Revised Schedule M and its impact on SSIs

Revised Schedule M and its impact on SSIs

Abstraction: –

Schedule M of Drug and Cosmetics Act trades with assorted demands for the fabrication of drugs and pharmaceuticals, which includes GMPs. GMPs stands for good fabrication pattern and they are indispensable for bring forthing quality merchandises. The current Schedule M is based on 1982 WHO GMP guidelines. Harmonizing to the revised Schedule M guideline all pharmaceutical units are required to guarantee that their air and H2O managing systems are of high criterions, control systems are in proper topographic point and certification is maintained. The clip bound to implement these guidelines has now been extended to July, 2005. Each industry requires about 1-2crores of capital investing. In India there are three thousand SSI ‘s ( Small Scale Industries ) size and it means six 1000 crore dead capital investing. This nightlong application of Schedule M is the major job for the SSI ‘s. There was an hegira of companies to strike free zones. The companies that were non in excise free zone started acquiring comfy with outsourcing fabricating to companies that were in these sectors. Therefore, without holding a mill they were basking the benefits of the excise free parts. On the other manus their new demands will let Indian pharmaceutical companies to spread out from non-regulated to regulated markets. This alteration will besides convey about new outsourcing chances both in generic and branded merchandises for the regulated markets. While most of the big and average pharmaceutical companies are reconstituting and upgrading their installations non merely in conformity with Schedule M but besides to international criterions, little units do non hold the resources to implement the Schedule M demands. In this reappraisal alteration of Schedule M and its impact on Small Scale Industry are discussed.

Issue of fading of agenda M

The Government has amended the Good Fabrication Practices ( GMP ) outlined in Schedule M to the Drugs and Cosmetics Rules to guarantee that fabricating units comply with the WHO and international criterions of production. Under the amended regulations, it has been decided that the accessory country demands for works and equipment for industry of bulk of preparations have been deleted. Certain alterations in the air managing system have besides been made apart from certain other minor alterations to streamline the demands. The State licensing governments have been given discretional powers to modify the demands in regard of certain classs of drugs if they are satisfied that it is necessary to loosen up or change the conditions in the peculiar instance which may be recorded in authorship. The commissariats of the revised Schedule will now be applicable to all the makers from July 1, 2005. Health ministry non merely rescinded the suspension of the three units but besides allowed these units three old ages ‘ clip to move in conformity with their GMP norms. The Health Ministry had suspended the fabrication licences of CRI Kasauli, PII Coonoor and the BCG Vaccine Laboratory Chennai on January 15, 2008 for non-compliance of GMP norms. After the Health Ministry ‘s determination to revoke the suspension of all the three PSU vaccinum units, the SSI drug company associations have been demanding to the authorities to loosen up the norms for them. Their demands stem from the statement that when the authorities itself, with its huge resources, could non follow with the GMP norms for its establishments for the last several old ages, how can the hapless SSI units can follow the norms, that excessively without any support from the authorities.

Since 2005, the authorities introduced the inflexible Schedule M norms, the SSIs, have been seeking for the dilution of the norms and for leting more clip to follow with the norms along with some fiscal aid from the authorities to upgrade their units to run into the strict Schedule M norms. After seeing the authoritiess ‘delay on the issue for several old ages, 100s of SSI units across the state closed their units as they could non follow with the Schedule M norms. As it involved a immense sum and it was beyond the capacity of the SSI units.SO most of the SSIs have been demanding to loosen up the regulations like infinite demands, air managing units and drawn-out certification in the revised agenda M. The SSIs are peculiarly upset over the compulsory infinite demand, air managing units and certification of all the processs, assorted stuffs used in the production. They found that where WHO GMP is soundless on infinite judicial admissions, The more stiff Schedule M has specified infinites for each subdivision viz. injectables, tablets, sirups and capsules, etc. irrespective of the fact whether it is SSI or big units. All this made the Schedule M an unbearable for most of the little graduated table industries which lead to the closing of assorted SSIs.

Amendment to Schedule M, Drug and Cosmetics Act

The amendment of the Schedule M of India ‘s Drug & A ; Cosmetics Act that came into consequence in conformity with the WHO footings was more relaxed and far less rigorous than the 1s insisted by US or European drug regulators. Interestingly, many of the Indian pharm companies who export to regulated markets follow US FDA or MHRA of UK criterions.

