Universidade de Lisboa

Faculdade de Farmácia

Evaluation of the generic substitution in Portuguese

and Latvian community pharmacies

Rita Isabel Jerónimo Batista

Mestrado Integrado em Ciências Farmacêuticas

2019
 Universidade de Lisboa

Faculdade de Farmácia

Evaluation of the generic substitution in Portuguese

and Latvian community pharmacies

Rita Isabel Jerónimo Batista

Monografia de Mestrado Integrado em Ciências Farmacêuticas apresentada à

Universidade de Lisboa através da Faculdade de Farmácia

Orientador: Doutora Ana Paula Mecheiro de Almeida Martins Silvestre Correia,

Professora Auxiliar
Co - Orientador: Doutura Elita Poplavska, Professora Auxiliar

2019
2
Resumo
Objetivo: A política de substituição de medicamentos de marca por medicamentos genéricos,
pode ajudar a reduzir os gastos em saúde, baixar os preços dos medicamentos e aumentar o
uso do medicamento bioequivalente mais barato. Este estudo teve como principal objetivo
descrever e comparar as práticas de substituição genérica dos farmacêuticos comunitários
em dois países europeus, Portugal e Letónia, e como políticas diferentes podem influenciar a
percentagem e a quota de mercado dos medicamentos genéricos.

Métodos: Um formulário, preenchido por farmacêuticos, foi utilizado para recolher os dados
das prescrições médicas. Foi utilizada estatística descritiva para analisar os dados. Para
complementar os dados quantitativos, foi criado um questionário de perguntas abertas que foi
respondido pelos mesmos farmacêuticos. As respostas foram analisadas por tema em relação
às suas diferenças e semelhanças. As farmácias foram escolhidas por conveniência.

Resultados: No total, foram recolhidas 713 prescrições. Em Portugal, a maioria das

substâncias ativas foram prescritas através da sua denominação comum internacional,
enquanto que na Letónia foram prescritas maioritariamente por marca. A substituição de
medicamentos por genéricos foi maior em Portugal (77,78%) do que na Letónia (62,50%).
Contudo, o grau de aceitação dos doentes foi maior na Letónia (57,14%) do que em Portugal
(47,27%). A maioria farmacêuticos têm conhecimento sobre a política de substituição e
reconhecem as suas vantagens e desvantagens.

Conclusão: Continua a existir uma maior preferência pelos medicamentos de marca

comparativamente aos medicamentos genéricos em ambos os países. Embora a maioria dos
farmacêuticos reconheça a importância da substituição e a taxa de recomendação de
substituição seja alta, a aceitação dos medicamentos genéricos, pelos doentes, permanece
baixa. Este facto tem vindo a ser associado coma falta de informação e confiança nos
medicamentos genéricos e os farmacêuticos concordam que fornecer mais informação
deveria estar no foco das autoridades reguladoras. Adicionalmente, uma vez que os
profissionais de saúde podem influenciar a opinião dos doentes, é preciso que estes tenham
ao seu dispor informação de confiança e que assumam um papel mais ativo na educação do
doente.

Palavras-chave: substituição genérica, medicamentos genéricos, medicamento de

referência, denominação comum internacional, gastos em saúde

3
Abstract
Objective: Generic substitution as a policy can help reduce health expenditures, lead to
reduced product prices and increased use of the cheapest interchangeable medicine. This
study aimed to describe and compare the generic substitution practices of community
pharmacists in two European countries, Portugal and Latvia, and how different country polices
can influence the percentage and market share of generic medicines dispensed.

Methods: A data collection form was designed, and pharmacists were asked to fill the form
with the details of the prescriptions. Pharmacies were chosen via convenience sample.
Descriptive statics was used to analyze the data. In order to complement the quantitative data,
a survey with open-ended questions was created and answered by the pharmacists that
collected the information. Responses were analyzed by theme for differences and similarities.

Results: In total, 713 prescriptions were collected. In Portugal, most of the active substances
were prescribing by its international nonproprietary name, while in Latvia the majority of the
active substances where prescribed by brand name. Generic substitution rate slightly higher
in Portugal (77,78%) than in Latvia (62,50%). However, patient acceptance of generic
medicines is higher in Latvia (57,14%) than in Portugal (47,27%). All pharmacist knew about
the generic substitution police and knowledge its advantages and disadvantages.

Conclusion: The results of this study showed that there is still a preference for the branded
name medicines over the generic medicines, in both countries. Although the majority of
community pharmacists surveyed acknowledged the importance of substitution and
considerably high generic substitution recommendation rates, patient acceptance of generic
medicines still remains low. This fact has been linked with lack of trust and misconceptions
about the generic medicines and pharmacists agreed that information should be at the focus
of regulatory authorities. Additionally, healthcare professionals can influence patient’s opinion,
they need to be provided with trustworthy information and have to take on a more active role
in patient education.

Keywords: generic substitution, generic medicines, reference medicine, international

nonproprietary name, health expenditures

4
Acknowledgments
This work marks the end of a journey that began five years ago. I want to use this space to
show my heartfelt appreciation to all of those who have been a part of this journey and shaped
me throughout these years.

Firstly, I sincerely thank Prof. Elita Poplavska for all the advice, guidance and support, as well
as, for believing in me and this project from day one.

To Prof. Ana Paula Martins, for accepting to supervise this project, availability to help me with
my many questions and precious reassurance during the final times of writing this project.

Special recognition Dra. Ana Madureira and all the pharmacists of Farmácias Silveira that
accepted to participate in this project and took time off their busy schedule to be a part of it.
Without all of you, this project would truly have been impossible to accomplish.

To those I have the pleasure to call my friends, specially Beatriz, Sara and Catarina – you are
not only my friends, but also my family. I'm utterly grateful to have you in my life. It would not
have been the same without you. Your endless love and support have kept me going in the
most difficult times of my life.

To Francisco, who in spite of everything, is a big part of this journey and will forever be linked
to it. Thank you for always believing and encouraging me. I know I can always count on you
no matter what.

To all of those whom I had the opportunity to work during these final months, thank you for
teaching me everything you know and make me desire to do and learn more.

Finally, to my amazing parents, a simple thank you will never be enough. Thank you for the
friendship, unconditional love and everlasting support you have shown me all my life. I would
not be who I am today without you. Thank you for all the opportunities and experiences you
enabled me to have.

