gmp in permises

7/30/2019 Gmp in Permises

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GMP IN PERMISES:

DESIGN,CONSTRUCTION,

MAINTENANCE & EQUIPMENT

YUB RAJ NEUPANE

M.PHARMA,SEM II

PHARMACEUTICS

JAMIA HAMDARD,NEW DELHI


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.. that part ofQuality Assurancewhich ensure thatproducts are

consistently producedand controlled to thequality standardsappropriate to their

use. GMP is an integral

part of QualityAssurance

GMP is.

QA

GMP QC


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Quality, safety and efficacy must be designedand built in the product.

Testing alone cannot be relied on to ensurequality.

Each step in the manufacturing process must becontrolled to ensure that the final product lies

within limits and specifications.

Basic Principle of GMP


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Why is GMP necessary?

Customer Protection & Satisfaction

Employee Protection

Fulfilling Legal Requirements

Good Business Practice

Pride in Workplace


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Basic Requirements for GMP

Clearly defined and systematically reviewed

processes. Critical steps validated. Appropriate resources: personnel, buildings,

equipment, materials. Clearly written procedures. Trained operators. Complete records, failure investigations. Recall system. Complaint handling.


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Food and Drug Administration : GMP

Code of Federal Regulations (Title 21)

Title 21, Code of Federal Regulations (21 CFR) is

updated April 1 of each year.

The current edition contains nine volumes.

1) 21 CFR 1-99. General regulations forenforcement of the FFDC (Federal Food, Drug

and Cosmetic ) Act and the Fair Packaging and

Labeling Act. Color additives.


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2) 21 CFR 100-169. General regulations for foodlabeling (contains the new regulations for nutritionlabeling).

Infant formula quality control procedures andlabeling.

Food standards and quality standards for bottled

drinking water.The CGMP regulations for food, bottled drinkingwater, low-acid canned foods, and acidified foods.

3) 21 CFR 170-199. Food additives.

4) 21 CFR 200-299. General regulations for drugs.


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5) 21 CFR 300-499. Drugs for human use.

6) 21 CFR 500-599. Animal drugs, feeds, and

related products.

7) 21 CFR 600-799. Biologics and cosmetics.

8) 21 CFR 800-1299. Medical devices, radiologicalhealth, and control of communicable diseases.Import Milk Act, Federal Tea Importation Act,and Federal Caustic Poison Act.

9) 21 CFR 1300-End. Regulations implementing theControlled Substances Act and the Controlled

Substances Import and Export Act.


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Under the 4 th volume:

Part 210: GMP in Manufacturing,

Processing, Packing, or Holding of Drugs;

General

Part 211: GMP for Finished

Pharmaceuticals.


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INTRODUCTION

A draft of GMP regulations was prepared in 1975 which was

implemented in 1988 in the form of amended Schedule M.

GMPs form the heart of quality.

GMPs comprises a set of practices that ensures quality at everylevel of operation in an industry.

GMPs provide quality assurances that off-the-shelf testing cant.

GMPs are more immediate and consistent way to controlquality.

Virtually every manufacturer adheres to in-house GMP std. butnow embracing on industrial std GMPs.


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Subparts of Schedule-M

Subpart:

A Finished Pharmaceuticals: General Provision

B Organization and Personnel

C Building and Facilities

D EquipmentsE Control of Components and Drug Product Container

and Closure

F Production and Process Control

G Packaging and Labeling Control

H Holding and Distribution

I Laboratory Control

J Records and Report


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SUBPART-C and D


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Principle

PremisePrinciple

Premises must be loPrinciple

Premises must be located, designed, constructed, adapted and maintained for the operations:

Minimize risks of errors and cross-contamination

Permit effective cleaning

Permit effective maintenance

Minimize build-up of dirt and dust

Eliminate any adverse effects on quality

cated, designed, constructed, adapted and maintained for the operations:






s must be located, designed, constructed, adapted and maintained for the operations:






Premises

PrinciplePremises must be located, designed, constructed,

adapted and maintained for the operations:

Minimize risks of errors and cross

contamination


Permit effective maintenance Minimize build-up of dirt and dust



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Principle

Premises must belocated to minimize

risks of cross-

contamination; e.g.

not located next to a

malting factory with

high airborne levels

of yeast


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Location

Geography, climate, noise and economic factors

Neighbours What do they do?

What impact can they have on the business?

Pollution/effluent control


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Premises should be built

to:

Facilitate sanitation.