However, even after five old ages of execution of cGMP ordinances in India, the little graduated table industries ( SSIs ) or little and average endeavors ( SMEs ) are yet to come to footings with the construct. Indian drug company makers ‘ intense politicization finally succeeded in coercing the Indian authorities to put up a parliamentary commission to see if the Schedule M ordinances were damaging to the little scale drug units. The commission headed by the former president of the Upper House Dr Najma Heptulla completed the probe after over two old ages. And the concluding study was tabled, though the Parliament did non take up the study for treatment due to miss of time.A Harmonizing to beginnings, the Committee has recommended that the Indian authorities should “ proactively make out to the SSIs to back up them ” as they graduate to go Schedule M compliant. Taking a serious position of the cases of shuting down of little scale units in certain provinces, the Committee sympathized with the concerns raised by the little graduated table makers in India over the possibility that the proposed amendments were likely to prefer the large makers and the MNCs and reject the smaller units the level-playing field even in the domestic market. ”A India ‘s Health Ministry, nevertheless, took strong expostulation to these positions. It pointed out that a big figure of SSIs have already complied the revised cGMP ordinances and the remainder are in the procedure. Besides, on the anxiousnesss that Schedule M conformity would necessitate costs intolerable to little industries the Ministry replied that 80 per cent norms do non necessitate investing and certain commissariats have already been relaxed.A The Indian authorities is more concerned with spread of substandard drugs in the state. As of now there is no clear estimation of the sham and forged drug company merchandises made in the state. India is besides widely alleged to be the possible hub of substandard and forge medical specialties across the universe.

Principles OF SCHEDULE M:

The first WHO draft text on GMP was prepared in 1967 by a group of advisers, at the petition of the Twentieth World Health Assembly. The revised text was discussed by the WHO Expert Committee on Specifications for Pharmaceutical Preparations in 1968 and published as an extension to its 22nd study. The text was so produced in 1971 as Addendum to the 2nd edition of The International Pharmacopoeia.In 1969, when the World Health Assembly recommended the first version of the WHO Certification Scheme on the Quality of Pharmaceutical Products Moving in The International Commerce in declaration WHA22.50, it was accepted and at the same clip the GMP text became an built-in portion of the Scheme. Revised versions of both the Certification Scheme and the GMP text were adopted in 1975 by declaration WHA28.65. Since so, the Certification Scheme has been extended to include the enfranchisement of: Veterinary merchandises administered to nutrient bring forthing animate beings – get downing with stuffs for usage in dose signifiers. The merchandises are subjected to command by statute law in both the exportation Member State and the importing Member State based on information of safety and efficaciousness. New types of guidelines have appeared in recent old ages. Another of import development in the industry at Large is the visual aspect of the guidelines of the International Organization for Standardization ( ISO ) , specifically the ISO 9000 to 9004 criterions for quality systems.

What agenda M says really

Agenda M1: Deals with the demands of mill premises for fabrication of Homeopathic readyings.

Agenda M2: Deals with the demands of premises, works and equipment for industry of cosmetics.

Agenda M3: Deals with the demands of premises, works and equipment for industry of Medical devices. GMP ordinances are used by makers to bring forth and prove merchandises that people use. GMP besides implies to the veterinary merchandises.

Most states have their ain GMPs for drug and medical device makers. GMPs are a

directive that describes the methods, equipment, installations, and controls required for bring forthing:

Human pharmaceutical merchandises and veterinary merchandises.

Biologically derived merchandises.

Medical devices.

Processed nutrients.

Part I


Harmonizing to the agenda M guidelines

Construction of edifice ;

The mill edifice ( s ) for industry of drugs shall be so located and shall hold such steps as to avoid hazard of taint. Including unfastened sewerage, drain, public toilet or any mill which produces disagreeable or objectionable, olfactory property, fumes, inordinate carbon black, dust, fume, chemical or biological emanations. Building ( s ) should be air conditioned where prescribed for the operations and dose signifiers. The designed / constructed / maintained to forestall entry of insects, plagues, birds, varmint and gnawers. The edifice ( s ) used for the mill shall be designed, constructed, adapted and maintained to accommodate the fabrication operations so as to allow 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 merely be used for all the operations except rinsing and cleaning operations where drinkable H2O may be used. Water shall be stored in armored combat vehicles, which do non adversely affect quality of H2O and guarantee freedom from microbiological growing. The armored combat vehicle shall be cleaned sporadically and records maintained by the licensee in this behalf.

