Moldova. Marketing Authorisation (Registration) of Medicines

The main issue is the conflicting role of the MMDA which is tasked to register products and also to procure them. In a few cases, this has led to pressure from manufacturers to register products quickly. Further, the legal provision requiring the demonstration of generics’ bioequivalence with the brand product is not implemented. This is mainly due to the lack of assessors trained in reviewing biowavera applications for highly soluble substances and to insufficient attention from authorities to the problem. Good manufacturing practice (GMP) inspections are currently not a mandatory part of the registration process and there is insufficient funding and staff trained with the necessary training to conduct GMP inspections.

Due to low salaries and general paucity of skilled professionals in the country, there is an insufficient number of assessors with relevant skills in the registration department and the national reference laboratory. In addition, the objectivity of the decisions taken by assessors is weakened due to lack of approved written procedures on how to assess registration applications. Another issue is the lack of stable management or a long-term planning process within the MMDA. In the past two years, there have been seven different directors and despite the staff’s genuine commitment to raise standards and meet internationally accepted requirements, there is very little evidence of planning and targets at the MMDA or department level to achieve these goals. Further, there are no COI guidelines for registration activities, rendering the system vulnerable to vested interests. This can be particularly problematic given the frequent use of external experts.

Moreover, the committee’s decisions are not publicly available. On average, about 70% to 80% of all registered medicines by foreign manufacturers were actually imported (Figure 1). However, analysis of the number of registered products for different international non-proprietary names (INNs) suggests that in many cases more products are registered than necessary. One of the most extreme examples is amlodipine 5 mg and 10 mg, for which, in 2012, there were 47 and 42 products registered by foreign manufacturers and 20 and 21 products imported, respectively. A less extreme example, yet still making the case, is metformin 500 mg and 850 mg, for which, in 2012, there were 16 and 15 products registered by foreign manufacturers and 5 and 5 products imported, respectively.

In most cases when a particular medicine was only registered by foreign manufacturers, even if not all strength were available, at least one strength per INN was imported. In a few cases, mostly cancer medicines, no product for any strength was available for a particular INN. These included bleomycin (not imported in 2012 and 2011), busulfan (not imported in 2012), cetuximab (not imported in 2012 and 2011), cytarabine (not imported in 2012), docetaxel (not imported in 2012), doxorubicin hydrochloride (not imported in 2012), everolimus (cancer indication not imported in 2012 and 2011), fludarabine (not imported in 2012 and 2011), imatinib (not imported in 2012 and 2011) and tamoxifen (not imported in 2012).

Unavailability of registered medicines is due to a number of reasons including unsuccessful pricing negotiations between manufacturer and the MMDA and disincentive on the part of distributors who may not have sufficient interest in importing certain medicines because of limited or absent demand. Low demand can be due to different reasons like irrational prescribing, heavy promotion of other medicines (outside the essential medicines list (EML)) and limited promotion of essential medicines. Finally, the financing of the MMDA is mainly based on registration fees which is likely to provide an incentive to register more products that actually necessary. Underfunding of the MMDA is a real challenge given that registration fees have not been revised in recent years (and thus does not take into account current expenses and inflation rate).

The issue of low availability of registered medicines has been already discussed at Ministry of Health and some measures have been taken. Following the recent introduction of a new regulatory requirement in 2012, if a medicine is registered but it is not available on the market (whether it has never been launched or it stops being available) for three consecutive years, its registration is suspended.

Positive developments

Despite challenges remaining, a number of positive developments have taken place in the past two years. The most important positive development is the introduction of GMP guidelines, which, by December 2014, should be implemented by all local manufacturers. In July 2012, the Ministry of Health approved a new regulation for medicines registration which includes a requirement to use the common technical document (CTD). This document contains all information on quality, safety and efficacy required by ICHb regulatory authorities in a standard format accepted in all ICH member countries.

Since January 2013, all registration dossiers are organised and presented according to the CTD format. In addition, the MMDA is developing an e-application system for registration. This should help with tracking progress and compliance with timelines. Concerning registration fees, a draft document with a revised fee structure and additional fees for activities not previously included (e.g. fee for GMP inspection, fee for pharmacovigilance related activities, etc.) has been drafted and presented to Government for approval in August 2013 but has not yet been approved.

Source: Journal of Pharmaceutical Policy and Practice