Quality issues ‘leading cause of drug shortages’
pharmafile | June 18, 2013 | News story | Manufacturing and Production |Â Â ISPE, shortagesÂ
Shortages of key medicines have been increasing in recent years, and a new survey from the International Society for Pharmaceutical Engineering (ISPE) says quality failures are the most common cause.
“Respondents weighted quality issues as the single most important factor leading to drug shortages,” according to ISPE, which found that problems with aseptic processing equipment was identified by a high proportion of those quizzed.
In a significant minority of cases the problems occurred during technology transfers or product development, says the survey, which also found that improved interaction with regulators was a key factor in avoiding shortages.
Overall, the industry could profit from the development of a collection of ‘best practices’ that would standardise and harmonise measures to overcome potential shortfalls in medicine supply.
While ICH Q10 on quality systems lays out the framework for a comprehensive system, it does not tackle implementation and “there is clearly scope for industry-led guidance, developed in collaboration with regulators, to assist in the establishment and operation of an effective quality system”, according to the report.
The new study comes against a backdrop of shortages in drugs around the world, particularly sterile injectables, which have caused public health crises. Towards the end of last year the European Medicines Agency (EMA) proposed various measures to try to tackle the issue, whilst criticising the pharma industry for taking a “reactive” approach to the problem.
In the meantime, patients continue to struggle to get hold of some life-saving medicines. For example, breast cancer drug doxorubicin continues to be in short supply following the shutdown of a contract manufacturing facility operated by Ben Venue in the US.
The ISPE surveyed 175 individuals and 37 companies around the world who had experienced an actual drug shortage or ‘near miss’, representing pharma and biopharma companies, generic manufacturers, contract manufacturing organisations (CMOs), and raw material and equipment manufactures.
The quality system – covering elements such as change control, reprocessing, batch release, annual record review, validation protocols, and regulatory reporting – was cited most often as the contributor to the shortage or near miss for both sterile and non-sterile products, and 28.6% and 24.7%, respectively.
The next most common factor was material systems – components, containers and closures (including water or gases) that are incorporated into the finished product – which were cited by around 20 per cent of respondents.
Problems with production systems (e.g. batch compounding, dosage form production, in-process sampling and testing, and process validation) led to the shortage or near miss in over 17% of both sterile and non-sterile cases, according to the survey. Within these responses the most common issues were non-conformances, process validation and change control systems.
Issues with laboratory control systems, facility/equipment failures and packaging/labelling problems were also cited at a lower frequency (ranging between 9% and 16% of cases).
Looking at equipment, ISPE’s survey found that production equipment was the major culprit for sterile products (80%) – with aseptic processing and freeze-drying technology most cited – while equipment qualification was the major source of issues for non-sterile products (62.5%).
The ISPE’s findings tie in with a study published by the US Food and Drug Administration (FDA) in 2011 which found that 46 per cent of all drug shortages in the US resulted from quality system failures, with other factors including inadequate capacity, raw materials issues, and packaging component problems.
Avoidance and regulation
The survey also found companies that successfully avoided drug shortages had a focus on strong quality systems, with greater involvement of senior management. All told, more than half (54%) of the respondents said they had a drug shortage prevention programme in place, but among these the same proportion also said that shortages occurred despite the provisions.
Meanwhile, around a quarter of respondents indicated that issues related to health authority inspections and approval processes also played an important role in drug shortages, according to the survey.
“Respondents identified a number of areas where they believed the level and quality of interaction with regulators could be improved,” said ISPE. “Interestingly, an additional differentiator of companies that successfully avoided shortages was their emphasis on building strong relationships with regulatory authorities.”
Respondents from companies that avoided shortages also cited the importance of fostering communication links between the companies and the regulators as an important success factor, it noted.
Regulators could help mitigate shortages by hastening the approval of new production lines, providing timely input on investigations and helping to identify alternative sources, according to those surveyed.
ISPE said it plans to organise an industry-regulatory network to discuss the findings of the survey and encourage the development of new manufacturing and regulatory practices, as well as to provide technical and scientific support to harmonisation efforts for quality requirements.
Phil Taylor
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