Principles and Practice of Pharmaceutical Medicine

License renewals

MAs are granted for five years in the first instance,
after which a renewal is necessary. This requires
submission of a review of all the product experi-
ence since the drug was first marketed. Essential
parts of this review are the periodic safety update
reports (PSURs), required every six months during
the first two years of marketing, and annually there-
after. Normally, after the five-year renewal, further
PSURs are required every five years. Under special
circumstances more frequent PSURs may be
required for products, which the authorities wish
to keep under closer review. There is never any
relaxation of the requirement for expedited report-
ing of serious, unexpected AEs.
For most products, the revised regulation fore-
sees only one renewal based on a reevaluation of
the risk–benefit balance, after which the validity of
the MA is unlimited. However, at its discretion,
national regulatory authorities can still require
subsequent five-year renewals (article 24 of
Directive 2004/27 and article 14 of Regulation
726/2004).

Reclassification

Reclassification (e.g. an ‘over-the-counter switch’)
remains the responsibility of each national RA.
The EU guideline on changing legal classification
for the supply of medicinal products (The rules
governing medicinal products in the European
Community – Vol. IIIb) sets out the standards
that must be fulfilled in order to change the legal
classification of a medicinal product.
New products, when first licensed, are usually
approved as ‘prescription only medicine’ (POM).
With increasing experience in the use of the med-
icine, it might seem likely that a medication is safe
for use with pharmacy supervision only; then, the
NCA may remove the prescription requirements
and allow sale or supply from a pharmacy without
prescription, that is the medicinal product is reclas-
sified as Pharmacy (P). If further experience shows
that access to professional advice is not required
for safe use of the medicine, it may finally be
reclassified as general sales list (GSL) to allow

sale from a wider range of retail outlets on an

over-the-counter basis.

In the United Kingdom, the post-licensing divi-

sion of the MHRA deals with all reclassification

requests. By law, all medicines are P unless they

meet the criteria for POM or GSL. Pack size

restrictions for GSL products are listed in theMed-

icines (Sale or Supply) (Miscellaneous provisions)

Regulations1980. For all licensed medicines, legal

status is ultimately determined by the MA.

Directive 2001/83 provides that prescription

control is applied to any product which:

is likely to present a direct or indirect danger to

human health, even when used correctly, if used

without the supervision of a doctor or dentist; or

is 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; or

contains substances or presentations of sub-

stances of which the activity requires, or the

side effects require, further investigation; or

is normally prescribed by a doctor or dentist for

parenteral administration.

Exemptions from prescription control may be

made with regard to

the maximum single dose;

the maximum daily dose;

the strength of the product;

its pharmaceutical form;

its packaging or

other circumstances relating to its use that would

be specified when reclassification is determined.

After the national RA has received and validated an

application, it classifies the application into one of

three types: standard, complex or ‘me-too’ appli-

cations not supported by full data.

34.13 MARKETING AUTHORIZATION VARIATIONS, RENEWALS AND RECLASSIFICATION 475