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Season one read draft EU GMP Annex 22 as the one text that drew a hard line on model type: static and deterministic machine learning only in critical GMP applications, with adaptive models, probabilistic models and generative AI told they should not be used there. On 2 October 2026 EMA published the report of its 30 June expert workshop, and its introduction says the drafting group has discussed opening that scope, provided the models comply with the annex and sit under a fully documented, risk-based control strategy. Sam and Sarah read the fifteen pages closely: industry's case against technology labels, the ICH Q9 vocabulary of uncertainty, importance, complexity and detectability, where the limits of mitigation lie, the report's distinction between human oversight and human-in-the-loop, layered controls that prevent, detect and contain, the lifecycle and supplier questions, and what the drafting group says it may now write. Then the four recurring systems go through the proposed test instead of the old gate, the agent longest of all, and the episode closes on what a site should build now because it is the same evidence package either way. Researched, scripted and voiced by AI systems under Jack Prior's direction. Sam and Sarah are AI characters; nothing in the episode is Jack speaking, and none of it is a statement of his views or his employer's. Generative AI can be confidently wrong — check the sources. Corrections: [email protected]. Transcript: https://jackprior.ai/podcast/transcript/10-annex-22-revisited.html Documents discussed: Report — Multistakeholder workshop on expert contributions to AI guidance development (Annex 22): https://www.ema.europa.eu/en/documents/report/report-multistakeholder-workshop-expert-contributions-artificial-intelligence-guidance-development-annex-22_en.pdf Annex 22 — Artificial Intelligence: https://picscheme.org/docview/9715 HMA-EMA AI group — meeting with industry stakeholders, summary notes: https://www.ema.europa.eu/en/documents/minutes/summary-notes-meeting-hma-ema-group-focused-ai-industry-stakeholders-february-2026_en.pdf Q9(R1): https://database.ich.org/sites/default/files/ICH_Q9%28R1%29_Guideline_Step4_2023_0126_0.pdf Considerations for the Use of AI to Support Regulatory Decision-Making for Drug and Biological Products: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/considerations-use-artificial-intelligence-support-regulatory-decision-making-drug-and-biological Annex 11 — Computerised Systems (revision): https://health.ec.europa.eu/consultations/stakeholders-consultation-eudralex-volume-4-good-manufacturing-practice-guidelines-chapter-4-annex_en GMP: Multistakeholder workshop on expert contributions to AI guidance development (Annex 22): https://www.ema.europa.eu/en/events/good-manufacturing-practice-multistakeholder-workshop-expert-contributions-artificial-intelligence-guidance-development-annex-22 AI CMC Regulatory Landscape: https://jackprior.ai/ai-cmc-landscape/ Fact check: 157 factual claims in this episode were checked against the source documents by an independent AI pass: 139 are supported by the primary text, 0 rest on secondary sources or are hedged as such (listed in the report), 18 open. Full report: https://jackprior.ai/podcast/factcheck/10-annex-22-revisited.html Open items: Under draft Annex 22, dynamic/probabilistic/generative models should not be used in critical GMP applications, and in non-critical applications a human in the loop is expected (the model drafts and a person decides), so the model-type restriction does not bar such non-critical use. [PARTIAL]; The third page of the report says the drafting group has discussed allowing generative AI in GMP applications, critical or not, provided it is supported by a documented control strategy. [PARTIAL]; Draft Annex 22 is the only text in the corpus that sorts AI by model type. [NOT-CHECKABLE]; The Annex 22 draft dates from July 2025. [UNSUPPORTED]; This report is the first official text in the corpus that moves the answer on adaptive models or generative AI in critical GMP. [NOT-CHECKABLE]; For each topic the report gives the drafting group's questions, the industry perspective, a Q&A, key messages, and a paragraph headed potential impact on Annex 22 drafting. [PARTIAL]; Industry at the workshop leaned on the Q9 sentence that formality should be commensurate with uncertainty, importance and complexity. [PARTIAL]; The reply at the workshop went back to ICH Q9's text: risk analysis is about likelihood and severity, and in some risk management tools the ability to detect the harm (detectability) also factors in the estimation of risk. [PARTIAL]; The report comes from EMA's GMP inspectors (an EMA inspectors' report). [PARTIAL]; 'Outsourced Activities' is the title of Chapter 7 of Part I of the EU GMP guide. [NOT-IN-CORPUS]; The draft's lines 12-25 still read as they did in July 2025 (no amended draft exists). [NOT-CHECKABLE]; No revised Annex 22 text has been published. [NOT-CHECKABLE]; The report's assessment dimensions are consequence, influence, uncertainty, complexity and detectability, while the July draft sorted by technology. [PARTIAL]; ICH M15 uses the vocabulary of consequence and influence (model influence, decision consequence) in its risk framework. [PARTIAL]; Under the draft, a soft sensor that retrains itself nightly (a model that adapts performance) should not be used in critical GMP applications. [PARTIAL]; The report refers to change triggers and re-optimisation or retraining criteria as lifecycle controls for adaptive models. [PARTIAL]; The report says supplier agreements should give the regulated user visibility of changes when a third-party or foundation model is updated. [PARTIAL]; No revised draft of Annex 22 exists. [NOT-CHECKABLE]

A site head wants one slide by Friday: four AI systems, three columns, do now, wait for, do anyway. Sam and Sarah close the season by reading the two documents that say where the rulebook is heading: the joint EMA–FDA Guiding Principles of Good AI Practice (January 2026), ten principles on two pages that put context of use, model risk, fit-for-use data, lifecycle and the human–AI team under both logos for the first time; and ICH's October 2025 reflection paper on advanced manufacturing, which names process modelling and continuous process verification as topics, lists the gaps in the 2011 Points to Consider in its own words, and proposes a process-models guideline as the first step, with no topic adopted yet. Then the calendar as the landscape verified it (CDER's promised manufacturing guidance, the Annex 22/11/Chapter 4 finals, the FDA draft, the AI Act's deferred dates), the EU machinery behind it (EMANS 2028, the NDSG and QIG workplans), the sandboxes that exist and the GMP sandbox that doesn't, the six open questions as the season found them, a scorecard for the four recurring systems, and Sam's verdict: nearly there on vocabulary, not on instruments, and the plant floor decides. Researched, scripted and voiced by AI systems under Jack Prior's direction. Sam and Sarah are AI characters; nothing in the episode is Jack speaking, and none of it is a statement of his views or his employer's. Generative AI can be confidently wrong — check the sources. Corrections: [email protected]. Transcript: https://jackprior.ai/podcast/transcript/09-convergence.html Documents discussed: EMA + FDA — Guiding Principles of Good AI Practice in Drug Development: https://www.ema.europa.eu/en/documents/other/guiding-principles-good-ai-practice-drug-development_en.pdf Reflection Paper on proposed ICH work to facilitate Advanced Pharmaceutical Manufacturing: https://admin.ich.org/sites/default/files/2026-03/ICH_ReflectionPaper_AdvancedManufacturing_2025_1008_0.pdf Impact of AI on the regulation of medical products (MHRA AI strategy): https://www.gov.uk/government/publications/impact-of-ai-on-the-regulation-of-medical-products European Medicines Agencies Network Strategy to 2028 (EMANS 2028): https://www.ema.europa.eu/en/documents/other/seizing-opportunities-changing-medicines-landscape-european-medicines-agencies-network-strategy-2028-final_en.pdf Quality Innovation Group (QIG): https://www.ema.europa.eu/en/human-regulatory-overview/research-development/supporting-innovation Network Data Steering Group (NDSG) Workplan 2026–2028: https://www.ema.europa.eu/en/documents/other/network-data-steering-group-workplan-2026-2028-data-artificial-intelligence-medicines-regulation_en.pdf BioPhorum — AI risk guidance for the pharmaceutical industry: Harmonizing frameworks for practical implementation: https://www.biophorum.com/download/artificial-intelligence-risk-guidance-for-the-pharmaceutical-industry-harmonizing-frameworks-for-practical-implementation/ Regulation (EU) 2024/1689 — AI Act: https://eur-lex.europa.eu/eli/reg/2024/1689/oj/eng AI CMC Regulatory Landscape: https://jackprior.ai/ai-cmc-landscape/ Considerations for the Use of AI to Support Regulatory Decision-Making for Drug and Biological Products: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/considerations-use-artificial-intelligence-support-regulatory-decision-making-drug-and-biological HMA-EMA AI group — meeting with industry stakeholders, summary