10:03 PM
Leo Group India
According to the schedule M guidelines
Construction of building;
The factory building(s) for manufacture of drugs shall be so situated
and shall have such measures as to avoid risk of contamination.
Including open sewage, drain, public lavatory or any factory which
produces disagreeable or obnoxious, odor, fumes, excessive soot, dust,
smoke, chemical or biological emanations. Building(s) should be air
conditioned where prescribed for the operations and dosage forms. The
designed / constructed / maintained to prevent entry of insects, pests,
birds, vermin and rodents. The building(s) used for the factory shall be
designed, constructed, adapted and maintained to suit the manufacturing
operations so as to permit production of drugs under hygienic
conditions. They shall conform to the conditions laid down in the
Factories Act, 1948 (63 of 1948).
Water supply
Water (as per the specifications of Pharmacopoeia) shall only be used
for all the operations except washing and cleaning operations where
potable water may be used. Water shall be stored in tanks, which do not
adversely affect quality of water and ensure freedom from
microbiological growth. The tank shall be cleaned periodically and
records maintained by the licensee in this behalf.
Disposal of water ;
Disposal of sewage and effluents (solid, liquid and gas) from the
manufactory shall be in conformity with the requirements of Environment
Pollution Control Board (EPCB). All bio-medical waste shall be destroyed
as per the provisions of the Rio Medical Waste (Management and
Handling) Rules, 1996.
Production area;
The production area shall be designed to allow the production
preferably in uni-flow and with logical sequence of operations. In order
to avoid the risk of cross-contamination, separate dedicated and
self-contained facilities shall be made available for the production of
sensitive pharmaceutical products like penicillin or biological
preparations with live microorganisms.
Quality control;
Quality-Control Laboratories shall be independent of the production
areas. Separate areas shall be provided each for physicochemical,
biological, microbiological or radio-isotope analysis. Quality Control
Laboratories shall be designed appropriately for the operations to he
carried out in them.
Ancillary area
Rest and refreshment rooms shall he separate from other areas. These
areas shall not lead directly to the manufacturing and storage areas.
Facilities for changing storing clothes and for washing and toilet
purposes shall be easily accessible and adequate for the number of
users. Toilets separate for males and females, shall not be directly
connected with production or storage areas.
Warehousing area
Adequate areas shall be designed to allow sufficient and orderly
warehousing of various categories of materials and products like
starting and packaging materials intermediates bulk and finished
products, products in quarantine released, rejected, returned or
recalled machine and equipment spare parts and change items.
Health clothing and sanitation of workers
The personnel handling Beta-lactam antibiotics shall be tested for
Penicillin sensitivity before employment and those handling sex
hormones, cytotoxic substances and other potent drugs shall he
periodically examined for adverse effects Smoking. Eating, drinking,
chewing or keeping plants, food, drink and personal medicines shall not
be permitted in production. 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.
Manufaturing operations and controls
The contents of all vessels and containers used in manufacture and
storage during the various manufacturing stages shall be conspicuously
labeled with the name of the product, batch no, batch size and stage of
manufacture. Each label should be initialed and dated by the authorized
technical staff.
Raw materials
There shall be adequate separate areas for materials "under test",
"approved ", and "rejected" with arrangements and equipment to allow
dry, clean and orderly placement of stored materials and products,
wherever necessary. Under controlled temperature and humidity. All
incoming materials shall be quarantined immediately after receipt or
processing. All materials shall be conditions and in an orderly fashion
to permit hatch segregation and stock rotation by a 'first in/first
expiry' - 'first-out' principle.
Documentation and records
Documentation is an essential part of the Quality assurance system
and, as such, shall be related to all aspects of Good Manufacturing
Practices (GMP). Its aim is to define the specifications for all
materials, method of manufacture and control, to ensure that all
personnel concerned with manufacture know the information necessary to
decide whether or not to release a batch or drug for sale and-to provide
an audit trail that shall permit investigation of the history of any
suspected defective batch. Records and associated Standard Operating
Procedures (SOP) shall be retained for at least one year after the
expiry date of the finished product. Data may be recorded by electronic
data processing systems or other reliable means, but Master Formulae and
detailed operating procedures relating to the system in use shall also
be available in a hard
copy to facilitate checking of the accuracy of the records.