5
Table of Contents
RESUMO ................................................................................................................................................. 3
ABSTRACT ............................................................................................................................................. 4
ACKNOWLEDGMENTS ......................................................................................................................... 5
TABLE OF CONTENTS .......................................................................................................................... 6
LIST OF TABLES.................................................................................................................................... 7
LIST OF FIGURES .................................................................................................................................. 7
ABBREVIATIONS AND ACRONYMS .................................................................................................... 8
1. INTRODUCTION ............................................................................................................................ 9
1.2 POLICIES USED TO ENCOURAGE THE USE OF GENERIC MEDICINES....................................................... 10
1.3 GENERIC SUBSTITUTION AS A POLICY TO CONSIDER ............................................................................... 11
1.4 ATTITUDES AND VIEWS TOWARDS GENERIC MEDICINES AND GENERIC SUBSTITUTION ..................... 12
1.5 OVERVIEW OF GENERIC SUBSTITUTION POLICY IN LATVIA AND PORTUGAL ........................................ 13
1.5.1 Latvia ............................................................................................................................... 13
1.5.2 Portugal .......................................................................................................................... 13
1.6 THE ROLE OF COMMUNITY PHARMACISTS .................................................................................................. 14
2. CONTEXT AND OBJECTIVES .................................................................................................... 15
3. METHODOLOGY ......................................................................................................................... 16
4. RESULTS ..................................................................................................................................... 18
4.2 GENERIC SUBSTITUTION PRACTICES IN PORTUGUESE PHARMACIES AND PATIENT ACCEPTANCE .. 18
4.3 GENERIC SUBSTITUTION PRACTICES IN LATVIAN PHARMACIES AND PATIENT ACCEPTANCE ........... 19
4.4 KNOWLEDGE ON GENERIC SUBSTITUTION POLICY AND ITS ADVANTAGES AND DISADVANTAGES OF
PORTUGUESE COMMUNITY PHARMACISTS ................................................................................................................. 21
5. DISCUSSION ................................................................................................................................ 26
6. CONCLUSION .............................................................................................................................. 30
7. REFERENCES ............................................................................................................................. 31
8. ATTACHMENTS........................................................................................................................... 35

6
List of Tables

TABLE 1 | INN PRESCRIPTION AND GENERIC SUBSTITUTION POLICIES IN DIFFERENT EU MEMBER

STATES, 2017 [13] ........................................................................................................ 11

TABLE 2 | OVERVIEW OF NATION GENERIC POLICIES IN LATVIA AND PORTUGAL [13] ................. 14
TABLE 3 | GENERIC SUBSTITUTION PRACTISE IN PORTUGUESE PHARMACIES ................................... 18
TABLE 4 | OVERVIEW OF GS RECOMMENDATION AND PATIENT ACCEPTANCE RATE BY
PHARMACOTHERAPEUTIC GROUP, PORTUGAL ................................................................................. 19

TABLE 5 | GENERIC SUBSTITUTION PRACTICE IN LATVIAN PHARMACIES ............................................. 19

TABLE 6 | OVERVIEW OF GS RECOMMENDATION AND PATIENT ACCEPTANCE RATE BY
PHARMACOTHERAPEUTIC GROUP, LATVIA ........................................................................................ 20

TABLE 7 | GENERIC SUBSTITUTION AND PATIENT ACCEPTANCE RATE, COUNTRY COMPARASION. 20

TABLE 8 | DEMOGRAPHIC CHARACTERISTICS OF PHARMACISTS SURVEYED ...................................... 21
TABLE 9 | OPINION ON THE GENERICS MEDICINES .................................................................................... 21
TABLE 10 | KNOWLEDGE ON THE GENERIC SUBSTITUTION POLICY ...................................................... 22
TABLE 11 | KNOWLEDGE ABOUT GENERIC MEDICATION REPLACEMENT BY GENERIC MEDICATION
POLICY....................................................................................................................................................... 23

List of Figures
FIGURE 1 | SHARE OF GENERICS IN TOTAL PHARMACEUTICAL MARKET, 2016 (OR LATEST YEAR)15

7
Abbreviations and Acronyms

AS Active Substances

EMA European Medicine Agency

EU European Union

INN International Nonproprietary Name

MM Mixed methodology

GM Generic Medicines

GS Generic Substitution

OECD Organization for Economic Co-Operation and Development

RM Reference Medicine

RRP Recommend Retail Price

WHO World Health Organization

NHS National Health Service

8
1. Introduction
Providing affordable healthcare at acceptable standards has become one of the biggest
challenges for European countries [1]. According to the Organization for Economic Co-
Operation and Development (OECD), “one-fifth of the health spending is wasteful and could
be minimized or eliminated without undermining health system performance”. Excluding those
used in hospitals, pharmaceuticals account for the third biggest source of spending on health
care [2].
Not providing patients with adequate medication at the lowest cost to them and their
community can be considered irrational use of medicines. Failure to prescribe in accordance
with clinical guidelines, non-adherence to dosing regimens or inappropriate use of medication
is also considered irrational use of medicines. World Health Organization (WHO) estimates
that irrational use of medicines accounts for more than a half of the medicines prescribed,
dispensed or sold [3].
The European Medicine Agency (EMA) states that generic medicines (GM) have the same
pharmaceutical active substance(s) (AS) as the reference medicine (RM), in the same dosage
form, with the route of administration, quality, safety, strength and are used to treat the same
disease(s). Nevertheless, the drug’s excipients, appearance (color or shape) and packaging
may differ [4]. In order to receive their marketing authorization, GM must demonstrate
bioequivalence to the RM. Normally, GM enter the market once the RM’s patent expires and
its market price tends to be 20-80% cheaper than the RM because of lower research and
development associated costs [5]. Thus, GM play a vital role in healthcare systems, as they
can help reduce and control pharmaceutical expenditures, since their market entry may lead
to a greater market competition which in turn may lead to lower prices [5], [6]. In 2014, the use
of generic medicines saved European payers up to 100 billion euros a year and provided
improved access to different therapeutic areas [1].
Although positive knowledge and perception of GM is helpful, by themselves, will not lead to
an increased use of GM. In order to promote the use of GM is essential that governments
create policies to stimulate its use [7]. Pharmaceutical policies deal with the adequate provision
and use of pharmaceuticals, and one of its main goals, is the minimization and cost-
containment of pharmaceutical expenditure [8]. Generic substitution (GS), is the act of
replacement of a RM for an interchangeable, less expensive medicine, but with the same
bioequivalence, safety, quality, effectiveness – the GM. As a police it can be used to help
reduce the pharmaceutical expenditure, lead to reduced product prices and increased use of
cheapest interchangeable medicine [6], [9]. Given the huge saving potential of GM and GS,
the aim of this study is to understand and compare generic substitution practices of community
pharmacists in two different European countries, Portugal and Latvia, and how different

9
demand-side polices used to stimulate the penetration of GM, may or may not influence the
percentage of GM dispensed.