Disposal of H2O ;

Disposal of sewerage and wastewaters ( solid, liquid and gas ) from the mill shall be in conformance with the demands of Environment Pollution Control Board ( EPCB ) . All bio-medical waste shall be destroyed as per the commissariats of the Rio Medical Waste ( Management and Handling ) Rules, 1996.

Production country ;

The production country shall be designed to let the production sooner in uni-flow and with logical sequence of operations. In order to avoid the hazard of cross-contamination, separate dedicated and self-contained installations shall be made available for the production of sensitive pharmaceutical merchandises like penicillin or biological readyings with unrecorded micro-organisms.

Quality control ;

Quality-Control Laboratories shall be independent of the production countries. Separate countries shall be provided each for physicochemical, biological, microbiological or radio-isotope analysis. Quality Control Laboratories shall be designed suitably for the operations to he carried out in them.

Accessory country

Rest and refreshment suites shall he divide from other countries. These countries shall non take straight to the fabrication and storage countries. Facilities for altering hive awaying apparels and for rinsing and lavatory intents shall be easy accessible and equal for the figure of users. Toilets separate for males and females, shall non be straight connected with production or storage countries.

Warehousing country

Adequate countries shall be designed to let sufficient and orderly repositing of assorted classs of stuffs and merchandises like get downing and boxing stuffs intermediates majority and finished merchandises, merchandises in quarantine released, rejected, returned or recalled machine and equipment trim parts and alteration points.

Health vesture and sanitation of workers

The forces managing Beta-lactam antibiotics shall be tested for Penicillin sensitiveness before employment and those managing sex endocrines, cytotoxic substances and other potent drugs shall he sporadically examined for inauspicious effects Smoking. Eating, imbibing, masticating or maintaining workss, nutrient, drink and personal medical specialties shall non be permitted in production. All employees shall be instructed to describe about their unwellness or unnatural wellness status to their immediate supervisor so that appropriate action can be taken.

Manufaturing operations and controls

The contents of all vass and containers used in industry and storage during the assorted fabrication phases shall be conspicuously labeled with the name of the merchandise, batch no, batch size and phase of industry. Each label should be initialed and dated by the authorised

proficient staff.

Natural stuffs

There shall be equal separate countries for stuffs “ under trial ” , “ approved “ , and “ rejected ” with agreements and equipment to let dry, clean and orderly arrangement of stored stuffs and merchandises, wheresoever necessary. Under controlled temperature and humidness. All incoming stuffs shall be quarantined instantly after reception or processing. All stuffs shall be conditions and in an orderly manner to allow hatch segregation and stock rotary motion by a ‘first in/first termination ‘ – ‘first-out ‘ rule.

Documentation and records

Documentation is an indispensable portion of the Quality confidence system and, as such, shall be related to all facets of Good Manufacturing Practices ( GMP ) . Its purpose is to specify the specifications for all stuffs, method of industry and control, to guarantee that all forces concerned with industry know the information necessary to make up one’s mind whether or non to let go of a batch or drug for sale and-to provide an audit trail that shall allow probe of the history of any suspected faulty batch. Records and associated Standard Operating Procedures ( SOP ) shall be retained for at least one twelvemonth after the termination day of the month of the finished merchandise. Data may be recorded by electronic informations treating systems or other dependable agencies, but Master Formulae and detailed operating processs associating to the system in usage shall besides be available in a difficult

transcript to ease checking of the truth of the records.

Labels and other printed stuffs

All containers and equipment shall hear appropriate labels. Different colour coded labels shall be used to bespeak the position of a merchandise ( for illustration under trial, approved. passed, rejected ) . Prior to let go of, all labels for containers, cartons and boxes and all handbills, inserts and cusps shall be examined by the Quality Control Department of the licensee.

Quality confidence

It is the entirety of the agreements made with the object of guaranting that merchandises arc of the quality required for their intended usage. The finished merchandise is right processed and checked in conformity with established processs. Every fabrication constitution shall set up its ain quality control research lab manned by qualified and experient staff. The country of the quality control research lab may be divided into Chemical, Instrumentation Microbiological and Biological testing.


For the assorted natural stuffs and packaging stuffs, containers, closings and finished merchandises assorted specifications should be written on the labels and should be maintained in the records.

