Against the backdrop of recent spurt in cases of non-compliance to good manufacturing practices (GMP), central as well as state regulators are sprucing up regulatory mechanism to bring the house in order, sending a positive signal to the global markets. This comes at a time when global GMP violations have hurt India’s image as an inexpensive and reliable supplier of generic drugs in international markets.
The Union health ministry is also planning to frame and release a draft guideline towards constant upgradation of GMP to align India-specific standards with global regulations. This according to a senior health ministry official will take some time aimed at taking steps further towards global regulatory harmonisation.
Central Drugs Standard Control Organisation (CDSCO) is in the process of upgrading its GMP standards to meet the requirements of global regulatory markets considering the fact that Form 483s issued last year to Indian manufacturing units had a high level of data integrity issues.
Maha FDA move
Maharashtra Food and Drug Administration (FDA) also took regulatory actions on the basis of Technical Report Series (TRS) issued by World Health Organisation (WHO) as a part of its guidelines on auditing and verifying of compliance of WHO- GMP units.
As part of the crackdown for GMP violations, Maharashtra FDA issued show cause notice to a Nashik- based firm for not complying to quality control protocols and GMPs. It was found during inspection that quality control officers were absent in the second and third shift and that explosive solvents like lsopropyl alcohol were stored in open space among other violations. The firm is a WHO-GMP certified unit and is leading exporter to several countries.
The state FDA has also enhanced its vigilance on manufacturers for non-compliance to GMP norms following recent cancellations of WHO GMP Certificate of two Maharashtra based WHO-GMP units - BDH Industries Ltd, Mumbai and Sydler Remedies Pvt Ltd, Pune. Meanwhile the Drug Controller General of India (DCGI) has also submitted a proposal to the Union health ministry to mandate upgradation of Schedule M units across the country to WHO-GMP level under the purview of Drug Rules towards good manufacturing practices adopted globally.
Says Dr G N Singh, DCGI, “Government will soon make it mandatory for schedule M units to raise their standards to WHO-GMP through a notification in the interest of the public under the current provisions of the law.”
This is also in line with CDSCO's plans to bring about uniformity in inspections of Schedule M units across the country as a part of its programme to upgrade Schedule M units to WHO-GMP standards.
The current upgradation to WHO-GMP level is being evolved around the learning from global regulatory counterparts on current good manufacturing practices (cGMP) which will help manufacturers in adopting global GMP practices.
GMPs is based on a criteria involving factors such as sanitation and hygiene, qualification and validation, self-inspection, quality audits, suppliers’ audits, prevention of cross-contamination and bacterial contamination during production, training employees and personnel.
As a part of the crackdown, the state regulator also recently detected a Navi Mumbai-based firm for not complying to provisions of Schedule L 1 and Schedule M regarding GMP of Drugs and Cosmetics Act 1940 and Rule thereunder.
The WHO-GMP certified company was performing export of injectables in huge quantities and not following mandatory statutory provisions. Intelligence branch of Maharashtra FDA got information that the said manufacturer is engaged in various clandestine operations like selling of drug prior to testing and manufacturing drugs for export by deviation in the compliance of GMPs. Accordingly, under guidance of FDA Commissioner Dr Harshdeep Kamble and Harish Baijal, Joint Commissioner, Vigilance, an FDA team inspected the factory premises at Rabale, Navi Mumbai.
Inspection report revealed that the firm is manufacturing various injectable drugs with contravention of provisions of Drugs and Cosmetics Act 1940 and Rules 1945.
The firm has violated in terms of selling or exporting injection Kocef 1 gm before final authorization of Quality Assurance. It has not carried out calibration of equipments like weighing balance, manufacturing tank, HVAC System, etc. and maintained false documentations. It has also not labelled the various drugs as per formula approved by State Licensing Authority. The label claims stated on various manufactured drugs were not in accordance with the formula approved by the State Licensing Authority.
Besides this, the firm had exported Capreomycin injection 1 gm by extending the shelf life of finished product beyond expiry of active ingredients added in it. The firm had manufactured injectable product prior to the declaration of the pass results of the raw material or active ingredients.
Harish Baijal, Maharashtra FDA Joint Commissioner, Vigilance, has also appealed to citizens to share information regarding such clandestine activity with the state FDA. The citizens can mail information at pavigilancefda@gmail.com or on toll free number- 1800222365
IDMA workshops
For the last two years, Indian Drug Manufacturers Association (IDMA) and Department of Pharmaceuticals (DoP) have jointly held a series of workshops for small and medium companies aimed at imparting technical skills and improving regulatory and quality standards of manufacturers.
After successfully organising a workshop series themed 'GMP workshops for SMEs – schedule M and beyond' last year, this year the focus is on meeting quality challenges and achieving global compliance.
DCGI in October 2016 proposed that the validity of licenses be made ‘perpetual’ and also that Schedule M GMP may be updated to be on par with WHO GMP. IDMA made a submission to DCGI welcoming the same. It was suggested that while the focus of Government is on ease of doing business for industry, it would be very beneficial to the manufacturers if the same facility is allowed to manufacture different types of medicines (including for humans and veterinary) as well as ayurvedic, phytopharmaceuticals, nutraceuticals and cosmetics, as long as specific GMP approvals as required for manufacture of drugs are complied with.
CDSCO initiatives
CDSCO has successfully concluded training sessions for drug inspectors in the past one year on risk-based inspection and GMP to help equip drug control officers with the latest GMP modalities.
At the same time CDSCO, as a part of its larger commitment towards harmonisation of global regulatory standards, is on its way to increase audits in the manufacturing units across the country towards compliance with GMP as per the requirements of the respective regulated markets.
Approximately 1,400 manufacturing units in India are WHO GMP certified, and over 800 are UK MHRA approved. India continues to have the highest number of US FDA registered manufacturing facilities outside the US. The industry has strong capabilities in product development. Also, Indian pharmaceutical companies have the largest share of DMFs and ANDAs outside the U S.
CDSCO has successfully concluded training sessions for drug inspectors in the past one year on risk-based inspection and good manufacturing practices (GMP) to help equip drug control officers with the latest GMP modalities. Around five such training programmes concluded last year with CDSCO having conducted 17 training programmes in the preceding year to train drug inspectors on carrying out GMP inspections.
Regulators globally during their audit visits at Indian sites have issued in total 19 Form 483 last year as a part of their observations on data integrity. Several Indian drug makers have come under the scanner of the global drug regulatory authorities in the recent years over a range of issues like data integrity, including production quality, sanitation standards and alleged data manipulation.
Any product which does not comply with good manufacturing practices of overseas markets is being considered as adulterated and hence has the chance of losing the market, a senior CDSCO official said emphasizing the purpose of the inspection in the interest of patient safety at large.