1.2 Policies used to encourage the use of generic medicines

In broad terms, there are two types of policies that can stimulate and encourage the use of
GM: demand-side and supply-side policies. Both must complement each other in order to
achieve the best results possible [7].
On the one hand, supply-side policies are related to market access, pricing and reimbursement
[9]. On the other hand, to have sustainable prices, at competitive levels, the volume of GM on
the market is crucial for pharmaceutical industries. Thus, demand-side policies are of upmost
importance as they increase the number of packages sold, by increasing demand and
encourage the use of GM [10]. These policies are aimed at those who determine the demand
for medicines, i.e. prescribers, pharmacists and patients [11].
One of the demand-side policies targeting prescribers is the prescription by International
Nonproprietary Name (INN). A medical product can be either identified by a brand-name or by
its INN. Normally, GM are identified by the drug’s INN. The INN is a unique name, with
characteristic sound and spelling, that identifies the pharmaceutical active ingredient(s).
According to the WHO, the main goal of INN system is to “provide health professionals with
universally available designated name to identify each pharmaceutical substance”.
Considering that INN is recognized worldwide and well established, it should mean a safer
prescription and dispensing (avoiding medication-related errors) and make the dialogue
between health professionals easier [12]. Prescription by INN enables and supports GS and
is mandatory in EU member states, for instance France, Greece, Italy and Portugal [13]. Other
demand-side policies targeting prescribers include encourage the use of clinical and
prescription guidelines, monitorization/feedback on prescribing patterns, utilization of
electronical prescribing, financial incentives and prescribing target and restrictions [7], [11],
[14]. As for pharmacists’ policies like implementing a fee-for-performance remuneration
system and allow to perform GS are several of the policies implemented [7], [14].
Lastly, it is important to remove any unfounded negative belief that patients may have
regarding GM. Media campaign on TV, radio, the internet and press are vital to reach as many
people possible, but it is also necessary that pharmacists and prescribers take on a more
active role in the demystification of wrong concepts about generics since, for patients, they are
the most trustworthy source of information. Moreover, it may be important to add differential
co-payments for more expensive medical products since it may drive patients to request GM
[7], [14], [15].

10
1.3 Generic substitution as a policy to consider
In the majority of EU member states, GS is legally allowed, and can be either indicative or
mandatory.
GS substation is mandatory in countries like Denmark, Estonia, Finland, Germany, Greece,
Spain and Sweden. In spite of that, the physician can prevent substitution but has to justify the
reason why substitution is forbidden. Furthermore, the patient can refuse the substitution and
opt for a more expensive medicine, however, has to cover the price difference or can also
receive an additional charge is the they choose a more expensive medicine, which is the case
in Greece. In Belgium, GS is only mandatory for antibiotics and antimycotics.
Some countries with indicative GS include France, Ireland, Latvia, Portugal and Switzerland.
Moreover, Switzerland has even implemented policies to incentivize GS by giving pharmacists
a fee for each time GS is performed. Although GS in France is only indicative, if the patient
chooses to refuse substitution, the patient only receive the reimbursement after paying the
medicine’s full price [13]. Table 1 shows examples of countries and their generic substitution
and INN prescription policies
As GS helps to generate savings by promoting the use of a less expensive medicines instead
of the RM. Moreover, it can not only help to increase the generic market shares, cost-
effectiveness and encouragement of generic entry. GS substitution can also boost price
competition, by incentivize producers to reduce their prices so they products can be
reimbursed by the NHS [6], [16]. Therefore, more should be done to promote and facilitate GS.

Table 1 | INN prescription and generic substitution policies in different EU member states, 2017 [13]

Country Prescription in INN Generic substitution

Albania Mandatory Indicative
Austria Not allowed Not allowed
Belgium Indicative Allowed (mandatory for
antibiotics/antimycotics)
Bulgaria Indicative Not allowed
Croatia Indicative Indicative
Denmark Not allowed Mandatory
Estonia Mandatory Mandatory
Finland Indicative Mandatory
France Mandatory Indicative
Germany Indicative Mandatory
Greece Mandatory Mandatory
Ireland Indicative Indicative
Latvia Generally indicative. Mandatory only Indicative
for newly diagnosed patients
Netherlands Indicative Indicative
Portugal Mandatory Indicative

11
 Spain Mandatory except for non- Mandatory
interchangeable medicines
Sweden Not allowed Mandatory
Switzerland Indicative Indicative
United Kingdom Indicative Not allowed

1.4 Attitudes and views towards generic medicines and generic

substitution
Literature reports that pharmacists hold both positive and negatives perceptions about GM.
Although the majority of pharmacists supports and as a full understanding of the definition of
generics and regards them as equally safe and effective, there is still some percentage of
pharmacists that don’t regard them as effective as the RM [17]–[19]. When it comes to
perception about the quality of generics, pharmacists, are amongst the ones that question it
the most [18].
Regarding GS, the majority of the pharmacist surveyed were in favor and has a positive
attitude towards it. Furthermore, they also believe that GS can help reduce the cost of
pharmaceuticals. Some of the GS advantages mentioned were: renewed image and influence
within the healthcare system and increased recognition of expertise [17], [19]–[21].
Nonetheless, some pharmacists still show some reluctance as they are afraid that substitution
may confuse and worry patients which can translate into poorer health outcomes. Some
pharmacists even reported difficulty trying to implement GS due to physicians and patients’
reluctance and therefore, tried to only target only a specific group of patients for substitution
[17].
When compared to pharmacists, there are more prescribers thinking that GM are more likely
to cause adverse reactions and are less effective. Also, some stated a preference from for RM
and older doctors had a worst opinion of GM. In spite of that, the great majority windily accepts
GM, however even though physicians may be accepting of GS because of economic and policy
pressures they still hold negative concern about the reliability, quality and interchangeability of
GM [17], [18].
The biggest challenge has been to try to gain the confidence of patients as there is still a great
lack of trust on GM. Reasons presented include: lack of trust in foreign manufactures, the belief
that a cheaper medicine means poorer quality and the belief that RM is more effective. Usually,
patients easily accept the generics to treat less serious illnesses. Furthermore, literature
reports that GS, in some cases, led to medications errors has it led to medication duplication
and made it more difficult for patient keep track of their medication because of packaging or
appearances issues. However, the level of acceptance, in developed countries, is steadily

