Indian pharmaceutical companies have recently come under the US Food and Drug Administration (USFDA) scrutiny after generic drug makers Ranbaxy and Wockhardt faced issues related to manufacturing practices.
Very recently, the US Food and Drug Administration (FDA) has also rapped pharma giant Hospira for serious lapses in manufacturing of drugs at its Sriperumbudur unit. The US agency has warned the firm that this could result in drugs made at the plant not being allowed entry into the US.
An issue of great concern is the credibility of standards of manufacturing followed by the pharma companies in the country. If a top company like Ranbaxy can compromise on manufacturing norms for products meant for the US market , what standards pharma companies could be adopting for India’s domestic market.
These incidents have badly hit the image of India as a global supplier of quality generic drugs. These are warning signals for the Indian pharma industry to put its act together on its Good Manufacturing Practices or it can badly impact the Indian drug industry in the long run .
Even as export promotion bodies like Pharmexcil are initiating campaigns like Brand India and events like Iphex in order to sensitize regulators across the world about India's commitment towards brand pharma which focuses on affordability, accessibility and quality of the products from India, the recent incidents like that of Ranbaxy will not only tarnish the image of India but will also give opportunity for vested interest to sully the image of the Indian pharma sector as a whole.
It is a moot point why the country's top drug regulator, DCGI, did not act on Ranbaxy even after reports of US FDA investigations at its manufacturing sites in 2006 and 2008.These inspections were widely known in the industry circles at that time.
The detection of unacceptable manufacturing practices followed by Ranbaxy has made the US authorities somewhat suspicious of entire Indian drug manufacturing. This is despite India having over 160 US FDA approved drug manufacturing facilities in different parts of the country.
The move against Wockhardt came just 10 days after Ranbaxy agreed to pay $500 million and plead guilty to several felonies to settle allegations it sold adulterated drugs to several government health care programs.
The import alert issued by the US FDA on Wockhardt products is a clear indication of what is going to follow from now onwards. Pharmaceutical exporters of all sizes to the US and Europe need to be extremely cautious in maintaining their manufacturing standards and filing of documents if they have to remain in the export business.
At a conference call, Wockhardt chairman Habil Khorakiwala said the development could impact the revenues of the drug maker to the tune of $100 million on an annualised basis. He added that the company was taking remedial steps to comply with various norms stipulated by the FDA.
In the meanwhile according to some reports, Glenmark Generics, a subsidiary of Glenmark Pharmaceuticals, is recalling multiple lots of three of its drugs from the US because of “odd smell”, according to the FDA. The three drugs are Gabapentin, Pravastatin Sodium and Topiramate.
Glenmark has initiated the recall because of complaints related to an off-odour described as moldy, musty or fishy in nature, a notification by the US regulator said.
In 2006, the FDA had issued a warning letter to Wockhardt after uncovering a litany of GMP violations at its Aurangabad site. That correspondence expressed alarm over poor record keeping that had been cited in two previous inspection but not corrected, leading FDA inspectors to write that the "firm may not have taken this type of discrepancy seriously." The same letter warned Wockhardt that continued failure might lead to an import ban.
The USFDA has also warned pharmaceutical giant Hospira that it has found contamination during drug manufacturing at the firm's Sriperumbudur unit. This could result in drugs made at the plant not being allowed entry into the US.
Hospira, in a regulatory filing, said that it has received a warning letter from the US regulator, citing serious lapses in manufacturing. The letter followed an October inspection of. the facility where the FDA said it had found significant violations of quality regulations for finished drugs.
The FDA said it found that surfaces in the facility were not always sanitized prior to use and that sterile drug products were not protected from contamination. "Aseptic manufacturing intervention is not performed. Gloves used during manufacture of sterile products are used without adequate assurance of their sterility" the warning letter said.
Hospira has been facing multiple regulatory issues at its manufacturing plants since 2010, and withdrew its 2013 profit and revenue outlook in February after the FDA banned the import of some of its products.
Reacting to the extensive media criticism about the quality of drugs manufactured in India for exports, in the wake of the recent action against Ranbaxy , the union commerce ministry has termed it as desperate attempts by other countries getting affected by the strength of Indian pharma industry.
“There are reasons to believe that vested interests are raking up isolated issues reported regarding technical deficiencies on manufacturing and GMP. India is enjoying a unique position of low cost manufacturing and highest quality medicine, best of both the worlds. Government has strong reason to believe that some of the spurious drugs detected in the international markets, alleged to be exported from India, are desperate attempts by other countries getting affected by the strength of Indian pharma industry,” the ministry said.
Clarifying on reports of malpractices of pharma manufacturing in India, the ministry said the pharmaceutical sector is a highly regulated one and the exports are heavily guided by various regulatory regimes of the importing countries and there is also a requirement for continuous monitoring of quality related aspects including complaints of sub-standard/falsified drugs from various countries. All the concerned organisations in the government are constantly interacting to ensure that India’s image as a safe exporter is protected from all angles. Government and the industry is already working on a ‘trace and track’ mechanism which would enable monitoring of the supply chain possible at all the three levels viz. Tertiary, Secondary & Primary.
It further said that the Indian pharmaceutical industry is a highly knowledge based industry which is growing steadily and playing a major role in the Indian economy. India has a large vendor base for supplying quality generics/ API/ contract manufacturing with state of the art facilities. Indian pharmaceutical companies have huge manufacturing built in capacities hence able to meet time schedules.
