Dear John,

Thank you very much for your comments and questions. I will try to answer the questions and explain the issues in sequence:

1.    Purpose of the reform - The purpose of the reform is quite ambitious as it includes access to medicines and vaccines. This probably implies that a reimbursement system (universal health coverage) should be created.

The purpose is really ambitious and is driven by the extreme need. People are getting poorer due to out-of-pocket payments and it is necessary to support them.

The task of the project is the complex preparation of the system (quality, efficiency, safety, price restraint, rational use ...) so that the state is able to rationally spend its limited financial resources.

In Georgia, 62.4% of out-of-pocket (OOP) health care costs come on medicines (MoILHSA 2017), which is 96% of the total pharmaceutical expenditures.

2.    Quality component GMP/GDP - GMP and GDP are required for medicinal products, but how can GMP be guaranteed when medicines are imported into Georgia? Will all medicinal products local batch release with the importer requiring a manufacturing authorization?

T.T. In addition to the planned and unplanned inspection of GMPs of local production, the draft law provides for so called "pre-registration inspection" of production during full and simplified registration procedures; this mechanism is provided for medicines produced in countries with a non-strict regulatory system, and finally the PIC / scheme assessment acts will help the regulator.

As for imported drug lots, importers only have the right to repackage (and not package) and relabel them, which does not give them the right to violate the original packaging. According to the project, it does not require any additional authorization, however it requires from the importer to have manufacturer’s permit for repackaging /relabeling. Based on your question, I think it would be advisable to specify the norm of serialization of repackaged products.

3.  Track and Trace - Does the track and trace system include manufacturers and distributors outside of Georgia? In how far can Georgia afford medicines from strictly regulated countries?

T.T. T&T System is not described in this project, PHTAC has been instructed to prepare it for the project, on condition that international functional components will be included in the system; The precise task is to be compatible with the international system and to be valid for imported products.

As for the affordability of medicines from strictly regulated countries, our task is to import their medicines at a fair price. Therefore, PHTAC has been instructed to develop price restraint mechanisms, including price regulation.

4.  Clinical trials - As ICH and WHO GCP requirements are quite extensive, my suggestion would be to focus on the clinical trials affordable medicines – generics – which are useful for local manufacturers. My advice would therefore be to start legislation and enforcement capacity with bioequivalence studies.

I absolutely agree with you about bioequivalence studies. Georgia is a market for generics and at this time the regulator does not have any mechanisms for the assessment of bioequivalence, moreover, the current definition of generics is completely incomprehensible, since it does not provide for bioequivalence (!!!). The project commissioned PHTAC to develop bioequivalence assessment methodologies, and it is also their competence to assess and enter it into OB.

As for clinical trials, according to Georgian law, clinical research is an activity that needs a permit and it is obligatory to write the permit conditions in the law. Therefore, in the project we have described in detail the technical and ethical requirements that must be observed in this process. We are concerned to note that many international clinical trials are being conducted in the country and they are not being inspected, most of these studies are placebo-controlled, including many II-III phase studies, ethical assessment of these clinical trials (without criteria) are conducted by Local Ethics Committees, which actually are the groups created by Investigators. The Clinical Trial Register contains extremely limited information and does not provide any transparency, so we have tried to sort out this issue in the draft law. This part came out quite big.

5.    Pharmacovigilance - The main responsibility for safety of medicines lies with the holder of the marketing authorization. I hope the law provides for their obligations as well.

Yes, I agree with you and it is written in our obligations (article 47)

6.    Orange book - I do not entirely understand the concept of the orange book. Is it like a formulary to assist INN prescribing? Is it something else than the websites of agencies in the EU providing information about all authorized medicines including the Summary of product characteristics from which you can find bioequivalence and other information?

It is also not clear to me if generic substitution has an effect on rational/irrational use of medicines, as generics are by definition just as rational as their reference medicinal products.