12
increasing mainly due information campaigns and a better communication between healthcare
professional and patients [17], [18]

1.5 Overview of generic substitution policy in Latvia and Portugal

1.5.1 Latvia
In the Republic of Latvia, the National Health Service (NHS) is the administrative institution in
charge of creating a positive reimbursement list and determines which medicines are to be
included in the list, as well as, the corresponding reimbursement rate. The reimbursement
system is based on the severity of the illness and the need for the chronic use of medication.
There are three reimbursement rates – 100%, 75%, 50%. The positive list can be divided in
three other different lists: list A (reference price list with interchangeable medicines), list B
(non-interchangeable medicines) and list C (non-interchangeable expensive medicines which
the annual treatment cost is greater than 4300€) [22].
Several strategies have been used to encourage the use of reference products of list A, such
as prescribing by INN and GS. Although INN prescribing is not always mandatory, according
to Regulation No. 899 [23], INN is mandatory if a patient is prescribed, for the first time, a
medicine that belongs to the list A. In this case, the pharmacist must dispense the lowest priced
reimbursable medicine which correspond to the common name, with the same pharmaceutical
form and strength. However, if there are two or more pharmaceutical products on the
reimbursable list with the cheapest basic reimbursement price, the patient has to be informed
that it has the right to choose any of them. Unless the patient doesn’t accept the cheapest
medicine or the physician has forbidden substitution, the patient must pay the difference
between the reference product and the product chosen or in some cases pay full price.

1.5.2 Portugal
In the case of reimbursement medicines, medical prescriptions must include the INN of the
active substance(s) as well as, the pharmaceutical form, the dosage, presentation, quantity
and posology of the medicine. Exceptionally, the prescription may include the product’s
commercial or the name of the marketing authorization holder, in one of the following
situations:
1. There is no reimbursable generic medicine or there are only available branded
originals and licenses for the active substance prescribed:
2. The prescriber has a technical justification for not allowing the replacement. All of
the exceptions must be identified by the prescriber, in the prescription. The cases
where technical justification is acceptable, are the following:

13
 a. Prescribe medicine has a narrow therapeutic margin or index, according to
the information provided by INFARMED, I.P.;
b. Suspected of intolerance of adverse effect, previously reported to
INFARMED, I.P., to a drug with the same active substance, but with another
commercial name
c. Prescribed medicine is intended to ensure continuity of treatment with ta
duration of more than 28 days.
For non-reimbursed medicines, medical prescription may include the product’s brand name of
the name of the marketing authorization holder.
During the dispensing act, and in compliance with what has been prescribed, the pharmacist
or other qualified person, must inform the patient regarding the medicine that has the lowest
price. Pharmacies must have available to dispense at least 3 medicines with the same active
substance, pharmaceutical form and dosage of the lowest five prices for each homogenous
group. Pharmacies must dispense the lowest priced medicines within these options, unless
the patient opposes, or the prescriber prevents it. If the patient opts for a more expensive
medicine the difference should be payed out-pf-pocket [24].

Table 2 | Overview of nation generic policies in Latvia and Portugal [13]

GS
legally Is generic substitution Is INN Patient can Doctor can
allowed? indicative/mandatory? indicative/mandatory? refuse? prevent it?
Latvia
Yes Indicative Indicative (*) Yes Yes
Portugal Yes Indicative Mandatory Yes Yes

(*) Only mandatory if the patient is newly diagnosed

1.6 The role of community pharmacists

Community pharmacies is one of the places where GS policy actually comes into practice.
Pharmacists play a vital role when it comes to influence the choice between the RM or GM, as
they are the most skilled healthcare professional to assure patients about the quality, safety
and effectiveness of generics as well as avoid any confusion that may be caused by
substitution. Not only that, but can also contribute to the decrease of pharmaceutical
expenditures as they are can advise prescribers and patients on the right GM. Although
pharmacies are legally bound to dispense the lowest priced medicine, the patient can always
refuse it. Patients who are indifferent may easily take the medicine provided by the pharmacist,
whereas those with stronger beliefs about the lack of quality and efficiency of GM may not [25],
[26].

14
2. Context and objectives
According to OECD Health Statistics [27], the share of generics in the total pharmaceutical
market for Portugal, in the year 2018, was by value (i.e., total expenditure on GM divided by
total pharmaceutical expenditures) 20,5% while by volume (i.e., number of packages sold) was
47,6%. However, for the Latvian total pharmaceutical market, in the year of 2016, the share of
generics by value was 42% and by volume was 74%, as seen in Figure 1.

Portugal

Latvia

0 10 20 30 40 50 60 70 80

Volume (%) Value (%)

Figure 1 | Share of generics in total pharmaceutical market, 2016 (or latest year) [27]

As stated above, GS can influence the market share of generics. Therefore, is crucial to
understand how pharmacists perceive substitution and related policies, since they are the main
influencers of GS. Although there are several studies done on the opinion, perceptions and
views of GM and GS [17]–[20] there are, to the best of the author’s knowledge, no studies that
compare how different policies influence the generic substitution rate and what are the
perceptions and knowledge that pharmacists have on the GS policies, barriers pharmacist face
daily when trying to perform substitution and what are the similar problems faced in different
countries.
Latvia and Portugal have different generic policies. In Latvia, prescription by INN is only
mandatory in specific cases as opposed to Portugal, where INN is always mandatory.
However, in both countries GS on only indicative.
Therefore, the aim of this study is to compare policies used to stimulate the use of GM, as well
as, GS rates and practices of community pharmacists in two different European countries,
Portugal and Latvia. Furthermore, it also aims to assess the rates and patient acceptance of
GS, identify barriers that pharmacists face when trying to perform GS and evaluate community
pharmacist’s knowledge of GS polices.