India has proven international quality standard capabilities as measured by number of ANDA approvals, DMF filings, US FDA/UK MHRA approved manufacturing facilities/bio equivalence centres, which are considered as key indicators for assessing the capabilities of any national pharma sector. This fact is further firmly demonstrated by the trends in the number of product approvals received from various major regulatory authorities of the world.
Regarding the actions taken by the government to ensure export of quality drugs, the ministry said that it has implemented the trace and track technology at tertiary and secondary level packaging. Steps are also being taken to ensure the authentication process for trace and track.
Besides, the government of India has demonstrated its keenness to meet international requirements for exports of pharmaceutical products yet again by taking timely action for complying with the new procedural requirements of the European Union (EU) for import of Active Pharmaceutical Ingredients (APIs) into the EU. This landmark achievement underlines the seriousness the Government of India towards pharma exports.
And in due course of time, online application filing and tracking system would be evolved to bring in sufficient expediency and transparency in the entire supply chain, the ministry said.
Admitting that all drug applications and dossiers filed by Ranbaxy Laboratories in the US will be examined by the authorities, Drug Controller General of India (DCGI), Dr G N Singh told Pharmabiz that all approvals given to its drugs in India were in order and as per the laws with no indication of the company violating Indian laws.
Without going into the steps taken to scrutinise the dossiers and documents filed by Ranbaxy in the wake of the recent controversies, Dr Singh however admitted that all matters including approvals in the past would be examined. He asserted that all the needful as per the law would be taken including setting up special team to examine the case or sending officials to the US as the situation demands.
“My most important concern is to assure the safety and efficacy of the drugs in India and action will be taken as per the Drugs and Cosmetics (D&C) Act, not just against Ranbaxy but other companies also if found guilty,” Dr Singh told .
In the meanwhile Ranbaxy Laboratories has highlighted some of the major specific actions the company has been taking in recent years to address certain conduct of the past and to ensure the safety and efficacy of all. These actions include, enhancing its compliance procedures and policies, upgrading its business and manufacturing processes, building a culture of accountability and excellence across all levels of the organization and complete reconstitution of the board of directors and executive management team.
Arun Sawhney, CEO & managing director, stated, “Ranbaxy is a different company today. The steps we have taken over the recent years reflect the wide-ranging efforts of the current board and management to address certain conduct of the past and ensure that Ranbaxy moves forward with integrity and professionalism in everything we do. We are fully committed to upholding the high standards that patients, prescribers and all other stakeholders expect.”
“All Ranbaxy products currently in the global market are safe and effective, and we remain focused on our philosophy of ‘Quality and Patients First.’ In the recent years we have made significant improvements in the way we conduct our business to ensure greater quality control and have made investments of over US$ 300 million in our manufacturing facilities to install state-of-the-art technologies. We have also instituted a rigorous new Code of Conduct for all Ranbaxy employees, with clear accountability for compliance.” Sawhney added.
The local industry has faced several US regulatory issues in the past. Besides the import ban imposed on Ranbaxy’s manufacturing plants in Himachal Pradesh and Madhya Pradesh, other key instances include a 2009 ban on one of the sterile plants of Hyderabad-based Aurobindo Pharma Ltd, an import ban on Claris Lifesciences Ltd’s plant in 2008 and a four-year ban on the manufacturing plant of Sun Pharma’s US subsidiary Caraco Pharma.
The local drug industry also faced intellectual property related issues while exporting drugs. In recent years, several export consignments from companies such as Cipla Ltd and Dr Reddy’s were seized at European ports on charges of patent infringements, though many of them were released later after they were proved to be legal consignments to either Europe or other markets.
According to some of the experts, India’s image as a low-cost generic drugs manufacturer of high quality could get a beating in the wake of recent developments. In the backdrop of such high falutin quality concerns raised by USFDA, the level of apprehension regarding effectiveness of generic drugs made in India may increase, unless some tangible remedial measures are taken.
However they say that these issues are company specific and it will not be appropriate to comment even remotely that all generic drugs manufactured in India are of dubious quality. Any impact on the overall industry will be short-lived, they add.
They don’t think quality is a concern as far as Indian generics are concerned as the country has several manufacturing plants which have been approved by many regulatory agencies including USFDA and those are products are there in the market for so long. Cases such as the Ranbaxy one will persuade deal makers and potential buyers to dig deeper during the due diligence phase Since many deals have gone wrong in the past not only in India but globally too, as exuberant buyers or deal makers tend to discount the impact of certain issues or factor them lightly, they added.
India exports generic drugs worth about Rs. 60,000 crore to least 200 key markets in the US, Europe, Africa and Asia. Of this, about 40 per cent is to the US, the largest drugs pharmaceutical market in the world in terms of value.
India, the country which has the largest number of USFDA-approved manufacturing plants outside the US, has been the largest generic drug exporter to the US and Europe. Top Indian drug makers including Sun Pharmaceutical Industries Ltd, Dr Reddy’s Laboratories Ltd, Lupin Ltd and Cadila Healthcare Ltd, besides Wockhardt and Ranbaxy, also operate several manufacturing plants abroad, including the US, to cater to markets there.