Last month, the US FDA has reportedly issued 483s to at least three more pharmaceutical companies in India, one of them the Indian subsidiary of a US generics company. In parallel inspections at two sites in the same state, spanning March 24-28, the Agency issued 14 -15 inspectional observations per site, some related to data integrity issues.
Unconfirmed reports say that the local unit of the US generic major received nine observations; three of a critical nature, pertaining to contamination of manufacturing equipment.
As we go to press, Sun Pharma’s takeover of Ranbaxy is being seen as a forerunner to a long overdue consolidation in the industry. There is hardly any doubt that the deal was a direct result of the Ranbaxy brand taking a beating in the past couple of years, due to import bans and product recalls triggered by US FDA inspections. Wilfully ignoring 483s or taking them too lightly can reverse years of brand building and therefore managements at all units facing 483s should take speedy action to rectify these problems lest they too lose credibility and become takeover targets.
But there is some good news as well. It’s worth recording that some companies in India are already meeting US FDA’s cGMP standards. Sources point out that of the five sites inspected by the US FDA in the same state as the above two units, from November 2013 to March this year, three sites did not trigger adverse observations. But 3/5 is not good enough for any industry and we need to improve this score.
While the nature of the 483s at the US generics plant could not be verified independently, state officials present during the two other inspections confirmed the news. But when quizzed on the seriousness of the observations, they seemed confident that none of the observations were critical and the respective managements were committed to rectify the lapses.
One recurring source of data integrity issues in past US FDA inspections of pharma plants in India is the lackadaisical approach to record keeping in key areas, especially quality control (QC) labs. As most pharma QC labs in India lack automated analysis equipment, readings are recorded manually and in most cases, this raw data is not archived adequately. Shared login IDs for key QC lab equipment and work stations, disabled audit trail functions: all these are ‘red flags’. As one Warning Letter (WL) states, ‘the lack of reliability and accuracy of data generated by your firm is a serious cGMP deficiency that raises concern for all data generated by your firm.’
Moreover, this WL squarely put the onus on the management: ‘Be advised that corporate management is responsible for ensuring the reliability of all data produced by your firm, including data submitted to FDA to support the safety, effectiveness, and quality of marketed products.’
Will the learnings from each inspection add to the collective know-how? Or will we keep repeating the same mistakes?
Post the March visit of the US FDA Commissioner, US and Indian drug authorities are working together on at least two fronts. Firstly, state or central inspectors are present as ‘observers’ during US FDA inspections. Secondly, the US FDA is conducting capacity building workshops. The third in the series of workshops is to be conducted on May 12-13 at Ahmedabad and will focus on regulations for finished drug products as well as introductory concepts for the establishment of effective quality systems.
State regulators who have been included in such inspections concede that the US authority sees such inspections not as a means to punish, but as a chance for improvement; with a clear emphasis on the Corrective and Preventive Action (CAPA) approach. Indeed the WL cited above mentions seven steps that the erring company’s data integrity consultant should follow to set things right and lays down clear timelines and punitive action.
The collaboration between Indian and US regulators, is in fact, upsetting crusader-commentators like Roger Bate, who on February 26, chaired a congressional briefing about the possibility that low-quality drugs from India are being sold in the US. Since then, Bates has accused the US FDA of suppressing concerns about Indian generics (http://bit.ly/1nb8Yot).
Irrespective of Bate’s views, he does make a valid argument in an article exclusively written for Express Pharma (http://pharma.financialexpress.com/ latest-updates/3630-why-are-indian-generics-under-attack-one-view-from-america). He points out that the laws overseeing drug production in India, date back to 1940 and I am sure that many in the country, including the DCGI himself, will agree with him when he advocates that the entire law needs to be rewritten to give the main regulator, the CDSCO, more status, funding and power.
Bate in fact puts the onus on the political machinery, urging the post-election Indian government to rewrite the laws, and properly fund a well constituted drug regulator. Industry leaders have a long list of recommendations for the next Prime Minister, which in fact form the cover story of this issue. Let us hope that at least some of them actually make it to the PM’s 100-day agenda.
Viveka Roychowdhury
Editor
