Generic Suppliers Research Articles

Lenacapavir to prevent HIV infection: current prices versus estimated costs of production.

Despite improvements in treatment and oral pre-exposure prophylaxis (PrEP) access, 1.3 million people acquired HIV in 2022. Six-monthly lenacapavir PrEP could benefit tens of millions of people at high risk of infection. However, prices are currently up to $44 819 per person per year (pppy). We projected minimum lenacapavir pricing based on generic mass production and a Cost-Plus (Cost+) model. Current active pharmaceutical ingredient (API) and key starting materials (KSMs) costs were obtained from export databases. The routes of synthesis (ROS) were analysed to project a cost of goods (COGs). Formulation, vials and profit margin costs were included using standardized algorithms and Cost+ pricing. We estimated prices with scale-up to supply 1 million then 10 million treatment-years, comparing this with national list prices. The lenacapavir API is currently exported from India for $64 480/kg on 1 kg scale. Based on the ROS and KSMs, API COGs of $25 000/kg and $10 000/kg are achievable for a committed demand of 1 million (2 million tonnes/annum of API) and 10 million treatment-years, respectively. Including formulation steps, injectable lenacapavir could be mass produced for approximately $94 pppy for 1 million and $41 for 10 million treatment-years, if voluntary licences are in place and competition between generic suppliers substantially improves. Greater scale-up with improvements in manufacturers' ROS could reduce prices further. Currently lenacapavir costs $25 395-44 819 pppy. Lenacapavir could be mass produced for <$100 pppy at launch. Voluntary licensing and multiple suppliers are required to achieve these low prices. This mechanism is already in place for other antiretrovirals. To date, Gilead has not agreed lenacapavir voluntary licences with the Medicines Patent Pool.

The Application of Competition Law to the Pharmaceutical Sector in the European Union and United Kingdom

This survey article discusses European competition law developments in the pharmaceutical sector from January 2021 through December 2021. Section II reviews developments that continue in the wake of the COVID-19 pandemic. Section III covers cases involving competition from generics and biosimilar suppliers. Section IV deals with recent judgments and cases on excessive pricing. Section V addresses developments on the ongoing issue of parallel trade and distribution. Section VI looks at investigations and recent national enforcement regarding cartels and information exchange. Finally, Section VII provides an overview of the scrutiny of mergers by competition authorities. In response to the COVID crisis, the European Commission (Commission) published a Temporary Framework in April 2020 indicating that certain forms of business cooperation among competitors might exceptionally be allowable in order to address the shortage of essential products and services triggered by the ‘rapid and exponential growth of demand’ engendered by the crisis.1 At the same time, the Commission issued its first comfort letter addressed to ‘Medicines for Europe’ (MfE), a trade association of generic and biosimilar suppliers, supporting MfE’s collective response to address medicine shortages caused by a surging demand for treatment of COVID-19 in hospitals.2

Four Facts Concerning Competition in US Generic Prescription Drug Markets

We establish four facts concerning competition among US generic drug suppliers, using IQVIA’s National Sales Perspective™ 2004 Q4–2016 Q3 data. We define a unique product market (“molform”), consisting of the combination of a molecule active ingredient and a route of administration formulation, aggregated over different doses and strengths. We find: (1) supply exhibits substantial churning in entrants and exits; (2) volume-weighted use concentrates in older generic molform cohorts; (3) the extent of competition is greatest for the oldest molform cohorts and is smallest for the youngest molform cohorts. With a median of one competitor, the extent of competition in the youngest molform cohort is very limited; and (4) supplier-molform annual revenues are typically small, are largest for relatively young drugs, but are heavily right skewed. These four facts provide an empirical platform on which to construct and empirically evaluate hypotheses regarding generic drug market structure, performance, and possible policy reforms.

Differentiating Generic versus Branded Pharmaceutical Tablets Using Ultra-High-Resolution Optical Coherence Tomography

Optical coherence tomography (OCT) has recently been demonstrated as a powerful tool to image through pharmaceutical film coatings. Majority of the existing systems can, however, resolve film coatings for thickness greater than 10 µm. Here we report on an ultra-high-resolution (UHR) OCT system, with 1 µm axial and 1.6 µm lateral resolutions, which can resolve thin coatings at approximately 4 µm. We further demonstrate a novel application of the system for differentiating generic and branded suppliers of paracetamol tablets.

