Schedule   T

Good Manufacturing Practice (GMP)

AS per PCI Syllabus

(T. Y.  B. Pharm Sem IV) Unit -V

Salient Features Of GMP under schedule-T for Indian 

System Drugs (ISM)


In India GMP was introduced under Schedule -M as an amendment to Drugs and Cosmetics rules 1945 in 24.06.88.

Then after this schedule-T was introduced for specifications for lSM drugs, this schedule was further elaborated in 23 June 2000 which specify the GMP features to be followed for ISM drugs.

Teaching institutes and registered qualified Vaidyas, Siddhars and Hakeems who prepare medicines on their own to dispense to their patients and not selling such drugs in the markets are exempted from the purview of Schedule-T. 

There is also a provision issuance of GMP certificate after proper inspection of unit. This GMP certificate has validity for two years from the date of issuance.

Objectives of GMP/ Principle

Implementation of GMP ensures total quality assurance covering all the Spheres in a manufacturing system. 

These are highlighted below

1.Raw material and Finished products-Their authenticity , quality, freedom from foreign matter and contaminant.

2.Manufacturing process confirms to prescribed  quality standards. Adoption of adequate quality control measures.

3. Documentation -Methodologies and procedures for reference and inspection .

COMPONENTS OF GMP

GMP schedule for ISM manufacturing units is quite elaborate and broadly covers each and every component of manufacturing process. Different components of GMP are given below in order of appearance in Schedule -T.
 
 Part-I

Factory premises

General requirements
1.Location and surroundings
2.Buildings
3.Water supply
4.Disposal of waste
5.Containers cleaning
6.  Stores (Raw materials, Packings material, Finished Goods stores).
7.  Working space
8.  Health, Clothing  Sanitation and Hygiene of Workers
9.  Medical Services
10. Equipment
11. Batch manufacturing Record
12. Distribution Record
13. Record of Market complaints
14. Quality control

Requirements for sterile product

A. Manufacturing area

B. Precautions against contaminations and mix 

Part-II

A. List of machinery, equipment and minimum manufacturing premises required for
the manufacture of various categories of Ayurvedic, Siddha system of medicines

B. List of machinery, equipment and minimum manufacturing premises required for
the manufacturing of various categories of Unani system medicine. 



A) Location and Surroundings

Points to be taken into consideration for selection of site for manufacturing unit

1.There should be no open sewage, drainage and public lavatory, factory emitting
fumes, excessive soot, dust, smoke, foul smell etc. in the vicinity to avoid
contamination.

2.Transportation facilities should be available for transportation of material as
well as for workers.

3.Government incentive such as cash subsidies, tax exemption etc.

4.Local statutory restrictions.

5.Availability of suitable quality  water.

6.Available skilled  and unskilled personnel.

7.Availability of maintenance facility ,

8.Availability of communication facility

9.proximity of facilities like education, housing, recreation, local transport,
shopping etc.

B) Factory premises

Factory premises should have adequate space for following different activities

1.Receiving and storing Raw material
2.Manufacturing process areas
3.Quality control Section
4.Finished Goods store
5.Office
6.Rejected Goods/ Drugs store

C) Buildings

The factory building is an important aspect. The total building plan should have
due consideration for dosage forms to be manufactured (product range) , Scale of
operation, (Small medium and large) and type of equipments (manufacturing of
medicine should qualify following conditions along with conformity with the Factory
act .

1.Building should be designed constructed and maintained in such way to prevent
entry of insect / rodents, files and dust

2.Hygienic conditions and no cobwebs.

3.No dampness or moisture and walls and floors should be even.

4.Interior surface should be smooth, easy for cleaning and disinfections.

5.Flooring should be smooth and even so as not to permit retention or
accumulation of dust or waste products .

6.Proper sanitary and drainage system in the unit.

7.Adequate provision , electrical fixtures,proper ventilation/ chimney & fire safety
measure Exits.

8. Provisions for different areas storage, weighing, production, quality control,
ancillary etc.

9. Specific requirements of a dosage form (e.g., segregated areas for granulation
compression. And coating process in manufacturing of tablets).

10.Specific requirements of a utilities ( e.g., boiler for generation of steam
bhattis [furnaces] , gas water etc).

11. Compatibility with manufacturing operations viz, manufacturing, processing,
packaging, labeling, etc,

12. Adequate working space for each operation.

13. Logical placement of equipment to avoid risk of mixing , to avoid cross
contamination and omission of a process.

14. Logical flow of material i.e. goods in-> stores --) production -->quarantine
and assembly -) warehouse -->goods out.

15. Provision for expansion or future projects .

D) Water supply

Water used in manufacturing should be pure and of potable quality. Adequate
provision for washing of premises should be made. Potable water should conform to
prescribed standards (ICMR standards) Ion -exchange treatment and distillation
plants may be installed for the availability of purified water and water for
injection respectively. Following periodicals schedules for monitoring the quality of
water is required to ensure the quality of water used in the manufacturing unit.

1.Once a year potable water
2.Once a month water from storage tank ( turbidity , dissolved solids, pH,
chlorine content , microbial test including salmonella and Coliform). 
3.Once a week Purified water and water for injection conformance with IP
specifications. 

