SCHEDULE M- GOOD MANUFACTURING PRACTICES

PART I- GMP FOR PREMISES AND MATERIALS:

GENERAL REQUIREMENTS
– Location and surroundings: Such as to avoid contamination
– Buildings and premises:
• Conform to Factories Act 1948
• Designed, constructed, adapted and maintained to suit manufacturing
operations so as to permit production of drugs under hygienic
conditions.
• Compatible with other drug manufacturing operations
• Orderly and logical placement of eqpt, materials, movement
Buildings and premises:
• Prevent entry of pests, birds, vermins, rodents
• Surface smooth, free from cracks, permit easy cleaning, painting ,
disinfection, shall not shed particles
• Operation and production premises air-conditioned
• Well-lighted, air Handling Systems (AHU)
• Monitored for Compliance with specification
• Drainage system of adequate size, designed to prevent back-flow,
prevent insects and rodents
• Open channels avoided in manufacturing or shallow to facilitate
cleaning and disinfection
Water system:
• Validated water system to produce Purified water I.P
• Water stored in tanks, free from microbiological growth
• Tanks cleaned periodically, record maintained
• Potable water –washing and cleaning purposes
Disposal of waste:
• As per Environmental Pollution Control Board and Biomedical Waste
Rules 1996
• Storage of hazardous, toxic and flammable material in suitable
designed and segregated enclosed areas
Warehousing area
– Proper racks, bins, platforms for storage
– Good storage conditions with temperature, humidity as required and
recorded.
– Appropriate housekeeping and pest control procedures, records maintained
– Receiving and dispatch bays protect materials
– Quarantine areas earmarked, demarcated, access restricted to authorized
persons
 – Separate sampling area for active and excipients
– Segregation for storage of rejected, recalled or returned materials or products,
access restricted
– Hazardous, poisonous, explosives, narcotics, psychotropics- safe and secure
areas
– Adequate fire protection
– Printed packaging materials- safe, separate areas
– Separate dispensing areas under differential pressure, filtered air, dust control-
special category
– Sampling , dispensing of sterile materials- Grade A
– Regular checks- spillage, breakage, leakage
– Rodent treatment at least once in a year and record maintained
Production area
– Uni-flow, logical sequence of operations
– Avoid cross-contamination, minimize risk of omission, wrong application of
mfg and control measures
– Dedicated and self-contained facilities for penicillin, sex hormones and
cytotoxic substances
– Pipe-work, electrical fittings, service lines designed, fixed, constructed to avoid
creation of recesses
– Service lines identified by colours, nature and direction of flow indicated
Ancillary areas
– Rest, refreshment rooms separate from other areas, shall not lead directly to
manufacturing and storage areas
– Facilities for changing, storing clothes, washing, toilet facilities easily
accessible, adequate
– Service lines identified by colours, nature and direction of flow indicated
– Written instructions for cleaning and disinfection
– Maintenance workshops separate, away from production areas
– Spares and tools in dedicated rooms or lockers in production
– Tools, spare parts disinfected before use in sterile areas
– Animal house isolated from other areas
– PART I- GMP FOR PREMISES AND MATERIALS
Quality Control areas
– Laboratory independent of production areas
– Separate sections for physicochemical, biological, microbiological, radio-
isotope analysis
– Air-locks, laminar air flow station in microbiology section
– Avoid mix-ups and cross-contamination
– Separate instrument room
 – Storage space for test, retained samples, reference standards, reagents and
records
– Suitability of construction materials, ventilation
– Separate AHUs and other requirements for biological, microbiological and
radioisotopes testing areas.
Personnel
– Competent technical staff
– Head of Quality Control laboratory independent of manufacturing unit
– QC, QA personnel qualified and experienced
– Training appropriate to duties and responsibilities
– Regular in-service training
Health, Clothing, sanitation of workers
– High level of personnel hygiene
– Medical examination, free from tuberculosis, skin, communicable contagious
diseases atleast once a year
– Penicillin sensitivity before employment
– Adverse effects examined – sex hormones, cytotoxic substances, potent drugs
– Personnel rotated in different sections as a health safeguard
– Apparent illness, open lesions: no handling
– Direct contact avoided
– Clean body coverings, separate change rooms
– Smoking, eating, drinking, chewing prohibited
Manufacturing operations and controls
– Approved technical staff
– Trained personnel under direct supervision of approved technical staff- critical
steps
– Contents of all vessels and containers labeled with name of product, batch no.
batch size and stage of manufacture.
