“SPECIALS” LEGAL BACKGROUND & INTRODUCTION TO GN14 Presented by Rob Lowe Director of Quality Assurance Specialist Services – East of England

THALIDOMIDE & THE MEDICINES ACT “ I come to my last main topic which is the control and safety of drugs. This is of course a subject which was thrust to the fore both in this House and in the public press a year or so ago as a result of the thalidomide tragedy. The House and the public suddenly woke up to the fact that any drug manufacturer could market any product, however inadequately tested, however dangerous, without having to satisfy any independent body as to its efficacy and safety and the public was almost uniquely unprotected in this respect.” Kenneth Robinson, in a parliamentary debate on 8th May 1963 (Source; Hansard)

PRODUCT LICENSES OF RIGHT  39,000 PLR’s issued in May 1971 for all medicinal products already on the UK market  CRM (Committee on the Review of Medicines) set up in 1975 to review all PLR’s with a deadline of completion by 1990  CRM review completed in Only 5,300 PLR licences had been renewed

THE MEDICINES ACT 1968  The Medicines Act is principally a licensing act  Introduced a comprehensive system of licensing controlling the manufacture, sale, supply & importation of medicines  It became unlawful to engage in these activities without the appropriate licence, certificate or exemption.  European law equivalent EC directive 65/65

THE MEDICINES AND HEALTHCARE PRODUCTS REGULATORY AGENCY (MHRA)  The Medicines Commission  The British Pharmacopoeia Commission  The Licensing Division  The Post-licensing Division (Committee on Safety of Medicines, Defective Medicines Report Centre)  Inspection & Enforcement Division

PRODUCT LICENCE APPLICATIONS  Clinical trial or bioavailability study data  Toxicity information  Manufacturing method  Manufacturing site or contract manufacturer  Container details  Labelling and packaging details  Patient Information Leaflet  EC 65/65 “Marketing Authorisation” or MA

MANUFACTURERS LICENCE  Required to manufacture a PL medicine  ML “specials” by product/activity type e.g. small volume injectables, pre-packs etc. Permits the holder to manufacture medicines without a PL to Dr/Dentists order  Inspected regularly by the MHRA to ensure compliance with GMP standards including raw material and finished product testing, documentation, release procedures, training and contamination control etc.  Also required now for clinical trial material

SECTION 9 EXEMPTION  Doctors/Dentists do not need to have a PL for any product prepared to their own prescription for administration to a particular patient.  Nor do they require a ML for the above though the manufacturer of the product may require a ML “specials”

SECTION 11 EXEMPTION A registered nurse or certified midwife does not require a ML in order to assemble medicinal products (i.e. reconstitute I.V.’s etc.) in the course of his/her professional activities.

SECTION 10 EXEMPTION  A registered Pharmacist does not require a ML to manufacture/prepare medicines in accordance with a Dr’s prescription, or for stock in anticipation of a prescription (limits apply on quantity and frequency).  A ML is not required to manufacture non- prescription medicines for sale in the course of counter-prescribing.  Preparation must be “by or under the supervision of a Pharmacist”

SECTION 10 AND ASEPTICS  Preparation for stock should be avoided  The preparation method uses closed systems  Licensed medicinal products are used as ingredients or ingredients are manufactured in licensed facilities (i.e. are “specials”)  Products have an expiry date of not more than 1 week (supported by stability data)  All activities are in accordance with defined NHS guidelines (i.e. “Orange Guide”)

WHAT IS A “SPECIAL”  Medicines for Human Use (Marketing Authorisations etc.) Regulations 1994 SI no.3144 (Schedule 1 Exemptions)  Exemption from the requirement for a MA “a medicinal product to fulfil special needs, supplied in response to a bona fide unsolicited order, formulated in accordance with the specification of a Dr or Dentist for use by his/her patients on his/her direct personal responsibility” Abridged

WHAT IS A “SPECIAL” 2  Is not “pharmaceutically equivalent” to a licensed medicine  Meets a “special need” of a patient e.g. liquid if cant swallow tablets, preservative free eye drops if allergic to preservative etc.  If the licensed medicine becomes unavailable then a “special” can be placed on the market for as long as the licensed product is unobtainable  Convenience, safety of use or cost are not justifications for manufacturing a “special”

PHARMACEUTICAL EQUIVALENCE  Contains the same amount of the same active substance (same concentration if a liquid) AND  Is in the same dosage form AND  It meets the same or comparable standards with regard to the clinical needs of the patient at the time (e.g. purity/impurity)

“PLACING ON THE MARKET”  A product manufactured by 1 legal entity (e.g. a Trust) and supplied to another is “placing on the market”  A product manufactured by a Trust for administration to a patient within its premises is not “placing on the market” BUT if supplied to an out-patient who takes it off the Trust’s premises this would be equivalent to “placing on the market”

A “SPECIAL” IS NOT….  Investigational medicinal products  A product prepared against a Dr’s prescription (i.e. Section 10 exemption)  “Off label” use of a licensed medicine  Repackaged licensed products  Reconstituted IV’s and CIVAS products  Intermediate products  Homeopathic and certain herbal remedies

PROCUREMENT & SUPPLY  Persons authorised to procure “specials” include UK registered Dr’s/Dentists, Pharmacists and licensed wholesalers who supply the above.  Supply must be for a bona fide unsolicited order. As “specials” are not licensed it is illegal to advertise them. This includes Price Lists and Catalogues.  A “specials” manufacturing service may be advertised.

How to obtain a FREE copy of GN14 Additional copies of GN14 are available from: The MHRA Information Centre Room 1207 Market Towers 1 Nine Elms Lane London SW8 5NQ phone fax MHRA Guidance Note No.14 Revised January 2008 THE SUPPLY OF UNLICENSED RELEVANT MEDICINAL PRODUCTS FOR INDIVIDUAL PATIENTS