15
3. Methodology
In order to be able to achieve the mentioned objectives the study took on a mixed methodology
approach. Mixed methodology (MM) incorporates “quantitative and qualitative paradigms,
approaches, concepts, methods and/or techniques in a single study” [28]
For the assessment of the rates of GS a quantitative approach was used. Community
pharmacists, in both countries, were asked to fill an anonymous data collection form. The form
is based on a form used on a study on generic medicines substitution practices of Malaysian
community pharmacists [29]. The form was provided to the pharmacists, in the corresponding
language. Pharmacists were asked to fill the form with the first three prescriptions at the start
of every hour throughout eight hours for three days. This was done in order to avoid bias
related to the working hours of the pharmacies, since is more likely that certain populations
only come to the pharmacy at a certain time. In the form, pharmacists were asked to register:
hour of which the medicine was dispensed, whether or not the patient asked for the generic,
whether or not GS was suggested, whether or not patient refused substitution, prescription
details (drug name, form, dosage, quantity) and medical product dispensed (drug name, form,
dosage, quantity);
Due to limited time and resources, convenience sampling was used. Convenience sampling is
a nonprobability sampling technique was used. Unlike probability sampling, in nonprobability
sampling all elements of the populations don’t stand the same change of being picked and
randomization is not applied [30]. Therefore, the sample population only has to meet certain
preestablished criteria, like availability, easy access and willingness to participate [30], [31].
Therefore, three pharmacies and two pharmacists per pharmacy in three different regions of
Lisbon were selected.
Since it is desired to determine the frequency at which substitution happens, OpenEpi [32]
used to calculate the sample size for a frequency in a population. The population size used for
this calculation was based on the minimum requirement of people in an area for the opening
of a pharmacy, which is minimum of 3500 people, in Portugal [33]. Therefore, for three
pharmacies the population size was 10500. In order to achieve a confidence level of 95%, is
was estimated that it was necessary to collect 371 prescriptions. The same methodology was
applied in Latvian community pharmacies, with the necessary alterations.
The data gathered from the forms was entered into Excel version 16.29.1 for analysis and
descriptive statistic was used.
To identify possible barriers/challenges that pharmacists are confronted with during their daily
activities, as well as, their knowledge of the GS substitution polices, a survey with open-ended
questions was designed. Although this survey was done for both countries, at the time of
writing the results from the surveys from Latvia were not available, since the Latvian
pharmacist were not available to answer them in the agreed time . In questionnaire four

16
different sections where established: demographic characteristic of the pharmacists (age and
numbers of years working as a community pharmacist), their opinion on GM, knowledge and
opinions on generic drug substitution policy and barriers faced when trying to perform GS. This
type of questionnaire helps to complement the quantitative data obtained and makes possible
to capture the views and opinions of the pharmacists. Furthermore, doesn’t allow the
responder to drift from the initial question, doesn’t pressure the responder to feel like has to
give the right answer and has no time constraints [34]. The answers were transcribed verbatim
and were analyzed by theme for their difference and similarities.

17
4. Results
In the following section the results for GS recommendation and patient acceptance rate are
presented for both countries. However, at the time of writing the data from the surveys to
Latvian pharmacist was not available.

4.2 Generic substitution practices in Portuguese pharmacies and

patient acceptance
Analysis of the prescriptions (table 3) revealed that in 371 prescriptions, 345 of the active
substances (AS) were prescribed by its INN. Moreover, the cases where prescribing by INN
wasn’t used are small. In 15 prescriptions INN was missing and in 11 prescriptions both the
INN and the commercial name was used. In some cases (29,65%) patients asked for the
generic directly. Recommendation of substitution of a branded-name medicine for a generic
was done in the majority of the cases (83,91%). The cases where substitution was not
suggested it was either because a GM wasn’t available (8,43%) or pharmacist didn’t ask
(7,66%). When the recommendation of substitution was performed the majority of the patient
refused the GM (52,97%).

Table 3 | Generic substitution practice in Portuguese pharmacies

Number of cases Percentage (%)

Yes 345 92,99

Prescription in INN? No 15 4,04

Both 11 2,96

Did patient ask for the Yes 110 29,65

generic? No 261 70,35

Yes 219 83,91

Was substitution No 20 7,66
recommended? No – GM not 22 8,43
available
Did patient refuse Yes 116 52,97
substitution? No 103 47,03

The three most prevalent pharmacotherapeutic groups were the medicines used in anti-
infectious, central nervous and cardiovascular disorders. The GS recommendation rate for
these groups were 95,24%, 88,71% and 81,41%, respectively. However, patient acceptance
was highest (52,27%) in medicines that belonged to the medicines used to treat cardiovascular
diseases and lowest (37,5%) in medicines used to treat anti-infectious diseases. Table 4
shows GS recommendation and patient acceptance rate for all the pharmacotherapeutic
groups that were prescribed in this study

18
Table 4 | Overview of GS recommendation and patient acceptance rate by pharmacotherapeutic group,
Portugal

Pharmacotherapeutic Group Number of GS recommendation Patient acceptance rate

prescriptions rate (%) (%)
Anti - infectious medicines 54 95,24 37,50
Central nervous system 97 88,71 47,27
Cardiovascular system 91 81,41 52,27
Blood 9 66,67 66,67
Respiratory system 10 42,86 66,67
Digestive system 22 91,67 45,45
Genito-urinary system 5 75,00 66,67
Hormones and medicines used to 26 63,64 57,14
treat endocrine disorders
Musculo-skeletal system 40 94,29 45,45
Antiallergic mediation 11 77,78 28,57
Medication used in
6 60,00 33,33
otorhinolaryngological disorders

4.3 Generic substitution practices in Latvian pharmacies and

patient acceptance
Analysis of the prescriptions (table 5) revealed that in 342 prescriptions, only 62 of the active
substances (AS) were prescribed by its INN. In the majority of the cases INN was not use and
the commercial name was used instead. There is only one case where both designations were
used. Recommendation of substitution of a branded-name medicine for a generic was done in
the majority of the cases (45,03%). The cases where substitution was not suggested it was
either because a GM wasn’t available (29,82%) or pharmacist didn’t ask (25,15%). When the
recommendation of substitution was performed the majority of the patient accepted the GM
(64,94%).

