As regulations and guidelines become broader, more electronic and increasingly data driven, manufacturers must adapt with ever changing demands. Regulators are shifting more responsibility onto manufacturers to instil quality throughout their operations and throughout their product lifecycles. In the past, small and emerging life sciences companies might have functioned sufficiently with manual processes and disconnected systems, but may now be unable to satisfy the requirements of regulators whose fundamental shift is a growing focus on electronic processes, data driven decisions and increased transparency to information.
Some examples where manufacturers will need to address their systems and processes based on recent changes in the industry, are discussed in this article:
The IT Perspective
From an IT perspective, the regulatory bodies were very active in 2016/2017 releasing new and updated regulations and guidance – all of which further describe what is expected of companies to demonstrate that their systems are fit for purpose, remain fit for purpose and protect the safety of patients and the integrity of data. The increase in regulatory requirements introduced by legislation has put industry and regulators under strain and inter-operability of systems has become the key for efficient use of data and resources. The European Medicines Regulatory Network established a roadmap for electronic Submissions (eSubmission) aimed at establishing secure, consistent and efficient electronic submission processes for medicinal products for human and veterinary use across the European Medicines Regulatory Network. As of January 2018 eCTD (electronic common technical dossier) only will be accepted for all submissions in EU procedures (Note: baseline submissions are not required). The requirement for eCTD only applications for new MAA’s in DCP and MRP has already been implemented. All manufacturers/marketing authorisation holders have either transitioned to a digital/electronic system or are at the final stages of completing this process. For small enterprises who will be outsourcing their electronic submissions, there may be large resource and cost implications. The improved version of the EudraVigilance system went live on 22 November 2017. Users of the EudraVigilance system needed to ensure that their processes and IT infrastructure are compatible with the new system and with the internationally agreed format (ISO/ICH E2B (R3)) before the above-mentioned launch date. The FDA’s electronic Medical Device final rule (eMDR) requires manufacturers and importers to submit Medical Device Reports to the FDA in an electronic format that the FDA can process. Like all regulations, the FDA’s eMDR final rule continues to change and evolve. In the first half of 2017, the FDA made a variety of enhancements to the eMDR system stressing that “submitters should begin planning updates to comply with these eMDR changes as soon as possible”. As we continue to innovate with technology in the industry we will continue to see an increased focus in our regulations. ICH E6 (R2) became effective in June 2017 and within it we saw the introduction of standards regarding electronic records and computer system validation. Within the industry we’ve long been adhering to the best practices outlined within GAMP 5 (Good Automated Manufacturing Practices), but there has been a move to bring regulations more in-line with industry standards.The Drug Supply Chain
Failures in the supply chain and lack of vendor oversight can lead to patient safety risks that come from counterfeit, stolen, contaminated or otherwise harmful products in the pharmaceutical supply chain. On June 30, 2017, the FDA issued a draft guidance for industry entitled Product Identifier Requirements Under the Drug Supply Chain Security Act – Compliance Policy, which updated the latest round of serialisation requirements. The FDA encourages manufacturers and re-packagers to serialise packages using a product identifier, serial number, lot number and expiration date by November 27th 2017, with enforcement commencing on November 27th 2018. In addition to the FDA, a number of other regulators around the world (e.g. EC Falsified Medicines Directive) have implemented, or are in the process of implementing, pharmaceutical serialisation regulations. It is estimated that by 2020, track and trace regulations will cover more than 80% of global drug supply. The pharmaceutical supply chain heavily relies upon vendors, regardless of the size or span of the organisation. The bigger the supply chain, the bigger the risk. Regulators expect companies to evaluate all suppliers in line with regulatory standards. Vendor oversight applies to both manufacturing and wholesaling and distribution.The FDA’s Quality Metrics Program
In January 2015, the FDA established the Office of Pharmaceutical Quality (OPQ) within its Centre for Drug Evaluation and Research (CDER), which encourages pharmaceutical firms to embrace continuous improvement and foster a culture of quality by collecting and reporting manufacturing quality data. Under the OPQ, the FDA plans to leverage its authority to collect product and site specific quality metrics records in place of or in advance of an inspection, and for companies with plenty of quality metrics data that could mean reduced site inspections. With regards to the quality metrics themselves, the FDA requests the following primary metrics:- Lot Acceptance Rate (LAR) as an indicator of manufacturing performance
- Product Quality Complaint Rate (PQCR) as an indicator of patient or customer feedback
- Invalidated Out-of-Specification (OOS) Rate (IOOSR) as an indicator of the operation of a laboratory