Labels and other printed materials
All containers and equipment shall hear appropriate labels. Different
color coded labels shall be used to indicate the status of a product
(for example under test, approved. passed, rejected). Prior to release,
all labels for containers, cartons and boxes and all circulars, inserts
and leaflets shall be examined by the Quality Control Department of the
licensee.
Quality assurance
It is the totality of the arrangements made with the object of
ensuring that products arc of the quality required for their intended
use. The finished product is correctly processed and checked in
accordance with established procedures. Every manufacturing
establishment shall establish its own quality control laboratory manned
by qualified and experienced staff. The area of the quality control
laboratory may be divided into Chemical, Instrumentation Microbiological
and Biological testing.
Specifications
For the various raw materials and packaging materials, containers,
closures and finished products various specifications should be written
on the labels and should be maintained in the records.
(a) The designated name of the product and the code reference
(b) The formula or a reference to the formula and the pharmacopoeial reference
(c) Directions for sampling and testing or a reference to procedures
(d) A description of the dosage form and package details
(e) The qualitative and quantitative requirements. With the acceptance limits for release
(f) The storage conditions and precautions where applicable, and
(g) The shelf-life.
Master formula records
There shall be Master Formula records relating to all manufacturing
procedures for each product and batch size to be manufactured. These
shall be prepared and endorsed by the competent technical staff. i.e.
Head of production and quality control. It should include:
(a) The name of the product together with product reference code relating to its specifications
(b) The patent or proprietary name of the product along with the
generic name, a description of the dosage form, strength, composition of
the product and batch size
(c) Name, quantity, and reference number of all the starting
materials to be used. Mention shall be made of any substance that may
'disappear' in the course of processing
(d) A statement of the expected final yield with the acceptable limits, and of relevant intermediate yields, where applicable
(e) A statement of the processing location and the principal equipment to he used
(f) The methods. or reference to the methods, to be used for
preparing the critical equipment including cleaning, assembling,
calibrating, sterilizing
(g) Detailed stepwise processing instructions and the time taken for each step
(h) The instructions for in-process controls with their limits
(i) The requirements for storage conditions of the products,
including the container, labeling and special storage conditions where
applicable
(j) Any special precautions to be observed
(k) Packing details and specimen labels.
Batch packaging records
A batch packaging record shall be kept for each batch or part batch
processed. It shall be based on the relevant parts of the packaging
instructions and the method of preparation of such records shall be
designed to avoid transcription errors.
Reference samples
Each lot of every active ingredient. in a quantity sufficient to
carry out all the tests except sterility and pyrogens or Bacterial
Endotoxin. Test shall be retained for a period of 3 months after the
date of expiry of the last batch produced from that active ingredient.
Product recalls
A prompt and effective product recall system of defective products
shall be devised for timely information of all concerned stockiest,
wholesalers, suppliers, up to the retail level within the shortest
period. The licensee may make use of both print and electronic media in
this regard. There shall be an established written procedure in the form
of Standard Operating Procedure for effective recall of products
distributed by the licensee. Recall operations shall be capable of being
initiated promptly so as to effectively reach at the level of each
distribution channel.
Sterile products, being very critical and sensitive in nature, a very
high degree of precautions, prevention and preparations are needed.
Dampness, dirt and darkness are to be avoided to ensure aseptic
conditions in all areas. There shall be strict compliance in the
prescribed standards especially in the matter of supply of water, air,
active materials and in the maintenance of hygienic environment. Air
Handling Units for sterile product manufacturing areas shall be
different from those for other areas. Critical areas, such as the
aseptic filling area, sterilized components unloading area and change
rooms conforming to Grades B, C and D respectively shall have separate
Air Handling Units The filling operations shall take place under Grade A
conditions which shall be demonstrated under working of simulated
conditions which shall be achieved by providing Laminar Air flow work
stations with suitable HEPA filters or isolator technology. There shall
be a written environmental monitoring program and microbiological
results shall be recorded. Recommended limits for microbiological
monitoring of clean areas "in operation" are given.
