On Saturday, India’s health ministry notified the Drugs (Amendment) Rules, 2023.

With this, the government has revised Schedule M of the Drugs and Cosmetics Rules, 1945.

Schedule M prescribes quality standards for manufacturing drugs under its “good manufacturing practices”—or GMP—and pharma companies must adhere to them. GMPs were first incorporated in 1988 and last amended in June 2005.

So what’s changed? Among other things, pharma companies are now required to inform the licensing authority about drug recalls, product defects, deterioration or faulty production. Until now, there was no such provision.

And why is this crucial? The reputation of the country’s drug industry—India was once called the pharmacy of the world—has taken a hit after a series of overseas deaths, especially those of children, were linked to Indian-made drugs. Since 2022, the government has been trying to step up its checks of suppliers and factories making these drugs to restore the industry’s image.

Let’s take a look at the changes.

Just what the doctor ordered: The new rules largely focus on quality control measures, digital records that cannot be tampered with, and a formal recall system.

First, the amendments replace the term “good manufacturing practices” with “good manufacturing practices and requirements of premises, plant and equipment for pharmaceutical products”. This is crucial because India’s drug regulator—the Central Drugs Standard Control Organisation—has found several cases where units that made drugs considered substandard or contaminated had ill-kept manufacturing facilities, contaminated equipment and lacked quality control, among other issues.

Second, the notification, dated 28 December, emphasizes responsibility on part of the manufacturer and management to ensure quality control. “The manufacturer must assume responsibility for the quality of the pharmaceutical products to ensure that they are fit for their intended use, comply with the requirements of the licence and do not place patients at risk due to inadequate safety, quality or efficacy.”

And to achieve this, the management must put in place “a comprehensively designed and correctly implemented pharmaceutical quality system incorporating Good Manufacturing Practices (GMP) and Quality Risk Management (QRM)”.

It also specifies criteria for key personnel’s hiring and for the management to ensure that only trained staff are handling the process and equipment.

Third, companies can only market a product after testing ingredients and getting “satisfactory results”. Additionally, they must set aside enough samples of manufactured drugs during the intermediate and final stages to allow repeated testing and verification of a batch in case issues are found later. It has also added requirements for testing these products across stages to identify where quality issues are emerging.

Apart from testing to check the quality of raw materials, manufacturers have been asked to only procure them from government-approved suppliers.

Fourth, the amendments require that hygiene should be maintained during the manufacturing process, including the water being used. “The scope of sanitation and hygiene covers personnel, premises, equipment and apparatus, production materials and containers, products for cleaning and disinfection and anything that could become a source of contamination to the product.”

This too holds significance because lack of appropriate hygiene at manufacturing and bottling plants was one of the major violations found during inspections of several cough syrup makers last year.

Lastly, the revised Schedule M identifies categories of drugs such as those containing hazardous substances like sex hormones, steroids (anabolic and androgenic), cytotoxic substances, biological products and those containing live viruses or bacteria for vaccines—and requires that they be produced in isolated facilities.

To smoothly transition to the revised Schedule M, large manufacturers (those with an over Rs 250 crore turnover) have been given six months while MSMEs (with a less than Rs 250 crore turnover) have been given 12 months.

However, what remains unclear is what kind of penalty, apart from licence cancellation, can be imposed on those who violate these rules and whether putting these rules to action will affect the drugs’ competitive pricing—which makes them attractive for exports.

Significance: Apart from restoring the country’s reputation, the revised practices could help the industry meet global standards.

“This would bring our GMP recommendations at par with global standards, especially to those of World Health Organization (WHO), and ensure production of globally acceptable quality of drug,” a health ministry official told The Hindu.

“The revised guidelines will address most deficiencies related to documentation, failure investigation and technically qualified personnel with the right person doing the right job. It will support development of robust quality management system in the company thereby enabling production of globally acceptable quality medicine,” another health ministry official told PTI.

The new guidelines were put in place after the health ministry’s inspections between December 2022 and August 2023 found issues such as “poor documentation, lack of process and analytical validations, absence of self-assessment, absence of quality failure investigation, absence of internal product quality review, absence of testing of incoming raw material, infrastructural deficiency to avoid cross-contamination, absence of professionally qualified employees, faulty design of manufacturing and testing areas, etc”.

At the time, the ministry had asked small and large manufacturers to ensure they had the WHO-sanctioned GMP certification within six and 12 months, respectively, while it was working on notifying these new guidelines.

The guidelines also come amid increased scrutiny of India’s export-grade drugs. Since 2022, Indian-made cough syrups and eye drops have drawn the ire of the WHO and countries importing these as they were found to be linked with the deaths of over 140 children in The Gambia, Uzbekistan and Cameroon. India is a major exporter to many low- and middle-income countries.

Between June and August last year, the WHO had flagged at least eight Indian-made syrups that had a high concentration of a toxic substance that was either diethylene glycol or ethylene glycol.

According to the WHO, the concentration of diethylene glycol and ethylene glycol in liquid preparations for oral use should be below 0.1% as they are toxic and can be fatal when consumed by humans. Some of the Indian-made cough syrups flagged by the WHO contained over 2% of this contaminant.

Noida’s Marion Biotech, Haryana-based Maiden Pharmaceuticals, Chennai-based Global pharma and Punjab’s QP Pharmachem are some of the companies that made these medicines.

Drugmakers ideally use propylene glycol or glycerine to give syrups a liquid base, which is safe for human consumption. But owing to the sharp spikes in prices of this substance, companies have resorted to diethylene glycol and ethylene glycol as substitutes. Sometimes they even use industrial-grade propylene glycol—generally used in liquid detergents—which has a high concentration of these two contaminants.