First Valsartan, now Irbesartan formulations are going thru a recall. As these recalls are happening world-over, the chaos is enormous...
For the affected patients, in addition to dealing with product shortages in pharmacies (due to several batch recalls), it is horrifying to learn that they have unsuspectingly consumed a medicine that contains a potential carcinogen. For pharma companies, this is a huge hit to their brand image as well as to their bottom-line.
Impurities in drugs and drug products are a part of manufacturing process, and companies strive hard to keep them at minimal and within specifications; be it as per ICH, FDA or company's internal standards. So what happened in case of Valsartan, Irbesartan? How did we miss the impurities? Are compendial testing procedures adequate?
Several such questions arise... A root cause analysis will dig into reasons for the lapse, but prevention is better than cure … this is more so true for defective pharmaceutical products. Lesson learnt from -sartan mishaps is as a wakeup call !
Recalls will surely stop patients from taking defective batches of Valsartan, Irbesartan. But what about the damage already done to patients who have consumed these defective products? And what is it that we must do to prevent something similar from happening again; not only for -sartans, but any other drug or drug product?
Impurities in drug/drug products: How NOT to miss them?
Pharma R&Ds follow rigorous procedures to keep impurities/ degradation products at minimal possible levels. Drugs and drug products are developed using high standards and elaborate regulated procedures, yet how did we miss these impurities? And what to do to NOT miss them?
A thumb rule whenever a 'defect' occurs means, underlying 'processes' are faulty and must be revisited- improved or re-designed.
Here's the starting point-
Drug and drug products are developed using ICH Quality norms, QbD (Quality-by-Design), PAT (Process Analytical Techniques) and similar such sophisticated guidances which facilitate 'risk-assessment'. Based on -sartan scenario, a logical question that pops up is- Are these 'risk- assessment' tools good enough? Or is there an application failure? In the former case, guidance documents need overhaul, while the later points to inadequate training (around appropriate implementation of these guidances).
Secondly, the whole concept of 'Mistake-Proofing' pharmaceutical products must be revisited ...
Impurities are consequence of drug/ drug product manufacturing process. Any potential carcinogenic impurity carry overs into medicinal products and patients is no doubt hazardous; but it doesn't end there. What about these carcinogenic impurities getting into effluent systems and perhaps into the environment? This puts a larger population at risk!
Existing IPQC, QA monitoring norms are not good enough when we deal with complex small molecule drug candidates. All processes (technical and/or operational) leading to the products must be studied comprehensively, supervised, modified and improved 'Continuously' ...
A comprehensive Continuous Improvement methodology such as Kaizen must be rooted into pharmaceutical company operations
Thirdly, stronger risk-assessment and risk-control tools must be adopted during development and processing of pharmaceutical products. Additionally, multiple risk-assessment and risk-control tools must be employed as standard operating procedure.
Besides CAPA, FMEA, QbD, ICH and compendial norms, a structured 'Mistake-Proofing' methodology such as Poka Yoke- a Japanese concept for 'Mistake-Proofing', must be adopted as an integral part of Drug Discovery and Drug Product Development programs.
Poka Yoke based Mistake-Proofing must be customized by companies for their line of business and product mix.
Practising such 'Mistake-Proofing-by-Design' principle will imbue pharmaceutical products with quality to face any rainy day. It main rain tomorrow!
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Shruti Bhat PhD MBA Certified Lean Six Sigma Black Belt is Pharmaceutical R&D and Continuous Improvement Director, Innoworks Canada
Shruti leads path-breaking product development programs such as Complex Generics, Nanotechnology and Targeted delivery systems for pharmaceuticals and natural products. Her mantra is to "Shorten development timelines, build quality-by-design, lean processes and bring products fast- to- market". Shruti integrates her proficiency in Design Thinking, Lean, Kaizen and other Continuous Improvement methodologies to improve R&D processes, productivity and profitability.
Shruti is Product Development & Continuous Improvement Advisor to several start ups, mid-size and growing firms in Canada, USA, India, Africa and other Emerging markets. Shruti has authored six books and is an invited speaker at several conferences and workshops.
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