[Stability Testing related News – vol.12]

◆  Work GMP Changes can we still expect for 2014? (180-Jun-14 ECA)

A work plan of EMA’s GMP/GDP Inspectors Working Group will answer what GMP environment change can we still expect for 2014.

The coming plans are as follows;

• Finalising the changes planned for the Chapters 3 and 5 of the EU GMP Guide
• Finalising the revision of Chapter 8 of the EU GMP guide (with regard to product shortage notifications and specific risk management concepts)
• Agreeing, in consultation with PIC/S, whether guidance is needed on biofilms concerning Annex 1 of the EU GMP Guide
• Finalising the revision of Annex 15 of the EU GMP Guide (comparison with the new EMA process validation guideline and inclusion of necessary changes in the light of ICH Q 8-10)
• Finalising the revision of Annex 16 of the EU GMP Guide
• Finalising the revision of Annex 17 of the EU GMP Guide
• Further measures regarding the EudraGMDP database
• The finalisation of the revision of Chapter 6 (Quality Control) of the EU GMP Guide is already completed (April 2014). The revised chapter will apply as of October 2014.

◆  India blocks further Expansion of the ICH Harmonisation (09-Jul-14 ECA)

India blocks the further expansion and therefore the success of the International Conference on Harmonisation (ICH). Together with some patient groups, the country wants to avoid that the World Health Organisation (WHO) continues to be involved in the ICH process.

The ICH is an organisation that has committed to the harmonisation of regulatory standards in the pharmaceutical industry. It was founded in 1990. Members are the drug regulatory agencies in the United States (FDA), in Europe (EMA/EU Commission) and in Japan (MHLW) as well as the industry associations of the three regions (PhRMA, EFPIA, JPMA). The WHO, the European Free Trade Association (EFTA) and Health Canada take part as so-called observers. The International Federation of pharmaceutical manufacturers & associations (IFPMA) is represented in the Steering Committee as a non-voting member.

Since its inception, the ICH has been a success story. While initially only rules were harmonised that were relevant for marketing authorisation/drug approval, a number of GMP relevant documents in the area of quality were developed later as well. These include ICH Q7 (GMP for APIs), ICH Q8 Pharmaceutical Development (Quality by Design), ICH Q9 Quality Risk Management, Q10 Pharmaceutical Quality System and ICH Q11 Development and Manufacture of Drug Substances, which are all relating to the harmonisation of GMP relevant requirements. This completed the extensive range of harmonised quality guidelines, beginning with Q1 Stability and continued with Q2 Analytical Validation, Q3 Impurities, Q4 Pharmacopoeias, Q5 Quality of Bio-technological Products and Q6 Specifications. In addition there are harmonised guidelines in other areas such as safety and efficacy.

That India now prevents the WHO from continuing the successful harmonisation is amazing at first glance. After all, it must be in the interest of all countries to ensure a high drug safety standard and to prevent countries from establishing their own regulations which bring no security gain but increase the cost of medicines.

India is supported in its efforts by various patient groups. The criticism is that in addition to authorities also industry organisations are represented in the ICH Steering Committee (as stated above). Thus, India suspects a misuse of ICH harmonisation. The reasoning behind is that ICH might establish standards that help only the world’s leading pharmaceutical companies to protect their drugs against low-cost alternatives from the third world.

It would be more than unfortunate if ICH harmonisation efforts slowed down due to this initiative. The ICH provided an enormous contribution to patient safety. ICH efforts and standards resulted in reduced regulatory costs for medicines. Critics still owe proof that ICH regulations artificially raise standards. It would be fatal if the standards for drug safety would be lowered in some countries beneath those in ICH regions.

◆  IMPs: How do GDP Guidelines apply? (30-Jul-14 ECA)

The 2013 Guidelines on Good Distribution Practice (2013/C 343/01) apply to medicinal products for human use. Investigational Medicinal Products (IMPs) are also medicinal products for human use. But is IMP distribution really covered by the new Guidelines? The Guidelines focus on wholesale distribution of medicinal products. And IMPs are normally not distributed via wholesalers. However IMPs are not particularly excluded. The Guideline may therefore give some guidance on how to supply clinical trial material. Better guidance might be given by the Questions and Answers documents of the European Medicines Agency (EMA). In the part on supplementary requirements, Annex 13, a few Q&As are dealing with storage and transportation of IMPs.

When it comes to transport of IMPs from the manufacturer to the distributor or investigator sites, the sponsor is responsible for controlling the distribution chain and assuring “that IMPs are stored, transported, and handled in a suitable manner”. The responsibility for storage and transportation lies with the manufacturer or an importer, when the IMP comes from outside the EU. To define the specific responsibilities of the parties involved, a contract should be in place.

During storage and transportation, conditions should at least be monitored. The sponsor should define the applicable storage (and transport) conditions for the IMPs. When the IMP arrives at the investigator site, IMPs should be stored in a restricted area where appropriate, with ongoing monitoring. Everything should be defined in SOPs.