Table 5 | Generic substitution practice in Latvian pharmacies

Number of cases Percentage (%)

Yes 62 21,58

Prescription in INN? No 279 81,58

Both 1 0,29

Yes 154 45,03

Was substitution No 86 25,15
recommended? No – GM not 102 29,82
available
Did patient refuse Yes 55 35,71
substitution? No 99 64,29

19
The two most prevalent pharmacotherapeutic groups were the medicines used in central
nervous and cardiovascular disorders. The GS recommendation rate for these groups were
80,0% and 75,8%, respectively. However, patient acceptance was highest (80,0%) in
medicines that belonged to the medicines used to treat central nervous system diseases and
lowest (42%) in medicines that belong to the cardiovascular system group. Overall, the mean
value for the GS recommendation rate was 72,7% and for patient acceptance rate 57,1%.
Table 6 shows GS recommendation and patient acceptance rate for all the
pharmacotherapeutic groups that were prescribed in this study.

Table 6 | Overview of GS recommendation and patient acceptance rate by pharmacotherapeutic group,

Latvia

Pharmacotherapeutic Group Number of GS recommendation Patient acceptance rate

prescriptions rate (%) (%)
Anti - infectious medicines 25 62,50 86,67
Central nervous system 50 71,43 84,00
Cardiovascular system 111 70,83 55,88
Others 39 26,67 100,00
Respiratory system 22 54,55 50,00
Digestive system 12 70,00 42,86
Skin condition 14 55,56 60,00
Hormones and medicines used to 18 70,00 57,14
treat endocrine disorders
Musculo-skeletal system 25 45,00 44,44

Diabetes 14 50,00 0,00

Eye conditions 12 87,50 85,71

Overall, the value for the GS recommendation rate was slightly bigger in Portugal than in
Latvia. However, in Latvia, patients are more willing to accept substitution. (table 7).

Table 7 | Generic substitution and patient acceptance rate, country comparison

Portugal (mean value) Latvia (mean value)

Generic substitution rate 77,78 62,50
Patient acceptance rate 47,27 57,14

20
4.4 Knowledge on generic substitution policy and its advantages
and disadvantages of Portuguese community pharmacists
In total six pharmacists were asked to respond to the survey. Respondents’ aged varied
between 26 to 40 years and the extent of experience working in community pharmacy also
varies significantly (see table 8).

Table 8 | Demographic characteristics of pharmacists surveyed

Characteristics Value
Age, mean (range) 30,5 (26-40)
Working experience in community pharmacy, mean (range) 6,5 (1-16)

The answers of the surveyed were transcribed verbatim and the answers to the three main
themes can be read bellow:

Table 9 | Opinion on the generics medicines

Bioequivalent medication to brand medication

In your opinion, generic
medication is:
Which generic medication
manufacturing
laboratories do you trust
the most? Why?
Medication equivalent to the original, but usually cheaper
than the original.
Medication with the same active substance as the original
It is medication which contains the same active principle and
the same dosage as the original.
Medication with equivalent properties to the brand
medication
A bioequivalent medication to the original
In those that have their own production and don’t just to buy
from other laboratories.
Sandoz, ratiopharm and generis
Original medication, due to the years of usage in patients
which present alterations regarding the study phase groups.
I trust more in generic medication made in the same
laboratory as the original, because the bioavailability must
be closer to the original.
Generis, Sandoz, Ratiopharm. Because of the
experience/feedback I have.

21
 Generis, Farmoz, Sandoz, Aurovitas
I trust them because the “mother houses” of these generic
medications are well known laboratories and because I know
they are produced in certifies laboratories with high accuracy
and control standards.

Table 10 | Knowledge on the generic substitution policy

Decrease health spending by replacing brand medication

with cheaper and same quality generic medication, leading
to a lowering of the prices, including brand medication due
to the decrease in reference prices;
What do you consider is Decrease health spending for the generic medication taking
the goal for replacing users.
brand medication by Give the patient decision power
generic medication? Give a cheaper and equally effective and safe alternative for
users and SNS (Portuguese Nation Health Service).
Reduce user spending
Economic savings for the user
Profitable purposes for the company
There are many laboratories for each molecule "producing"
generic medicines, with very different RRP, which pressures
pharmacies to stock all brands, many of them with little
rotation.
In many prescriptions, doctors prescribe a certain generic
laboratory and often patients do not do this laboratory and
Do you feel this policy is that we can’t replace.
fulfilling its purpose? Yes, to the extent that the majority of patients know what
Explain. generic medication is and accept or not replacement when
suggested.
I don't know the policy so I can't answer.
Not in all situations. Many people still think that because it's
cheaper, the effect is not quite the same.
I think we need more knowledge about the laboratories and
their products to make sure they are trustworthy and
credible.

22
 The SNS could only reimburse generic RRP5 for example.
This would force the remaining laboratories to reduce the
RRP of their brands to be reimbursed as well.
Doctors prescribing by active substance and not mentioning
generic laboratories.
More information and training aimed at the user and provided
by doctors, as the generic replacement policy exists due to
Which strategies would
the information or disinformation the doctor provides the
you wish to see
user.
implemented to ensure
More available information on televisions and newspapers.
this policy is successful?
So that the majority of the population could acquire
knowledge about generic medication.
More information to users.
More training and information with scientific studies to
support information

Table 11 | Knowledge about generic medication replacement by generic medication policy

Cheaper for the patient, better profitability for the

pharmacy.
Give the user power of decision

Always give the patient a choice, as there is often a non-

In your opinion, what adherence to therapy because the patient does not have
are the advantages to enough income to purchase it.
generic substitution? Save the client’s money
The user can pay less.
To be cheaper for the user, benefits for the SNS, financial
advantages for the company.
When the patient is loyal to a generic brand that does not
exist in the pharmacy’s stock and they do not want to switch
brand, which requires ordering if the client waits or losing the
dispensing.
Creates doubts in the users. Many of them don’t trust generic
medication.

23
 To give the power of decision to the user who is not
trained/well-informed on the issue, making them more
confused and doubt-filled relating their therapy.
Changing the medication in situations where the doctor
doesn’t agree, if the patient is finding it difficult to stabilize
In your opinion, what
therapeutic goals.
are the disadvantages
Lower bioavailability. And different taste or aroma, which the
to generic replacement?
patient may not be able to handle.
Often, when the patient doesn’t improve, they associate the
lack of improvement with the fact that the medication was
generic.
Generic medication is unreliable and does not have the
same effect as the reference medication.
Patient loyalty to certain generic laboratories with low
rotation, doubts regarding the price of the generic that the
patient will pay.
Not relying on generic to brand equivalence and the price
of prescription medication (often these prices are out of
date).
Lack of information on the subject;
the pharmacy does not have the generic that the patient
What are the most
usually takes;
common difficulties you the doctor "locking" the prescription and not allowing the
face? patient’s preferred generic;
no generic stock in the pharmacy with the patient’s
preferred price.
Fear / doubts of patients regarding generic medication.
The doctor telling the patient to not switch medication. The
low confidence of some users in "generic drugs".
Patients do not always want to replace their medication
with the generic version.
Make the RRP more homogeneous and closer to the
reference price.
In the new prescriptions, there should be no reference to
prices (because they are often incorrect and raise problems
for the pharmacy).

