1. Prescription-only vs. over-the-counter medicines
Jana Klimasová, PhD.
Department of pre-clinical and clinical assessment, Registration section, SIDC

2. „Legal status“ of medicinal product
conditions and restrictions under which the medicinal product should be made available to patients
National, DCP, MRP procedure – national decision
Centralised procedure – part of the CHMP opinion
Legislation – Directive 2001/83/EC and national laws
Legal status given at the time of registration – during renewal or when new facts are brought up legal status can be changed
May differ between strengths/forms/presentation of the same MA

3. Directive 2001/83/EC
Subject to medical prescription
Medicinal products on renewable or non-renewable medical prescription
Medicinal products subject to special medical prescription
Medicinal products on restricted medical prescription, reserved for use in certain specialized areas
Not subject to medical prescription

4. Levels of categories for the supply of centrally authorised
medicinal products
EMEA/186279/2006

5. Subject to medical prescription
– likely to present a danger
- frequently used incorrectly
- activity or adverse reactions not well known yet
- parenteral medicinal products
Subject to special medical prescription
- narcotic or psychotropic substances
- risk of medicinal abuse, addiction, misuse
Subject to restricted prescription
- treatments (diagnose) in a hospital environment
- requiring a prescription drawn up by a specialist (due to adverse reactions) and special supervision throughout the treatment
Not subject to medical prescription
– non of the above

6. Assessment of legal status:
1) Does medicinal product present a danger (directly/indirectly), even if used correctly, if utilized without medical supervision?
- Direct danger/safety profile
- Indirect danger /safety profile
- Self-assessment
- Risk and consequences of incorrect use
- Patients information
2) Is medicinal product frequently and to a very wide extent used incorrectly, and as a result is likely to present a direct or indirect danger to human health?
- Known incorrect use

7. Assessment of legal status:
3) Does medicinal product contain substances thereof the activity and/or side-effects of which require further investigation?
- Recent authorisation/limited experience
- New strength, dose, route of administration, indication, age group or combination of substances
4) Is medicinal product administered parenterally?

8. Acceptable exceptions:
There are certain cases, when MP eligible for legal status „subject to medical prescription“ can be classified as „OTC“
OTC status must be made „appropriate“:
Pack size and package form – intended length of treatment
(small pack size – possible safeguard against misuse (overdose), or delay in seeking medical attention)
Maximum dose, maximum daily dose
(restriction, however, must retain efficacy)

9. Data supporting the change of the legal status:
Non-clinical and/or clinical overview (expert report)
- critical analysis of the proposed availability of the product without a medical prescription with the dose and indications as stated in the application
- demonstration why none of the Rx criteria apply
Non-clinical and/or clinical safety
- low toxicity
- patient exposure, adverse events,
- experience of OTC use
- potential for interaction with other MP/ misuse/overdose
- consequence of delayed diagnosis

10. Data supporting the change of the legal status:
Clinical efficacy
- considered only if change of indication or posology intended
4. Product information
- proposed labelling and package leaflet
- examined for comprehensive information and effectiveness in protecting patients from any safety hazards
- readability
5. Other
- change of container

11. Data Exclusivity for data submitted
for a ‘switch’ of the legal status
Directive 2001/83/EC :
„Where a change of classification of a medicinal product has been authorised on the basis of significant pre-clinical tests or clinical trials, the competent authority shall not refer to the results of those tests or trials when examining an application by another applicant for or holder of marketing authorisation for a change of classification of the same substance for one year after the initial change was authorised.“
Name of the medicinal product
- Possibility to choose new invented name (up to applicant)

12. References:
Directive 2001/83/EC
Regulation (EC) No 726/2004
Guideline on legal status for the supply to the patient of centrally authorised medicinal products (EMEA/186279/2006)
The Rules governing Medicinal Products in the European Community Volume 2C: A guideline on changing the classification for the supply of a medicinal product for human use

13. CASE STUDY 1: Orlistat
Available documents:
EMA press release concerning switch of orlistat (60mg) from POM to OTC
Product information – Alli
Product information – Xenical
Assessment report – Alli
EMA press release concerning Art. 20 evaluation of orlistat
Two orlistat-containing medicines hold an EU-wide marketing authorisation. Xenical was authorised in 1998 and is available as capsules (120 mg) which can only be obtained with a prescription. Alli was authorised in 2007 and is available as capsules (60 mg) and chewable tablets (27 mg) which can be obtained without a prescription (‘over-the-counter’).

14. CASE STUDY 1: Orlistat
Tasks:
Compare the product information of Alli and Xenical. What are the differences? Is the product information for Alli appropriate concerning the self-medication by patients?

15. CASE STUDY 2: Omeprazol
Available documents:
Losec – annex III
- SmPC for Rx – pg 32-43
- PIL for Rx – pg
- SmPC for OTC – pg 78-86
- PIL for OTC – pg
Tasks:
Compare the SmPC and PIL of prescription only omeprazol with SmPC and PIL of over the counter omeprazol. Are the criteria necessary for OTC/Rx status taken into consideration in these product informations?

16. Thank you for your attention!