Alexion Pharma International Trading

Transcription

1 Alexion Pharma International Trading Impact of Revised Annex 16 on Outsourced Activities Eva Duffy (Sr. QP) April 2016

2 Alexion: Background information for the purpose of this presentation Alexion Pharma International Trading (APIT) holds an MIA for the QP certification of Biotechnology Sterile Products Manufacture of WCB, DS, DP, packaging, testing, and distribution activities are carried out globally at multiple Alexion sites and outsourced manufacturing sites within the EEA or outside the EEA APIT QP certifies finished product in the EU for the release for sale and supply in the EU or for export outside EU 2

3 Annex 16 Certification by a QP and batch release Revised to reflect the globalisation of the pharmaceutical supply chain and the introduction of new QC strategies Covers 4 areas: Process of certification Relying on GMP assessment by 3 rd parties Handling of unexpected deviations Release of a batch 3

4 Annex 16: Process of certification The certification by QP for EU or export must include all aspects of finished product (FP), including importation, all global manufacturing and the transit conditions for sample versus product The certification of the FP represents quality release of the batch, signifying compliance with Regulatory Filing and GMP. Transfer to saleable stock, if performed at a different site, this arrangement can be documented in a written agreement between the sites Regardless of the number of sites involved, QP certifying finished product for release to market is ultimately responsible for all the various steps of manufacture, importation, testing and storage of the batch (e.g. WCB, DS, DP, FP), even those already certified by another QP. QP may take account of the confirmation by, and share defined responsibilities with, other QPs in relation to any manufacturing or importation operations taking place at other sites in the EU and other MAH defined in the relevant MA, through quality agreements 4

5 Annex 16: Process of certification Each QP must have detailed knowledge for the steps they are taking responsibility for Understanding supply chain, production processes, sampling, testing, shipping, distribution, regulatory requirements (Regulatory Filings /GMP) Reliance on quality systems, QC / QA teams / technical teams, audit, quality agreements, site visits, PQR, QP handshakes. 5

6 Annex 16: Process of certification Sampling of release samples in 3 rd country manufacturing site (section & 1.5.6) o Sampling may either be taken after arrival in the EU, or taken at the manufacturing site in the 3 rd country in accordance with a documented technically justified approach Audit of the manufacturing activity including any sampling activity at the third country site and evaluation of subsequent transportation steps of both the batch and samples to ensure that the samples are representative of the imported batch Comprehensive scientific study (data driven) o Description of the sampling process in the 3 rd country o Description of the transported conditions of the sample and the imported batch. Any differences to be justified. o Comparative analysis of samples taken in the 3 rd country and samples after importation o Consideration of the time interval between sampling and importation of the batch and generation of data to support defined limits o Provision of random periodic analysis of samples taken after importation to justify reliance on 3 rd party sampling o A review of any unexpected result or confirmed OOS, (notification to Supervisory authority by site of certification) 6

7 Annex 16: Process of certification Guidelines on import testing for FP (section 1.5.7) QP may base their decision on the QC testing of the first imported batch testing, where batches are sent in multiple consignments Documented evidence (QRM principles) Storage of bulk product prior to packaging Product has been stored and transported under the required conditions Tamper proof, security during storage / transportation Correct ID of product Samples tested are representative of the product Entire supply chain traceability from API to Medicinal product up to the stage of certification available to QP (section 1.7.2) Comprehensive diagram of starting materials, packaging materials and other materials deemed critical and critical steps 7

8 Annex 16: Reliance on GMP assessments of 3 rd parties QP reliance on quality system of audits (section 2) Guidance on what the audit report should address quality management, all relevant production and QC procedures relating to the supplied product Reliance on Corporate auditors Oversight of audit schedule Auditor s experience, qualification Scope of audit covers products and processes Audit reports QP RIGHT to audit (through Supply and Quality Agreements) QP aware of the outcome of an audit with critical impact on product quality prior to batch certification Support QP declarations, batch certification and QP s knowledge 8

9 Annex 16: Handling of unexpected deviations (section 3) QP discretion: QP may consider confirming compliance or certifying a batch where an unexpected deviation concerning the manufacturing process and / or the analytical control methods from details contained within the MA and/or GMP has occurred. Considerations: One-off minor deviations, thoroughly investigated and root cause corrected Impact on quality, safety and efficacy of batch is negligible Consideration of the need to include affected Batch on stability QP certifying the finished product should be aware and take into consideration any deviations which have the potential to impact compliance and /or compliance with MA ( via QP handshake / Quality Agreements) 9

10 Regardless of the number of sites involved, the certification by QP for EU or export of finished product for release to market is ultimately responsible for all the various steps of manufacture, importation, testing and storage of the finished product batch 10