US pharmaceutical firms ‘fear change’ and need guidance on assessing safe excipient supply to become more like their European counterparts, says a senior IPEC expert.
Kevin McGlue, quality director at excipient consultancy Colorcon , is leader of a taskforce rewriting IPEC’s Significant Change Guide for Bulk Pharmaceutical Excipients and has previously been Vice Chair of IPEC Europe’s board.
He told In-Pharmatechnologist.com that change and its management have become a key topic in the pharmaceutical industry.
“The FDA and the MHRA are very concerned about potentially unmanaged change in Asian markets. All the various problems they’ve had with various Asian companies have made the FDA and Europe nervous about practices in Asia.”
‘People are not catching up’
The guidance document, whose last major revision was in 2000, establishes when changes in the manufacture and supply of excipients are important enough to inform pharmaceutical companies and regulatory authorities. Relevant changes include alteration of raw materials, specification, the manufacturing process, the location or temperature of a plant, or supply chain route.
Risk surrounding supply chain change is managed differently on either side of the Atlantic, he told In-Pharmatechnologist.com.
The US Food and Drug Administration (FDA) typically uses a rule-based approach “saying what must and mustn’t be done,” compared to the UK Medicines and Healthcare products Regulatory Agency (MHRA)’s more flexible risk evaluations. In Europe, pharmaceutical companies are typically left to do their own risk assessment, whereas the FDA is more prescriptive, the IPEC advisor explained.
However, while the FDA has started moving towards a risk assessment model, US-based companies are making slow progress, said McGlue. “People are not catching up with the way the FDA has made because a lot of US companies are afraid. Typically the pharmaceutical industry has run itself by very prescriptive rules for many years. Adjusting to the idea of not having prescriptive rules but assessing yourself will take adjusting.
“Take the FDA and EMA’s recent guidance on validation in the pharma industry. What the FDA has done particularly in its guidance is turn down the concept of three-batch validation.”
Companies typically use three batches of drugs for compliance validation, which McGlue said was “a very cautious approach” prompted by safety concerns.
“But you can grind yourself to a halt. The regulator very sensibly said you can use risk assessment to see where the level of risk dictates where you should do more work or less work. It’s a pragmatic approach to the application rules.”
Guidance ‘black hole’
The latest addition of IPEC’s Significant Change Guide would address North American need for direction, he said.
“They need good guidance about change because for all the fear of change in the industry, change will happen. There’s been a big black hole and a lack of guidance around how to manage it.”
Secondly, he said there was also a gap in understanding from excipient manufacturers themselves about how to interact with sponsors on supply safety matters. “There’s a combination of reluctance or lack of guidance about what they should be doing.
“At IPEC we’re hoping this guidance will help people to really line up and understand a) what pharmaceutical companies should expect and b) what excipient manufacturers should be doing to support their customers.”
‘Very large’ rewrite
The current taskforce is composed of four members from IPEC Americas and four from IPEC Europe, with McGlue leading the European team, made up of excipient and pharmaceutical representatives.
“We’ve done a very large rewrite of guidance. For example we’ve simplified categories into ‘significant’ and ‘non-significant’ change. More importantly, to find out if change is significant or not needs risk assessment. That aligns to the European approach.”
While IPEC’s Significant Change Guidance has existed since the 90s, it was initially published as IPEC Americas’ guide and aligned to the FDA’s prescriptive approach. With the current rewrite, IPEC aims to address the imbalance and will be influenced by the EMA and MHRA’s preference for risk assessment.
The revised document is expected to be released to the public in April after comment from the MHRA and FDA, and published as formal guidance by the end of 2014.
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