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Regulatory changes were required in order to allow the use of an electronic signature for the ETP pilot projects. These were introduced in 2001. The amendment to pharmacists' terms of service also included an amendment to the Misuse of Drugs Regulations 1985 to enable prescriptions for temazepam (but not other Schedule 2 or 3 controlled drugs) to be included in these trial arrangements. Equivalent amending Directions for GPs under Personal Medical Services came into force on the same day. Many of these regulations have now been superseded by those which provide the legal framework for the full Electronic Prescription Service.

The Medicines for Human Use (Prescribing) Order 2005 amended the Prescription Only Medicines (Human Use) Order 1997 to allow a prescription to be signed by an advanced electronic signature. However, current NHS legislation states that PCTs must be authorised by the Secretary of State before contractors in their area operating under an NHS contract can use EPS. This will allow the controlled rollout of electronic prescribing to the NHS. Initially, EPS will not use electronic signatures. A paper prescription, issued in parallel with the EPS message, will remain the legal prescription.