Changing the Legal Status of a Medicine in the UK

1. Changing the Legal Status of a Medicine in the UK Changing the Legal Status of a Medicine in the UK

2. Introduction Legal Status Control of Prescription Medicines Reclassification Application Application Procedure P to GSL Reclassification across the EU

3. Legal Status at Authorisation - EU Directive 2001/83/EC (article 70) Directive 2004/27/EC (article 70) Regulation 2004/726 (cross referral to Directive 2001/83/EC (article 70)) Medicinal product subject to medical prescription Medicinal product not subject to medical prescription

4. Legal Status at Authorisation – UK Medicinal product subject to medical prescription Prescription Only Medicine (POM) available only on a prescription Medicinal product not subject to medical prescription Pharmacy Medicine (P) available under the supervision of a pharmacist General Sale List (GSL) available in general retail outlets such as supermarkets Presumption under law is that all medicines are POM unless they meet the criteria for P or GSL status

5. Control of Prescription Medicines A direct or indirect danger exists to human health, even when used correctly, if used without medical supervision There is frequently incorrect use which could lead a direct or indirect danger to human health Further investigation of activity and/or side-effects is required They are normally prescribed by a doctor to be administered parenterally

6. Control of Prescription Medicines Exemptions from prescription control may be made having regard to: the maximum single dose the maximum daily dose the strength of the product its pharmaceutical form its packaging such other circumstances relating to its use as may be specified in the determination

7. Control of Prescription Medicines Reclassifications apply to products, not to substances MHRA documents: List A (Consolidated list of substances in prescription only medicines (POM), with exemptions for Pharmacy (P) sale or supply). List B (Consolidated list of substances in authorised medicines for general sale) . List C: Consolidated list of substances which are present in authorised products which have been reclassified since 1 April 2002 http://www.mca.gov.uk/ourwork/licensingmeds/legalstatus/legstat.htm

8. Control of Prescription Medicines - Examples Acrivastine: POM unless Max daily dose: 24mg Max pack size: 240mg of acrivastine Piroxicam: POM unless Max. strength: 0.5% Route of admin: External use - For the relief of rheumatic pain, pain of non-serious arthritic conditions and muscular aches, pains and swellings such as strains, sprains and sports injuries. For use in adults and children not less than 12 years Treatment limitations: For maximum period of 7 days Max pack size: Container or package containing not more than 30g of medicinal product

9. Reclassification Application UK Application Reclassification Application Form Reclassification Summary Safety/Efficacy Summary Patient Information Training and Education Clinical Expert Report EU procedures based on UK model

10. Application Procedure Submitted as part of MAA, renewal or variation Submit at any time of the year Cannot have more than one legal status on one MA require duplicate licences if retaining POM status licence different tradenames etc Determined on a national basis One year’s data exclusivity for ‘first’ switch MHRA encourage pre-submission advice and meetings

11. Application Procedure Complex application 180 calendar days for review Requires Committee (CSM) referral 6 week public consultation period Standard Application 120 calendar days for review 4 week public consultation period No Committee referral required

12. Application Procedure Public consultation Consultation with interested parties Applications to reclassify medicines (ARMs) consultation letters Based on the Reclassification Summary Published on MHRA website Application determination Positive outcome legal status in new MA, renewal or variation Negative outcome applicant informed of assessment report appeal to Medicines Commission

13. Application Procedure

14. Application Procedure ‘Me-too’ application Analogous product has already been reclassified has the same active ingredient, route of administration and use has the same strength or a higher strength has the same dosage or daily dosage, or a higher dosage or daily dosage is for sale or supply at the same quantity or a greater quantity e.g. generics etc. Variation submission No committee referral or public consultation

15. Application Procedure – Fees Complex (new application or variation) £ 6 558 Standard (new application or variation) £ 3 279 Analogous product £ 500

16. Reclassification Summary Comprehensive overview Essential aspects of the reclassification request Public health impact of the change Non-confidential information Provided for the public consultation

17. Safety/Efficacy Summary Summaries from PSURs with full bridging data for any intervening period Availability, classification for sale and patient exposure for all countries where marketed Safety profile spontaneous reports of adverse reactions post-marketing surveillance studies clinical trials published literature safety reviews

18. Safety/Efficacy Summary Adverse drug reactions extrapolation of data from a 'prescription only' to a 'non-prescription' population Therapeutic overdose, misuse or abuse for cases of misuse, the consequence of delay in seeking medical attention Drug interactions OTC products herbal remedies nutritional supplements justification for pack size

19. Training and Education For health care professionals Information and training needs current treatment options warnings and precautions recognising symptoms and mis-diagnosis answering common questions support and monitoring of patients

20. Clinical Expert Report Critical evaluation of the proposed P product Demonstration of why none of the criteria for prescription control apply

21. First POM Criterion Likely to present a danger either directly or indirectly, even when used correctly, if utilised without medical supervision Direct danger adverse reactions benefit-to-risk in relation to similar products drug interactions with commonly used medicines Indirect danger masking of an underlying condition requiring medical attention increased risk of development of resistance symptomatic treatment without management of the underlying disease

22. First POM Criterion Self-diagnosis diagnosis without medical supervision excluding conditions with similar symptoms possibility and consequences of reoccurrence Contraindications essential precautions and warnings Risk of misuse danger to health is small if The product is used when not indicated The recommended dose is exceeded Contraindications or warnings are ignored medical advice is delayed

23. Second POM Criterion Frequently and to a very wide extent used incorrectly, and as a result are likely to present a direct or indirect danger to human health known to be used frequently incorrectly pharmacy status is not appropriate

24. Third POM Criterion Contain substances or preparations thereof the activity and/or side-effects of which require further investigation Limited experience number of patients exposed is relatively small evidence of safety in wide range of patients children elderly certain medical conditions New strength, dose, route of administration, age group or indication re-evaluation of risk:benefit according to proposed use extrapolation from safety data for existing prescription product

25. Fourth POM Criterion Are normally prescribed by a doctor or dentist to be administered parenterally involves breaching the skin or mucosa not appropriate for availability without medical supervision additional risks and complexity of administration

26. Patient Information Clear instructions to aid correct diagnosis and prevent mis-diagnosis will be needed Additional precautions and warnings due to the absence of medical supervision if no response is obtained circumstances requiring pharmacist and/or medical advice In line with relevant sections of Summary of Product Characteristics (SmPC)

27. P to GSL Application content and procedures very similar to POM to P Justify absence of health professional advice hazard to health risk of misuse significant special handling precautions wider availability Certain products excluded from GSL anthelmintics parenterals eye drops and ointments irrigations for wounds, bladder, vagina or rectum aspirin or aloxiprin for administration to children enemas

28. Reclassification across the EU Products authorised by Centralised Procedure Not national licences Guidance document under preparation Products authorised by Mutual Recognition Procedure Harmonised SmPC across EU Changes to SmPC in one MS must be reflected in all others potential harmonisation difficulties Duplicate applications?