T.T. You have understood correctly, “OB” is a formulary, indeed, for a choice from INN. As for the concept of equivalence, as you know, American and European ones are a little bit different and we have selected European, it is noticeable even in definition.  

As for substitution and rationalization, actually the problem for Georgia (and in general for all post-Soviet countries in contrast to developed markets) is not a substitution of originals with generics (in reality, the amount of originals in Georgian market is about 3-5%), but our problem is the substitution of similar products of dubious therapeutic value by generics! And thus make the cost rational.

7.  EML - I am not sure if it is good policy to exclude all non-essential medicines from reimbursement. Sometimes healthcare is challenged with a new disease (corona-virus) or a rational cure is developed for a smaller group of patients and it could be rational to fund these before inclusion on the EML.

The WHO EML compilation methodology provides for the introduction of innovations and medicines for the latest diseases; also, if additionally needed, changes in the list are not limited, and finally, there is a private insurance system that is completely free from this restriction. Do you think it will not be enough? Shall we still make a reservation in the project?

8.    Authorization procedures - I am curious about the different types of procedures presented and also how the new law deals with so-called parallel imports.

The project provides for 5 registration regimes:

a)     Full procedure (full registration dossier is submitted), a trade license is issued.  

b)     Simplified procedure (incomplete (established types of documents) dossier is submitted). A trade license is issued.  

c)     Recognition procedure (administrative module is submitted). Parallel trade license is issued.

d)     Registration of changes in registered data.  

e)     Re-registration.

The recognition procedure is not analogous to the European recognition procedure, it is more like a parallel import, a parallel trade license is issued, the applicant can be any person ... Only the products of the domestic market of the countries selected by the government are recognized by the recognition regime.

We also have a simple form of parallel import, which envisages admission of products with packaging and labeling, which are different from ones registered in Georgia.

9.    Import of medicines in original batch - How will the origin of the batch be controlled including the legality of the distribution chain from the point of batch release? How does the register connect to the track and trace system?

As I have mentioned above, Track and Trace System is not described in a draft law, the draft law establishes the obligation of creating this system and defines the responsible entity for preparing this system (PHTAC).

10.   Off-label use - In most countries I know the choice of a treatment is a matter to decide by the patient and the physician. Even if a medicinal product is not authorized for a specific patient or condition, treating the patient with that medicine may be the best care and physicians should be allowed to act in accordance with their Hippocratic Oath.

Off – Label use in Georgia is not allowed by applicable legislation. Of course, it is not correct. Therefore, we made such exceptions in the draft law and the Ministry was instructed to develop this rule.  

11.  Independence of regulatory bodies- Both the GDA and PHTAC should not be funded by grants and donations, because this could lead to undesirable financial relationships. Furthermore, I advise to ensure that the decisions about authorization of medicinal products et cetera are taken on scientific grounds, so an advice committee independent from both the pharmaceutical industry and any politician (including the Minister of health). The budget for such a scientific body should be guaranteed in the law.

T.T. I agree with you that financial independence is essential! By grants we mean state grants that the state receives from partner countries; as far as philanthropy is concerned, I have been cautious here too not to hinder any good initiative; however, I see the risks as well.   

As for the systemic independence of the GDA, we have a bit of difficult data here. As of today, we do not have an independent regulator of medicines, its functions are assigned to the Medical Regulatory Agency, which is formally an independent legal entity of public law within the system of the Ministry, but de facto it is fully integrated with the Ministry.

Separation of GDA from the Regulatory Agency obviously will not change the degree of its independence, so we shall try to make activities of GDA as transparent as possible.

In my opinion, PHTAC will be more systematically protected from the influence of politics and business, since decisions in PHTAC will be made by expert commissions (invited Georgian and foreign experts) and not employees.

Dear John, there will unfortunately be technical inaccuracies in the translation of the draft law, since the text is being translated by non-specialists; therefore, we are ready to further clarify all the issues of interest to you.

I hope for successful collaboration and project success!

Best regards,

Tiniko Turdziladze