notes: https://www.ema.europa.eu/en/documents/minutes/summary-notes-meeting-hma-ema-group-focused-ai-industry-stakeholders-february-2026_en.pdf Reflection Paper on the Use of AI in the Medicinal Product Lifecycle: https://www.ema.europa.eu/en/documents/scientific-guideline/reflection-paper-use-artificial-intelligence-ai-medicinal-product-lifecycle_en.pdf Annex 11 — Computerised Systems (revision): https://health.ec.europa.eu/consultations/stakeholders-consultation-eudralex-volume-4-good-manufacturing-practice-guidelines-chapter-4-annex_en Q12: https://database.ich.org/sites/default/files/Q12_Guideline_Step4_2019_1119.pdf Q8/Q9/Q10 Points to Consider — ICH-endorsed implementation guide: https://www.ema.europa.eu/en/documents/scientific-guideline/international-conference-harmonisation-technical-requirements-registration-pharmaceuticals-human-use-ich-quality-implementation-working-group-points-consider-ich-q8q9q10-guidelines_en.pdf Data Integrity and Compliance with Drug CGMP Q&A: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/data-integrity-and-compliance-drug-cgmp-questions-and-answers PI 041-1: https://picscheme.org/docview/4234 Computer Software Assurance for Production and Quality System Software: https://www.fda.gov/regulatory-information/search-fda-guidance-documents?search_api_fulltext=computer+software+assurance Good Machine Learning Practice (GMLP): Guiding Principles: https://www.fda.gov/medical-devices/software-medical-device-samd/good-machine-learning-practice-medical-device-development-guiding-principles Assessing the Credibility of Computational Modeling and Simulation in Medical Device Submissions: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/assessing-credibility-computational-modeling-and-simulation-medical-device-submissions Marketing Submission Recommendations for a PCCP for AI-Enabled Device Software Functions: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/marketing-submission-recommendations-predetermined-change-control-plan-artificial-intelligence Process Validation: General Principles and Practices: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/process-validation-general-principles-and-practices Q8(R2): https://database.ich.org/sites/default/files/Q8%28R2%29%20Guideline.pdf Annex 15 — Qualification and Validation: https://health.ec.europa.eu/system/files/2016-11/2015-10_annex15_0.pdf Reading list, in order: 1. Considerations for the Use of AI to Support Regulatory Decision-Making for Drug and Biological Products: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/considerations-use-artificial-intelligence-support-regulatory-decision-making-drug-and-biological 2. Annex 22 — Artificial Intelligence: https://picscheme.org/docview/9715 3. Reflection Paper on the Use of AI in the Medicinal Product Lifecycle: https://www.ema.europa.eu/en/documents/scientific-guideline/reflection-paper-use-artificial-intelligence-ai-medicinal-product-lifecycle_en.pdf 4. BioPhorum — AI risk guidance for the pharmaceutical industry: Harmonizing frameworks for practical implementation: https://www.biophorum.com/download/artificial-intelligence-risk-guidance-for-the-pharmaceutical-industry-harmonizing-frameworks-for-practical-implementation/ 5. Regulation (EU) 2024/1689 — AI Act: https://eur-lex.europa.eu/eli/reg/2024/1689/oj/eng 6. Reflection Paper on proposed ICH work to facilitate Advanced Pharmaceutical Manufacturing: https://admin.ich.org/sites/default/files/2026-03/ICH_ReflectionPaper_AdvancedManufacturing_2025_1008_0.pdf 7. Annex 11 — Computerised Systems (revision): https://health.ec.europa.eu/consultations/stakeholders-consultation-eudralex-volume-4-good-manufacturing-practice-guidelines-chapter-4-annex_en 8. Chapter 4 — Documentation (revision): https://health.ec.europa.eu/consultations/stakeholders-consultation-eudralex-volume-4-good-manufacturing-practice-guidelines-chapter-4-annex_en 9. EMA + FDA — Guiding Principles of Good AI Practice in Drug Development: https://www.ema.europa.eu/en/documents/other/guiding-principles-good-ai-practice-drug-development_en.pdf 10. Q12: https://database.ich.org/sites/default/files/Q12_Guideline_Step4_2019_1119.pdf 11. Q8/Q9/Q10 Points to Consider — ICH-endorsed implementation guide: https://www.ema.europa.eu/en/documents/scientific-guideline/international-conference-harmonisation-technical-requirements-registration-pharmaceuticals-human-use-ich-quality-implementation-working-group-points-consider-ich-q8q9q10-guidelines_en.pdf 12. Data Integrity and Compliance with Drug CGMP Q&A: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/data-integrity-and-compliance-drug-cgmp-questions-and-answers 