NEW DELHI :
Swiss drug maker Novartis AG’s shares tumbled on Wednesday after the US Food and Drug Administration (FDA) said the company had manipulated data, while seeking approval for Zolgensma, the “world’s most expensive drug", used to treat children with spinal muscular atrophy. The development has brought the spotlight back on drug makers, frequently in the news for alleged data integrity violations.
The FDA said the Swiss drug maker was aware of the data problem on 14 March, but did not inform the regulator for more than a month. Subsequently, the agency approved the drug on 24 May.
Zolgensma, which sells for $2.1 million, is the first gene therapy for the most severe form of spinal muscular atrophy (SMA), a lifesaving treatment for infants. It was developed by AveXis, which was acquired by Novartis in April 2018.
The FDA, which continues to review the data, has threatened to take “criminal action" against the company. The regulator said in a statement that it was considering whether further action was required, which may lead to “civil or criminal penalties".
Multinational companies, including Indian drug makers, have often been criticised for flawed data by the FDA.
In fact, the trend of such violations is on the rise. The 2018 annual report by the Centre of Drug Evaluation and Research under the US FDA showed that out of the total 84 drug-related warning letters for current good manufacturing practice (CGMP), 30 involved data integrity violations.
“At no time during the investigation did the findings indicate issues with product safety, efficacy or quality. We remain fully capable of releasing high-quality, fully compliant Zolgensma to patients in need. We have and will continue to work in close cooperation with the FDA to appropriately update our submission and address any quality gaps identified. We are committed to ensuring the highest levels of transparency and integrity with health agencies, as well as with the patients and providers we serve," the Novartis spokesperson said in a statement.
Earlier last year, the FDA charged Immunomedics Inc with a data integrity breach in its August 2018 inspection, citing manipulated samples and backdated batch records. In its report, the FDA said there was no assurance that samples, batch records and commercial batches manufactured before February 2018 were not impacted by the data manipulation.
Nevertheless, in June this year the FDA sent warning letter to Akorn’s Inc manufacturing centre in New Jersey, following an inspection. It found that its sterile injectables facility failed to meet current Good Manufacturing Practice (cGMP). The FDA commented that the pharmaceutical company “does not adequately ensure the accuracy and integrity of data to support the safety, effectiveness and quality of the drugs, it makes. The data integrity issue led to the termination of the akorn deal by fresenius of Germany.
In November 2018, the FDA warned Spanish over-the-counter (OTC) drugmaker Proandre SL over good manufacturing practice (GMP) and data integrity issues that landed the firm on import alert in November. FDA inspected Proandre’s Barcelona facility over the course of four days last June, finding that its OTC Proandre antibacterial soap and hand sanitizer liquid adulterated and misbranded.
Pharma experts believe that such issues are universal and are not confined to the Indian pahrma industry, as perceived. “The issue of data integrity is universal and across many aspects of the life sciences sector and beyond. From BE and BA studies , to patient data and outcomes in clinical studies, to development data of new products to even the way safety data for new drugs we have faced issue of data integrity. Over 150 drugs have been withdrawn or banned in the last 40 years across the world, most due to some critical side effects that were seen post launch, this could be an indication that there were some gaps or observations that were not reported prior to launch. Due to the large number of generic drugs and the very visible inspection reports , data integrity is often linked only to generic medicines but the problem is much wider within the sector and much beyond the sector too," said said Sunil Attavar, president, Karnataka Drugs and Pharmaceuticals manufacturers’ Association.