Drug Shortage Impacts Patient Receipt of Induction Treatment

Examine the impact of the 2011 shortage of the drug cytarabine on patient receipt and timeliness of induction treatment for Acute Myeloid Leukemia (AML). A retrospective cohort was utilized to examine odds of receipt of inpatient induction chemotherapy and time to first dose across major (N=105) and moderate (N=316) shortage time periods as compared to a nonshortage baseline (N=1,147). De-identified patient data from 2008 to 2011 Surveillance, Epidemiology, and End Results (SEER) were linked to 2007-2013 Medicare claims and 2007-2013 Hospital Characteristics. Compared to prior nonshortage time period, patients diagnosed during a major drug shortage were 47 percent less likely (p<.05) to receive inpatient chemotherapy within 14days of diagnosis. Patients who were younger, had a lower Charlson Comorbidity score, and for whom AML was a first primary cancer were prioritized across all periods. Period of major shortage of a generic oncolytic, without an equivalent therapeutic substitute, reduced timely receipt of induction chemotherapy treatment. More favorable economic and regulatory policies for generic drug suppliers might result in greater availability of essential, older generic drug products that face prolonged or chronic shortage.

Can the generic antiretroviral industry support access to a universal antiretroviral regimen?

The generic antiretroviral (ARV) industry played a critical role in the massive scale-up of HIV treatment in low-income and middle-income countries since 2000. As the global community looks ahead to a universal antiretroviral regimen, this article considers the industry's role in supporting universal access to affordable, simpler, more durable, and tolerable HIV treatment regimens. Generic manufacturers made treatment scale-up in low-income and middle-income countries possible through reducing prices, combining molecules from different originator companies to develop optimal fixed-dose combinations, and investing in production capacity to meet escalating demand. Achieving scale-up of a universal regimen will require continued partnership in these areas. Collaboration on the demand and supply sides of the ARV marketplace will be required to foster a healthy and sustainable marketplace for new regimens. This includes clear priority setting from the global treatment community on priority products; predictable demand; regulatory prioritization of optimal products; effective tendering and procurement practices that enable multiple suppliers to participate in the market; coordinated product introduction efforts between Ministries of Health, partners, and civil society; and transparency from both buyers and suppliers to promote and monitor supply security. New regimens will benefit people living with HIV, as well as buyers and generic suppliers, by maximizing existing production capacity and treatment budgets to reach the 90-90-90 goals.

The Application of EU Competition Law in the Pharmaceutical Sector

This survey article discusses the major EU competition law developments in the pharmaceutical sector from 1 November 2015 through 31 December 2016. Section 2 addresses cases on restrictions of competition from generic suppliers, including the Lundbeck and Servier cases now on appeal to the EU courts, the new GlaxoSmithKline (GSK) decision in the UK, the European Commission's annual patent settlement monitoring exercise and the judgement of the French Supreme Court in Sanofi-Aventis. Section 3 covers the recent cases prosecuting excessive pricing, including the Aspen case in Italy and the Pfizer/Flynn and Actavis cases in the UK. Section 4 addresses the cases before the EU Court of Justice concerning licensing agreements, including Hoechst/Genentech and Roche/Novartis. Section 5 addresses recent decisions, judgements, and regulations in EU Member States on the ongoing issue of parallel trade. Finally, Section 6 covers the results of sector inquires reported by competition authorities in five EU Member States covering a broad range of issues arising in the pharmaceutical sector.

How much could be saved in Chinese hospitals in procurement of anti-hypertensives and anti-diabetics?

