Consultant: Commercial bioequivalence software in need of validation in wake of Thermo Scientific's review
Last week, Outsourcing-Pharma.com reported that Thermo Scientific was reviewing its Kinetica software for PK/PD data analysis, simulation and reporting after a paper in the American Association of Pharmaceutical Scientists (AAPS) Journal found data discrepancies with the platform that could have led to some drugs being wrongly approved.
The European Medicines Agency (EMA) is currently reviewing the severity of the situation but a consultant who has worked for many years in drug metabolism, pharmacokinetics and bioanalysis told us there is a need for independent validation of such software systems, echoing the call from one of the paper’s authors, Anders Fuglsang.
A consultant we spoke to cited American biologist Paul Ehrlich's epithet “to err is human, to really foul it up takes a computer,” and warned that when it came to software validating bioequivalence, drug developers need to be aware that the vendor may not always have the end user in mind.
“People forget several important points about any product, particularly computer-related,” including the fact vendors often only show the best side of their product, multi-purpose products are designed to maximise the sales with a lot of trade-offs, and products are not always used as intended.
“Excel and Lotus were not designed for pharmacokinetic data analyses, but they are being used for that” she said.
The consultant also told us she had spoken to a QA validator from a Big Pharma company regarding the Thermo Scientific issue who said this is “just another reason to get it through these users’ heads that COTS vendor-tested functionality needs to be challenged during validation.
“You cannot just take their word for it. Although it may not catch everything, it’s better than relying solely on the vendor’s work!”
Such sentiment is shared by the US Food and Drug Administration (FDA) which in a docket responded to a comment claiming that validation of commercially available software is not necessary because such software has already been thoroughly validated:
“The agency believes that commercial availability is no guarantee that software has undergone ‘thorough validation’ and is unaware of any regulatory entity that has jurisdiction over general purpose software producers.
"The agency notes that, in general, commercial software packages are accompanied not by statements of suitability or compliance with established standards, but rather by disclaimers as to their fitness for use.”
The public will pay!
We contacted Thermo Scientific for comment as to the need for software validation and any repercussions a glitch in software could have, but while the firm confirmed it was conducting a review of the issue raised in the AAPS journal, the firm declined to say anything more.
Helmut Schütz from BEBAC Consultancy Services who co-authored the paper told us only regulators and the drug manufacturers have access to the original study reports which would state which software was used, but said the number of drugs affected could be huge.
“Kinetica was rarely used in the US and Western Europe, but bioequivalence studies leading to approval in these regions may not have been performed in these countries.”
Furthermore, “Bioequivalence studies are almost always outsourced to CROs,” he added and as Kinetica is cheaper than other packages mentioned in the paper it is likely to have been used in India and MENA-states.
Schütz did not know what the consequences would be for drugmakers, CROs or software vendors if approved drugs need to be validated but speculated that while “some lawyers might get rich soon, at the end the public will pay for it.”