GOOD MANUFACTURING PRACTICES IMPLEMENTATION

WHAT IS GOOD MANUFACTURING PRACTICES?

Good Manufacturing Practises (GMP) are part of the quality assurance that ensure products
are consistently produced and controlled to meet a certain quality standards and safety
requirements appropriate to their intended use.
Procedures describe the methods, equipment, facilities and controls for all manufactured
goods.

BASIC REQUIREMENTS OF GMP

All manufacturing processes clearly defined, systematically reviewed and shown consistency.
Critical processes and significant change are validated.
All necessary facilitates for GMP are provided:
-appropriately qualified and trained personnel;
-adequate premise and space;
-suitable equipment and services;
-correct material, containers and labels;
-approved procedures and instructions;
-suitable storage and transport.
Procedures and instructions are written in an instructional form in clear and unambiguous
language.
Operators are trained to carry out procedures correctly.
Records of manufacture including distribution are made, retained in a comprehensive and
accessible form.
Any significant deviations are fully recorded and investigated.
A system is available for complaints and product recall.

MANAGEMENT RESPONSIBILITIES
Understand the benefits of GMP, its implementation and coordination.
Know the consequences of not having a good quality assurance program.
Ensure line workers and QA/QC personnel are brought to a knowledge level commensurate
with the needs of their jobs.
Management communication and employee training.
Provision for effective QMS.
Facility improvement.
Total commitment and involvement.

Programs include:
Premise and environment.
Equipment and utensils.
Personnel.
Production and process control.
Complaints and product recall.
Pest control program.
Quality control.
Storage and distribution.
Suppliers.

Contaminants
Three categories:
Biological;
Physical;
Chemical.
Common Pathogenic Bacteria
Bacillus cereus
Campylobacter jejuni
Clostridium botulinum
Clostridium perfringens
Escherichia coli
Salmonella spesies
Shigella dysenteriae
Staphylococcus aureus
Vibrio cholerae
Yersinia enterocolitica

Physical Contaminants
Feathers, hair
Rodent’s droppings
Metal, glass, nuts
Sand, rocks
Paint flakes
Jewelry
Cigarette butts
Pen caps

Sources Of Physical Contaminants

Contaminated raw materials
Design of facilities and equipment
Faulty production procedure
Improper employee practices

Chemical Contaminants
Commercially Added-pesticides, herbicides, coloring, additives
Unintentionally Added-cleaners, sanitizers, lubricants

How Medical Device Can Be Contaminated?

Direct contact
Contact surfaces

Premise Environment
Grounds
Suitable location
Good housekeeping- proper equipment storage, litter and waste disposal
Prevent entry or harborage of pests
Adequate drainage
General maintenance- roads, yards, and parking lot

Buildings
Layout-unilateral flow
Design, construction and maintenance
-sufficient space
-prevent cross-contamination or mix-ups
-facilitate cleaning
-adequate lighting
-adequate ventilation
-adequate screening-protection against pests
Steps should be taken in order to prevent the entry of unauthorized people.
Maintained in a good state of repair
Equipment
Design, material and construction
-prevent hygienic hazards and permit easy cleaning
-visible for inspection
-contact surfaces-corrosion-resistant, nontoxic, withstand cleaning and sanitizing agents
-non-contact surfaces-clean condition, maintained
-installation-facilitate cleaning
-instruments and control-temperature, pH, acidity, water activity etc
-adequate in number
-maintenance, calibration
-compressed air and gases from equipment - treated to prevent against contamination

PERSONNEL
DISEASE CONTROL & MONITOR
-written policy
-health questionnaire- upon employment
-medical examination
-communicable diseases
-open lesion- boils, sores, infected wounds
-report to supervisors
-medical facilities
-discourage visitors

PERSONAL HYGIENE
Personal cleanliness-hygienic practices
Education and training-appropriate training
Supervision-assign competent supervisors