Background: Efficient use of government funding has been increasingly relevant for the success and sustainability of ongoing health-system reform in China; however, as there is no generic substitution policy, patients and basic health-insurance programs pay more for public-preferred brand originators. Such phenomenon is especially typical in public hospitals. The objective of this study is to estimate the potential cost savings in procurement by Chinese public hospitals when switching from brand originators of anti-hypertensive and anti-diabetic medications to their generic equivalents between 2012–2014.Method: IMS Health volume and value consumption data (IMS China Hospitals Audit system 2012–2014) were used, which covered all Chinese hospitals with 100 beds and above. The top 60% IMS volume consumption of respective anti-hypertensive and anti-diabetic medication with unique dosage form and strength were included. The potential cost savings were calculated from a switch of brand originators with their generic equivalents on the Chinese and international market. An independent sample t-test was conducted to compare the difference of proportion of cost savings in value between the Chinese and international market.Results: An average of 44% (US$44 million) and 87% (US$90 million) and a total of US$1.4 and 2.8 billion (2014 US$) could be saved from a switch from originator brand anti-hypertensives and anti-diabetics to domestically and internationally available generic equivalents, respectively. The differences of cost savings (in proportion) between domestic and international market were statistically significant (α = 0.005, p = 0.003, p = 0.002, p = 0.000).Conclusion: Expensive brand originators dominated the anti-hypertensive and anti-diabetic market in Chinese hospitals between 2012–2014. Preference of brand originators wastes a huge amount of health resources in China and these limited resources could have been used more efficiently. As one of the world’s key generic suppliers, if China wants to use its health resource more efficiently on medicines, comprehensive measures are needed to address both demand-side (consumers’ low trust in the quality of local generics) and supply-side barriers (health professionals’ preference of brand originators).

Pharmaceutical Applications of Relaxation Filter-Selective Signal Excitation Methods for 19F Solid-State Nuclear Magnetic Resonance: Case Study With Atorvastatin in Dosage Formulation

We recently developed several new relaxation filter-selective signal excitation (RFS) methods for 13C solid-state nuclear magnetic resonance (NMR) that allow 13C signal extraction of the target components from pharmaceuticals. These methods were successful in not only qualification but also quantitation over the wide range of 5% to 100%. Here, we aimed to improve the sensitivity of these methods and initially applied them to 19F solid-state NMR, on the basis that the fluorine atom is one of the most sensitive NMR-active nuclei. For testing, we selected atorvastatin calcium (ATC), an antilipid BCS class II drug that inhibits 3-hydroxy-3-methylglutaryl-coenzyme A reductase and is marketed in crystalline and amorphous forms. Tablets were obtained from 2 generic drug suppliers, and the ATC content occurred mainly as an amorphous form. Using the RFS method with 19F solid-state NMR, we succeeded in qualifying trace amounts (less than 0.5% w/w level) of crystalline phase (Form I) of ATC in the tablets. RFS methods with 19F solid-state NMR are practical and time efficient and can contribute not only to the study of pharmaceutical drugs, including those with small amounts of a highly potent active ingredient within a formulated product, but also to the study of fluoropolymers in material sciences.

Analysis of minimum target prices for production of entecavir to treat hepatitis B in high- and low-income countries

BackgroundIn 2013, an estimated 686,000 people died from hepatitis B virus (HBV) infection worldwide. Mass treatment programmes for hepatitis B will require very low drug costs. International treatment guidelines recommend first-line monotherapy with either entecavir or tenofovir disoproxil fumarate (TDF). While the basic patent on TDF expires in 2017/8, entecavir is already generic in several countries, including the US. The chemical structure of entecavir is related to abacavir, which costs <$200 per person-year in low-income countries. MethodsThe clinical efficacy, chemical structures, daily doses, routes of chemical synthesis, costs of raw materials and patent expiry dates were analysed for entecavir and TDF. Costs of sustainable, generic production were calculated for entecavir, and compared with published originator and generic prices in high- and low-income countries. ResultsWith a daily dose of 0.5 mg, one year's supply of entecavir treatment requires <0.2g of active pharmaceutical ingredient (API) per person, estimated to cost $4/year, based on quotations of API production from generic suppliers. With an additional $20 per year for formulation/packaging and a 50% profit margin, entecavir was estimated to cost a minimum of $36/person-year, substantially lower than current originator and generic prices. Entecavir is no longer under patent protection in the USA, China, Brazil and South Africa, with European expiry in 2017. Given differences in daily dosing, production volumes for entecavir would be 600 times lower than TDF (300 mg once daily) for treating the same numbers of patients. ConclusionsMass treatment for hepatitis B with generic entecavir could be achieved at very low cost in all countries, provided that important projections can be met in terms of pricing for the API and finished dosage form.

