GMP IN MANUFACTURING PROCESSSCHEDULE M

BINDU

DEFINITION●WHO defines Good Manufacturing Practices

(GMP) as “that part of quality assurance which ensures that quality products are consistently produced and controlled to the quality standards appropriate to their intended use and as required by the marketing authorization”.

●The guiding principle of GMP is that quality is built into a product, and not just tested into a finished product. Therefore, the assurance is that the product not only meets the final specifications, but that it has been made by the same procedures under the same conditions each and every time it is made.

● All of the controls must follow prescribed, formal, approved procedures, written as protocols, SOPs, or Master Formulae, describing all the tasks carried out in an entire manufacturing and control process.

AREAS TO BE COVERED● Personnel● Premises● Equipment● SOP’s● Raw Materials● Self Inspection And Audit● Master Formula Records● Batch Manufacturing Records● Warehousing Area● Reference Samples● Validation

Good Manufacturing Practices (GMP)● Production● Utilities● Equipment● Dosage form and data verification

(development, validation, BMR and specification)

PERSONNEL

PERSONNEL●Qualified Personnel a)Experienced b)Sufficient Number

●Written job description●Trained●Health●Diseases

PRODUCTION

● Product focus● Premises● Utilities● Equipment● Dosage form and data verification

(development, validation, BMR and specification)

● Documentation

RAW MATERIALS● An Inventory should be maintained for Raw

materials to be used at any stage of manufacture

●Records should be maintain as per Schedule U●Should be purchased from approved sources●Must be checked by QC department on recipt ●Should be labeled.

STANDARD OPERATING PROCEDURE● Standard operating procedures (SOPs) are the detailed

written instructions that specify how a test or administrative procedure is to be performed, or how a piece of equipment is operated, maintained and calibrated. SOPs describe the "standard" approved procedures that are routinely carried out in a GMP facility. They indicate exactly how things are done, and are kept current by review and approved revision on a predetermined schedule (usually annual), or when planned changes are made to the procedure or equipment and reagents used in the procedure.

● It include- a)For Equipments b)For sampling c)For Testing d)For Process e)For Packaging

MASTER FORMULA RECORDS● There shall be MFR relating to all manufacturing

procedures for each product and batch size to be manufacture

● It should include- The name of the product Quantity of all starting materials to be used A statement of the expected final yield with

acceptable limits Principal equipment to be used Detailed stepwise processing instructions and the

time taken for each step Any special precautions Packing details and Specimen labels

BATCH MANUFACTURING RECORDS●There shall be Batch processing record for each

product.●During Manufacturing or Processing the

following information shall be recorded●It include-●The name of the product●The number of Batch being manufactured●Dates and time of commencement of batch and

completion●Amount of Product obtained

PREMISES

LOCATION●Geographical, climate and economic factors● Premises must be located to minimize risks of

cross-contamination e.g. not located next to a malting factory with high airborne levels of yeast

●Pollution/effluent control

DESIGN● Minimize risks of errors●Permit effective cleaning●Permit effective maintenance●Avoid cross-contamination, build-up of dirt and dust●Maximum protection against entry of insects, birds

and animals●Separate facilities for other products such as some

antibiotics, hormones, cytotoxic substances● Hygiene●Eating,Drinking,Smoking Should not be allowed in

the Production area

CONSTRUCTION●Measures should be taken to prevent cross-

contamination●Dust control measures (including extraction of

dust and air)●No areas for dust accumulation●Easily cleanable surfaces●Proper air supply●Use of HEPA filter’s

FACILITY LAYOUT

Zone: Clean Zone: Packaging Zone: Controlled

ACTIVITIES

• Sampling (starting materials and packaging materials)

• Weighing• Mixing• Milling• Sieving/sifting/screening• Granulation• Drying• Sieving• Blending• Compression• In process bulk stores• Packaging areas (primary and secondary packaging)• Finished product

EQUIPMENTS

●Equipment shall be located,designed,constructed,adapted and maintained to suit the operation to be carried out.

