Ken Appel summarises recent reforms and new co-operative initiatives to move to worldwide standards that have potential impact for pharmaceutical and life sciences industries.
Shifting economies and pharmaceutical mergers are driving legislation by the major regulatory regions of the world - EU, US, Australia, New Zealand, Switzerland and Japan - to be more vigilant in protecting the health of its citizens.In the past few years, the movement has accelerated in medicine research and manufacturing organisations as seen by enforcement actions of the European Medicines Agency (EMA), the US Food and Drug Administration (FDA) and the agencies of countries mentioned above.
Expansion of the industry geographically to reduce costs and the number of drugs under development are occurring at a much faster rate than agencies' ability to inspect laboratories, manufacturing and distribution facilities.
In North America, both Canadian and US regulatory agencies have accelerated regulatory enforcement to protect patient safety and revamp auditing methodologies for best utilisation of regulatory resources.
Now, global regulatory bodies and standards organisations such as the World Health Organisation (WHO) and International Committee on Harmonisation (ICH) are drawing upon common language to harmonise guidelines worldwide.
Inside Europe
In September 2010, the European Parliament committed to adopt new pharmacovigilance legislation, expected to come into force by 2012. The proposed directive and regulation is designed to strengthen the methods for monitoring the safety of medicines for human use in the EU. proposed "changes include enhanced monitoring of the benefits and risks of medicines post-authorisation, replacement of the pharmacovigilance working party with a committee, and an increased level of transparency of safety information."
In Nov 2009, the UK Medicines and Healthcare products Regulatory Agency (MHRA) scoped out its strategy for good distribution practice (GDP) risk assessments.
Once an audit has taken place, the frequency of future inspections will be determined by the agency's risk ranking.
The top three GDP ranking deficiencies between January and June 2010 were temperature control and monitoring for cold and general storage, lack of or inadequate written procedures, and facility equipment and calibration.
Again, the common theme is a move towards using agency resources to isolate high risk areas for inspections.
Europe and North America
Also in September 2010, the EMA and FDA extended their confidentiality arrangements related to medicinal products for human and veterinary use. It allows both agencies to exchange confidential information as part of their regulatory and scientific processes.
Information exchange will cover scientific advice, orphan drug designation, pediatric development, GMP and GCP inspection planning and reports, marketing authorisation and change procedures and post-marketing surveillance.
These new commitments, which have been extended indefinitely, are based on the achievements of the previous arrangements between the EMA, the European Commission and the FDA.
A report of the current status of agreement was issued in Oct. 2009, the 'Medicines Regulation: Transatlantic Administrative Simplification Action Plan Implementation Report'.
The main objective, as the title suggests, is to better utilise agency resources to "maintain or increase current levels of public health protection". The report identifies areas of cooperation such as biomarker development and joint qualification, combating counterfeit medicines, collaboration on development of medicinal products for children, convergence of risk management formats and others.
Streamlined process
In Febuary 2010, the FDA and EMA agreed to accept a single orphan drug designation annual report. The streamlined process is designed "to help regulators better identify and share information throughout the development process of orphan drug and biologic products, which are developed specifically to treat rare medical conditions. Both agencies have agreed to accept the submission of a single annual report from sponsors of orphan drug and biologic products designated by both the US and the EU."
In April 2009, the EC, EMA and Health Canada signed an Implementation Plan for Regulatory Cooperation on Medicinal.
This plan puts into affect a sharing of arrangement of such things as listings of GCP and GMP inspections outside of respective territories, database information, guideline and guidance documents, and passing of information through periodic meetings between the parties.
The plan also calls for ad-hoc exchanges with specific timeframes to respond depending on the category of need - urgent, expedited or standard. Initially, ad-hoc areas will focus on evaluation of applications for marketing authorisation, post-authorisation pharmacovigilance data, advance notice of regulatory sanctions before release of information to public domain, cooperation respecting the development of guidance documents, among others.
Europe and China
In 2007, the European Commission signed a 'consultation and cooperation mechanism' between the Directorate-General for Enterprise and Industry and the Chinese State Food and Drug Authority (SFDA).
The agreement is designed to help with the implementation of similar good manufacturing practice (GMP) and good clinical practice (GCP) standards to those applied in the European Union, to facilitate the use of products and data coming from China and helping to ensure a global approach to the manufacture and supervision of medicinal products in the long term.
In 2010, the European Commission and the SFDA agreed to a specific action plan on GMP and GCP inspections.
International organisational reforms
In August 2010, the WHO published proposed additions and changes for sections of the WHO GMP Main Principles for Pharmaceutical Products.
The draft proposes language is in line with how other major regulatory agencies have updated their documents.
The draft introduces the idea of a system for quality risk management as a systematic way of assessing, controlling, communicating and reviewing risks to the quality of a medicinal product. It offers suggested wording for areas of overall quality assurance, and specifically product quality review, supplier's audits, personnel over quality units of QA and QC functions, packaging operations, batch record review and more.
In June 2010, the European Commission hosted a meeting with regulatory bodies to discuss enhanced international cooperation in the field of APIs.
The response, according to PIC/S, is that "the PIC/S Expert Circle on APIs has started developing, in co-operation with other partners (for example, EDQM, EMA, ICH, US FDA, WHO, etc), an international training for inspectors on APIs. The training will focus on i) an introduction to ICH Q7 (basic course) and ii) on how to inspect APIs (advanced course)". This is another example of attempts to harmonise the interpretation of regulations with inspections conducted across the globe.
Implications for industry
It was not long ago when regulations were created in isolation by regulators within each respective country. Problems were addressed with more regulation on top of existing laws.
Many factors have combined to boost governments' desires to collaborate on pharmaceutical regulatory issues: explosive new technologies such as gene sequencing and diagnostic imaging; an aging population in parts of the world and underserved populations on other parts; pandemics and similar health crises requiring industry to mobilise rapidly to develop and produce medicines; among other factors.
The tipping point for harmonisation has arrived. Not only are regulators establishing agreements to share information among agencies but also to be more transparent about how they operate.
This is good news for industry. The days of different interpretations of the same rule are fading away thanks to the work of The Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme (jointly referred to as PIC/S). Currently 37 participating authorities recognise the PIC/S GMP for guidance to assure high standards of quality in the development, manufacture and control of medicinal products.
The organisation trains inspectors from member agencies to develop consistency of handling audits. The PIC/S and EU GMPs virtually mirror each other in terms of GMP requirements, positioning the group as a central resource for regulatory and industry guidance.
In Octber 2010, the meeting of the WHO Expert Committee on Specification for Pharmaceutical Preparations will underscore this point with its draft advice on risk assessment.
The text draws from guidelines of regulatory bodies in this area, aligning its thinking with them.
As the union of co-operation among independent agencies progresses so too will the spread of harmonised quality standards be adopted by any country wishing to export its medicines and raw materials. In the ever shifting economies where development, trials and manufacturing can easily move about the globe, harmonisation will ultimately encompass every geographic location.
Regulatory compliance
Globalisation of regulatory standards is thankfully matched by growth of worldwide availability for state-of-the-art technology to ensure regulatory compliance.
These technologies automate processes, removing manual-intensive error-prone activities - key to meeting GMP requirements while at the same time managing costs.
Ken Appel is Manager Regulated Markets for Veriteq, Richmond, BC, Canada. www.vaisala.com/veriteq.