13. PI 041-1: https://picscheme.org/docview/4234 14. Computer Software Assurance for Production and Quality System Software: https://www.fda.gov/regulatory-information/search-fda-guidance-documents?search_api_fulltext=computer+software+assurance 15. Good Machine Learning Practice (GMLP): Guiding Principles: https://www.fda.gov/medical-devices/software-medical-device-samd/good-machine-learning-practice-medical-device-development-guiding-principles 16. Assessing the Credibility of Computational Modeling and Simulation in Medical Device Submissions: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/assessing-credibility-computational-modeling-and-simulation-medical-device-submissions 17. Marketing Submission Recommendations for a PCCP for AI-Enabled Device Software Functions: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/marketing-submission-recommendations-predetermined-change-control-plan-artificial-intelligence Fact check: 88 factual claims in this episode were checked against the source documents by an independent AI pass: 68 are supported by the primary text, 9 are confirmed by official web sources, 3 rest on secondary sources or are hedged as such (listed in the report), 8 corrected before release, 0 open. Full report: https://jackprior.ai/podcast/factcheck/09-convergence.html

A vision vendor pushes a new model version at two in the morning and a language-model provider deprecates the version a site validated. Sam and Sarah split 'change' into four kinds (the environment drifts, the owner retrains, the model learns, the vendor pushes) and read the instruments inside out, anchored on ICH Q12: Q10 and the Annex 11 and Annex 22 drafts inside the quality system; Q12's reporting categories, Established Conditions and the post-approval change management protocol in the filing; FDA's 2025 draft tying them together with a lifecycle maintenance plan; and the device-side predetermined change control plan as the template nobody has married to the PACMP. Then the two questions FDA asked in 2023 and ICH repeated in 2025, a tier-by-tier rule for which instrument applies, the vendor update no document covers, and the four recurring systems taken through all four kinds of change, ending with what an AI PACMP for the soft sensor would actually say. Researched, scripted and voiced by AI systems under Jack Prior's direction. Sam and Sarah are AI characters; nothing in the episode is Jack speaking, and none of it is a statement of his views or his employer's. Generative AI can be confidently wrong — check the sources. Corrections: [email protected]. Transcript: https://jackprior.ai/podcast/transcript/08-change.html Documents discussed: AI CMC Change Control Instruments: https://jackprior.ai/ai-cmc-landscape/ Q12: https://database.ich.org/sites/default/files/Q12_Guideline_Step4_2019_1119.pdf Marketing Submission Recommendations for a PCCP for AI-Enabled Device Software Functions: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/marketing-submission-recommendations-predetermined-change-control-plan-artificial-intelligence Considerations for the Use of AI to Support Regulatory Decision-Making for Drug and Biological Products: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/considerations-use-artificial-intelligence-support-regulatory-decision-making-drug-and-biological Annex 11 — Computerised Systems (revision): https://health.ec.europa.eu/consultations/stakeholders-consultation-eudralex-volume-4-good-manufacturing-practice-guidelines-chapter-4-annex_en Q10: https://database.ich.org/sites/default/files/Q10%20Guideline.pdf Artificial Intelligence in Drug Manufacturing: https://www.fda.gov/media/165743/download Reflection Paper on proposed ICH work to facilitate Advanced Pharmaceutical Manufacturing: https://admin.ich.org/sites/default/files/2026-03/ICH_ReflectionPaper_AdvancedManufacturing_2025_1008_0.pdf Annex 22 — Artificial Intelligence: https://picscheme.org/docview/9715 Computer Software Assurance for Production and Quality System Software: https://www.fda.gov/regulatory-information/search-fda-guidance-documents?search_api_fulltext=computer+software+assurance Fact check: 68 factual claims in this episode were checked against the source documents by an independent AI pass: 63 are supported by the primary text, 2 are confirmed by official web sources, 1 rest on secondary sources or are hedged as such (listed in the report), 2 corrected before release, 0 open. Full report: https://jackprior.ai/podcast/factcheck/08-change.html

