Noting recent regulatory run-ins – such as Ranbaxy’s last week – Ajit Dangi, Chairman of Fulford India, a Merck & Co.subsidiary, said “continuous emphasis on data integrity” is needed to improve India’s reputation.
Dangi claimed to have seen statistics showing “in life sciences, almost 35% of the bio data are embellished – I’m using a very polite word. If that’s the case, you know the culture has a problem and that’s why data integrity and GMP go hand in hand.”
But Dangi – backed up by fellow panellist Dilip Shah, the Secretary General of the Indian Pharmaceutical Alliance (IPA) – was at pains to emphasise the difference between “outright fraud” and lesser data violations caysed by “cultural” differences.
Shah too said Indian production problems could be resolved if the country’s manufacturers understand “a basic culture change” surrounding expectations of data recording between India and regulators in Europe and the US.
“As one small example, an educated, qualified chemist working in a lab is doing an analysis of a batch and he misses one step. He discards that and starts doing it again. He doesn’t know that when the US FDA comes they will look at the fact you discarded this and didn’t take direct note of this [and find fault]. This is the issue of data integrity.”
Doctored data
The panel’s comments were echoed during in-Pharmatechnologist.com’s interview with Bharat Shah, the Director of UK pharmaceutical importer Sigma.
Shah said some Indian companies “doctor their data [on manufacturing methods] to get the same end result,” cutting corners to deliver on time.
The quality of the drugs produced is not substandard, said Sigma’s Director, but the production method is different from the one agreed.
“They know that the end results are not going to be different but the fact remains if they have diverted from the [agreed] manufacturing process, it is a lapse in GMP.”
While, he said, the US FDA and UK MHRA are “not happy” with deviations, the UK regulator is more flexible:
“MHRA looks more to the finished product than the procedures. Whether you do your mixing for 10 mins or 15 mins [is less important].
“They say if you diverted from the licence you can register a deviation in the [Drug Master] File.
“Basically if the patient is not harmed with the end product and you’ve done a bit of deviation but done it officially with the right paperwork [it may be acceptable].”
Shah said MHRA had told him of examples when the regulator had inspected Indian facilities and found “some papers by an incinerator that were supposed to be destroyed. They were handwritten and recent and differed from typed records. And they were caught.
“But basically the product they made had little deviation from the original method.” Because the company had not raised a deviation correctly, “the MHRA said actually this is fraud, and we’ve got to take your GMP away.”
MHRA
Shah believes while manufacturers need to improve, some of the burden lies with regulators who should educate facilities managers.
“Regulators should have regular liaison with manufacturers in India and China to explain to them how GMP works and that they don’t have to cheat.”
MHRA spokeswoman Kate Cleaver told in-Pharmatechnologist.com the regulator has provided training in EU GMP requirements, including data integrity expectations, to Indian manufacturers at meetings and symposia in India for several years, sometimes in collaboration with the Indian CDSCO and US FDA.
She added that all relevant process deviations should be reported to the certifying Qualified Person, who can make a decision on the impact of the deviation on a regulatory filing.
The MHRA suggested that if a communication breakdown exists, it is not with the regulator, but between API manufacturers and makers of finished drug products.
“QPs can accept one off unplanned deviations to manufacturing conditions on APIs without notification to MHRA or raising batch specific variation.
“In practice this is not always managed effectively by companies and in many cases the relationship between API manufacturer and dose form manufacturer/MIA holder is not always adequately developed to promote this.”