( a ) The designated name of the merchandise and the codification mention

( B ) The expression or a mention to the expression and the pharmacopoeial mention

( degree Celsius ) Directions for trying and proving or a mention to processs

( vitamin D ) A description of the dose signifier and bundle inside informations

( vitamin E ) The qualitative and quantitative demands. With the credence bounds for release

( degree Fahrenheit ) The storage conditions and safeguards where applicable, and

( g ) The shelf-life.

Master expression records

There shall be Master Formula records associating to all fabrication processs for each merchandise and batch size to be manufactured. These shall be prepared and endorsed by the competent proficient staff. i.e. Head of production and quality control. It should include:

( a ) The name of the merchandise together with merchandise mention codification associating to its specifications

( B ) The patent or proprietary name of the merchandise along with the generic name, a description of the dose signifier, strength, composing of the merchandise and batch size

( degree Celsius ) Name, measure, and mention figure of all the get downing stuffs to be used. Mention shall be made of any substance that may ‘disappear ‘ in the class of processing

( vitamin D ) A statement of the expected concluding output with the acceptable bounds, and of relevant intermediate outputs, where applicable

( vitamin E ) A statement of the processing location and the chief equipment to he used

( degree Fahrenheit ) The methods. or mention to the methods, to be used for fixing the critical equipment including cleansing, piecing, graduating, sterilising

( g ) Detailed stepwise processing instructions and the clip taken for each measure

( H ) The instructions for in-process controls with their bounds

( I ) The demands for storage conditions of the merchandises, including the container, labeling and particular storage conditions where applicable

( J ) Any particular safeguards to be observed

( K ) Packing inside informations and specimen labels.

Batch packaging records

A batch packaging record shall be kept for each batch or portion batch processed. It shall be based on the relevant parts of the packaging instructions and the method of readying of such records shall be designed to avoid written text mistakes.

Mention samples

Each batch of every active ingredient. in a measure sufficient to transport out all the trials except asepsis and pyrogens or Bacterial Endotoxin. Test shall be retained for a period of 3 months after the day of the month of termination of the last batch produced from that active ingredient.

Merchandise callbacks

A prompt and effectual merchandise callback system of faulty merchandises shall be devised for timely information of all concerned stockiest, jobbers, providers, up to the retail degree within the shortest period. The licensee may do usage of both print and electronic media in this respect. There shall be an established written process in the signifier of Standard Operating Procedure for effectual callback of merchandises distributed by the licensee. Remember operations shall be capable of being initiated quickly so as to efficaciously make at the degree of each distribution channel.

Sterile merchandises, being really critical and sensitive in nature, a really high grade of safeguards, bar and readyings are needed. Dampness, soil and darkness are to be avoided to guarantee sterile conditions in all countries. There shall be rigorous conformity in the prescribed criterions particularly in the affair of supply of H2O, air, active stuffs and in the care of hygienic environment. Air Managing Unit of measurements for unfertile merchandise fabrication countries shall be different from those for other countries. Critical countries, such as the sterile filling country, sterilized constituents droping country and alteration suites conforming to Grades B, C and D severally shall hold separate Air Handling Units The filling operations shall take topographic point under Grade A conditions which shall be demonstrated under working of fake conditions which shall be achieved by supplying Laminar Air flow work Stationss with suited HEPA filters or isolator engineering. There shall be a written environmental monitoring plan and microbiological consequences shall be recorded. Recommended bounds for microbiological monitoring of clean countries “ in operation ” are given.

Air Borne Particulate Classification For Manufacture of Sterile Product






( Microns )

























Types of Operationss To Be Carried Out in The Various Grades For Aseptic Preparations


Types of operations for sterile readyings


ISO Class


Aseptic readying and filling




Background room conditions for activities necessitating Grade A




Preparation of solution to be filtered




Managing of constituents after rinsing



Part II


( 1 ) EXTERNAL Preparation

The undermentioned equipment is recommended for the industry of `External readyings ‘ i.e. , Ointments. Emulsion, lotions, Solutions, Pastes, Creams, Dusting Powders and such indistinguishable merchandises used for external applications whichever is applicable viz. :

( 1 ) Mix and storage armored combat vehicles ( Stainless steel )

( 2 ) Jacketed Kettle ( steam, gas or electrically heated )

( 3 ) Mixer ( Electrically operated )

( 4 ) Planetary sociable

( 5 ) A colloid factory or a suited emulsifier.

( 6 ) A ternary roller factory or an unction factory.