– Products not prepared under aseptic conditions- free from pathogens,
Salmonella, E. coli, Pyocyanea
Precautions against mix-up and cross-contamination
– Required levels of temperature, humidity, cleanliness
– Records and SOP
– Processing of sensitive drugs in segregated areas
– Precautions observed to avoid mix-up
– Recalled or rejected material shall be kept in segregated, enclosed areas
Sanitation in the manufacturing premises
– Cleaned, maintained in an orderly manner such that it is free from
accumulated waste, dust, debris and other similar material
– Validated cleaning procedure
– Routine sanitation program drawn, observed, recorded
 – Production areas well lit, where visual on-line controls are carried out
Raw materials
– Purchased from approved sources under valid purchase vouchers
– Separate areas for under test, approved, rejected materials
– Incoming materials quarantined
– Stored in orderly fashion, Stock rotation by First in/ first expiry, first out
principle
– Authorized staff shall examine.
– Released by QC, within their shelf-life shall be used
– All containers on raised platforms/ racks and not on floor
Equipment
– Located, designed, constructed, adapted, maintained
– Layout and design aim to minimise the risk of errors
– Logbook wherever necessary
– Measuring equipment calibrated and checked periodically in accordance with
SOP, records maintained
Documentation and records
– Specifications, decision on whether or not to release a batch, audit trail
– Approved, signed and dated
– Records, SOPs retained for at least one year after the expiry date of the
finished product
– Master formula, operation procedures in hard copy, electronic data processing
– For electronic data processing user levels, passwords, entry of critical data
independently checked
Labels and other printed materials
– All prescribed details, bright colors, legible
– Color codes for under test, approved, rejected
– QC shall examine prior to release
– Records maintained
– Unused coded, damaged labels destroyed, recorded
QA
– GMP, GLP, GCP
– Correct starting and packaging materials
– Adequate controls on in-process, finished products
Self-inspection and quality audit
– Compliance with GMP
– Documented procedure, evaluation, conclusions, recommended corrective
actions with effective follow-up program
Self-inspection and quality audit
– Written instructions for self-inspection
 – Documented procedure, evaluation, conclusions, recommended corrective
actions with effective follow-up program
– Include personnel, facilities, maintenance, storage, QC documentation,
sanitation and hygiene, validation and revalidation, calibrations, recall
procedures, complaints, labels control, results of previous inspections,
corrective steps taken
QC
– Qualified, experienced staff
– Sampling, specifications, testing, documentation, release procedures
– Reference/ retained samples twice the quantity of drug required to conduct all
tests except sterility, BET, pyrogen, in final pack for a period of 3 months after
date of expiry
– All materials approved, maintained by QC
– Periodic revisions of specifications
Specifications
Master formula record
– Name of product, reference specification no., proprietary, generic name, form,
strength, composition, reference no. of starting material, Final yield with
acceptable limits, intermediate yields, processing location, principal
equipment, cleaning, assembling, calibrating, sterilizing critical equipments,
step-wise process, time for each step, in-process controls with limits, storage
conditions, labelling, special precautions, packing details, specimen labels
Packaging record
– Name of product, form, strength, composition, pack size, list of requirements,
reproduction of packing material with specimens, special precautions, in-
process controls with sampling and acceptance limits, reconciliation
Batch Packaging record
– For each batch or part batch processed
– Clear of previous batch documents, materials etc
Batch processing records
– Name of product, Batch No., date and time of commencement, initials of
operator, checker, control no. of starting material, operation, equipment used,
in-process controls records with initials and results, yield at stages with
explanation for significant deviations, Special problems with signed
authorization for any deviation from master formula, addition of recovered,
reprocessed material
SOPs and Records
– Site master file- specific and factual GMP, general information, personnel,
premises, equipment, sanitation, documentation, production, quality control,
loan license manufacture and license, distribution, complaints, product recall,
self-inspection, export of drugs.
Reprocessing and Recovery
– If a product batch has to be reprocessed, suitable reprocessing procedure
should be adopted and recorded. An investigation should be carried out into
the cause necessitating reprocessing and appropriate corrective measures
should be taken for prevention of recurrence. Recovery of product residue
may be carried out in subsequent batches of the product, if permitted in the
master formulae.
Distribution Records
– Records for distribution of drug should be maintained for distribution of
finished batch of a drug product in order to facilitate, promote and recall of
the batch if necessary.
Record of Complaints and Adverse Reactions
– Reports of serious reaction resulting from the use of drug along with comment
should be informed to the licensing authority concerned.