The relevance of polymorphism in rifampicin

Tuberculosisis is an infectious Neglected Tropical Disease (NTD) considered a public health problem in several countries. Rifampin (RIF) is one of the first choice drugs in the treatment of this disease since it has bactericidal action on susceptible strains of Mycobacterium tuberculosis, the etiological agent of tuberculosis affecting humans. According to the literature RIF can exist in two polymorphic forms, namely forms I and II, a penta-hydrate and an amorphous solid1. Each form has different solubility in aqueous medium affecting the bioavailability of the drug when it formulated in solid dosage forms for oral administration since they are expected to content form II2. The objective of this research is to characterize and understand in detail the pharmaceutically relevant forms of RIF. It is an important and challenging problem related to the development of formulations because the physical mixture of these forms is usually observed in raw materials from generic suppliers. Thus, the reference sample (USP standard) and two lots from different suppliers were investigated by electron microscopy, Raman and infrared spectroscopies, X-ray diffraction powder and thermal analysis. In addition, pure samples of these solid forms were produced by recrystallization under different conditions in order to establish the structural reference standards. The results of this study will be useful for the development of efficient quality control methods for a drug which is very important to the social health programs.

Reverse-Payment Patent Settlements in the Pharmaceutical Industry: An Analysis of U.S. Antitrust Law and EU Competition Law

In the pharmaceutical industry, originator companies researching and developing new medicines typically obtain a range of patents to protect these medicines against generic competition. On the other side, generic suppliers seeking to enter the market will often challenge the validity of these patents or may simply launch their products, forcing the originators to bring litigation to enforce their patents and prevent the generics' entry. In the context of the corresponding litigation, the originators and generic suppliers often decide to enter into a settlement. While the settlement terms will vary from case to case, a number of settlements have involved a payment made from the patent holder (the originator) to the accused infringer (the generic supplier) in order to settle the dispute (reverse-payment patent settlements). Against this background, this paper seeks to analyze the compatibility of such settlements under U.S. antitrust law and EU competition law drawing on recent cases.

When Competition Law Analysis Goes Wrong The Italian Pfizer/Pharmacia Case

The January 2012 decision of the Italian Competition Authority (“ICA”) to fine Pfizer and Pharmacia €10.6 million is an illustration of the more aggressive trend taken by competition authorities in the pharmaceutical sector. In this case, the ICA alleges that the parties sought to delay entry of generic suppliers by implementing a “complex strategy” to “artificially” extend its patent rights, hence committing an abuse of a dominant position in breach of Article 102 of the Treaty on the Functioning of the European Union (“TFEU”).The purpose of this paper is to show that the decision of the ICA is fundamentally flawed as it fails to provide any evidence that the parties’ patent filings were misleading or “artificial” under the applicable patent laws. Instead, the decision is based solely on the ICA’s unsubstantiated view that Pfizer’s conduct did not constitute “competition on the merits”, a vague standard unable to satisfy the basic requirements of the rule of law and legal certainty. Following this unreasoned decision, pharmaceutical companies and their counsel face an impossible task of assessing which IP strategies are compatible with competition law. This legal uncertainty, combined with the risk of large fines, means that pharmaceutical firms may no longer dare to take steps to obtain patent protection to which they are legally entitled, and more importantly, may have less incentive to invest in future research and development.

Pharmaceutical Pricing in Emerging Markets: Effects of Income, Competition, and Procurement

This paper analyzes determinants of ex-manufacturer prices for originator and generic drugs across countries. We focus on drugs to treat HIV/AIDS, TB, and malaria in middle and low-income countries (MLICs), with robustness checks to other therapeutic categories and the full income range of countries. We examine the effects of per capita income, income dispersion, competition from originator and generic substitutes, and whether the drugs are sold to retail pharmacies versus tendered procurement by non-government organizations.The cross-national income elasticity of prices is 0.27 across the full income range of countries but is 0.0–0.10 between MLICs, implying that drugs are least affordable relative to income in the lowest income countries. Within-country income inequality contributes to relatively high prices in MLICs. Although generics are priced roughly 30% lower than originators on average, the variance is large. Additional generic competitors only weakly affect prices, plausibly because generic quality uncertainty leads to competition on brand rather than price. Tendered procurement that imposes quality standards attracts multinational generic suppliers and significantly reduces prices of originator and generic drugs, compared with their respective prices to retail pharmacies. ©2013 The Authors. Health Economics Published by John Wiley & Sons Ltd.