PERSONAL CLEANLINESS
Protective outer garments - clean, light color and change when soiled or contaminated
Gloves - disposable gloves, medical grade, cotton gloves not permitted
Effective hair restraints - cover all hair, beard cover
Jewelry - no loose jewelry, earrings, brooches, rings and wrist watches
Footwear - shoes, boots
Proper hand wash
Fingernails - clean and neatly trimmed, polish and artificial nails not allowed
No hand cream and other cosmetics, medicines
No smoking, eating, gum chewing, drinking beverages
Laundry services
Worker welfare - canteen/cafeteria
- locker room

HAND WASHING
Before start work
After absence from work station
After going to toilet
After handling raw material
When hands soiled or contaminated

EDUCATION AND TRAINING

Personnel in-charge - education and experience
Gloves handlers and supervisors-proper gloves handling techniques
Technical training - understand the processes and assigned tasks.
Refresher training (continuous)
SUPERVISION
Competent supervisors
Responsible - assuring compliance by all personnel with all requirements
Inspection
Employee improvement worksheet

Water supply
-sufficient
-suitable temperature and pressure
-stainless steel tanks
-conduct sedimentation and microbiology tests

Plumbing
Carry sufficient water
-provide adequate floor drainage
-no back flow, cross-connection between sewage/waste water and water for manufacturing
Non-rust material

Sewage disposal
Adequate and proper

Toilet facilities
Adequate, easily accessible
Good repair at all times
Clear and proper signs

Hand washing facilities

Adequate, essential location
Hand cleaning and sanitizing agents provided
Paper towels or drying devices
Foot or knee operated or sensor type taps
Proper refuse bin (foot operated)

Rubbish and offal disposal

Stored and disposed properly
Avoid accumulation of waste
Easy cleaning

Written instructions
A planned cleaning schedule.
Cleaning schedule should have details on.
-the equipment/area cleaned
-name of person in charge
-frequency
-method
-type of detergent and sanitizer

Set cleaning standards

How clean is clean?
General appearance
Microbiological test
-contact method
-swab method
STORAGE AREAS
Free from contamination, safe, adequate
Compliance-supplier certification, examination
Identified, held and stored to protect against contamination
Separate locked rooms or cabinets
Separate area for ‘QUARANTINE’
Practice good stock rotation

PEST CONTROL
Control of insects, rodents, birds or other vermin
Effective, on-going written program
Trained personnel or professional pest control
Regular inspection
Layout-bait or trap station
Proper measures to prevent cross-contamination
Inspection, action, record and verify
Do not feed or encourage stray animals

WHAT ARE THE SIGNS OF INFESTATION?

LOOK OUT FOR
-smell
-droppings
-smears
-path
-part of body
-damage

HOW PESTS GET INTO THE PREMISE?

Deliveries-raw material
Attracted by smell of food
Encouraged by employees
Cracks, gaps, holes
Drainage system
Windows, doors, ventilation

PEST CONTROL
Maintain good housekeeping
All employees trained to recognize pest infestation signs and procedures on how to prevent
and control them
Premise kept in good repair
Traps kept clean and in good repair
Proper hygienic practices
Practice good stock rotation
Screens at doors, windows, and other outlets
SUPPLIES
Raw materials and other ingredients
Inspect, segregate, clean, store
Receiving area away from processing area
Inspection upon receipt, storage and before use
Wash and clean-contaminant and minimize deterioration
Store under proper condition
Compliance with requirements
Requirements
-level of microorganisms
-other hazards
-physical specifications
-packaging
-temperature

Supplier Quality Assurance (SQA)

Compliance with requirements verified by a planned and managed Supplier Quality Assurance
(SQA)
SQA
-agreed specifications
-audits
-Certificates of Analysis

Supplier Audit
All raw materials, priority to high-risk raw materials
Trained and experienced personnel/third party auditors
Once a year, etc

Packaging Material
Comply with specification
Inspected, sampled and tested
Protected
No adverse interaction
Provide necessary characteristics and integrity
Carry information required

PROCESS CONTROL
Shown consistency, reproducibility and capability
Any significant deviations are fully recorded and investigated
Cleaning requirements, cleaning intervals, pest control measures, microbial and environmental
monitoring procedures, etc
Production procedures- do not contribute contamination from any source
Testing methods- chemical, microbiology and extraneous material

