Procurement of internationally quality assured (IQA) second-line drugs (SLDs): past, present, future

Transcription

1 Procurement of internationally quality assured (IQA) second-line drugs (SLDs): past, present, future 12 November 2012 Dr Kaspars Lunte Team Leader MDR-TB medicines supply, GDF

2 What is the Global Drug Facility? An initiative of the Stop TB Partnership (2001), hosted in WHO and managed by the Stop TB Partnership secretariat The mandate of GDF included: expanding access to quality-assured first-line drugs (FLD) and diagnostics; and second-line TB drugs (SLD) for GLC approved projects, contributing to the development of sustainable procurement and supply management for countries in need GDF began supplying FLDs in 2001, and in 2008 added regular supply of SLDs, pediatric TB medicines and diagnostics, and is major source for GeneXpert today

3 GDF Facts GDF operates without a fee, therefore it is primarily a donor-supported organization (USAID) GDF is an agency for placing planned orders Has successfully catalyzed rapid DOTS expansion Has developed the market for FLDs (Fixed dose combinations and patient kits) Substantially increased the number of quality-assured MDR-TB second-line drugs (SLDs) available for procurement through GDF from 11 in 2008, to 32 in end 2011 Conducts international bidding regularly to achieve competitive, transparent, sustainable for SLDs, pricing Has aligned quality assurance policy with the Global Fund Provides technical assistance in drug management during periodic in-country monitoring visits

4 GDF is the largest supplier of anti-tb Products on the public market In just over 10 years GDF procured : 22 M FLD Patient treatments SLD patient treatments (x 4 in 4 years) Orders with a total value of 685 M USD

5 GDF Model Client Stop TB Partnership/ Global Drug Facility Procurement Agents Manufacturers (pre-qualified) Freight Forwarders Quality Control

6 Business Volume 2011 (US$, ex works) GeneXpert New Diagnostics $6,489,297 $6,405,667 FLD $56,511,227 SLD $85,291,452

7 Countries where we work ( ) WHO Region Number of Countries AFRO 39 EMRO 17 AMRO 5 SEARO 10 WPRO 13 EURO 17 Total 101 All are low income countries if receiving grants (is GDF criteria) and low to lowmiddle income countries if NTP orders by direct procurement

8 GDF Market and Health Impact Pool of suppliers of IQA medicines established for FLDs and great progress for SLDs Predictable quantification, but needs some improvement Stabilized access to IQA medicines in WHO - recommended formulations/regimens Price per treatment reduced for FLDs and contained for SLDs (with price decrease for some important SLDs)

9 GDF Market and Health Impact 2012 (cont) Suppliers of non-iqa FLDs pushed out of global market New suppliers introduced for SLDs FLDs formulations standardized (and available globally) FDC to avoid monotherapy Packaging for easy dose administration Patient kits New products promoted Kits, pediatrics, diagnostic kits Monitoring of use and performance Technical assistance

10 TB Drug Supply Chain Management Cycle

11 SLD Patient Treatments Supplied Running Total GDF is the largest public sector supplier of quality assured SLD patient treatments GDF calculations are based on the recommended length of injectable drug use. The 2011 update of the WHO s guidelines for MDR-TB treatment recommends to prolong use of injectable drugs from six to eight months. However, the current calculation algorithm for the 2012 is based on the 6 months regimen and may need to be revisited based on the evidence (treatment regimens reported by the countries) in 2013 Source Live report: +Live+report+Rev+1-May &userid=GDF_ro&password=gdfread1

12 SLD Patient treatments supplied p.a. 30,000 26,859 25,000 19,605 20,000 15,000 10,000 5,000 3,494 9,303 10,990 12, * GDF calculations are based on the recommended length of injectable drug use. The 2011 update of the WHO s guidelines for MDR-TB treatment recommends to prolong use of injectable drugs from six to eight months. However, the current calculation algorithm for the 2012 is based on the 6 months regimen and may need to be revisited based on the evidence (treatment regimens reported by the countries) in 2013 *Data extracted 16/10/ % increase vs full year 2011

13 Market shaping role of GDF: experience and future actions responding to increased SLDs demand 12 November 2012 Dr Kaspars Lunte Team Leader MDR-TB medicines supply, GDF

14 Pricing examples, USD GDF Product Code Am-500/2-(V)-1/(A)-1 amp Cm-1-(V)-1 vial 3.21* Eto-250-(B)-1 tabl Lfx-250-(B)-1 tabl Mfx-400-(B)-5-1 tabl Mfx-400-(B)-70-1 tabl PAS-(H)-(S)-30-1 sachet Cs (B)-1 caps Km-1-(V)-1 vial USD pricelist information: 2010 January 2011 Feb 2012 actual prices *- concessional price, Eli Lilly

15 QA and supplier engagement

16 Manufacturers Engagement: Roles of Key Players - 1 Global Drug Facility (GDF) ensuring, via contracted agents/suppliers, delivery of QA drugs to countries/programs and proactive identification of new potential suppliers. Promoting Quality of Medicines Program of USP- USAIDs funded PQM is assisting GDF in its efforts to increase the availability of good quality second-line anti-tb medicines at an affordable price. WHO Prequalification Programme (WHO PQ) Responsible for prequalification of products and APIs to ensure that products meet international standards of quality before they are procured. Stringent NDRAs also have an important role 17

