Schedule M of Drugs & Cosmetics Act deals with various requirements for the manufacture of Drugs and Pharmaceuticals, which include GMPs. GMP stands for good manufacturing practices and they are essential for producing quality products.
The objectives of GMP are to build quality through a well-defined quality management system. The current Schedule M is based on 1982 WHO GMP guidelines i.e., to say that they are almost two decades old. In the last two decades the concept of quality and the technologies used in the manufacture of drugs and pharmaceuticals have improved substantially. What was considered, as good in the year 1982 are no more considered as good as 1982 technologies and has become obsolete. A quality in 1980s is determined by end product testing, whereas today the objective is to build quality into the product adopting various GMPs. They are always called current Good Manufacturing Practices (cGMPs) to ensure continuous upgradation of technologies and techniques to make a drug product/drug substances of best quality.
The attempt by Government of India to revise the Schedule M is to upgrade standards to meet the 1992 GMP requirements thereby ensuring supply of better quality drugs. Even in the revised Schedule M, the requirements are updated to the level of 1992 GMPs.
The focus of current GMP is to ensure that there is no contamination or cross contamination during the manufacture of drugs either from environment or from products or from personnel.
It also aims to produce consistent quality of the product and assure the quality till the end of shelf-life by adopting validation of facilities, equipment, production processes, testing etc. and carrying out a meaningful stability studies of all the products.
To achieve this objective of producing a product free form contamination and of a consistent quality, the revised schedule M includes changes involving structural, equipment, testing, production, documentation, training etc.
It's a known fact for all the personnel and the environment involved in drug manufacturing are major source of microbial and extraneous matter contamination. That's the reason the revised Schedule M insists for a filtered air supply, which can protect the products from the environmental contamination. The requirement of air quality for each dosage category varies from revised Schedule M specifies these air quality requirements.
Majority of the pharmaceutical plants in India are engaged in multi products manufacturing and they need to ensure freedom from cross contamination.
The revised Schedule M advises proper pressure differentials in the areas of operation, which can be achieved through dedicated air handling units with adequate number of air changes. These pressure differentials will help to eliminate/reduce the chances of cross contamination between the products. In addition to these, revised schedule M demands proper cleaning validation of the equipment and the processing areas whenever there is change in products. It is also mandatory to specify status of each equipment material to avoid mix-ups which leads to cross contamination.
As the stability of a pharmaceutical product is important, it is not good enough that product is of a standard quality at the time of release but it has to be of the same quality conforming to the label claims till the expiry of the product during which period it can be used by any customer/patient.
It is a known fact that an addition of drug as per label claim do not guarantee the activity of the drug till the end of shelf-life unless the manufacture/pharmacists develops a formula and appropriate packing and prescribing proper storage conditions on the labels of the containers. The retention of the activity/potency of the drug till the expiry, can be proved by proper evaluation through a well-defined stability study programme applicable to Indian conditions. (India is classified as a Zone-IV i.e. hot and humid conditions)
Some of the drugs have to be taken by patients for a long time for their chronic ailments such as asthma, epilepsy etc. A quality variation from batch to batch though well within the defined limits of standards prescribed, may not give required relief for the patients. To ensure batch consistency, the pharmaceutical scientists have developed a technique known as validation. Validation assures that each of the step in the manufacturing process when performed as per defined procedures, consistently achieve the objective of the procedures. The validation encompasses all the activity connected to pharma manufacturing, starting from facility qualification to equipment qualification, production processes, cleaning testing etc. For this reason Schedule M emphasizes as a mandatory requirement i.e. validation of facilities, equipment, production processes etc.
The Government of India has recognised pharma industry as a technology driven industry and is focusing on the growth of the industry both for domestic as well as for the expanding global markets. To create a confidence about the quality of drug manufactured in this country, it is essential that the regulators of the country define standard, which are on par with global standards through proper legislation. This is another important reason for revising Schedule M which helps production of quality products as well as improves the opportunities in the global market.
To conclude I would like to say that the current 1982 Schedule M requires a revision as (i) the Indian population deserves better quality of drugs (ii) Indian pharmaceutical industry must compete globally by complying with global standards.
As a matter of fact, the Indian pharmaceutical industry still has to go a long way in achieving the global standards by establishing bio-availability and bio-equivalence of the products manufactured by them with that of the inventors' or introductors' standards.
Drugs defined as New Drugs under the Drugs and Cosmetics Act are subjected to bioavailability/bioequivalence evaluations through clinical trials which is reviewed by the Drugs Controller General (India). A drug has a New Drug status for four years from the date of first permission. After four years, the State Licensing Authority grants license but they do not insists for BA/BE and clinical trail studies which are essential to establish the efficacy of the drugs. These can only be achieved by bringing Drug Master File (DMF) concepts in tune with the global requirements.
- (The author is Dy. Drugs Controller (India) CDSCO West Zone Mumbai)