OSPAP Programme: Human Medicines Regulations

OSPAP Programme: Human Medicines Regulations 2012 - Licensing System (Part 1)

• Learning Outcomes:
• Briefly explain the licensing system and the licenses.
• Explain marketing authorization and SmPCs.
• Explain the MHRA's role in granting licenses, focusing on criteria for marketing authorization.
• Understand manufacturer and wholesale dealer licenses.
• Explain biosimilar medicines and why they aren't generic equivalents.
• Explain herbal medicine licensing.
• Define pharmacovigilance and its importance.
• Explain the early access scheme and orphan drugs.

The Licensing System

• The licensing system was introduced in the Medicines Act 1968 (now governed by the Human Medicines Regulations 2012)
• Three types of license: Marketing Authorization (MA), Manufacturer's License (ML), and Wholesale Dealer's License (WDL)
• Two types of certificate: Clinical Trials Certificate (CTC), and Clinical Trials Exemption Certificate (CTX)
• Licenses and certificates allow specific activities; companies may need multiple licenses for complex processes.
• It is illegal to perform certain activities without the proper license, except in exempted situations.
• Each license/certificate is used at a specific point in a medicine's development.

The Licensing Process

• Starts with clinical trials on patients with the disease (CTC/CTX granted)
• Data compilation regarding drug properties/formulation (MA submission)
• Marketing Authorization granted (MA)
• Production planning, batching, assembly (ML submission)
• Manufacturer's License granted (ML)
• Distribution planning by wholesale (WDL submission)
• Wholesale Dealer's License granted (WDL)

Key Criteria for Licensing a New Medicine

• Safety
• Quality
• Efficacy
• Cost

Marketing Authorisations (MA)

• Previously known as 'product licenses'
• Regulatory approval for specific medicines, allowing marketing.
• Approving authority is the MHRA.
• It's illegal to sell/supply a medicine without a UK MA, with some exceptions for pharmacists.
• MAs are issued for a set period (usually 5 years or less)
• Periodic renewal is required.
• MHRA may revoke, amend, or suspend a MA.

Marketing Authorisations (MA) 2

• Full information on manufacturing, testing (including clinical trial results) must be submitted to the MHRA for new products.
• An international "fast track" recognition is possible for medicines already licensed in EEA countries.
• A MA allows the holder to sell, supply, or export the medicine.
• Obtain manufacturing or assembly procedures and produce a summary of product characteristics (SmPC)

Summary of Product Characteristics (SmPC)

• Prepared by the MA holder, forming the only public part of the application.
• Regulations specify required content.
• Detailed summary of the medicine's properties, use conditions.
• Formatted in a standard manner, and is a reference source for healthcare practitioners.
• Non-promotional and MHRA-approved.
• Basis for patient information leaflets (PILs).
• Must be updated during the medicine's lifetime with new safety data. Accessible online at www.medicines.org.uk.

What Information Does an SmPC Contain? (1 and 2)

• Detailed list of the content within the SmPC

Marketing Authorisations (MA) 3 - Generics

• A product is a generic medicine if: identical qualitative and quantitative composition as the reference medicinal product (RMP), same form as the RMP. Demonstrates bioequivalence with the RMP.
• Data on safety and efficacy can be used from the RMP after a "data exclusivity period" of 8 years. This allows use of the RMP data and an "abridged application.".
• Data exclusivity period is different from the patent protection period.

Biologics and Biosimilars

• Biologics are medicines derived from natural sources (human, animal, or microorganism)
• Examples include insulin glargine, infliximab, epoetin alfa.
• A biosimilar is a medicine that is very similar to an already licensed biologic medicine in terms of safety, quality and efficacy, and is for treatment of similar diseases.
• A biosimilar cannot be marketed until the patent for the originator biologic has expired.

Marketing Authorisations (MA) 5 - Biologics and Biosimilars

• Due to biologic complexity, a perfect copy cannot be created
• Biosimilars may differ slightly in molecular weight, method of synthesis and stability.
• Biologics and biosimilars should be prescribed by brand name.
• Required to report adverse events for biosimilars.
• Biosimilars generally are more affordable and provide cost savings to the NHS.

Early Access to Medicines Scheme

• Scheme for life-threatening medicines without suitable alternatives.
• Voluntary 2-part procedure:
• Early clinical data to the MHRA, well in advance of a MA application.
• Scientific advisors assess medicine's benefit-risk profile.
• An opinion supports the use before the MA.

Orphan Drugs

• Medical treatments for extremely rare conditions.
• May not be easily cost-effective to develop due to low market demand.
• Requirements for "life-threatening or chronically debilitating" conditions and low incidence (less than 5 per 10,000)
• Offer significant benefit over existing treatments, given market exclusivity for up to 10 years.
• Orphan drugs for paediatric conditions receive another 2 years of exclusivity.
• The originator drug is listed in the GB Orphan Register.

Manufacturer's License

• Used to manufacture/assemble medicines.
• No person can manufacture medicine without a license.
• Manufacturing processes do not include simple mixing.
• Includes the description of the manufacturing site, equipment, people and qualifications.
• "Good Manufacturing Practice" (GMP) standards apply.
• Regularly inspected by the MHRA.

Wholesale Dealer's License

• Required for selling/supplying medicine in bulk (not to end-users)
• The license specifies the permitted wholesale dealing activities.
• Includes details of premises, distribution, security, and records.
• "Emergency recall plan for medicines"
• Responsible person must be named in the application
• MHRA inspectors carry out site visits.
• Manufacturer sales not covered under this license.

Pharmacovigilance

• Post-marketing surveillance of medicine safety.
• All MA holders must operate a pharmacovigilance system.
• Focuses on "black triangle" medicines (see additional monitoring).
• Completing a "yellow card" report for adverse drug reactions is crucial.
• MHRA constantly evaluates medicines based on yellow card data and other safety assessments. Includes clinical studies and global medical literature.
• May restrict, change dosage, introduce warnings, or remove products from the market after assessment.

Medicines Subject to Additional Monitoring

• A black triangle in the BNF, SmPC, and PIL indicates additional monitoring requirement.
• This indicator is used whenever the medicine: contains a new, active substance, a biological medicine, a conditional approval is granted, or has exceptional circumstances requiring further data.
• Requires additional studies for long-term use or rare side effects.

Herbal Medicines

• Definition: medicinal products with only herbal ingredients/preparations.
• Must be licensed or registered under the THR scheme.
• No efficacy data is required to be licenced.
• Provides guidelines on quality, safety, manufacturing standards, PILs and packaging requirements.

Homeopathic Medicines

• Licensing not covered in detail.
• The information is widely available elsewhere.
• The Royal Pharmaceutical Society (RPS) does not endorse homeopathy due to lack of scientific evidence.
• The National Health Service (NHS) England stopped recommending homeopathic medicines in 2017.

E-cigarettes

• E-cigarettes & e-liquids (non-medicinal) require MHRA notification before sale.
• Must meet minimum safety and quality standards.
• Reported via the yellow card scheme (side effects).
• Medicines that help people quit smoking must be licensed (MA).
• These medicinal products may have higher strength and volume than non-medicinal ones.

Explore the key aspects of the Human Medicines Regulations 2012 within the OSPAP Programme. This quiz covers the licensing system, marketing authorization, the role of the MHRA, and various types of licenses including those for biosimilar and herbal medicines. Test your understanding of pharmacovigilance and the early access scheme.