MS Vs MIA GMP

The MHRA have issued an interesting guidance document regarding GMP inspections of MS or 'Specials' licensed facilities.  'Specials' manufacturing is a predominately a UK based activity which allows MS license holders to manufacture large quantities of medications without the requirement for a marketing authorisation.  This general concept comes under the special clinical need umbrella as described in Article 5 of Directive 2001/83/EC.


The guidance document makes for some interesting comparisons and regulatory expectations compared to the EU GMP guide.  I've highlighted some below:

1.  Continuous Particle Monitoring

Clearly defined in Annex 1 to the EU GMP guide, continuous particle monitoring is required to be performed during the aseptic filling process.  The 'Specials' guideline (3.5.22 & 23) states that where closed systems are utilised (eg isolator technology) or where residual particle generation is unavoidable (eg IMS spray, opening needles) then the requirement for continous particle monitoring may be waved. 

This is a common sense approach by the MHRA.  Fill times for 'specials' can be short (eg minutes) compared to the commerical scale filling lines where fill times may fun for days.  Also the majority of starting materials used within 'specials' manufacture will be sterile, licensed medicinal products (eg vials of antitbiotics, cytotoxics etc).  Together with the closed system processing (ie the product does not contact the external environment) then the risk of particulate contamination is low.

2.  API controls

The FMD has introduced tight controls around the importation & distribution of APIs for human commercial products.  The 'Specials' guideline (3.5.3) states that the FMD and its transposition into UK law (SI 2013/1855) does not cover APIs used in 'Specials' manufacturing.  The guidance document goes onto explain that full supplier approval procedures are expected including supplier audits, desk audits etc.

3.  Dedicated Facilities

Updates to both Chapter 3 and 5 reiterate the requirement for dedicated facilities for products deemed necessary by the MIA holder.  Section 3.3.4 of the 'Specials' guideline states that dedicated facilities are not required where closed systems are used.  Most 'Specials' manufacturers will have dedicated isolators for penicillins but would often have single isolators for cytotoxics, monocloncals and non-penicillin antibiotics. 


These 3 highlights only provide a very brief overview of the MHRA's guideline.  It is well worth a read especially for commerical trainee QPs as a number of your products will be manufactured in 'specials' licensed units across the UK.