Data Integrity Questioned at Indian API Manufacturer; Indian Pharma Faces Compliance Challenges

Last week brought news that Health Canada had asked for a quarantine of active pharmaceutical ingredients (APIs) made or tested by Polydrug Laboratories at its facilities in Maharashtra, India, due to concerns about data integrity.  Stopping well short of a recall, this preliminary warning asks that importers stop distributing materials from the manufacturer, pending further investigation into current good manufacturing practices (cGMP) compliance at the facility.

What prompted this move was a June 12 report filed by Slovenian regulatory authorities, and posted on The Europoean Medicine Agency’s (EMA’s) cGMP inspection database Eudrap, alleging serious cGMP noncompliance for products made at facilities on the site, which include chlorobutanol hemihydrate, as well as metoprolol tartrate, metoprolol succinate, anhydrous chlorobutanol and fluconazole, as well as ferrous fumarate, losartan potassium and carisoprodol.

Plant inspectors found 17 cGMP failures, five of which were considered major:

·      Failure to record and register customer complaints in the official logbook

·      Quality documents stored in an insecure location

·      Deficient management of paper documents and computerized systems

·      Failure to address risks of cross-contamination for APIs sent out to a micronization subcontractor. 

This is only the latest in a number of regulatory inspections, over the past few years, that have highlighted the need for better data management and overall cGMP compliance in Indian pharmaceutical manufacturing facilities.

Currently, pharmaceutical outsourcing (excluding the nation’s large contract pharmaceutical manufacturing market) is a $2.5-to-$3.1-billion business in India, according to recent Ernst & Young data, accounting for 75% of India’s business process outsourcing. 

“Analyzing the State of Data Integrity Compliance in the Indian Pharmaceutical Industry,” a survey published by Ernst & Young in June, analyzed responses to questions of data integrity and manufacturing and quality staffing and goals from over 170 pharmaceutical industry professionals in India, who work in areas that include quality, business management, and compliance. 

Over 30% of respondents said that their companies had received inspectional observations, such as Form 483s, warning letters, import alerts, and statements of non-compliance with cGMPs, from global regulators. 

71% reported that their companies' manufacturing staff were subject to significant stress at work, and acknowledged its potential impact on overall efficiency and quality. 57% of respondents reported seeing manufacturing staff pressured to meet key performance indicators (KPIs) such as volume of output, low reject ratio and overall equipment effectiveness. 18% reported that their companies did not have adequately staffed Quality Assurance teams to review the manufacturing and testing of all the products independently.

In addition, the survey found that one third of respondents had not conducted reviews to pinpoint potential weaknesses in data integrity.  13% of respondents noted that their companies did not have clearly documented Standards Operation Procedures (SOP) on backup and deletion of laboratory data files generated by high pressure liquid chromatography (HPLC) or gas chromatography (GC) instruments.

“The industry is still struggling to deal with challenges around pricing in domestic markets, increased regulations and data integrity,” said Arpinder Singh, Ernst & Young partner and national leader, fraud investigation and dispute services, at the company’s Indian division. “Companies need to take these issues seriously, especially those around data integrity as it is a critical aspect within the overall compliance framework.” 

Ajaz Hussain, former FDA officer and advisor to Ernst & Young, called the survey an “apt reminder, and means to improve awareness and communicate” the importance of data integrity, which he called the “foundation on which we make decisions on quality, safety and efficacy. "

"Recording of data and information with accuracy protects life; without it, we cannot differentiate between counterfeit and authentic medicines<" he went on. "At the end, any lapse in the assurance of data integrity is a serious deviation from expected practices, and can have adverse repercussions,” he said.

On a more granular level, the survey revealed the need for best practices to be advanced, particularly where electronic data are concerned.  For instance, 25% of respondents were not all that familiar with FDA's regulations covering electronic data management, 21 CFR Part 11, which sets best practices.  Almost one third said their companies' IT departments had employees share login IDs and passwords for key instruments.

28% of respondents indicated that their organizations did not have a fraud reporting mechanism in place.

These gaps might be expected for any growing industry, but, if senior management fails to address them, they could have a serious impact on Indian pharma, and the global pharma supply chain. Indian companies have already been dealt huge financial penalties for failure to comply. 

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