A Seminar on GOOD MANUFACTURING PRACTICES PREMISES

Presented By Mr. Jagadeesh Tekkali

M.Pharmacy 1st year15AC1S0414

VIGNAN INSTITUTE OF PHARMACEUTICAL TECHNOLOGY An ISO 9001:2008, 14001:2004, OHSAS 18001:2007 Certified Institution Beside VSEZ, kapujaggarajupeta, Duvvada,VISAKHAPATNAM-530046 (Approved by A.I.C.T.E & PCI and affliated to JNTUK)

Location Design Construction Maintenance Plant layout Sanitations Environmental control Sterile areas Contamination control

CONTENTS

Principle

Important aspects to be kept in mind to ensure the Quality product several operations to be carried out for different dosage forms and product range:

Location Design Construction Adaptation Maintenance

Location Geography, climate, noise and economic factors Neighbours

What do they do? What impact can they have on the business?

Pollution/effluent control Minimum risk for contamination of products and

materials

PrinciplePremises must be

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

Plant layout

The plant layout and design should aim to: Minimize risks of errors Permit effective cleaning Permit effective maintenance Avoid cross-contamination, build-up of dirt

and dust Avoid any adverse effect on the quality of

products

Design PrinciplesKeep in mind: Material flow People flow Process flow Ensure logical flow

Design

Suitable design and construction to facilitate good sanitation

Cleaning and disinfecting according to detailed written procedures – records maintained

Maximum protection against entry of insects, birds and animals

Procedure for rodent and pest control

Construction

Suitable materials Electrical supply Suitable lighting (especially for visual on-line checks) Temperature and relative humidity control Appropriate and effective ventilationThese may affect products during manufacture or storage

as well as functioning of equipment

The temperature and relative humidity should be controlled, monitored in accordance with an SOP, and the results recorded. The limits should be appropriate according to the materials stored and product processed

Construction Dust generating operations

e.g. during sampling, weighing, mixing, packing of powders, etc.)

Measures should be taken to prevent cross-contamination

Measures to facilitate cleaning

Maintenance

Careful maintenance done Repairs and maintenance should not present

any hazard to the quality of the products

some recommendations for specific areas Ancillary areas Storage areas Weighing areas Production areas Quality control areas

Control of contamination maintain few specific areas such as

Ancillary Areas Rest and refreshment rooms separate from

manufacturing and quality control areas Changing, washing and toilet areas accessible

and appropriate numbers Maintenance workshops separated from

production - if not possible – tools in reserved areas

Animal houses well isolated – separate air handling and entrance

Cleaning of incoming containers

Cleaning with a cloth, or duster

Cleaning by using a vacuum cleaner

Use of air curtains and air tunnels

Storage areas Storage areas of sufficient capacity Orderly storage of categories of materials and

products Separate and segregated areas: starting

materials, packaging materials, intermediates, bulk, finished products, quarantined, released, rejected, returned and recalled products and materials

Storage areas Appropriate temperature and relative humidity

conditions within defined limitsProvided, controlled, monitored and recorded

Good storage conditions: clean, dry and appropriate lights

Storage areas Quarantine area: clearly marked and access

restricted A separate sampling area is the norm: no risk

for contamination or cross-contamination Segregated areas for rejected, recalled and

returned materials and products Safe and secure areas for highly active,

radioactive materials, narcotics and other materials (risk of abuse, fire, explosion)

QC laboratories should be separate from production areas

Separate areas for biological, microbiological and radioisotope methods

Suitable design with sufficient space to avoid mix-ups and cross-contamination

Suitable space for storage samples, reference standards, solvents, reagents and records

Quality Control areas

Quality Control areas Suitable construction materials Prevention of fumes Ventilation Separate air supply (production and QC) Separate rooms for some instruments to

protect them from interference (e.g. electrical, vibration, moisture, etc.)

See supplementary training on QC laboratories

Health, clothing ,sanitation of workers – The personnel handling Beta-lactum antibiotics shall be tested for Penicillin

sensitivity before employment and those handling sex hormones, cytotoxic substances and

other potent drugs shall be periodically examined for adverse effects. These personnel should

be moved out of these sections (except in dedicated facilities), by rotation, as a health

safeguard. Prior to employment, all personnel, shall undergo medical examination including eye

examination, and shall be free from Tuberculosis, skin and other communicable or contagious

diseases. Thereafter, they should be medically examined periodically, at least once a year.

Records shall be maintained thereof. The licensee shall provide the services of a qualified

physician for assessing the health status of personnel involved in different activities. All persons, prior to and during employment, shall be trained in practices which

ensure personnel hygiene. A high level of personal hygiene shall be observed by all those

engaged in the manufacturing processes. Instructions to this effect shall be displayed in

change-rooms and other strategic locations.

No person showing, at any time, apparent illness or open lesions which may adversely affect the quality of products, shall be allowed to handle starting materials, packaging materials, in-process materials, and drug products until his condition is no longer judged to be a risk.

All employees shall be instructed to report about their illness or abnormal health condition to their immediate supervisor so that appropriate action can be taken.

Direct contact shall be avoided between the unprotected hands of personnel and raw materials, intermediate or finished, unpacked products

Environmental Monitoring –

All environmental parameters shall be verified and established at the

time of installation and thereafter monitored at periodic intervals.

The recommended frequencies of periodic monitoring shall be as follows:

( a ) Particulate monitoring in air – 6 Monthly

(b) HEPA filter integrity testing (smoke testing) – Yearly

(c) Air change rates – 6 monthly

(d) Air pressure differentials – Daily

(e) Temperature and humidity – Daily

(f) Microbiological monitoring by settle plates and/or swabs in aseptic

Class 100 Area - parentrals

Class 1000 Area- manufactring,production

Class 10000 Area-filling,sealing.

Class 100000 Area-packaging,labeling.

STERILE AREAS

Terminally Sterilized Products – Preparation of primary packaging material such as glass bottles, ampoules

andrubber stoppers shall be done in at least Grade D environment. Where there isunusual risk to the product from microbial contamination, the above operationshall be done in Grade C environment. All the processes used for componentpreparation shall be validated. Filling of products requiring terminal sterilization shall be done under GradeA environment with a Grade C background. Preparation of solutions, which are to be sterilized by filtration, shall be donein Grade C environment, and if not to be filtered, the preparation of materialsand products shall be in a Grade A environment with Grade B in background. Filtration ( Membrane )—( i ) Solutions for Large Volume Parenterals shall be filtered through a nonfiberreleasing, sterilizing grade cartridge/membrane filter of nominal poresize of 0.22 μ for aseptic filling whereas 0.45 μ porosity shall be used forterminally sterilized products

ii ) A second filtration using another 0.22 μ sterilizing grade

cartridge/membrane filter shall be performed immediately prior tofilling. Process specifications shall indicate the maximum time duringwhich a filtration system may be used with a view to precludingmicrobial build-up to levels that may affect the microbiological qualityof the Large Volume Parenterals.( iii ) The integrity of the sterilized filter shall be verified and

confirmedimmediately after use by an appropriate method such as Bubble

Point,Diffusive Flow or Pressure Hold Test.