Every document that lets AI into GMP lets it in on one condition: a human in the loop. Sam and Sarah read what that phrase actually means across six documents, anchored on EMA's 2024 reflection paper: BioPhorum's three oversight settings and the grade each one earns, the EU AI Act's Article 14 list of what an overseer must be able to do, draft Annex 22's operator monitored like any other manual process, FDA's and the GMLP principles' human-AI team, and the paradox the documents state themselves, that oversight is both a control and a risk. Then Sam's question, parked since episode four: which human, with which competence, evaluating which inputs, measured how. The four recurring systems get the three questions, the agentic assistant gets the night-shift test, and Sam's position is offered for the listener to test: encode every check a computer can run, name the human judgment by competence, and if that competence is not on shift, the control is fiction and the grade must not get credit for it. Researched, scripted and voiced by AI systems under Jack Prior's direction. Sam and Sarah are AI characters; nothing in the episode is Jack speaking, and none of it is a statement of his views or his employer's. Generative AI can be confidently wrong — check the sources. Corrections: [email protected]. Transcript: https://jackprior.ai/podcast/transcript/07-humans.html Documents discussed: Reflection Paper on the Use of AI in the Medicinal Product Lifecycle: https://www.ema.europa.eu/en/documents/scientific-guideline/reflection-paper-use-artificial-intelligence-ai-medicinal-product-lifecycle_en.pdf Regulation (EU) 2024/1689 — AI Act: https://eur-lex.europa.eu/eli/reg/2024/1689/oj/eng Annex 22 — Artificial Intelligence: https://picscheme.org/docview/9715 Considerations for the Use of AI to Support Regulatory Decision-Making for Drug and Biological Products: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/considerations-use-artificial-intelligence-support-regulatory-decision-making-drug-and-biological Good Machine Learning Practice (GMLP): Guiding Principles: https://www.fda.gov/medical-devices/software-medical-device-samd/good-machine-learning-practice-medical-device-development-guiding-principles BioPhorum — AI risk guidance for the pharmaceutical industry: Harmonizing frameworks for practical implementation: https://www.biophorum.com/download/artificial-intelligence-risk-guidance-for-the-pharmaceutical-industry-harmonizing-frameworks-for-practical-implementation/ AI CMC Regulatory Landscape: https://jackprior.ai/ai-cmc-landscape/ Fact check: 47 factual claims in this episode were checked against the source documents by an independent AI pass: 43 are supported by the primary text, 2 are confirmed by official web sources, 0 rest on secondary sources or are hedged as such (listed in the report), 2 corrected before release, 0 open. Full report: https://jackprior.ai/podcast/factcheck/07-humans.html

Every framework this season assumes the data under the model are trustworthy. Sam and Sarah read what the rulebook actually requires: ALCOA and its pluses from FDA's 2018 Data Integrity Q&A, PIC/S PI 041 and the Annex 11 revision; FDA's 2025 'fit for use', which adds relevance to reliability; and the data-governance clauses of the AI Act, EMA's reflection paper and draft Annex 22. The Annex 11 revision turns the training-data pipeline into a GMP computerised system, with validated transfers, unique accounts, audit trails and backup. Then the gap: nobody says how to get from a historian, a batch record and a LIMS to a fit-for-use dataset. The soft sensor's training set is interrogated attribute by attribute, the batch model's golden batches become exclusion decisions, the camera's labels and vials get their clauses, and the agentic assistant's data turn out to be documents, versions and all. Researched, scripted and voiced by AI systems under Jack Prior's direction. Sam and Sarah are AI characters; nothing in the episode is Jack speaking, and none of it is a statement of his views or his employer's. Generative AI can be confidently wrong — check the sources. Corrections: [email protected]. Transcript: https://jackprior.ai/podcast/transcript/06-data.html Documents discussed: Annex 11 — Computerised Systems (revision): https://health.ec.europa.eu/consultations/stakeholders-consultation-eudralex-volume-4-good-manufacturing-practice-guidelines-chapter-4-annex_en Data Integrity and Compliance with Drug CGMP Q&A: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/data-integrity-and-compliance-drug-cgmp-questions-and-answers PI 041-1: https://picscheme.org/docview/4234 Considerations for the Use of AI to Support Regulatory Decision-Making for Drug and Biological