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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:
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
s 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
Premises
PrinciplePremises 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
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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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