Most of the pharma units are failing in documentation, and validation processes, and many don't have full-fledged quality control laboratories.
Sohini Das
Around 36 per cent of the pharmaceutical manufacturing units inspected by the Indian drug regulator in recent times were forced to shut down due to non-compliance with quality standards, a senior government official said here.
The Central Drug Standards Control Organisation (CDSCO) has been conducting risk-based inspections of manufacturing facilities since December 2022.
Speaking at the Indian Pharmaceutical Alliance's Global Pharmaceutical Quality Summit, 2024, Drugs Controller General of India (DCGI) Rajeev Raghuvanshi said that about 400-odd units were inspected and nearly 36 per cent had to be closed as they failed to meet the standards.
"Of those who had to temporarily shut down, around 10 per cent of the units were permanently moved out of the system as they realised they would not be able to comply with the quality standards.
"The remaining came back with corrective and preventive action plans," Raghuvanshi said, adding that the move helped in getting rid of the sub-standard facilities.
India has around 10,000 pharma manufacturing units, of which nearly 80 per cent are micro-small and medium-scale facilities.
Most of the pharma units are failing in documentation, and validation processes, and many don't have full-fledged quality control laboratories. In essence, the quality management system is failing, Raghuvanshi said.
The stringent audits and inspections seem to have helped, Raghuvanshi said, adding that since July 2023, there have been no significant international quality complaints.
"Earlier, we were getting around two complaints every month," Raghuvanshi said, alluding to the aftermath of the Gambia cough syrup controversy where children died in the African nation, following consumption of Indian-made cough syrups.
The CDSCO is stepping up efforts for auditing facilities connected with the pharma ecosystem.
It started with the manufacturing sites, then moved on to public testing labs, and now is also inspecting clinical research organisations (CROs). In all, around 600 units have been inspected.
Come July 1, the regulator will start auditing large pharma units to check for compliance with the revised Schedule M guidelines which were notified in early January.
Schedule M of the Drugs and Cosmetics Rule 1945 prescribes good manufacturing practices (GMP) for pharmaceutical products.
Around 250 companies have been identified for the audits starting next month.
The regulator is also ramping up its manpower by planning to recruit at least 250 engineers.
Raghuvanshi also floated the idea of having an internal scientific cadre at the CDSCO that will review the applications made by companies.
"This is a big gap area that we have identified. There is no scientific cadre to review the applications that come, and we depend entirely on external subject expert committees.
"We have spoken with the Centre on this, and hopefully things will move forward soon," he said.
The official expects that having an in-house scientific cadre can lead to 50-60 per cent of the file reviewing process internally, which will improve consistency in decision-making.
The CDSCO is also adopting tough measures to ensure commitment to good practices internally within the organisation.
Raghuvanshi said 207 transfers were done last year, and there have been departmental enquiries for malpractices that have also led to the termination of employees.
A process of internal auditing has been initiated and the CDSCO is looking into its own working -- auditing ports and airports for process improvements.
The coordination with states has increased too. There are monthly meetings with state drug controllers.
The DCGI has been meeting stakeholders twice a week at his office since February.
"More than 100 issues have been solved as a result of these walk-in meetings with stakeholders," he said.
A request for proposal (RFP) has been floated for the Digital Drug Regulatory System (DDRS) which will be an umbrella portal for all things related to pharmaceutical regulations.
Initially, Raghuvanshi said, it would be an improved version of the SUGAM portal, and all activities of the CDSCO will be on the portal.
Eventually, the state drug controllers will also come on board, followed by other agencies like the Customs, and GST departments, the Indian Council of Medical Research, Indian Pharmacopoeia Commission (IPC) that will be linked.
The supply chain track-and-trace mechanism will also be added to track raw material sources, and lastly, the retailers will also be connected to know about real sales in the market.
Raghuvanshi said the idea is to have a raw material-to-patient structure all under the same roof.
Anjali Singh
Such persistent quality issues could tarnish the reputation of the generic medicine industry, and raise questions about the reliability of generic drugs, which comprise over 90 per cent of US prescriptions.
The Center for Drug Evaluation and Research (CDER), a division of the US Food and Drug Administration (FDA), has expressed concern over the quality of drugs manufactured in India, asserting that it found violations at 11 per cent of the facilities it inspected in the country, the highest in any other global region, a senior official said.
Data integrity problems were found in bioavailability and bioequivalence studies conducted by contract research organisations (CROs).
These data integrity issues found in Indian manufacturers, included falsified pharmacokinetic (PK) data which is the study of how the human body interacts with administered substances, deliberate distribution of subject data into distinct cohorts to pass the bioequivalence study, questionable practices in reanalysing samples schemes and deficiencies poor quality management of systemic procedures.
Such persistent quality issues could tarnish the reputation of the generic medicine industry, and raise questions about the reliability of generic drugs, which comprise over 90 per cent of US prescriptions.
USFDA emphasised the importance of strong quality culture and proactive problem-solving to maintain drug quality and public trust.
Patrizia Cavazzoni - Director, CDER, USFDA stated: The FDA plays its part by collaborating closely with manufacturers to ensure that there is a strong quality culture in their organisations, and that everybody understands what is expected of them, and that is to operate with integrity and to the highest quality.
We urge organisations to cultivate a culture where any concerns about data quality are promptly communicated to the FDA.
This approach will allow us to address issues before they escalate into serious problems that could necessitate FDA actions, manufacturing interruptions, shortages, and other critical issues, Cavazzoni said.
Concern was also raised over the entry of new manufacturers, including industrial firms, into the drug-making business.
These newcomers often lack awareness of US regulatory requirements, leading to quality issues.
Cavazzoni called for stronger management support and a robust quality culture within pharmaceutical organisations to ensure continuous improvement in drug manufacturing standards.
The US FDA also revealed that they were piloting the Quality Management Maturity (QMM) programme to assess the quality culture of drug manufacturers.
The FDA's QMM programme, highlighted at IPA's 9th Global Pharmaceutical Quality Summit 2024, aims to reduce drug shortages and improve supply chain resilience by promoting advanced quality management practices.
The QMM programme aims to encourage drug manufacturers to implement quality management practices that go beyond current good manufacturing practice (CGMP) requirements
US FDA claimed the QMM programme offered advantages to patients, manufacturers, healthcare professionals, and the FDA itself. Patients can expect a more reliable supply of drugs with fewer recalls and shortages.
Manufacturers can leverage the programme for continuous improvement and gain a competitive edge.
Healthcare professionals will have access to medications needed by their patients, and pharmacies will face fewer risks of stockouts.
Finally, the FDA will benefit from a risk-based approach to inspections, allowing them to focus on areas of higher concern.
Feature Presentation: Ashish Narsale/Rediff.com
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