On December 12 and 13, 2012, the MHRA held its annual GMP Symposium. I was able to attend this event and have captured some of the major themes within this blog.

December 12 – Good Manufacturing Practices Update

MHRA Future Directions

The UK’s MHRA has recently confirmed its short-term areas of criticality. These include:

Product realisation,
The industry driven expansion of the ‘biologicals’ sector,
Generic medicines and the rise of the Indian generics manufacturers, and
Risk based methodologies; in particular, risk based clinical trials.

The MHRA has provided ongoing support and direction to the EU GMP Updates by establishing an International Working Group (IWG) to ensure arrangements such as International Agreements are reached with major ‘partners’.

Finally, the Falsified Medicines Directive (2011/62/EU) publication is imminent.

Product Realisation

The first objective of ICH Q10 Pharmaceutical Quality System is ‘product realisation’. In line with this objective the MHRA’s core mission is to ensure, through effective quality systems and secure supply chains, that compliant, safe and effective medicinal products are brought to the market place.

Pharmaceutical Quality Systems must be established, implemented and maintained. Using an ICH Q10 methodology is seen as one key approach – central to this approach is well-defined Pharmaceutical Development (ICH Q8) and Quality Risk Management (ICH Q9) incorporated into all aspects of the Quality System.

At the MHRA’s most recent annual conference, reference was made to the extensive time for medicinal products to move through the product pipeline.

Biologicals Growth

It is anticipated that the biological sector of the pharmaceutical industry will continue to grow and that specialist inspection skills may be needed to ensure the ongoing compliance and effectiveness of the relevant quality systems.

Generic Medicines

The MHRA is in the midst of generic medicines ‘boom’ and the specific challenge of off shore manufacturers of generic medicines requires careful planning and management.

Many generic medicines are manufactured in India and this poses specific inspection challenges where compliance with PIC/S GMP and the status of International Agreements are critical to success.

Falsified Medicines Directive

The Falsified Medicines Directive (FMD) is expected to be published before the end of 2012 with implementation proposed for June 2013.

The key challenge for the FMD is to maintain the safety and effectiveness of imported products and driving industry to implement ongoing measures to counter falsification and weaknesses in supply chains.

Quality Risk Management

It is no surprise that the MHRA continues to promote Quality Risk Management (QRM) as a key enabler of compliance. The MHRA is now clearly focused on implementation of QRM methodologies and ensuring that organisations already have well established policies and procedures that are effective and functioning.

Establishing risk based clinical trials and handling novel products and previously recognised products is an area for Clinical Trial providers to improve their project planning and approaches of trials.

In summary, the MHRA has committed to a compliance pathway and has identified several areas of focus, including product realisation, secure supply chains (including imported generics) and the ongoing implementation of QRM.

December 13 – Good Distribution Practices Update

Proposed updates in the short term:

Chapter 1 Quality Management System
The alignment of Chapter 1 of the code of GMP and the ICH Q10 Pharmaceutical Quality System is proceeding at pace. The title of the chapter is expected to be changed to the Pharmaceutical Quality System and much of the terminology and concepts detailed in ICH Q10 will be included in the updated Chapter 1.

Chapter 7 Contract Manufacture and Analysis
To be re-named Outsourced Activities, Chapter 7 of the code of GMP will include ICH Q9 and Q10 processes and terminology. Detailed responsibilities and technical/GMP agreements are clearly an area that MHRA want to see improved. Quality Risk Management and handling new outsourced activities suppliers will be incorporated to Chapter 7.

Annex 2 Manufacture of Biological Medicinal Products For Human Use
The MHRA has expressed its desire to better regulate and control biological products, and sees this industry as one of sustained growth and increasing proliferation in the marketplace.

Proposed updates in the medium term:

Chapter 2 Personnel
Incorporating ICH Q9 and Q10 methodologies is the aim of updating GMP Chapter 2 Personnel. While a title change is not expected, training, handling contractors and specific hazards faced by personnel are expected to be included within the new Chapter 2.

Chapter 5 Production
The term “pedigree” in reference to starter materials and revised controls for starter materials will be included in Chapter 5. This is an extension of the Falsified Medicines Directive, and it appears as though regulators will monitor industry’s response and feedback to the FMD and use this to provide detailed direction for the update to Chapter 5.

Proposed updates in the long term:

Chapters 3 and 5 Facilities and Equipment and Production respectively
Dedicated facilities and stricter controls of segregation for different types of products will be included into Chapters 3 and 5.

Chapter 6 Quality Control
Q9 and Q10 processes and terminology will be included within Chapter 6. Specific reference and guidance on Out of Specification Results and trends will be made within Chapter 6.

Chapter 8 Complaints and Recalls
Reporting strategies, product shortages, Corrective and Preventative Action systems and root cause analysis will be clearly detailed within Chapter 8. The inclusion of QRM methodologies will also feature in the update of this chapter

Annex 16 Qualified Person and Batch Release
‘Harmonisation’ is the key word here, and mechanisms for ensuring consistent approaches for Qualified Persons and batch release.

Concept Papers

Annex 15 Qualification and Validation
Continuous Process Verification will become a formal requirement of validation methodologies.

Annex 17 Parametric Release
The rise of new technologies and on line testing technology will shape annex 17 in the future.

Consideration of Future Directions

Annex 1 and the impact of ISO 14644 revisions
The regulators see harmonisation with ISO 14644 parts 1 and 2 as desirable.

Blood components and blood products
This industry sector requires more detailed and sophisticated controls and the creation of specific “Good Practices” for Blood components and products is likely to proceed. Better clarification for collection and test strategies is another likely inclusion.

GDP for Active substances
Good Distribution Practices for active substances.

Excipients handling
Establishing QRM guidelines for excipients.

The Eudra GMP Database will have a new Good Distribution Practice module and the MHRA will continue with its strategy of Regulatory Convergence which will include:

A pilot project for Active Substances with the EU, US FDA, TGA and EDQM
Continuing joint inspections for finished products
Incorporating ICH Quality guidelines throughout GMP
Pursuing Mutual Recognition Agreements and aiming for reduced or no inspections in these countries.

Enhanced EU and US FDA cooperation is seen as very desirable for all involved. Moving from confidence building to “reliance upon” relationship with the US FDA and establishing EU criteria for US sites inspection and monitoring is progressing.