WHO Cites India’s Svizera Labs for GMP, Data Integrity Issues
Yet another Indian drugmaker has been dinged for serious data integrity and GMP issues — this time during a June 4 to 7 inspection by the World Health Organization.
WHO issued a Sept. 2 notice of concern letter to Mumbai-based Svizera Labs for “critical and major deviations” from WHO GMP standards with its fixed-dose combination tuberculosis drug. The drug — rifampicin, isoniazid and pyrazinamide — was cleared in September 2008 for WHO’s Prequalification of Medicines Programme, which is used in countries that don’t have stringent national regulatory authorities and serves as a formulary for international aid organizations.
The letter comes as Indian drugmakers are increasingly in U.S. and European regulators’ crosshairs for lapses in quality manufacturing and data integrity. Earlier this year, the FDA issued warning letters to Cadila Pharmaceuticals and Mahendra Chemicals over data issues, and slapped Nosch Labs with a Form 483 for the same problem. And in July, the European Commission suspended sales and distribution of 700 formulations of more than four dozen generic drugs after determining that the bioequivalence testing on which their approvals were based included manipulated echocardiogram data.
While WHO has no authority to pull drugs from world markets, it can remove drugs from its prequalified list. That’s what Sanofi’s Shantha encountered when it lost prequalification status in 2010 for its pediatric pentavalent vaccine. It took the company four years to regain the status in May 2014, at huge cost to Sanofi.
WHO’s letter to Svizera cites 10 deviations, including data integrity issues and possibly falsified analytical test data, failure to maintain adequate standards of hygiene, failure to maintain adequate in-process controls, failure to package products under adequate conditions and failure to ensure clean air supply to manufacturing areas. Four of the deviations were deemed major concerns. The letter followed a June 4 to 7 inspection.
Regarding allegedly falsified data, WHO says the amount of product used in the fixed-dose combination doesn’t correspond with the number of tests claimed to have been performed. When pressed by the investigator, the company produced invoices for supplementary bottles, but there was no information on when the bottles were opened and finished, and where the remaining bottles were stored.
WHO also points to sample trial injections that didn’t match batch records, and to data that was deleted, and cites the drugmaker for making false and misleading statements in stability reports and failing to ensure data integrity in production.
Svizera also failed to adequately perform dissolution tests and may have manipulated results, the letter says. The firm’s proposed corrective action to buy new equipment was deemed unacceptable because it didn’t address the “inability of your current quality management system to detect and prevent poor practices in the first place,” the letter says.
WHO told Svizera to have a third party evaluate the extent of the deleted records and prepare a risk-assessment plan to address the potential impact on quality. The organization says it will withhold prequalification of all new products manufactured at the Mumbai site until the deviations are corrected and will suspend products listed as prequalified if the deviations aren’t corrected in within a reasonable timeframe.
Read the unredacted letter here: http://apps.who.int/prequal/info_applicants/NOC/2015/NOC_Svizera02September2015.pdf.
Information on WHO prequalification is here: www.who.int/mediacentre/factsheets/fs278/en/. — Tamra Sami
Subscribe to International Pharmaceutical Regulatory Monitor and save $200 off the regular one-year price of $895 – plus receive a FREE copy of our book Japan's Pharmaceutical Regulatory Environment – a $287 Value!
LINKS TO KEY DOCUMENTS — Each issue provides English-language texts of important, hard to obtain proposals, regulations, guidelines and other documents.
FDANEWS DRUG DAILY BULLETIN — This daily email brings you important FDA and international regulatory, legislative and business news in the pharmaceutical industry.
ONLINE ACCESS — Consider our newsletter archive your personal library! Search your current issue — and hundreds of past issues — by keyword and relevancy.
Copyright ©2019. All Rights Reserved. Design, CMS, Hosting & Web Development :: ePublishing