Products: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/considerations-use-artificial-intelligence-support-regulatory-decision-making-drug-and-biological Regulation (EU) 2024/1689 — AI Act: https://eur-lex.europa.eu/eli/reg/2024/1689/oj/eng Reflection Paper on the Use of AI in the Medicinal Product Lifecycle: https://www.ema.europa.eu/en/documents/scientific-guideline/reflection-paper-use-artificial-intelligence-ai-medicinal-product-lifecycle_en.pdf Annex 22 — Artificial Intelligence: https://picscheme.org/docview/9715 AI CMC Regulatory Landscape: https://jackprior.ai/ai-cmc-landscape/ Fact check: 69 factual claims in this episode were checked against the source documents by an independent AI pass: 65 are supported by the primary text, 4 are confirmed by official web sources, 0 rest on secondary sources or are hedged as such (listed in the report), 0 open. Full report: https://jackprior.ai/podcast/factcheck/06-data.html

Once a model is allowed through the gate, what do you owe on paper? Sam and Sarah read FDA's 2025 draft for its credibility assessment plan and report, sized to model risk, and then read draft EU GMP Annex 22 sections three to nine as the most concrete evidence recipe in the corpus: an intended use owned by a process expert, acceptance criteria fixed before testing and no lower than the process being replaced, a designed test set with verified labels, test-data independence enforced by access control and staff separation, and explainability and confidence recorded as evidence. FDA's Computer Software Assurance guidance, the ten Good Machine Learning Practice principles and the 2023 credibility vocabulary explain how validation became assurance. The fill-volume camera's evidence package is built clause by clause, then the soft sensor, the batch model and the agentic assistant go through the same recipe. Researched, scripted and voiced by AI systems under Jack Prior's direction. Sam and Sarah are AI characters; nothing in the episode is Jack speaking, and none of it is a statement of his views or his employer's. Generative AI can be confidently wrong — check the sources. Corrections: [email protected]. Transcript: https://jackprior.ai/podcast/transcript/05-evidence.html Documents discussed: Considerations for the Use of AI to Support Regulatory Decision-Making for Drug and Biological Products: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/considerations-use-artificial-intelligence-support-regulatory-decision-making-drug-and-biological Annex 22 — Artificial Intelligence: https://picscheme.org/docview/9715 Good Machine Learning Practice (GMLP): Guiding Principles: https://www.fda.gov/medical-devices/software-medical-device-samd/good-machine-learning-practice-medical-device-development-guiding-principles Computer Software Assurance for Production and Quality System Software: https://www.fda.gov/regulatory-information/search-fda-guidance-documents?search_api_fulltext=computer+software+assurance Assessing the Credibility of Computational Modeling and Simulation in Medical Device Submissions: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/assessing-credibility-computational-modeling-and-simulation-medical-device-submissions BioPhorum — AI risk guidance for the pharmaceutical industry: Harmonizing frameworks for practical implementation: https://www.biophorum.com/download/artificial-intelligence-risk-guidance-for-the-pharmaceutical-industry-harmonizing-frameworks-for-practical-implementation/ AI CMC Regulatory Landscape: https://jackprior.ai/ai-cmc-landscape/ Fact check: 58 factual claims in this episode were checked against the source documents by an independent AI pass: 52 are supported by the primary text, 4 are confirmed by official web sources, 1 rest on secondary sources or are hedged as such (listed in the report), 1 corrected before release, 0 open. Full report: https://jackprior.ai/podcast/factcheck/05-evidence.html

For twenty years the model you picked was an engineering choice. Draft EU GMP Annex 22 makes it a compliance decision: static and deterministic machine learning only in critical GMP applications, with dynamic models, probabilistic models and generative AI told they should not be used there at all. Sam and Sarah read the six-page draft in full, set it against FDA's 2025 draft, which tells sponsors to anticipate self-evolving models and never mentions language models, and against the device world's predetermined change control plans. EMA's reflection paper and NIST's generative AI profile supply the vocabulary for the risks. The four recurring systems go through the gate, and the episode ends with how a site keeps a retraining loop outside the