4.Twice a week purified water and water for injection  for microbial purity (total
bacteria less than lOO/ml molds , gram negative & pathogenic organism absent).  

E] Containers cleaning

There should be provision for independent area for cleaning of containers
adequate arrangement for washing, cleaning, and drying of containers (bottles,
vials, jars. etc used for packing of various dosage forms) should be made. 

F) Disposal of waste 

Waste water and residue should be disposed only after suitable treatment as per
the guidelines of pollution control authorities following important legislations
enforced by in this regard should also be consulted.

•Air (Prevention and control of pollution) act 1981
•The environment (protection) Act 1986 & 1975
•The water (prevention & control of pollution) act 1974 & 1975
•Manufacture, storage, & Import of Hazardous chemicals Rules 1989

•Hazardous waste (Management and Handling) Rules 1989 etc.
•Central pollution control Board & state pollution control Board.
Requirements for the sterile products 
There should be provision of separate enclosed area specially designed for sterile 
products. 

Salient points for the production of sterile products are given below

•Manufacturing area
• Air lock for entry
•Free from dust and ventilated with an air supply
•Air supply through bacteria retaining filters (HEPA filter)
•Periodical checks of filters and their maintenance record,
•Area designed to facilitate  cleaning and disinfections
•Routine microbiological checks,

•Restricted entry, procedures for entering and leaving.
 Preclude possibility of mix up between non sterile and sterile products .
•Precautions against contamination and mix
•independent block or isolated enclosure,

•Appropriate pressure differential in the process area,
•Suitable exhaust system
•Laminar flow sterile air system

•Monitoring devices UV lamps etc,
•checking individual containers to ensure freedom from contamination
•Process controls shall be checked and recorded.

Working space and storage area

A, Working space

Manufacturing area should have adequate space & arrangement to prevent cross
contamination Space Requirements for manufacturing of Ayurveda & Siddha
Medicines 1200 sq. ft. covered area with separate cabins /partitions for each
activity is required.

 If Unani medicine are manufactured in the same premises an additional area of
400sq ft will be required. Minimum space requirement for manufacturing individual
category of medicine of Ayurveda / Siddha as per GMP requirement.



B) Storage area

Storage area should have independent adequate space and may be marked as per
requirement of manufacturing unit to store the starting material (raw ingredients),
Intermediates, bulk finished products, products in quarantine, release products,
rejected products, returned products, recalled products, and packing material.

These stores should be properly ventilated and free from dampness. 

I) Raw material stores

For the storage of raw materials appropriate containers as per material (physical
and chemical properties) may be used to prevent from dampness, microbiological
contamination, rodents and insect infestation.

In ISM manufacturing unit raw material may be categorized as follows for their
appropriate storage. 
•Fresh herbs, Dry herbs, Plant extracts and exudates/resins etc.
•Volatile Oils / perfumes and flavors
• Animal Origin, Metallic Origin, Mineral Origin, Excipients

Each container should be properly labeled and

informative in following format:

Name of raw material
Source of Supply.
Status -Under test / Approved / Rejected
Batch/Lot No,
Date of Receipt
The raw material should be sampled and subjected for quality control testing
before its use. First in first out system should be followed for use.
Record of receipt, testing and approval or rejection and use should be invariably
maintained.

II) Packing Material Stores

There should be separate space for storage of bottles, jars, capsules, etc.

All the containers and closures lids should be adequately cleaned and dried before
packing the products. 

III) Finished Goods store

The finished products from the production area after proper packaging should be
stored in the finished goods store within an area marked as Quarantine and
subjected for quality control test for conformance to standards, packing and
labeling.

Only after the approval of quality control department it should be moved to
finished goods stores which should be facilitated with proper shelves and specific
storage conditions required for finished products. Distribution records should be
invariably maintained. 

Machinery & Equipments

Machinery and equipment should be according to the size of Operations and nature
of product. Manufacturing process could be manual, semi-automatic or automatic.

In an ISM manufacturing unit different processes are crushing, grinding powdering
boiling, mashing, burning, roasting, filtering, drying, filling I labeling and packing
etc. There should adequate space between machines to facilitate the cleaning and
maintenance operations.




Standard Operating Procedures (SOP) 

Standard Operating procedures (SOP) are written documents specifying the
procedures that must be followed to carry out o operations.

A) Benefits

1. Outline the critical aspects of procedures. 
2. Need not to rely on memory or word of mouth communication 
3. Prevent introduction of errors and variations. 
4. Can be used to impart training to personnel. 
5. Preparation of SOP identify the potential problems and their solutions thus
improve planning and organization.
6. Eliminate need to redevelop the procedure every Operational time 

B) Areas of application 

1.Receipt of materials .
2.Equipments 
3.Sampling 
4.Batch/lot numbering system
5.Testing material and products at different stages of process 
6.Release or rejection of material and finished products 
7.Maintenance, cleaning and sanitization
8.Environmental monitoring 
9.Test control and quality control procedures 
10.Complaints 
11.Recalls
12.Returns