Earlier this year, the European Medicines Agency (EMA) updated Annex 15 in its Guidelines for Good Manufacturing Practice (GMP) to reflect the need for ongoing process verification in medicinal products.
“This update reflects a paradigm change from static to flexible, inclusive sustainable rationales through the entire lifecycle of a product,” said Holger Fabritz, Head of QVA at pharma engineering services firm NNE Pharmaplan, at the ACHEMA tradeshow in Frankfurt this week.
“Old API [active pharmaceutical ingredient] were rather simple molecules but nowadays we are seeing a change to biotech production and high-potency APIs with more complicated molecular structures,” he explained.
“More and more companies are changing their processes to cater for biological, not chemical entities, and it is this shift that is the major driver for the changes in GMP regulations over the past few years.”
The new Annex 15 has been enforced since the end of March 30 and among other details, makes qualification and validation applicable for the API as well as the finished product, while also reflects advances in IT systems by including data integrity as a topic of GMP inspection.
String of Updates
However, Fabritz continued, this revision of the original 2001 document is the latest in a string of guidances issued by both the EMA and its US counterpart as the regulatory bodies play catch-up to industry’s increasingly complex manufacturing methods.
In 2010, Part II of the EU GMP Guide was issued which changed the way APIs were viewed in the GMP process to have as much accountancy as the finished pharmaceutical, and once again this was driven by the growth in biopharmaceuticals.
“For bioprocessing it was self-understood that naturally the API is part of the pharma production process,” but this guidance reflected the growing shift away from small molecule manufacturing.
Other updates reflecting the paradigm shift include changes to ICHQ9 on quality and risk management, a 2008 revision to Annex 1 of the EU GMP affecting sterile manufacturing, and the US FDA’s 2011 Process Validation guidance which, Fabritz said was the force behind the EU’s latest update.