Be maintained and

cleaned easily

Services availability

Protection against entry

of insects or other

animals


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Specific areas

Storage areas

Weighing areas

Production areas

Quality control areas

Ancillary areas (change rooms, toiletfacilities, sampling, Rest and refreshment

rooms )


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Weighing areas:

Weighing operations

in separated areas Appropriate design (see also training material

on HVAC)

Provision for dust control

Smooth, impervious, durable, easy-to-cleanfinishes

Cleaning procedures and records

Documentation, e.g. SOPs, logs and records


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Design of areas for

weighing of materials

Proper air supply

Dust control measures

(including extraction of dustand air)

Easily cleanable surfaces

No areas for dust

accumulation

Protection of material,

product and operator


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Manufacturing and Packaging I

Dedicated and self-contained facilitiesfor:

Logical flows of materials and people Adequacy of working space and

orderly and logical positioning of

equipment Interior surfaces smooth/crack-

free/easy to clean


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Aseptic processing, which includes as appropriate:

(i) floors, walls, and ceilings of smooth, hard surfacesthat are easily cleanable;(ii) temperature and humidity controls;

(iii) an air supply filtered through high-efficiency

particulate air (HEPA) filters under positive pressure,regardless of whether flow is laminar or nonlaminar;

(iv) system for monitoring environmental conditions;

(v) system for cleaning and disinfecting the room andequipment to produce aseptic conditions;

(vi) system for maintaining any equipment used tocontrol the aseptic conditions.


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Operations relating to the manufacture,

processing, and packing ofpenicillin shall

be performed in facilities separate from

those used for other drug products for

human use.


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Other Areas

Personnel rest areas/cafeterias/changing

roomsaway from operating areas

prevention of cross-contamination

prevention of operators going outside in work clothes

provision of access control

prevention of visitors access to operating areas

Maintenance service areas separated from production areas whenever possible


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Finish of Floors,Walls andCeilings

Difficult but notimpossible to get

right, smooth,impervious, hard-wearing, easy to

clean; but not bricks,

tiles, wood orsliding doors!

Not These


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These pictures illustrate a much better approach to achieving

smooth, impervious durable surfaces for floors, walls andceilings.

The light fixtures fit flush with the ceiling, the floor uses weldedvinyl which is covered to the wall face are very smooth andeasy to clean and there are no gaps

Finishing of floors, walls and ceilings


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Methods to reduce cross-contamination :

1. Segregated areas2. Airlocks and pressure differentials

3. Treatment of re-circulated air

4. Protective clothing5. Effective cleaning procedures

6. Closed production systems

7. Residue testing8. Status labelling


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Manufacturing and Packaging I

Pipe work and other fittings sited to avoid

recessesDrain design:

equipped to prevent backflow

open channels avoidedEffective air handling to suit product

temperature

humidity filtration

monitoring


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Manufacturing and Packaging II

Specifically designed and laid out to avoid mix-

ups and cross-contaminationChanging facilities to provide segregated access

Prevention of cross-contamination

Suitable lighting levels


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MAINTENANCE

Cracks and holes in walls, floors, or ceilings canprovide access for insects, rodents, birds, dirt, ormicroorganisms.

Adequately drain areas that may contribute tocontamination of food by food borne filth, or provide

conditions for nesting and breeding of for pests;

Operate systems for waste treatment and disposal

in an adequate manner.


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In-Process and QC laboratories

Located separate from but near manufacturingprevention of cross-contamination

separate biological , microbiological, radioisotopic

areas

Designed for the operations being carried out

suitable storage space


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Equipment (Subpart D)

EQUIPMENT DESIGN, SIZE, AND LOCATION:

used shall be of:

appropriate design,

adequate size,

suitably located

constructed materials shouldnt be

reactive,

additive,

absorptive


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lubricants or coolants, shall not come into

contact with

components,

drug product containers,

closures,

in-process materials,

Records shall be kept for maintenance, cleaning,

sanitizing, and inspection as specified in211.180 and 211.182.


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References

Good manufacturing practices for pharmaceutics. APlan for total quality control 4th edition, Revised &

Expanded Vol. 78, Sidney H. willing James R Stoker,

page 33-51

Quality assurance of pharmaceuticals A

compendium of guidelines and related materials

Volume 2, 2nd updated edition Good manufacturing

practices and inspection-WORLD HEALTH ORGANISATION Encyclopedia of PHARMACEUTICAL TECHNOLOG Third Edition VOLUME

1, James Swarbick, page 1941

http://www.fda.gov/Food/GuidanceComplianceRegulatoryInformation/

CurrentGoodManufacturingPracticesCGMPs


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