●Should be made of non reactive material such as High grade of steel

●Equipment should be- a) Calibrated b)Checked c)labelled d)Sterilized

● Sieving/sifting – sifter (e.g. vibrosifter)● Mixing – mixer● Granulation - granulator● Drying – fluid bed drier● Blending – octagonal blender● Compression – compression machine● Packaging - blister machine

● Others include Metal detector, sieves, punches and dies

● In process quality control instruments and equipment may include hardness tester, disintegration tester, balance, Vernier caliper

• Compressed air – machine operation, drying of equipment and parts• Water – washing, rinsing, manufacture• Steam – cleaning

UTILITIES● DRAINAGE SYSTEM●VENTILATION AND AIR CONDITIONING● GAS SYSTEMS ● SANITATION ●WATER

DRAINAGE SYSTEM● It remove effluent from spaces ,systems, or

process. ● Drains shall be of adequate size , connected

directly to sewerage , shall be provided with an air break or other mechanical device to prevent back-siphon age.

● it should be easy to clean and must be cleaned at a proper interval.

● They must be well closed and air tight. ● Dissolved oxygen content in the waste to be

disposed in lake or river must be within limits.

GAS SYSTEM●Many types of gases are utilized in the

manufacturing process. The most prevalent of these include compressed air use in process and controls, breathing air for hazardous environments, nitrogen, vacuum, vacuum cleaning, natural gas, propane, and other process systems.

●All gases used in manufacturing and processing operations, including the sterilization process, should be sterile filtered at points of use to meet the requirements of the specific area. Gases to be used in sterilizers after the sterilization OR used at the filling line or microbiological testing area must also be sterile filtered.

SANITATION● The manufacturing premises shall be maintained clean and

in orderly manner, free from accumulated waste, dust, debris, etc;

● Eating, chewing, smoking or any unhygienic practices shall not be permitted in manufacturing area

● Routine sanitation programme shall be drawn up and observed which shall be properly recorded and which shall indicate: Specific areas to be cleaned and cleaning intervals; Cleaning procedure to be followed, including equipment and materials to be used for cleaning;

● Objectives of sanitation are● Removal of dirt and other waste material● Minimize the risk of cross contamination between different

products in the same area● Reduce the number of micro-organisms in work area;

Red: Supply Green: Exhaust

Air supply and extraction

Re-circulation Air System

ISPE Baseline Vol. 2 #6.3.3 (d)

WHO HVAC Guideline

HEPA filters installed?

Examples of control measures:

Temperature Cooling coil

Relative humidity Dehumidifier

Particulate matter Filters

Air movement and pressure differentials

Fan

DOCUMENTATION REVIEW

HVAC• DQ, IQ, OQ, PQ• Important aspects including air

flow direction, filtration, air changes, pressure differentials

Water• DQ, IQ, OQ, PQ• Sampling and testing

DOCUMENTATION REVIEW

Equipment and utilities• SOPs (operation, cleaning,

calibration)• Records and use logs• Calibration records/certificates• Preventative maintenance and

maintenance• Qualification

DOCUMENTATION REVIEW

Product related• Batch Manufacturing document as

per product dossier• Process Validation protocol and

report• Stability batches• Batch records

VALIDATION● Essential part of GMP● Necessary to achieve the intended results● A written record is prepared summarizing recorded result

and conclusions shall be prepared ,documented and maintained

● Should be necessary when a)Any new new master formula or method of preparation is adopted b)For critical process c)any changes in the equipment,or when using a new

equipment,it is first validated to demonstrate its consistency of required quality

VALIDATION STATUS• Validation Master Plan

• Manufacturing areas• Utilities• Equipment• Manufacturing process• Cleaning validation• Computer systems

SELF INSPECTION AND QUALIY AUDIT

●To evaluate the manufacturers compliance with GMP in all aspects of production and quality control, concept of self-inspection shall be followed.

●The manufacturer shall constitute a team of independent, experienced, qualified persons from within or outside the company, who can audit objectively the implementation of methodology and procedures evolved.

REFERENCE SAMPLES

•Should be taken in sufficient quantity from each lot of active ingredient to carry out all the testsThese samples should be retained for a period of 3 months after the date of expiry of the last batch produced from that active ingredient

• Samples of raw material should be stored in suitable container(plastic or glass) as mentioned in the SOP Samples of finished formulations shall be stored in the same containers in which the drug has been actually marketed

WAREHOUSING AREA●Warehousing area should be designed and

adapted to ensure good storage conditions.●Should be Clean,dry and maintained with

acceptable temperature limits.●Should have appropriate house-keeping and

rodents, pests control.●Seprate sampling area for active raw material

and excipients.●Every Material stored should be labeld properly.●Fire Prevention

THANK YOU