Moldova. Inspections and Market Control of the Pharmaceutical Industry
There are currently no written procedures or mechanisms in place to prevent regulatory capture between inspectors and the manufacturers or distributors that they inspect, rendering the system vulnerable to corrupt practices. While inspectors follow available regulations, these do not provide detailed description of the procedure to conduct inspection (SOPs). Another important gap is the lack of a quality management system for the inspectorate.
Written criteria for the selection and recruitment of inspectors are available, requiring inspectors to have passed a specific training in inspection. Once recruited, inspectors are not regularly trained on key areas such GMP, good distribution practices (GDP) or good clinical practice (GCP). Further, there is no documented process on qualification and review to confirm the competencies of existing inspectors. The legislation relating to MMDA inspectors involvement in pre-licensing activities is unclear and inspectors are not involved in any stages preceding the opening of a pharmacy. Further there is no clear legal provision designating the inspectors and their powers.
As a result, inspectors do not have adequate powers and authority to carry out their tasks. Another issue relates to the fragmentation problems mentioned previously in that only the Licensing Chamber, and not the MMDA, can initiate the process to revoke a license. Due to an insufficient number of competent staff and underfunding, the MMDA does not have resources to inspect manufacturers with the frequency stated in the law. Importing of low cost medicines from countries like India and China has increased in recent years, yet there is very limited capacity to inspect overseas suppliers and to raise questions about the quality of the products imported. This problem has now been addressed for reimbursed outpatient medicines (as explained in the next paragraphs in the positive developments subsection) but remains a challenge for inpatient medicines and nonreimbursed medicines.
The recall system for faulty products is not well described in the law and there are no SOPs. As a result, its implementation does not work well in practice; for example, suppliers who underperform are not blacklisted. Based on doctors’ and patients’ reports, there is evidence of the presence of low efficacy products in hospitals. This leads to overuse, increase of dosage or to patients having to purchase medicines, which they should receive for free at the hospital, in private pharmacies. These circumstances are supported by findings during one of the missions, when three different products with the same batch number from a local manufacturer were found in a hospital.
There were also specific reports of low effectiveness in three different medicines: ceftazidime, an antibiotic imported from China which required two to three times the standard dose to elicit the response which is usually obtained with the standard dosage; methyl prednisolone and betamethasone, both locally produced corticosteroids (from a non-GMP compliant local manufacturer) which were reported to have no effect on patients
Yet, in the case no product is registered from a GMP compliant manufacturer, products from manufacturer with national GMP certificates or, as a last resort, non-GMP compliant manufacturer need to be sourced. As a result of this, a number of medicines from non-GMP compliant manufacturer (particularly a local manufacturer which produced the two products discussed before) are still in the reimbursement list. For inpatient medicines, all products tendered should comply with GMP (no specification whether national or according to the WHO, European Medicines Agency (EMA) or Food and Drug Administration (FDA) criteria).
The exception is psychotropic and TB medicines for which GMP certification according to either WHO, EMA or FDA is required. Further, by December 2014 all local manufacturers are expected to comply with GMP requirements. This will help to gradually remove existing double standards within the country as revealed during the procurement and supply mission, where an exporting facility was found to have voluntarily developed a quality assurance (QA) system because GMP compliance is required for product registration in the majority of the countries where the company exports its products. On the contrary, a domesticallyoriented facility visited did not implement GMP (this was the local manufacturing facility which produced the two products mentioned previously, methyl prednisolone and betamethasone).
These efforts were complemented with training organised for inspectors in GMP and GDP. Improvements were also observed in the way inspections are conducted. The new law on state control of entrepreneur activity, implemented in March 2013, includes a provision for inspection of enterprises (which includes also pharmaceutical establishments). It defines the principles of control and the procedures to conduct controls. As of March 2013, the Inspectorate is publishing the schedule of visits to pharmacies and warehouses. Moreover, the old procedure (as per the previous legislation) to inspect the pharmaceutical facilities has been revised; now, to visit a pharmaceutical establishment the inspector has to inform the facility five days in advance of the planned visit.
