Legislation Lecture 2:Licensing of Medicinal Products Flashcards
Marketing AuthorisationFormerly known as PRODUCT LICENCE (PL)
Needed for every Medicinal Product
Before being prescribed / sold.
Licensing body – Either or both of the Ministers
Functions carried out by MHRA
Usually submitted by Pharmaceutical Industry
But, anyone can submit a request.
Can take up to 210 days to go through process
Can take 30 days to inform approval granted
Sets out the rules for manufacturing, importing and wholesale dealing
It requires these activities to be subject to a licence
Establishes what the licencing authority must consider when assessing an application
Sets out requirements for Responsible Persons and Qualified Persons
Manufacturer’s or wholesale dealer’s license
Granted by licensing authority
Within 90 days
Remains in force until surrendered/revoked
Licensing authority may suspend/revoke/vary
28 day notice
Immediate suspension possible for safety reasons
Max 3 months + further 3 months…..
Manufacturer’s licence.
Medicinal products manufactured in the UK must be produced on a site that holds an appropriate manufacturer’s licence (ML).
A person may not, except in accordance with a licence (a “manufacturer’s licence”)
(i)Manufacture, assemble or import from a state other than EEA state any medicinal product; or
Possess a medicinal product for the purpose of any activity in (i) above.
Marketing Authorisation issued by a competent authority
MHRA
Manufacturing license not needed by a person who imports a medicinal product for personal use.
Manufacturing license does not apply to the mixing of medicines.
The site is inspected by the MHRA Inspectorate to ensure that the following criteria and standards are met:
Appropriate facilities, equipment and suitably trained staff are available and maintained
All products are manufactured to the standards detailed by the EC Guide to Good Manufacturing Practice
Quality Assurance measures are built into each step of the manufacturing process to ensure the safety, quality & efficacy of the product
The site is inspected by the MHRA Inspectorate at least every two years
Wholesale dealer’s licence
Any company or individual wishing to wholesale deal (defined as selling, supplying or procuring to anyone other than the end-user) medicinal products within the EU must hold a wholesale dealer’s licence (WDL)
Distributing by way of wholesale dealing is a reference to –
Selling or supplying it; or
Procuring or holding it or exporting to another EEA state for the purpose of sale or supply,
To a person who receives it for a purpose of –
Selling or supplying the product or
Administering it or causing it to be administered to one or more human beings, in the course of a business carried on by that person.
The licensing is primarily concerned with:
Identification of the Distributor
Suitability of the premises used for storage, distribution and stock control
Wholesalers are inspected before a WDL is granted, and at least once during the 5-year period of the licence
Wholesale dealer (GSL) available
Only deal in GSL medicines
RP needed to oversee process.
Clinical trial authorisation
Needed by new products under development.
Needed before being tested on humans
licensing
Manufacturer’s licence
Wholesale dealer’s licence
Clinical trial authorisation
(All are issued by MHRA)
So No WDL needed if
- It takes place on an occasional basis
- The quantity of medicines supplied is small
- The supply is made on a not for profit basis
- The supply is not for onward wholesale distribution
Product development
New Chemical Entity
Clinical trials
Marketing Authorisation
Production (Manufacturer’s Licence)
Distribution to patients (Wholesaler Dealer’s Licence)
Development Process
Discovery: 5,000 to 10,000 molecules
Preclinical testing: approx. 250 molecules
Phase I: approx. 5 molecules
Phase II: approx. 2-3 molecules
Phase III: approx. 1-2 molecules
Phase IV: Post marketing trials)
Registration Approval: 1 molecule
Time - 10 years? (range: 4.2 to 25 years)
Cost – $2.5billion (2014 Scientific American)
Clinical Trials
Phase 1 trials usually involve healthy people to find out how the medicine works in the body
Usually less than 100 people
Phase 2 trials look at how the drug works in a particular condition
Several hundred people
Phase 3 looks at how well the medicine works and how safe it is in the general population
Several hundred to several thousand people
Clinical Trials Application
New legislation introduced May 2004
Emphasis shifted from controlling the product to authorisation of the trial
Trial approval by MHRA within 60 days
Regulation of healthy volunteer trials
Manufacturer’s trials licence required
Inspections for standards of Good Clinical Practice (GCP) & Good Manufacturing Practice (GMP)
Labelling requirements
Ethics committee system
EvaluationSafety & Efficacy
Nature of the active ingredients
Dosage form
Nature of disease or condition treated
Type of Patient
Duration of treatment
More effective than placebo
Risk to Benefit ratio
EvaluationQuality
Product’s physical, pharmaceutical & biological characteristics to ensure that each batch of the medicine is capable of performing reliably and consistently
Granting of MA- marketing authority
Submission of necessary documentation
Fees
Validation
Ensure forms completed accurately
Assessment
Assessor determines whether there is sufficient information to evaluate the Safety, Quality and Efficacy of the product.
Assessor may seek further advice from CHM or EAG.
CHM / EAG may advise to license or refuse.
Applicant has the right of appeal.
Valid for 5 years initially
On renewal, unlimited period unless safety concerns.
On renewal, up to date data must be supplied
New medicines are usually POMs
Product must be on market within 3 years of granting of MA.
Subject to pharmacovigilance
‘Black triangle’ drugs
‘Yellow card’ reporting
All applications to the MHRA
What are the Systems to Register Medicines
Centralised
Decentralised
Mutual Recognition
National
Centralised
One single application is made to the EMA (used to based in London)
One single European Authorisation is granted by EMA
Certain medicines can only be licensed in this way to ensure that they are automatically available to every EU member state
Gene therapies
Medicines for HIV/AIDS, cancer, diabetes, Altzheimer’s
Orphan drugs (medicines for rare diseases, occurring in less than 5 in 10,000 people)
