GOOD MANUFACTURING PRACTICES (GMP) IN PHARMACEUTICALS

GOOD MANUFACTURING PRACTICES (GMP) 

I.  INTRODUCTION :

       

The purpose of this guideline steps, which should be taken, as necessary and appropriate by manufacturers of drugs i.e./ individual products with the object of ensuring that the products are  of  the nature & quality intended. Methods other than those described but which achieve the same ends may be equally acceptable.

II. Basic requirements of good manufacturing practices ( Manufacturing  Control ) includes :

             

       1)  Sanitary requirements

             2)  Personnel

             3) Training

             4) Hygiene

             5) Equipment

             6) Control Procedures

             7) Packaging

             8) Ware housing

             

1. Sanitary requirements: 
  
The ware housing, manufacturing and packaging areas shall be maintained in  a clean, orderly condition free from vermin, accumulated waste and debris.The following preventive  measures  shall be looked into:

a) All manufacturing, packaging & ware housing area shall be constructed & painted in such a way that allows efficient clearing.

b)   All ceilings, Walls, duct lines, floors, ventilation facilities should be maintained in such  way that will avoid or minimize the introduction of extraneous materials into the drug products.

c) All the drains should be such type and size that there should be no accumulation of waste water which become the continual source of contamination  of  drugs.

d)  Adequate lighting should be provided in all working areas.

e)Floor drains, ventilation and similar openings should be covered with grating, wire screen sufficiently fine and strong to prevent entry of rodents, insect’s etc.

f)  Sufficient working and storage area shall be provided to permit adequate cleaning and house keeping.

g) Working conditions (i.e. temperature, humidity) shall be such that there is no adverse effect on the product either directly or indirectly.

h)   All operation shall be carried out in such a way that the risk of contamination of one product or material by another is avoided.

i)   There should be written cleaning procedures and schedules for manufacturing and storage area.

2. Personnel:


  
There shall be sufficient personnel at all levels with the ability, training and experience. Their duties and responsibilities shall be clearly explained and recorded as job descriptions. Training should cover not only specific tasks, but  good manufacturing practice generally and the importance of personal hygiene.

                                     

3. Training: 

All production personnel shall be trained in the principles of good manufacturing practices and in practice
of the tasks assigned to them. Similarly, all other personnel i.e. maintenance, cleaning whose  duties take them into manufacturing areas, shall receive appropriate training. after all coaching shall be in accordance with the written programme approved by the competent authority. Special   attention shall be given to coaching of personnel operating in aseptic/clean areas.

4. Hygiene : 


a)  Toilet facilities shall be adequate and proper, with sufficient lighting and ventilation, and to be maintained clean at all times. Hand washing facilities shall be conveniently available for manufacturing personnel and there shall be rules for washing before returning to work. 
 b) All persons entering production areas shall wear clean and prescribed garments including head-gear,   change rooms should be provided. 
c) Direct contact shall be avoided between the operators hands and beginning materials, intermediates and products. 
d)  No person shall be allowed to work known to have a disease or a carrier of a disease, and no person with open lesions on the exposed surface of the body where drug as a result become contaminated. 
e)   Eating, drinking, chewing, smoking and spitting is strictly prohibited in the area where drug as a result become contaminated.

5. Equipment :

 

a)   The type and amount of equipment shall be adequate for the intended operations.

b)   All manufacturing and packaging  machinery / equipment shall be adequate & cleaned and maintained in a manner to prevent contamination of drugs with extraneous materials.

c) All manufacturing packaging machinery/equipment and ancillary items shall be constructed of such materials which must not contaminate the drugs.

d)  Equipment/ machinery shall be checked for cleanliness prior to use.

e)  A programme shall exist for maintenance, adjustment and repair of manufacturing machinery/ equipment.

f)  Scales shall be calibrated periodically and checked for accuracy. There shall be a written down programme for frequency of inspection depending upon the nature of job, weights shall be inspected and checked for accuracy and reproducibility  with that of standard ones.

6) Control Procedures:  

Control procedures involved in ware housing, manufacturing and packaging shall be written up and subject to a system of reviewing and updating.

a)   Written procedures and specification:

(i) All raw materials and product specifications , methods of sampling and analysis, and criteria for acceptance, shall be in writing and subject to a system of periodic review and updating.

(ii)  All manufacturing formulas and all working directions shall be in writing. All working direction shall specify the machinery, equipment to be used and all details such as time, r.p.m., etc. necessary to assure batch to batch reproducibility.

b)  Operating procedures:

( i ) Raw material  component of drugs:

(a) Material shall be controlled by written specifications designed to assure identify, strength, quality and purity of the material.

(b) Each container of a raw material shall  bear an identifying name, batch/lot no. supplier’s name shipment mark etc.

(c)  Raw materials shall be quarantined until approved by quality assurance dept.

(d) Each raw materials shipment or batch/ lot  shall be sampled and tested as per laid down specifications.

(e)  Approved raw materials shall be stored in a manor to avoid deterioration or contamination.

2. Formula cards ( Manufacturing order) :

 Each batch of a product shall have a formula/ batch card or manufacturing order.

3. Manufacturing :

a)    General

(i)  Before any manufacture starts steps should be taken to ensure that the work area and equipment are free from any  material , drug products, documents etc not required for current operation.

(ii) Each product shall be manufactured in accordance with standard working directions for that product. Any deviation from such standard working directions shall be subject to the prior approval of  quality control in each instance.

(iii) The identify and correctness of weight ( or Volume) of each raw material, and its addition to the batch, shall be independently checked.

(iv)  Measures to assure maintenance of product identity shall checked at all stages during manufacturing .

(v)  The final wt., volume or yield of the batch shall be recorded & independently checked. Any discrepancy arises shall be recorded and resolved on the spot.

(vi)  The Batch shall be quarantined until a representative sample has been tested and approved by quality control department.

(vii)   Al  in-process results shall be recorded in the process control sheet by the operator & shall be signed by him. The section head shall check these results for the correctness.

b) Sterile Products :   

   

In addition to above general manufacturing procedures the following shall be taken into account for sterile product preparations:

                                                                                    

(i)  Sterile products  shall be manufactured in areas and under conditions that assure freedom from microbial contamination.

(ii)  Sterile products shall be filled in rooms completely enclosed areas having positives air pressure that are segregated from all other operations. Such area shall be designed and maintained to assure aseptic conditions conforming to good manufacturing practices.

(iii)  Personnel involved in filling sterile products should be trained in aseptic techniques, be properly garbed, and observe all other precautionary measures to assure maintenance of sterile conditions.

(iv)  Periodic air sampling shall be performed in sterile filling areas to assure that micro organism counts do not exceed those consistent with good practice.

(v)  HEPA Filters and Laminar air flows shall be checked and maintained to achieve the desired condition.

7. Packaging :

(a)   General:

(i)  There shall exist written specification for packaging materials.

(ii)  There shall exist written packing instructions for each product as well as operations involved.

(b)  Before start up and after packing operations the following system shall exist:

(i)  System for inspection and issuance of label, carton, carton box, Al-foil, insert etc.

(ii)  System for inspection for the correctness of printing of batch number  manufacturing date, expiry date etc.

(iii) System for reconciliation and disposal of unused printed label, cartons, inserts etc.

(iv) System for checking the yield of finished goods against the theoretical yield.

(v) System for sampling while packing operations, quantity of finished goods, inspection and release of goods by Quality Assurance Department.

              

8. Ware housing of finished Goods:

 (i) System for proper storage, segregation and identification of batch or lot, systematic rotation of stocks (FIFO), system for ‘hold up’ if exigency  arises; and inspections of stocks etc.