24
 Training / informing to patients about generic medication;
patients should be more informed and responsible with
their medication.
Giving the patient better information about the difference
What suggestions do
between generics and originals.
you have for solving
There should be more information regarding the effects of
these difficulties?
brand vs generic medication accessible to the general
public.
Provide more training to healthcare professionals
More information available for patients, debunking the lack
of quality and efficacy of generic medication.
The doctors give more information to their patients more,

What do you think as they trust them with their therapy.

encourages generic Greater consistency in the efficacy of generics. And more

information available to patients
medication acceptance?
There should be more information regarding the effects of
brand vs generic medication available to the general public.
There should be more control, rigor in the manufacturing of
the generic medication.

25
5. Discussion
The promotion of the generic drug market and the use of GM has been one of the principal
goals of Portugal and Latvia’s drug policy and its increased use has been one of the most
relevant cost-control measures. In order to increase market share, mandatory INN and
allowing pharmacist to perform substitution of prescribed medicines by the generics have been
introduced, in Portugal, in 2012 [35], [36]. Although the use of GM has been promoted
throughout the years, in Portugal, its market share is still bellow OECD average [37].
Conversely, in the year of 2016, Latvia presented a high penetration rate of GM [37]. Measures
like INN prescribing, GS and information campaign were also introduced in Latvia to stimulate
and promote the use of GM [38]. The combination of GS and INN prescribing has been adopted
by many European countries to help reduce pharmaceutical expenditures [39].
Portuguese legislation states that medical prescription must include the INN except under
certain conditions, yet, Latvian legislation states that prescribing by INN is only mandatory if
the patient is prescribed a medicine, from list A, for the first time. The results revealed that in
the Portuguese case the majority of the medicines were prescribed through INN, however, in
Latvia the opposite occurred. This finding is somehow expected because in Portugal,
prescribing by INN it’s a legal obligation for all reimbursed medicines, while in Latvia is not.
The use of INN in prescriptions is said to improve patient acceptance of GM, since it can
enhance patient familiarity with the generic names instead of the brand name and reduce
confusion with the difference of appearance/packing when generics are dispensed [17].
When substitution was suggested, more patients accepted the GM in Latvia than in Portugal.
A study done on the use of GM in Latvia showed that the people in Latvia considered
themselves to be well informed on the GM and its availability, nevertheless the majority of the
respondents said, if they had to make a choice, they would prefer not using the GM [38]. Lack
of acceptance of the GM may be associated with the patient’s lack of trust in generics which
in turn is caused by a lack of information and education. Studies have shown that it is crucial
to educate and inform patients in order to demystify unfounded beliefs in order to gain people’s
confidence and improve generics acceptance [40]. Additionally, it is important to consider
where this information is coming from [40]. In Latvia, physicians were shown to provide
negative information about GM. This may be due to close relations with the pharmaceutical
industry since payments from the pharmaceutical industry have been associated with
preference for brand-name medicines or lack of knowledge about the concept of
bioequivalence [38].
In Portugal, the underuse of GM was also associated with patients’ lack of trust in GM and
information. Quintal et. al [41] stated more should be done in terms of information and the main
massage should be centered on the positive financial aspect that GS can have on patient’s
finances; this factor was associated with enhanced willingness to accept substitution [42].

26
Results from this study also showed that pharmacists agreed that patients still trust physician’s
opinion the most and they can easily influence patients’ opinion on GM. Therefore, it is vital to
make sure that physicians are also provided with correct and trustworthy information, because
their negative opinions and beliefs may incorrectly influence patients [40]. Not only that, but
respondents also agreed that in order to improve substitution acceptance and GM, more
should be done in terms of information not only to the patients but also to all healthcare
professionals.
When it comes to the knowledge on GS policy findings from this study revelated that the
majority of the respondents knew about the policy and pharmacists believed that the main goal
of the GS policy is to lower pharmaceutical related expenditures by replacing a more expensive
medicine with a cheaper alternative, which is equally safe and effective. However, they
believed this policy fails to achieve its intended purpose and there are still many problems that
should be addressed. Reasons mentioned for failure where: too many generics for the same
molecule with very different recommended retail prices (RRP), patient lack of trust in generics
and failure to substitute because physicians prescribed a certain generic laboratory and unable
substitution. In spite of this, the majority agreed that as a policy helps to reduce pharmaceutical
expenditures for the NHS and the patients.
All the pharmacists had a clear understanding of what a GM is, which is consistent with
literature [43], however there are doubts about the laboratories where the generic is produced
and some considered that the laboratories where the RM is also produced are more reliable.
Five out six respondents agreed that there are laboratories more reliable than others and a
study done by Josef Maly et. al [43] found that some pharmacists think that good
manufacturing practices requirements are not followed by some GM laboratories. This fact
may be worrisome because some generics may be preferred over others during the dispensing
act.
Regarding the GS policy, half of the respondents said they would like to receive more
information and/or training about the policy as they didn’t fully understand the policy and its
main goals. This fact may lead to infrequent application of GS due to lack of confidence in
performing substitution. Some of the reasons pharmacists may have not to suggest
substitution include fear of adverse drug reaction and risk of medication errors like duplication
of medication [43]. Another reason that should be considered is pharmacists’ lack of trust in
generic also highlighted by this study. Some pharmacists believe that the generic may not be
bioequivalent and are not as safe as the RF. Although this is uncommon, literature reports [19],
[43], [44] that some pharmacists holds negative beliefs and opinions about GM. It would be
important to have more in-depth knowledge about the reasons why pharmacist may not always
suggest substitution and the reasons some consider generics to be of low inferiority.

