Moving Beyond Compliance – A CDMO Perspective on Quality
In the highly regulated pharmaceutical industry, quality assumes significant implications and rightfully so, since sub-standard medicines can jeopardize human life. Pharmaceutical firms, including contract manufacturers that supply into the firms, constantly try to balance the speedy access of cost-effective and innovative medicines to patients, while ensuring that there is no compromise on their quality.
Though traditionally, Quality has been the cornerstone for the US FDA, a systematized and unified way to measure, manage and report quality is still an ongoing process. In order to bring an integrated approach towards reviews and inspections, the US FDA opened its Office of Pharmaceutical Quality in 2015. Some of the issues identified by the FDA that rationalize quality as a focus include high incidence of product recalls, drug shortage due to lack of quality management systems and manufacturing modernization.
Additionally, the US FDA introduced the idea of reporting quality metrics in 2015 with a view to encourage drug manufacturers’ adoption of robust quality management systems. The data generated through the reporting would be used to efficiently evaluate the quality of manufacturing facilities and processes, target inspection resources and predict drug shortages. Published in November 2016, US FDA’s latest guideline on quality metrics suggested a voluntary reporting of three metrics (including lot acceptance rate; invalidated or out-of-spec rate; and production quality complaint rate) from Jan 2018.
CDMOs are not immune to scrutiny and shoulder a great responsibility as they serve multiple clients across the globe and in some cases are a single source of supply. As a result, apart from the regulatory agencies, the CDMOs are also audited by their customers. For CDMOs, customer audits are as critical as regulatory audits as they ensure that the manufacturing sites are perpetually audit ready, while driving them towards continuous improvement. At Piramal, 90% of the audits across sites are customer audits.
The nature of regulatory inspections has undergone a significant change – until recently, citing non-compliance used to be the norm, however lately regulators have started citing improvement opportunities during inspections. This shifts the onus of proof of compliance to the CDMOs. It has therefore become essential to continuously collaborate with regulatory authorities by participating in meetings concerning quality metrics. As for Piramal, we are constantly in touch with regulatory authorities and often invite FDA inspectors to train us on certain aspects of manufacturing like sterile injectable or high potency products.
Piramal has been consistently upgrading internal quality processes to be on a par with not only the regulatory agencies’ compliance standards but also some of their quality initiatives. Quality team at Piramal has developed and regularly makes use of multiple proprietary tools to evaluate quality health of sites within the organization and mitigate potential risks. The most important tools for this purpose include:
- SENSOR/Site Health Barometer® – Measures the Quality Health of Piramal sites and predicts audit readiness
- Audit Readiness Scorecard® – Assesses probable outcome of regulatory audits at a site; any potential issues are identified and corrected. Among the multitude of factors cited for regulatory non-compliance, data integrity has become one of the key reasons affecting the product quality. Data integrity issues arise when regulators are not convinced of the data based on which products are launched in the market. In 2015, 74% of the total warning letters issued by the US FDA were linked to DI and the number increased to 79% in 2016. At Piramal, we determine quality compliance based on various check points including assessment of Raw Material Suppliers and engineering controls using a proprietary tool called the
Data Integrity Calculator®.
- We also employ a
- Platform to proactively track all regulatory updates including 483s, observations, and new regulations in the industry on a daily basis and also share them internally.
With a strong quality framework in place, Piramal seeks to be competitive by building a brand that stands out. Quality has been long viewed as a means limited to successful clearance of regulatory audits and obtaining product approvals. Firms must shift focus from Quality for Compliance to Quality as a Culture by keeping the end patient in mind. We view Quality as our identity – something which represents our DNA. We employ the concept of “Global Vision, Local Execution” which enables each site to serve their customers at their location but with the global standard of quality upheld by Piramal. Finally, we channelize our efforts to ensure that Quality is our differentiator – which attracts customers scouting for ‘preferred’ partners.