GMP boundary. Researched, scripted and voiced by AI systems under Jack Prior's direction. Sam and Sarah are AI characters; nothing in the episode is Jack speaking, and none of it is a statement of his views or his employer's. Generative AI can be confidently wrong — check the sources. Corrections: [email protected]. Transcript: https://jackprior.ai/podcast/transcript/04-model-type.html Documents discussed: Annex 22 — Artificial Intelligence: https://picscheme.org/docview/9715 Considerations for the Use of AI to Support Regulatory Decision-Making for Drug and Biological Products: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/considerations-use-artificial-intelligence-support-regulatory-decision-making-drug-and-biological PDF: https://nvlpubs.nist.gov/nistpubs/ai/NIST.AI.600-1.pdf Reflection Paper on the Use of AI in the Medicinal Product Lifecycle: https://www.ema.europa.eu/en/documents/scientific-guideline/reflection-paper-use-artificial-intelligence-ai-medicinal-product-lifecycle_en.pdf Marketing Submission Recommendations for a PCCP for AI-Enabled Device Software Functions: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/marketing-submission-recommendations-predetermined-change-control-plan-artificial-intelligence AI CMC Regulatory Landscape: https://jackprior.ai/ai-cmc-landscape/ Fact check: 64 factual claims in this episode were checked against the source documents by an independent AI pass: 58 are supported by the primary text, 4 are confirmed by official web sources, 2 rest on secondary sources or are hedged as such (listed in the report), 0 open. Full report: https://jackprior.ai/podcast/factcheck/04-model-type.html

Seven documents grade models seven ways, and they grade different things. Sam and Sarah start with the 2011 ICH Points to Consider, which graded models low, medium and high by their role in assuring quality and made 'sole indicator' the line, then set beside it FDA's and M15's model risk, Annex 22's critical-or-not test and model-type gate, the AI Act's product tiers, and BioPhorum's redefinition of model influence as maturity. Four tiers emerge for the season. All four recurring systems are placed and moved, and the agentic assistant's tier turns out to be an argument about criticality that has to be won first. Researched, scripted and voiced by AI systems under Jack Prior's direction. Sam and Sarah are AI characters; nothing in the episode is Jack speaking, and none of it is a statement of his views or his employer's. Generative AI can be confidently wrong — check the sources. Corrections: [email protected]. Transcript: https://jackprior.ai/podcast/transcript/03-grading.html Documents discussed: Q8/Q9/Q10 Points to Consider — ICH-endorsed implementation guide: https://www.ema.europa.eu/en/documents/scientific-guideline/international-conference-harmonisation-technical-requirements-registration-pharmaceuticals-human-use-ich-quality-implementation-working-group-points-consider-ich-q8q9q10-guidelines_en.pdf AI CMC Model Impact Crosswalk: https://jackprior.ai/ai-cmc-landscape/ Q9(R1): https://database.ich.org/sites/default/files/ICH_Q9%28R1%29_Guideline_Step4_2023_0126_0.pdf Annex 22 — Artificial Intelligence: https://picscheme.org/docview/9715 Regulation (EU) 2024/1689 — AI Act: https://eur-lex.europa.eu/eli/reg/2024/1689/oj/eng BioPhorum — AI risk guidance for the pharmaceutical industry: Harmonizing frameworks for practical implementation: https://www.biophorum.com/download/artificial-intelligence-risk-guidance-for-the-pharmaceutical-industry-harmonizing-frameworks-for-practical-implementation/ Fact check: 69 factual claims in this episode were checked against the source documents by an independent AI pass: 62 are supported by the primary text, 6 are confirmed by official web sources, 1 rest on secondary sources or are hedged as such (listed in the report), 0 open. Full report: https://jackprior.ai/podcast/factcheck/03-grading.html

The one idea in nearly every document: context of use. Sam and Sarah read FDA's January 2025 draft closely, from question of interest to role and scope to model risk as influence times consequence, trace the vocabulary from ASME's device standard through FDA's 2023 device guidance to ICH M15, and set EMA's two axes beside it. FDA's fill-volume camera is medium risk only because a sample test stays in place. All four recurring systems go through steps one to three, and the agentic assistant turns out to be the one whose scope sentence is hardest to write honestly. Researched, scripted and voiced by AI systems under Jack Prior's direction. Sam and Sarah are AI characters; nothing in the episode is