Reverse-Payment Patent Settlements in the Pharmaceutical Industry: An Analysis of US Antitrust Law and EU Competition Law

In the pharmaceutical industry, originator companies researching and developing new medicines will typically obtain a range of patents to protect these medicines against generic competition. On the other side, generic suppliers seeking to enter the market will often challenge the validity of these patents or may simply launch their products, forcing the originators to bring litigation to enforce their patents and prevent the generics’ entry. In the context of the corresponding litigation, the originators and generic suppliers often decide to enter into a settlement. While the settlement terms will vary from case to case, a number of settlements have involved a payment made from the patent holder (the originator) to the accused infringer (the generic supplier) in order to settle the dispute (these settlements are known as “reverse-payment patent settlements”). The legality of such settlements is the subject of a heated debate, both in Europe and in the United States (“US”). Competition authorities on both sides of the Atlantic are concerned that such settlements may unduly delay market entry of generic drugs, to the detriment of consumers and governments’ health care budgets. In June 2013, both the US Supreme Court and the European Commission (“Commission”) addressed the legality of reverse-payment patent settlements between originator and generic drug companies, reaching rather different conclusions. In order to explain the causes and consequences of this divergence, this paper discusses first the relevant Hatch-Waxman Act provisions and explore the evolution of the US case-law with regard to patent settlements (Part II). Thereafter, we analyse the EU regulatory context and current investigation activity of the Commission and the national competition authorities (Part III). Finally, we compare the US approach to reverse-payment patent settlements, as highlighted by the recent Actavis ruling, to the approach endorsed by the Commission in the Lundbeck decision (Part IV).

Pharmacodynamic Differences in the Two Generic Brands of Enoxaparin

Abstract 1251Several generic versions of enoxaparin have recently become available. While these generic versions of enoxaparin exhibit similar molecular profiles and comparable anti-Xa activities; product specific differences in global anticoagulant (APTT, Heptest and thrombin generation inhibition) have been reported. The purpose of this study was to compare a generic version of enoxaparin Sandoz from Argentina (Fibrinox lot 002) and from the US (enoxaparin lot 914786) in various in vitro whole blood and plasma based clotting tests. Despite comparable molecular profile and anti-Xa potency, product specific differences were noted between the products and the US generic enoxaparin showed a cumulatively stronger activity in most of the assays. To further test the pharmacodynamic profile of these products, individual groups of monkeys (n=4–8) were administered with each product at a 1 mg/kg SC and blood samples were collected for up to 28 hours. Clot based assays such as the APTT, Heptest, thrombin time, amidolytic anti-Xa and anti-IIa activities were carried out. In addition, tissue factor pathway inhibitor (TFPI) antigen, thrombin activatable fibrinolysis inhibitor (TAFI) activity and thrombin generation assays were also performed. Variable differences were noted in the clot based and amidolytic assays. Interestingly, the US generic product exhibited a lower release in the TFPI antigen whereas in the thrombin generation assays it produced a stronger inhibition of thrombin in terms of the AUC. TAFI activity profile also showed wide variations. These differences were more prevalent during the 1–4 hour time period. No differences were noted at >6 hours. The hysterisis PK/PD plots revealed marked differences between the two products. These results indicate that the products for the same generic suppliers may exhibit variations according to market places. Moreover, these observations underscore the need for a more stringent pharmacodynamic profile to demonstrate product equivalence. Disclosures:No relevant conflicts of interest to declare.

Modeling HIV/AIDS Drug Price Determinants in Brazil: Is Generic Competition a Myth?

BackgroundBrazil became the first developing country to guarantee free and universal access to HIV/AIDS treatment, with antiretroviral drugs (ARVs) being delivered to nearly 190,000 patients. The analysis of ARV price evolution and market dynamics in Brazil can help anticipate issues soon to afflict other developing countries, as the 2010 revision of the World Health Organization guidelines shifts demand towards more expensive treatments, and, at the same time, current evolution of international legislation and trade agreements on intellectual property rights may reduce availability of generic drugs for HIV care.Methods and FindingsOur analyses are based on effective prices paid for ARV procurement in Brazil between 1996 and 2009. Data panel structure was exploited to gather ex-ante and ex-post information and address various sources of statistical bias. In-difference estimation offered in-depth information on ARV market characteristics which significantly influence prices. Although overall ARV prices follow a declining trend, changing characteristics in the generic segment help explain recent increase in generic ARV prices. Our results show that generic suppliers are more likely to respond to factors influencing demand size and market competition, while originator suppliers tend to set prices strategically to offset compulsory licensing threats and generic competition.SignificanceIn order to guarantee the long term sustainability of access to antiretroviral treatment, our findings highlight the importance of preserving and stimulating generic market dynamics to sustain developing countries' bargaining power in price negotiations undertaken with originator companies.