27
All the pharmacists surveyed claimed that they suggest substitution every time it’s possible to
substitute the RF and only a few face problems during substitution. However, this is not
consistent with data from this study. Even though GS was suggested most of the time, there
are cases where substitution is not suggested, either because the GM was not available or
because it was not suggested. Moreover, it is important to consider whether or not the
substitution recommendation rate is that high because pharmacists might have felt pressure
to suggest substitution more frequently. Once again, the main problem is the patient’s lack of
trust in the GM and information. Also, doctors telling the patients not to change generics or
“lock” the prescription to make it impossible to dispense the generic the patient wants is
regarded as an issue. Other problems reported include the “loyalty” some patient have to
certain generic manufacturer which may arise problems in the cases the pharmacy does not
have the generic available and the patient does not want to substitute. Doubts about the prices
shown is the prescriptions have also been mentioned since sometimes that prices are incorrect
and causes problems in the pharmacy. It was suggested that the new prescriptions should not
show the prices of the medication.
The advantages and disadvantages of GS have also been acknowledged. According to the
respondents, the main advantage is the financial aspect of substitution. Furthermore, it was
mentioned that substitution for a cheaper medicine improves patient’s therapeutic adherence,
because sometimes patient’s may not have the financial means to acquire all the medication.
However, some recognize that substitution may confuse patients about their medication. Some
respondents also question the reliability of generics stating that one of the downsides of
substitution is that the medicine dispensed has inferior efficacy.
It is also important to notice the Portuguese pharmacists were picked through convenience
sampling and only them answered the surveys. Therefore, we cannot extrapolate these
findings to the general population. Additionally, because of the sampling method, there is
potential bias related to under-representation of the population and therefore, the power to
detect differences within the is limited [45]. Since it was not possible to include the answers
of the Latvian pharmacists it is important to consider that we are missing relevant issues that
the Portuguese pharmacists are also facing and forgot to address, as well as, different issues
that Portuguese pharmacist are not being faced with.
The qualitative results (i.e. views and opinions on GS policy) were obtained through a survey
with open-ended questions, instead of interviews or a focus group, mostly due to time
constrains. Although it allows to complement the quantitative data of this study and it gives the
change for pharmacists to answer the surveys when they are available, the views, opinions
and issues addressed are limited to the questions being asked. Moreover, although they don’t
drift from the initial question, other issues they may be facing will not be addressed. Therefore,
additional research using interviews, or a focus group would be relevant to consider it would

28
provide a deeper understanding of the issues and detailed insight into their experiences and
opinions.

29
6. Conclusion
The results of this study showed branded name medicines are still preferred over the GM.
Although the majority of community pharmacist surveyed acknowledged the importance of
substitution and considerably high GS recommendation rates, patient acceptance of GM still
remains low. This fact has been linked with lack of trust and misconceptions about the GM. If
patients are ill-informed about the equivalence of GM it is more likely that brand-named
medicines will always be preferred and the possible savings from the use of GM will not be
generated [18].
There is a need to do more in terms of information, not only to the patients but also to
healthcare professionals. By preferring a certain type of medication, healthcare professionals
can influence patient’s choices, thus making the acceptance of GM more difficult. Moreover,
the information should target not only concepts of quality, safety, efficacy but also explain why
GM are cheaper and regulatory process that GM have to go through in order to enter the
market. Correct knowledge and understanding of GM are regarded as vital factors to increase
the acceptance and use of GM [46].
Both pharmacist and physicians have a vital role in the promotion of GM, GS and patient
acceptance. Therefore, it is crucial that they have a more active role in educating and
recommending the GM more often.
Also, it is important to considerate prescribing by INN may not be affective as is, in Latvia.
Since it is not always mandatory, the physician can opt out of it and prescribe by brand name
instead. Therefore, healthcare authorities should reconsider their correct legislation, as it has
been seen that INN prescribing can help with better acceptance of GM.
This study had the following limitations - due to the reduce number of pharmacists surveyed
and the fact that the sample was generate through convivence sample, it is not possible to
consider this sample as representative of the population. Consequently, is not possible to
extrapolate the results to the general population. However, this study provides meaningful
insight to GS rates and patient acceptance of GM, as well pharmacist’s opinion on generic
substitution. Thus, this study can serve as preliminary study and be valuable as a starting point
for further research. Also, may be interesting to considerer focus-group or semi-structured
interviews to pharmacists in order to expand on the issues reported.

30
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8. Attachments

Survey instruments – Prescription data collection form

Prescription in Patient Substitution for Patient refused Prescription Medicine
INN? asked for a GM the GM? details (drug dispensed
(Yes/No/Both) the GM? suggested? (Yes/No) name, form, (drug name,
(Yes/No) (Yes/No) dosage, form, dosage,
quantity) quantity)

Survey instruments – Survey

Evaluating Pharmacists Perceptions: How Do They Think and How Do They Act Regarding
Medication Replacement

This questionnaire aims to discover the daily practices, difficulties and perceptions of
pharmacists regarding generic replacement.
Generic replacement consists of the replacement of brand medication by a generic version
with the same bioequivalence, safety, quality and efficacy. In this way, and considering the
pharmacist is the main connection between medication and patients, it is important we
understand how these health professionals may influence the practice of generic replacement.
Lastly, we aim to understand the pharmacist’s perceptions and attitudes regarding the
replacement, and which challenges they face when applying the concept.

Age:
Professional experience (no. of years working as a pharmacist)

Opinion Regarding Generic Medication

1. In your opinion, generic medication is:
2. Do you agree some generic medication manufacturing laboratories are more
trustworthy than others? (Agree, Don’t Agree)
3. Which ones do you trust the most? Why?

Knowledge About Brand Medication Replacement by Generic Medication Policy

1. What do you consider is the goal for replacing brand medication by generic medication?

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 2. Have you ever received any training or information regarding the generic replacement
policy? (Yes/No).
3. Explain where you obtained this information or training
4. Do you agree more training or information regarding this policy and its goals is
necessary? Explain.
5. Do you feel this policy is fulfilling its purpose? (Yes/No) Explain.
6. Which strategies would you wish to see implemented to ensure this policy is
successful?

Challenges Faced During the Replacement

1. Do you suggest replacement when it’s possible to replace brand medication by generic
medication? (Yes/No).
2. In your opinion, what are the advantages to generic replacement?
3. In your opinion, what are the disadvantages to generic replacement?
4. Do you face difficulties when you apply this policy? (Yes/No).
5. What are the most common difficulties you face?
6. What suggestions do you have for solving these difficulties?
7. What do you think encourages generic medication acceptance?

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