Jack speaking, and none of it is a statement of his views or his employer's. Generative AI can be confidently wrong — check the sources. Corrections: [email protected]. Transcript: https://jackprior.ai/podcast/transcript/02-context-of-use.html Documents discussed: Considerations for the Use of AI to Support Regulatory Decision-Making for Drug and Biological Products: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/considerations-use-artificial-intelligence-support-regulatory-decision-making-drug-and-biological M15 — General Principles for Model-Informed Drug Development: https://database.ich.org/sites/default/files/ICH_M15_Step4_Final_Guideline_2026_0129.pdf Assessing the Credibility of Computational Modeling and Simulation in Medical Device Submissions: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/assessing-credibility-computational-modeling-and-simulation-medical-device-submissions Reflection Paper on the Use of AI in the Medicinal Product Lifecycle: https://www.ema.europa.eu/en/documents/scientific-guideline/reflection-paper-use-artificial-intelligence-ai-medicinal-product-lifecycle_en.pdf AI CMC Regulatory Landscape: https://jackprior.ai/ai-cmc-landscape/ Fact check: 74 factual claims in this episode were checked against the source documents by an independent AI pass: 70 are supported by the primary text, 4 are confirmed by official web sources, 0 rest on secondary sources or are hedged as such (listed in the report), 0 open. Full report: https://jackprior.ai/podcast/factcheck/02-context-of-use.html

Before reading any single document, you need the map. Sam and Sarah sort the AI-in-manufacturing rulebook into its four layers, replace "binding or not" with maturity and who-will-ask, and trace five trends across the documents: from models to AI, from model-agnostic to Annex 22's line on model type, from validation to lifecycle, from regional to the joint EMA-FDA principles and ICH's reflection paper, and from silence on generative AI to a gap everyone can see. The recurring cast is introduced, and the agentic assistant that drafts deviation investigations is walked down the maturity axis to show how little the documents yet say about it, and how a site reasons about it anyway. Researched, scripted and voiced by AI systems under Jack Prior's direction. Sam and Sarah are AI characters; nothing in the episode is Jack speaking, and none of it is a statement of his views or his employer's. Generative AI can be confidently wrong — check the sources. Corrections: [email protected]. Transcript: https://jackprior.ai/podcast/transcript/01-five-moves.html Documents discussed: AI CMC Regulatory Landscape: https://jackprior.ai/ai-cmc-landscape/ EMA + FDA — Guiding Principles of Good AI Practice in Drug Development: https://www.ema.europa.eu/en/documents/other/guiding-principles-good-ai-practice-drug-development_en.pdf Reflection Paper on proposed ICH work to facilitate Advanced Pharmaceutical Manufacturing: https://admin.ich.org/sites/default/files/2026-03/ICH_ReflectionPaper_AdvancedManufacturing_2025_1008_0.pdf Considerations for the Use of AI to Support Regulatory Decision-Making for Drug and Biological Products: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/considerations-use-artificial-intelligence-support-regulatory-decision-making-drug-and-biological Fact check: 148 factual claims in this episode were checked against the source documents by an independent AI pass: 121 are supported by the primary text, 20 are confirmed by official web sources, 6 rest on secondary sources or are hedged as such (listed in the report), 1 corrected before release, 0 open. Full report: https://jackprior.ai/podcast/factcheck/01-five-moves.html

Jack Prior introduces the show: a bioprocess engineer who started out in the late eighties at MIT looking at how to apply AI to bioprocesses, on why 2026 is the year that time has arrived — and the question the podcast asks of our data readiness, of machine learning and agentic AI, and of the regulatory frameworks: are we there yet? Season 1 works through the forty-odd guidances and white papers that make up the regulatory landscape, in a narrative format produced with AI and fact-checked against the source documents. Everything at https://jackprior.ai/podcast Researched, scripted and voiced by AI systems under Jack Prior's direction. Sam and Sarah are AI characters; nothing in the episode is Jack speaking, and none of it is a statement of his views or his employer's. Generative AI can be confidently wrong — check the sources. Corrections: [email protected]. Transcript: https://jackprior.ai/podcast/transcript/trailer.html