New Drug Applications Decline In Turkey As GMP Requirements Lead To Long Approval Process

Turkey is seeing inordinate delays in licensing new products because of bottlenecks in clearing mandatory GMP inspections, leading to a 33% drop in new applications in 2012.

ISTANBUL – Multinational drug companies looking to license new products in Turkey face an increasingly long process because of a bottleneck in clearing a mandatory Good Manufacturing Practice (GMP) certification process that could take two or more years.

Turkey’s Ministry of Health has required GMP certificates issued by its own inspectors since 2009, even for products already approved by U.S FDA or EMA. This has, according to the Association of Research Based Pharmaceutical Companies (AIFD), lengthened drug approval timelines significantly.

While the requirement for Turkish inspectors to visit plants abroad and issue GMP certificates if standards are met is several years old, AIFD has called attention to the backlog in a report issued in July 2013 that uses data collected from members covering the period up to April 30, 2013. The mean time to GMP certification was roughly 677 days, leading to a 33% drop in new applications in 2012, according to the report.

The issue is especially urgent for Turkey, which faces shortages of newer oncology drugs and has seen public protests and major counterfeit efforts as a result (Also see "Fake Cancer Drugs Labeled As Bayer, Roche, Novartis And Celgene Products Confiscated In Counterfeit Raids In Turkey" - Scrip, 16 Dec, 2013.).

The results were compared to findings of three previous versions of the same survey, conducted in January 2012, April 2012 and August 2012, respectively, AIFD said. Key reasons for the delay are an insufficient number of qualified inspectors at the Turkish Ministry of Health and bureaucratic procedures that slow down the process.

Over the period of December 2009 to April 2013, GMP applications for a total of 1,447 product-site pairs were made, covering 939 products and 352 manufacturing sites. Of these applications, 93% were processed through physical inspections, and the remaining 98 product-site pairs are being inspected by file review.

Out of 1,349 product-site pairs that were physically inspected, 543 took an average of 476 days to complete, in some cases taking up to 1,029 days. Roughly 806 products were still waiting for completion of the GMP certification process for an average of 548 days, and some applications had been waiting as long as 1,159 days.

Out of 98 product-site pairs, which qualified for inspection by file review, only 21 could be completed, taking an average of 166 days, with the shortest one taking 69 days and the longest one 300 days.

GMP A Major Focus In Emerging Markets

Achieving global GMP standards is a major focus across emerging markets. Several Indian firms have recently seen intense scrutiny by U.S. FDA for plants deemed insufficient in maintaining GMP standards, including Ranbaxy Laboratories Ltd., which received Import Alerts blocking the company from bringing major generic launches to the United States (Also see "Ranbaxy Seeks Allies On Valsartan Market Exclusivity To Comply With FDA Manufacturing Requests" - Scrip, 17 Dec, 2013.).

While U.S. FDA has increased its overseas inspection teams by establishing local offices in countries like China and India, China FDA is also enhancing its supervision of imported drugs, including overseas GMP inspections (Also see "China Looks To Step Up Overseas GMP Inspections With New Draft Guidance" - Scrip, 30 Aug, 2012.).

At stake for Turkey however is access to newer drugs with applications that were on the rise from 2010 to 2011 with 69% of applications submitted in 2010 completed by April 2013, compared to 32% of those made in 2011, and only 22% of those in 2012.

According to survival analysis projections, which analyze both the completed and ongoing submission timelines, the mean time to GMP certification is 677 days. Comparison of data from the last four surveys indicates a steady increase in the average time for both completed and pending applications.

Turkey Seeks PIC/S Membership

A solution to this problem, according to industry sources, will be reached with the acceptance of Turkish GMP certificates by FDA and EMA, which requires Turkey’s membership in the Pharmaceutical Inspection Convention and Pharmaceutical Inspection Cooperation Scheme, referred to as PIC/S.

The 43-member organization represents nations that import pharmaceuticals and includes drug regulators involved in ensuring compliance with international standards on behalf of governments.

Southeast Asian nations have led in seeking PIC/S membership as part of a broader push to harmonize standards before the advent of the Association of Southeast Asian Nations free trade bloc in 2015, and Taiwan has recently become a member (Also see "ASEAN Agreement On Pharma Manufacturing Standards Clears Hurdle For Closer Integration" - Scrip, 10 Apr, 2013.).

Turkey submitted applications for PIC/S membership in May 2013, and evaluation has been ongoing since then. Ireland and Switzerland are the rapporteur countries for Turkey, which aims to become a full member within two years.

India is also considering becoming a member of PIC/S (Also see "India Mulls Joining International Group To Protect Drug Exports" - Scrip, 5 Sep, 2013.).

An industry analyst, who requested anonymity, said that AIFD has been negotiating with the government on this issue since 2009.

“AIFD admits that demanding international reciprocity and inspecting the quality of products is a natural right for the Turkish government,” the analyst said.

“However, the only solution for this is Turkey’s PIC/S membership and that will take time. A temporary solution is needed to avoid any more delays and backlog. AIFD proposed that the processes of GMP certification and licensing should be started simultaneously, but the Ministry of Health has not accepted that so far. It seems like the industry might have to wait until Turkey’s PIC/S membership for a solution to this problem.”