EU pharma package: what the new pharmaceutical regulation changes

The two acts are negotiated as one package but work differently. The directive (the new Union code) sets the general rules for medicinal products for human use, including the national procedures, and Member States must transpose it into national law. Our overview of the ten main changes in the new pharmaceutical directive covers that half.

The regulation applies directly in every Member State without transposition. It repeals Regulation (EC) No 726/2004 and absorbs the orphan (Regulation (EC) No 141/2000) and paediatric (Regulation (EC) No 1901/2006) regulations (Art. 185). Some topics span both acts: the protection periods are set in the directive and apply to centrally authorised products through Article 30 of the regulation, while the antimicrobial voucher that extends them sits in the regulation.

As today, the clock stops while the applicant answers. The 180-day limit is suspended while you supplement the dossier or prepare oral or written explanations, and the CHMP can extend the analysis on a duly justified request (Art. 7(6) and Art. 11(1)). New is an early exit: if within 90 days of validation the CHMP finds the data not mature enough, it can set a deadline to fix the deficiencies and terminate the assessment if they are not addressed (Art. 11(2)).

After the opinion, the Commission has 12 days to send a draft decision to the Standing Committee and 12 days from that committee's opinion to decide (Art. 14). For planning, the change mostly affects launch sequencing: dates that depend on the opinion and the decision (pricing and reimbursement filings, supply readiness, artwork) may move earlier.

Article 148 lists the scientific committees for human medicines as the Committee for Medicinal Products for Human Use (CHMP) and the Pharmacovigilance Risk Assessment Committee (PRAC). The Committee for Advanced Therapies (CAT), the Committee for Orphan Medicinal Products (COMP), the Paediatric Committee (PDCO) and the Committee on Herbal Medicinal Products (HMPC) are not on that list.

Their expertise moves into working parties. The CHMP must set up working parties for quality, methodology, non-clinical and clinical evaluation and a scientific advice working party, and where necessary working parties on paediatric and orphan medicines and on environmental risk assessment (Art. 157(2)). Herbal medicines get a Herbal Medicinal Products working group under Article 145 of the directive. The committees keep final responsibility for opinions (Art. 157(1)). Orphan designation, paediatric investigation plans and advanced therapy assessments continue; EMA's procedural guidance will show who adopts which opinion and when.

The baseline periods sit in the directive. Article 30 of the regulation applies them to centrally authorised products, so the rules are the same whichever route a product took. Market protection can be extended by a year for an unmet medical need or for a new active substance meeting comparator and EU-filing or multi-country trial conditions, and by another year for a significant new indication. The conditions are covered in how the new data and market protection periods work.

The orphan rules sit in the regulation. Market exclusivity is nine years, eleven for breakthrough orphan medicines (no authorised treatment and a clinically relevant reduction in morbidity or mortality, Art. 72), and four years for orphans authorised on bibliographic data (Art. 73(2)). It can be extended by 12 months, up to twice, for new indications in different orphan conditions (Art. 74).

Protection periods drive generic entry dates. See planning loss of exclusivity across your portfolio for how Regunaut tracks these dates per product and market. Reference products whose application is submitted before the regulation applies keep the current periods (Art. 186(5)).

The Commission can grant a transferable data exclusivity voucher to a priority antimicrobial: one that addresses a multi-drug resistant organism, shows significant clinical benefit against resistance, and has a new mechanism of action or a new active substance for a serious infection (Art. 41). The applicant must show it can supply the EU market, disclose direct research funding, and file in the EU first or within 180 days of its first filing elsewhere.

The voucher adds 12 months of data protection to one centrally authorised product, the antimicrobial itself or another product of the same or a different company. On another product it can only be used in the fifth or sixth year of data protection, and only if EU gross sales stayed at or below EUR 490 million a year in the first four years. It can be transferred once, the buyer must report the price to EMA within 30 days, and it lapses if unused after five years (Art. 42 and 43). The scheme ends after five vouchers or 15 years from entry into force, whichever comes first (Art. 44). The other antimicrobial obligations, such as stewardship plans, are covered in antimicrobial stewardship and the new obligations for antimicrobials.

The Bolar provision sits in the directive, but it affects any reference product, centrally authorised or not. The covered activities can include manufacture, supply, storage and import, including by third-party suppliers, and tender submissions are covered as long as nothing is sold or offered for sale during the patent or SPC term. Placing the product on the market is not covered (Art. 87(3)). Competitors can therefore be ready to launch soon after protection ends.

The shortage rules sit in the regulation and apply to nationally and centrally authorised products alike. Marketing authorisation holders must notify at least 12 months before permanently ceasing supply in a Member State or requesting withdrawal of an MA, and at least six months before a temporary suspension or a disruption expected to last more than two weeks (Art. 120). Every prescription medicine needs an up-to-date shortage prevention plan, to be handed over within two days of a request (Art. 121). Holders of critical medicines must offer to transfer the MA or grant a letter of access before withdrawing (Art. 120(4)).

Timing differs from the rest of the package: the agreed text provides for Articles 120 to 132 to apply six months after entry into force, and the critical medicines provisions (Articles 133 to 140) from entry into force (Art. 187). Notice periods, plan contents and the scope of products covered are explained in shortage prevention plans and notification duties.

The Commission may set up a regulatory sandbox case by case, on EMA's recommendation, where a medicine cannot be developed and authorised in full compliance with the current requirements because of its methods or characteristics, and those features are likely to improve quality, safety or efficacy or patient access (Art. 116). A sandbox allows targeted technical adaptations under the direct supervision of the national competent authorities, for a limited time.

The product still needs an MA with a favourable benefit-risk balance (Art. 117).