Data integrity – currently the hottest topic in quality management – should be a straight forward subject to understand. Yet, for those who have doubts about how to get it right, the FDA published “Data Integrity and Compliance with cGMP” guidance last week. It follows similar publications by the UK’s Medicines and Healthcare Regulatory Agency (MHRA) and the World Health Organization (WHO).
Sri Krishna’s flagrant data integrity violations
While regulatory authorities are publishing guidance documents for good data and document management practices, major Indian paracetamol manufacturer, Sri Krishna Pharmaceuticals’ warning letter was published by the FDA earlier this month. The findings didn’t come as a surprise, as European regulators had highlighted similar concerns in early 2015 and the FDA had placed Sri Krishna’s Unit II facility on an import alert since August 2015.
However, the FDA finding that the “firm was destroying original batch records and backdating revised replacement pages” indicates a malaise that runs far deeper than what any guidance document can help resolve.
FDA uncovers serious data integrity problems at an Indian clinical research organization (CRO)
It was just last week when PharmaCompass raised the issue of data-integrity concerns at clinical research organizations (CROs) in India. This week, FDA issued an ‘untitled letter’ to Semler Research Center Private Limited located in Bangalore, India.
The FDA also notified “sponsors of New Drug Applications (NDAs) and Abbreviated New Drug Applications (ANDAs) that clinical and bioanalytical studies conducted by Semler Research Private Limited (Semler) located in Bangalore, India, are not acceptable as a result of data integrity concerns, and need to be repeated.”
A summary of the observations at Semler are available at Barbara Unger’s blog post, “Data Integrity Issues at a CRO and Consequences for Sponsors”.
Four Chinese firms on FDA’s import alert
Companies placed on FDA’s import alert list before their warning letters are made public are invariably organizations the FDA believes have severe compliance problems. Four companies in China were placed on the FDA’s import alert list this month – Beijing Lunarsun Pharmaceutical, two facilities of Chongqing Lummy Pharmaceutical, Xinxiang Pharmaceutical and Xinxiang Tuoxin Biochemical.
Back home, FDA confronts a defiant Pharmakon
While India and China have been making headlines for manufacturers failing to comply with regulations, none of the problems compare with what the FDA is encountering with the US-based compounder, Pharmakon Pharmaceuticals.
On February 16, 2016, the FDA received reports of serious adverse events experienced by three infants associated with the use of the recalled super-potent morphine sulfate, products produced by Pharmakon. FDA test results showed the product was nearly 2,500 percent the labeled potency.
A subsequent FDA inspection found “insanitary conditions, including poor sterile production practices, and other deficiencies”. On April 11, 2016 the FDA recommended that Pharmakon cease sterile operations until appropriate corrective actions were implemented by the facility. It also recommended a recall of all non-expired drug products that are intended to be sterile.
However, Pharmakon informed FDA that it would neither initiate a recall nor cease sterile production leaving the FDA with little choice but to immediately inform healthcare professionals not to use the products marketed as ‘sterile’ from Pharmakon.
A voluntary nationwide recall was announced by Pharmakon only after the FDA had sent out their alert.
The FDA had previously inspected Pharmakon in March and April 2014, and issued a warning letter in May 2015. The April 2014 inspection was a “follow up on adverse event reports related to super-potent midazolam products administered to neonatal infants.”
2015 saw the highest generic drug approvals ever
While some manufacturers of generic drugs struggle with their quality systems, the FDA’s Office of Generic Drugs (OGD) completed its first full year of operations. In its 2015 annual report published recently, the office highlighted that last year “marked the highest number of generic drug approvals and tentative approvals ever awarded by the FDA – more than 700 in all.”
The office had a pending list of 2,866 abbreviated new drug applications (ANDAs) and 1,873 prior approval supplements (PASs), as of October 1, 2012. However, by the end of 2015, the FDA completed first actions on 84 percent of ANDAs and 88 percent of PASs. Therefore, the regulatory body is already close to 90 percent of its goals set for 2017.
Although companies in India continue to make headlines for failure to comply with manufacturing standards, others won key approvals in 2015 indicating that the compliant ones have enormous opportunities they can capitalize on in the United States – the largest pharmaceutical market in the world.
For companies interested in looking for opportunities in the US market, PharmaCompass’ compilation
“Drugs with no patents and no competition – here’s our list of new ‘price-gouging’ targets” is a good place to get started.