REG. NO. 090506016


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` GMP is that part of quality assurance which ensures thatproducts are consistently produced and controlled to thequality standards appropriate to their intended use and asrequired by the marketing authorization.

` The F D & C Act states that a drug is determined to beadulterated unless the methods used in its manufacturing,processing, packaging and holding as well as the facilitiesin which it was prepared and the controls used during itsproduction, confirm to the GMPs so that it has the correctidentity and strength to meet the quality and puritycharacteristics that it is represented to possess.


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` 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 thedifferent aspects of herbal medicine production

viz. cultivation, collection, storage, extraction,

formulations, processing, quality control and

packaging, etc. must be implemented so as toobtain herbal drugs of uniform quality


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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 unstableB. 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


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1. Organization & personnel

2. Building & facilities

3. Equipments

4. Control of components and drug product containersand closures

5. Production and process controls

6. Packaging and labeling control

7. Drug product container and closures

8. Laboratory controls9. Records and reports

10. Returned and salvaged drug products


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PLANT

MANAGER

SAFETY,MATERIAL

MANAGEMENT

PRODUCTION,EMPLOYEERELATIONS

FINANCE, QA


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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. throughrecognized institute or university.

` Employees should be provided with initial training before assigning them towork.

` 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 contactwith 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 ofworkers.

` While working personnel must wear gloves, aprons, mask, safety glasses toavoid contamination of product.


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Design and construction:

` Environment surrounding the building facilities must befree 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.


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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 variousdisinfectants. The walls are usually covered with epoxy coating and floors

with tetrazo coating.


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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


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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 tohave specification of total viable microorganisms.

MATERIALTYPE MICROBIAL

ALERT

YEAST AND

MOULD/g

INDICATOR

ORGANISM

Natural (plant,animal & mineral

origin)

1000 500 Salmonella, E.coli,

staphylococcus

aureus,

pseudomonas

aeruginosa.


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` 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 compatibility5. Moisture barrier

6. Toxicity for plastics

7. Sterility and permeation for parental containers

8. Drug stability for all packaging


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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 thatthe 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


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Following factors must be considered for closures and containers:

` Leaching: means the release of container constituents into the drug product therebyleading to contamination.

` Chemical reactivity :certain constituents of container or closure may react with drugproduct. 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 dosageform)

II. Suspensions & emulsions must bear the instructions shake well beforeuse

III. As per various formulations following cautions must be mentioned store inwell closed container , store in cool and dry place etc.

IV. Labels must bear the batch number & license number and alsomanufacturer name.


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` Laboratory controls shall include the establishment ofscientifically sound and appropriate specifications,standards, sampling plans and the test proceduresdesigned to assure that components, drug productcontainers, closures, labeling conform to appropriatestandard 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.


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` 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

` INTERMEDI ATE STUDY 300C/ambient humidity

` LONG TERM 250C/ambient humidity


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` 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


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` To assure uniformity from batch to batch masterproduction records & control records for each drugshall be prepared.

It includes following :

I. Name and strength of drug product anddescription of dosage form

II. Name and weight of each active ingredient

III. Statement of theoretical yield

IV. Description of product containers and closuresV. Complete sampling and testing procedure


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Batch production record shall be prepared for each batch of drugproduct.

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.


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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 theproduct and the product disposition


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