GMP Problems with critical Medicinal Products - what now?

A recent EU Statement of Non-Compliance with GMP issued by the Malta Medicines Authority attests that the Indian pharmaceutical company Akriti Pharmaceuticals does not meet the requirements of Good Manufacturing Practice (GMP). As a consequence, Qualified Persons (QPs) from Manufacturing Authorisation Holders directly affected by this statement are unable to perform the batch certification. The problem here was that critical medicinal products could have been potentially affected.

So what happened?

A routine onsite GMP inspection was conducted, also focussing on the outcome and findings from the preceding GMP inspection which was conducted as a Distant Assessment in February 2022 (with 5 major and 22 other issues). During the recent onsite inspection, the inspectors observed 3 critical, 5 major and 17 other issues. Amongst these are:

• Ineffective implementation of the quality management system
• Data integrity issues
• Unreliable stability studies
• Lack of control in production and packaging operations including of cross contamination measures
• Deficiencies concerning analytical testing

Because critical medicinal products could have been potentially affected, a draft supervisory risk assessment was circulated through the rapid alert network for any comments by the National Competent Authorities (NCAs). So far, no replies were received, confirming that there are no medicinal products on the EU/EEA market and no critical medicinal products on MRA partner markets. As a consequence, the GMP certificate MT/002HM/2023 has been withdrawn from EudraGMDP database.

But what if there had been any "critical medicinal products" on the market? Here, the statement provides the appropriate instructions:
"In exceptional circumstances there may be no objection to the Qualified Person certifying affected batches thereby allowing their release provided all of the following conditions are fulfilled":

• Batch certification is performed in order to maintain supply of critical medicinal products only
• A documented risk assessment has been performed
• A thorough risk-benefit evaluation has been performed taking into account the nature of the non-compliance with the involvement of the Manufacturing Authorisation Holder(s) and the Qualified Person of the site responsible for batch certification.

Irrespective of this, the report also reveals the limitations of distant assessments, as the above-mentioned findings show.