Foreword: Importation testing: an unnecessary burden on industry?
One of the principle objectives of the Internal Conference on Harmonisation (ICH) initiatives was to introduce harmonised approaches, prevent duplication and eliminate wasteful and unnecessary testing. Although good progress was made initially, there was evidence that certain countries, regions and trans-national organisations were unhappy with some of the proposed harmonised guidances, as exemplified by the withdrawal of ICH Q1F.
Another area that has prompted concern within industry is the proliferation of importation testing or in-country testing. A recent article highlighted some of the practices and related issues. Based on a survey of six multi-national pharmaceutical companies under the auspices of International Federation of Pharmaceutical Manufacturers and Associations, a total of 184 data sets covering 149 countries were collected over a three-month period in 20142. The survey assessed import testing and other categories of country-specific re-testing, e.g., post-market surveillance or waivers. The participating companies reported that 18,616 re-tests were requested per annum and this extra testing resulted in one additional batch failure, i.e., a rejection rate of 0.005%2. This substantiates the view that this additional testing is not enhancing quality or safety benefits to the end user, provided that good distribution practice (GDP) and an appropriate control strategy is implemented throughout the entire supply chain.
It was estimated that the average delay caused by this additional testing was four weeks in duration, with a maximum delay of 22 weeks experienced in China. Some countries, such as China, stipulate the minimum remaining shelf-life (RSL) should be 12 months, hence a five-month-or-greater delay can significantly impact on the RSL, particularly for biologicals. In addition, the safety implications for these additional test samples need to be understood. Security/tamperevident seals need to be breached to allow for additional testing, which increases the risk of batch contamination and/or samples being lost or diverted (increasing counterfeit concerns). In contrast, all of these risks are significantly reduced when robust GDPs are in place.
Re-testing typically covers the import of the product. However, testing can also cover the registration process (in conjunction with the original approval, post-approval changes or license renewals) and these are legal requirements in some countries. Registration testing often requires the setting up of innovative analytical methodologies in a specified country, which in turn can cause significant delays and additional costs. Finally, surveillance testing is aimed at detecting falsified or counterfeit medicines. Re-testing may be performed by local company subsidiaries, contract research organisations or government laboratories. Additionally, the extra testing from a batch can often be significant and extra local inventory/warehouse storage capacity is required. Increased costs (ca. €3000 for each imported batch) are also incurred. The estimated expense2 of local testing is about €20 million/annum. €38 million/annum is required for longer storage of inventory at customs, so the total can reach €58 million/annum.
A survey conducted by the European Federation of Pharmaceutical Industries and Associations in early 2015, which assessed the impact of import testing into the EU from the US, identified an impact on over 8,000 product batches during 2014, equating to costs in excess of €25 million/annum2. Import testing can be waived4 when there is clear evidence that good manufacturing practice and GDP processes are in place for the manufacture, packaging, testing, storage and distribution of pharmaceutical products, respectively. In addition, an effective pharmaceutical quality system (as per ICH Q106), together with regular audits/inspections by local and trans-national regulatory authorities should be in place7,8.
- Explanatory Note on the Withdrawal of ICH Q1F for the ICH Website. http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q1F/Q1F_Explanatory_Note.pdf. Accessed on 01st September, 2015
- Garbe, J.H.O., Ennis, K., Furer, G.M., Jacobs, M.G., Roenninger, S.K. Import testing of pharmaceurtical products has limited safety benefits and can add risk to patients. Pharmaceutical Technology Europe, Supplement to the August 2015 issue, S6-S20
- European Commission, “Technical Barriers to Trade”, Initial EU TTIP Position Paper, 16th July 2013
- Appropriate Control Strategies Eliminate the Need for Redundant Testing of Pharmaceutical Products. 23rd April 2012 http://www.ifpma.org/uploads/media/IFPMA_Position_Paper_on_Redundant_Testing_05.pdf. Accessed on 01st September, 2015
- China State Food and Drug Administration (SFDA). Medical Product Import Regulation. Administration of import drug. SFDA Order No. 4. 2004
- ICH Q10. Pharmaceutical quality systems. Current step 4, June 2008
- IFPMA, 2010. Global GMP Inspection landscape – Industry point of view and the way forward http://www.ifpma.org/fileadmin/content/Quality/Inspections/Foreign%20inspections%20IFPMA%20presentation%202010.pdf. Accessed on 02nd September 2015.
- EFPIA, 2014. Enhanced good manufacturing and good distribution practice (GMP/GDP) Inspection Efficiency http://www.efpia.eu/uploads/documents/EFPIA_Enhanced%20Inspection%20Practice%20-%20Final_v8a_19May2014.pdf. Accessed on 02nd September 2015