HHS’s 340B program rules moved again as CMS and HRSA advanced complementary changes aimed at reshaping how covered entities are paid and how manufacturers supply ceiling-price rebates. CMS proposed revised 340B Drug Pricing Program payment rates effective calendar 2027, citing hospital acquisition costs and addressing site-of-care disparities. In parallel, HRSA rolled out a revised 340B Rebate Model Pilot Program that allows qualifying manufacturers to provide 340B pricing through post-dispensing rebates for selected drugs under the Medicare Drug Price Negotiation Program. HRSA’s pilot emphasizes claims-level visibility, transaction verification, and guardrails intended to prevent duplicate discounts. The operational burden remains significant for manufacturers and covered entities, with required technology platforms, quarterly pricing files, and tight rebate payment deadlines. The pilot’s implementation timeline—manufacturer submissions due Aug. 24, 2026, with starting Jan. 1, 2027—sets a near-term compliance milestone. For biotech and pharma, the immediate impact is heightened attention to 340B program mechanics ahead of broader policy evaluation. Companies that rely on 340B-eligible product access will likely re-run reimbursement and claims reconciliation models to align with the revised rebate structure.