Raw materials and other ingredients

Inspected
Stored
Washed or cleaned, if necessary
Not contaminated
Holding identification
MANUFACTURING OPERATIONS
Manufacturing -control physical factors and manufacturing operations
Measures to destroy or prevent growth of undesirable microorganisms
Work in progress
Effective measures to protect finished product

STORAGE
All raw materials and other supplies inspected upon receipt or unloading
End products inspected prior loading
Storage area designed and constructed to protect against contamination or mix-ups

Raw materials
Proper conditions (temperature, humidity)
Appropriate stock rotation
Pest control programs
Sufficient space
Cleaning and sanitizing programs
Labelled (batch no., date-marked)
Well ventilated
Building, all equipment, vehicles and fixtures maintained

End Products
Stored and handled to prevent deterioration and mix-up
Returned, defective products identified and isolated
Stock rotation
Adequate lighting
Pest control programs
Cleaning and sanitizing programs
Well ventilated

INSPECTION
ELEMENTS TO CONSIDER
Contamination
Product complaints
Product recall programs
CAPA programs
Validation programs
Management controls
Training records
Device History Records

PRODUCT COMPLAINT AND RECALL PROCEDURES

Written product complaint and recall procedures
-person responsible
-step-by-step procedures described
-product traceability- product coding - distribution records
-means of notifying customers, retailers or wholesalers
-means of coordinating recall with regulatory agencies
Take the complaint and obtain information (forms and procedures)
Evaluate the complaint
-involve regulators, outside advisors
Thorough investigation
Means of notifying the regulatory agency
-reason of reporting/recall
-product identification
-total amount of recalled product
-areas of distribution
Regulatory agency may:
Take samples
Prevent the sale of product
Order the facility to be closed
Deal with the media
Regular analysis, summarizing and review of reports
Take proper preventative measures
Avoid recurrence

DOCUMENTATION
Quality Manual - policy statements on the way a company intends to carry out its business
Operating Procedures - what a company does and how it achieves stated policies
Support Documentation - how a company carries out what it says it does (in detail)

DOCUMENTING PROCEDURES
What we do
Defines process by which a task is carried out
Structure:
-Objectives and scope
-Definitions and references
-Responsibilities
-Procedure details

SOP (Standard Operating Procedures)

What to do, who does it and when
Not static; continuously adjusted
Simple
Training aid
Prevent ‘subject-to-change-without-notice’ situation
Provide written standard for audits
Effective; detail, simplicity and practicality

SUPPORT DOCUMENTS
Working Instruction
Codes of Practice
User Manuals
Technical Documentation
Job Description
Job Specification
Forms
Checklists
 FACILITIES

Hand washing facilities

-essential location such as entrance to production area
-foot or knee operated or sensor type taps
-hand cleaning and sanitizing agents
-paper towels or drying devices
-proper refuse bin (self-enclosed and foot operated)

Toilet facilities
-kept clean, dry, in good repair, prevent harborage of pest especially cobwebs
-proper hand washing facility
-paper towels or drying devices
-proper refuse bin (self-enclosed and foot operated)

Rubbish disposal facilities

-proper refuse bin (self-enclosed and foot operated)
-clean condition, properly maintained

Canteen
-clean, good housekeeping, prevent entry or harborage of pest especially flies
-proper rubbish and offal disposal facilities
-locker room (for employees food)

Quarantine area
-physically isolated area whilst awaiting a decision on release of in-coming materials, work-in-
progress or finished products on their release or refusal.
-essential location

Former storage & off-line cleaning facilities

-clean condition, maintained
-good house keeping
-identified, held and store to protect against contamination
-permit easy cleaning

Premises
-designed, constructed and maintained to prevent entry of inserts and other animals and also
prevent the migration of extraneous materials into the buildings and from one area to another
-doors, windows, walls, ceilings, and floors are such that no holes or cracks are evident (other
than the intended design)
-designated main entrance
-doors giving direct assess to exterior from manufacturing and packing areas are for
emergency only