Positive developments in access to narcotics for pain management have also occurred. Previously, the control over the supply chain of narcotic substances used to be too strong and fear of sanction was acting as a deterrent for pharmacists to stock narcotics. This situation was likely to cause problems for patients needing narcotic painkillers, particularly in rural areas where availability is low. In October 2012, the Ministry of Health released an order which introduced important changes in the regulation on dispensing narcotics medicines. Limits on the quantity of medicine prescribed were removed; doctors can now issue prescriptions for up to 30 days. Doctors can now also prescribe additional doses before the 30 day treatment period ends, in case the patient condition has changed.
The recall system for faulty products is not well described in the law and there are no SOPs. As a result, its implementation does not work well in practice; for example, suppliers who underperform are not blacklisted. Based on doctors’ and patients’ reports, there is evidence of the presence of low efficacy products in hospitals. This leads to overuse, increase of dosage or to patients having to purchase medicines, which they should receive for free at the hospital, in private pharmacies. These circumstances are supported by findings during one of the missions, when three different products with the same batch number from a local manufacturer were found in a hospital.
There were also specific reports of low effectiveness in three different medicines: ceftazidime, an antibiotic imported from China which required two to three times the standard dose to elicit the response which is usually obtained with the standard dosage; methyl prednisolone and betamethasone, both locally produced corticosteroids (from a non-GMP compliant local manufacturer) which were reported to have no effect on patients
Positive developments
The Republic of Moldova has already taken concrete steps to gradually move towards GMP compliance for imported as well as locally produced medicines. The first step was the development and approval of GMP guidelines in March 2013. With the release of the new reimbursement list in May 2013, medicines registered in the EU, the United States of America (USA), Canada, Australia, or Japan (and therefore compliant with GMP) were given preferred supplier status. This is expected to provide a strong incentive, particularly to local manufacturers, to improve their manufacturing practices according to internationally accepted GMP.Yet, in the case no product is registered from a GMP compliant manufacturer, products from manufacturer with national GMP certificates or, as a last resort, non-GMP compliant manufacturer need to be sourced. As a result of this, a number of medicines from non-GMP compliant manufacturer (particularly a local manufacturer which produced the two products discussed before) are still in the reimbursement list. For inpatient medicines, all products tendered should comply with GMP (no specification whether national or according to the WHO, European Medicines Agency (EMA) or Food and Drug Administration (FDA) criteria).
The exception is psychotropic and TB medicines for which GMP certification according to either WHO, EMA or FDA is required. Further, by December 2014 all local manufacturers are expected to comply with GMP requirements. This will help to gradually remove existing double standards within the country as revealed during the procurement and supply mission, where an exporting facility was found to have voluntarily developed a quality assurance (QA) system because GMP compliance is required for product registration in the majority of the countries where the company exports its products. On the contrary, a domesticallyoriented facility visited did not implement GMP (this was the local manufacturing facility which produced the two products mentioned previously, methyl prednisolone and betamethasone).
These efforts were complemented with training organised for inspectors in GMP and GDP. Improvements were also observed in the way inspections are conducted. The new law on state control of entrepreneur activity, implemented in March 2013, includes a provision for inspection of enterprises (which includes also pharmaceutical establishments). It defines the principles of control and the procedures to conduct controls. As of March 2013, the Inspectorate is publishing the schedule of visits to pharmacies and warehouses. Moreover, the old procedure (as per the previous legislation) to inspect the pharmaceutical facilities has been revised; now, to visit a pharmaceutical establishment the inspector has to inform the facility five days in advance of the planned visit.
Positive developments in access to narcotics for pain management have also occurred. Previously, the control over the supply chain of narcotic substances used to be too strong and fear of sanction was acting as a deterrent for pharmacists to stock narcotics. This situation was likely to cause problems for patients needing narcotic painkillers, particularly in rural areas where availability is low. In October 2012, the Ministry of Health released an order which introduced important changes in the regulation on dispensing narcotics medicines. Limits on the quantity of medicine prescribed were removed; doctors can now issue prescriptions for up to 30 days. Doctors can now also prescribe additional doses before the 30 day treatment period ends, in case the patient condition has changed.
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