( 7 ) Liquid make fulling equipment ( Electrically operated ) .

( 8 ) Jar on table filling equipment ( Electrically operated ) .


The undermentioned equipment is recommended for the industry of oral/internal usage readyings, i.e. , Syrups, Elixirs, Emulsions and Suspensions. Whichever is applicable, viz. :

( 1 ) Mix and storage armored combat vehicles ( Stainless steel ) .

( 2 ) Jacketed Kettle/Stainless steel armored combat vehicles ( steam, gas or electrically heated ) .

( 3 ) Portable scaremonger ( Electrically operated ) .

( 4 ) A colloid factory or a suited emulsifier ( Electrically operated ) .

( 5 ) Suitable filtration equipment ( Electrically operated ) .

( 6 ) Semi-automatic/automatic bottle filling machine.

( 7 ) Pilfer cogent evidence cap sealing machine.

( 8 ) Water distillment unit or deionizer.

( 9 ) Clarity proving review units.

( 3 ) Tablet

The following electrically operated equipment is recommended for the industry of tight tablets and subcutaneous tablets. In each of the above subdivisions, viz. :

( 1 ) Disintegrator and sifter

( 2 ) Power sociable

( 3 ) Mass mixer/Planetary mixer/Rapid sociable granulator

( 4 ) Granulator

( 5 ) Thermostatically controlled hot air oven with trays ( sooner mounted on a streetcar )

( 6 ) Weighing machines.

( 4 ) SURGICAL Dressing

Surgical dressings other than Absorbent Cotton Wool, viz. :

( 1 ) Rolling machine

( 2 ) Trimming machine

( 3 ) Cuting equipment

( 4 ) Protein folding and pressure machine for gauze

( 5 ) Blending armored combat vehicles for processing medicated dressing.

( 6 ) Hot air dry oven

( 7 ) Steam autoclave or dry heat autoclave or other suited equipment.

( 8 ) Work tablets/benches for different operations.


For the industry of Ophthalmic readyings separate enclosed countries with air lock agreement shall be provided. The undermentioned equipment is recommended for industry under sterile conditions of Eye-Ointments. Eye lotions and other readyings for external usage, viz. :

( 1 ) Thermostatically controlled hot air ovens ( sooner double ended )

( 2 ) Jacketed kettle/Stainless steel armored combat vehicles ( steam, gas or electrically heated )

( 3 ) Mix and storage armored combat vehicles of chromium steel steel/Planetary sociable

( 4 ) Colloid factory or unction factory.

( 5 ) Tube filling and crimping equipment ( semi-automatic or automatic filling machines ) .

( 6 ) Tube cleaning equipment ( air jet type )

( 7 ) Tube rinsing and drying equipment, if required

( 8 ) Automatic vial lavation machine

( 9 ) Vial drying oven.

( 10 ) Rubber spile rinsing machine.

( 11 ) Sintered glass funnel, Seitz or filter taper ( sooner cartridge and membrane filters )

( 12 ) Liquid make fulling equipment ( semi-automatic or automatic filling machines )

( 13 ) Autoclave ( sooner ventilator sterilizer )

( 14 ) Air-conditioning and dehumidification agreement.

The demands for installing and accessory country for assorted readyings are given in guidelines. Areas for preparations meant for external usage and internal usage shall be individually showed to avoid mix up. Separate country and equipment for blending. Granulation, drying tablet compaction, surfacing and packing shall be provided for Penicillin group of drugs. The industry of effervescent and soluble or dispersible tablets shall be carried out in air-conditioned and dehumidified countries. Workers shall be provided with masks, baseball mitts, lab coats and feeding and imbibing shall be avoided in the production country.




Unit of measurements


























Most of the big and average drug company companies are reconstituting and upgrading their installations non merely to follow with Schedule M but besides to international criterions. Small units do non hold the resources to implement the Schedule M stipulations.A On the other manus authorities is seeking for capacity and quality up step to run into the International criterions.

The fact that Indian pharm companies are bring forthing a immense sum of the medical specialties that excessively at really cheaper rates. The SSIs should be given some more clip to follow with the Schedule M guidelines. The above demands of machinery, equipment ‘s, infinite, makings are made capable to the alteration at the discretion of the Licensing Authority. If there is an sentiment sing the nature and extent of the fabrication operations it is necessary to loosen up or change them in the fortunes of a peculiar instance.