The Tourism Global Commodity Chain in Namibia: Industry Concentration and its Impacts on Transformation

Applying Global Commodity Chain (GCC) theory, this article uncovers governance patterns in the Namibian tourism industry. The sector, it is argued, is best characterized as a buyer-driven GCC, in which large tour operators and accommodation groups control most economic transactions, and in which local actors remain generic suppliers with limited power to capture a significant share of the value. In a context of rapid globalization and fierce competition, horizontal and vertical integration have further concentrated economic powers in the hands of larger groups (national or international). With such an ownership structure, previously disadvantaged Namibians lack economic leverage to be fully involved in the largely white-dominated tourism sector.

Differentiating Low-Molecular-Weight Heparins Based on Chemical, Biological, and Pharmacologic Properties: Implications for the Development of Generic Versions of Low-Molecular-Weight Heparins

Low-molecular-weight heparins (LMWHs) are polypharmacologic drugs used to treat thrombotic and cardiovascular disorders. These drugs are manufactured using different chemical and enzymatic methods, resulting in products with distinct chemical and pharmacologic profiles. Generic LMWHs have been introduced in Asia and South America, and several generic suppliers are seeking regulatory approval in the United States and the European Union. For simple small-molecule drugs, generic drugs have the same chemical structure, potency, and bioavailability as the innovator drug. Applying this definition to complex biological products such as the LMWHs has proved difficult. One major issue is defining appropriate criteria to demonstrate bioequivalence; pharmacopoeial specifications alone appear to be inadequate. Whereas available generic versions of LMWHs exhibit similar molecular and pharmacopoeial profiles, marked differences in their biological and pharmacologic behavior have been noted. Preliminary studies have demonstrated differences in terms of anti-Xa activity and tissue factor pathway inhibitor release after subcutaneous administration, as well as antiplatelet and profibrinolytic effects. The current data emphasize the need to consider multiple functional parameters when defining bioequivalence of biologic drugs with complex structures and activities and also underscore the importance of further pharmacologic studies involving animal models and human clinical trials. The U.S. Food and Drug Administration and the European Medicine Evaluation Agency are currently developing guidelines for the acceptance of biosimilar agents including LMWHs. Until such guidelines are complete, generic interchange may not be feasible.

HIV/AIDS Drugs for Sub-Saharan Africa: How Do Brand and Generic Supply Compare?

BackgroundSignificant quantities of antiretroviral drugs (ARVs) to treat HIV/AIDS have been procured for Sub-Saharan Africa for the first time in their 20-year history. This presents a novel opportunity to empirically study the roles of brand and generic suppliers in providing access to ARVs.Methodology/Principal FindingsAn observational study of brand and generic supply based on a dataset of 2,162 orders of AIDS drugs for Sub-Saharan Africa reported to the Global Price Reporting Mechanism at the World Health Organization from January 2004-March 2006 was performed. Generic companies supplied 63% of the drugs studied, at prices that were on average about a third of the prices charged by brand companies. 96% of the procurement was of first line drugs, which were provided mostly by generic firms, while the remaining 4%, of second line drugs, was sourced primarily from brand companies. 85% of the generic drugs in the sample were manufactured in India, where the majority of the drugs procured were ineligible for patent protection. The remaining 15% was manufactured in South Africa, mostly under voluntary licenses provided by brand companies to a single generic company. In Sub-Saharan African countries, four first line drugs in the dataset were widely patented, however no general deterrent to generic purchasing based on a patent was detected.Conclusions/SignificanceGeneric and brand companies have played distinct roles in increasing the availability of ARVs in Sub-Saharan Africa. Generic companies provided most of the drugs studied, at prices below those charged by brand companies, and until now, almost exclusively supplied several fixed-dose combination drugs. Brand companies have supplied almost all second line drugs, signed voluntary licenses with generic companies, and are not strictly enforcing patents in certain countries. Further investigation into how price reductions in second line drugs can be achieved and the cheapest drugs can actually be procured is warranted.