17 Manufacturers Engagement: Roles of Key Players - 2 Programs and Governments Responsible for planning patient enrolment and treatment; forecasting drug needs; communicating forecasts and delivery schedules to GDF; coordinating with financing mechanisms to ensure payment in advance of supply; facilitating timely registration and importation of drugs; properly managing drugs received. Donors and financing mechanisms (governmental and non-governmental) Responsible for approving and overseeing expenditures; releasing funds upon demand; advocating with other key actors to eliminate bottlenecks to ensure the greatest possible impact. Defining which QA standards apply to drugs procured with their funds. Manufacturers of finished products and APIs: Product sourcing; receipt of orders for drugs; timely delivery at negotiated or competitively determined prices. 18

18 GDF Quality Assurance Policy - 1 WHO Report: A Model Quality Assurance System for Procurement Agencies, Report recommends that pharmaceutical procurement is restricted to only approved suppliers to ensure that drugs of acceptable quality are procured This is reflected in the GDF QA policy implemented June 2010, in full harmonisation with Global Fund QA policy

19 GDF Quality Assurance Policy - 2 Prequalification criteria for manufacturers and medicines: Finished Pharmaceutical Product (FPP) is authorized by the relevant national Medicines Regulatory Authority (NMRA) in the country of use; AND 1. Product is pre-qualified by WHO under the WHO PQP; OR 2. Product is approved by an SRA; OR 3. Product is found acceptable through a quality risk/benefit assessment process involving an Expert Review Panel (ERP). Time limited approval for 12 months pending WHO PQP or SRA approval

20 ERP process Interim approval of 12 months under the following conditions: 1. FPP manufactured at an approved site Inspected by WHO PQP Inspected by an SRA Inspected by inspectors of a regulatory authority participating in the Pharmaceutical Inspection Cooperation Scheme 2. Product approval is pending i.e. dossiers have been accepted for assessment by WHO PQ or SRA

21 Bidding and LTAs Objective: adherence with principles of public procurement 1. Best value for money 2. Fairness, integrity and transparency 3. Effective international competition 4. Interest of the organisation Evaluation of the tender and awards based on: Price Delivery Time Technical compliance: Quality assurance status, Minimum batch quantity, Production capacity, Product registration, Shelf life Market share allocation* 65%/35% in case of primary/secondary supplier 60%/25%/15% in case of primary/secondary/tertiary supplier *allocation is indicative only, and the actual allocation might deviate due to importation requirements, client preferences, registration status and other factors as deemed necessary by GDF or its clients.

22 Importance of additional suppliers When the number of suppliers increase, total manufacturing capacities increase, also increasing competition between manufacturers, thus impacting positively prices of medicines for the entire TB community GDF has significantly increased the number of suppliers thus production capacity and access: especially in fragile SLD market

23 SLD product demand vs. No of Suppliers From 2008 GDF SLD demand has quadrupled. Key IQA products manufacturers have increased from 6 to 10 resulting in increased production capacity & prices decrease Source live report: count_suppliers&userid=gdf_ro&password=gdfread1 Note: Partial data for 2012

24 GDF Added Value Pooled procurement for GDF customers: GDF is able to aggregate demand for anti-tb products for more timely & simplified procurement Pricing: GDF conducts international bidding for Procurement Agent (PA) services and for medicines (via PA) regularly in order to achieve competitive, transparent pricing. New SLD bidding due November 19, 2012 Quantification & Forecasting: GDF assists client countries in identifying their drug needs Quality assurance policy aligned with the Global Fund Technical Assistance & monitoring: periodic monitoring of GDF clients and identification of their PSM challenges

25 Is GDF ready to respond to scale-up needs?

26 GDF is ready to double its SLD business We are ready today: To double its number of patient treatments to on short notice : 3 to 6 months and Can deliver treatments for all global cases to be enrolled by 2015 as per Global TB report 2012 If funding ensured and no delays in payment from projects/donors to procurement agent for the medicines

27 Capacity analysis of SLD manufacturers, September 2012

28 Introduction GDF has updated the available information on existing and potential manufacturers capacities of selected SLDs The SLDs studied were based on following criteria: Only MDR-TB specific products (no widely available products such as fluorquinolones (i.e. levofloxacin), used for other indications were studied) 4 SLDs contribute to 80% of a standard regimen and the costs of it (PAS products combined (sodium and acid formulations), cycloserine, kanamycin and capreomycin) Questionnaires were sent to 9 eligible and high potential future manufacturers of these 4 SLDs on 12/09/2012. GDF continues engagement work with more potential suppliers. No of treatments required for each of the 4 major SLDs (for total treatments) was estimated based on their respective share in the regimens as provided by GDF to our clients 29

29 General feedback 100% of manufacturers provided the information within deadline Important comments received: The manufacturers don't see the scale up materializing in their orders yet Order consolidation via stockpile is seen to be key for regular order placement and reaching the minimum order quantity (MOQ) Additional scale up steps are possible such as introduction of additional shift, re-planning of manufacturing lines, this can be done on short notice Increase even further of the manufacturing capacity is possible via obtaining new/larger/higher capacity machinery. Investments to be justified via firm order commitments from GDF (Olainfarm, Vianex)

30 Assumptions All suppliers mentioned will become/stay eligible No new manufacturers by 2015 (opposite scenario much more likely) GF directs all their SLD grants via GDF Full funding and in-country capacity to treat is ensured No API supply interruptions No registration bottlenecks in countries GDF can justify and commit to future orders to increase the existing capacity even further (especially for PAS products)

31 Global estimations 2012 Expected cases to be enrolled Source: Global tuberculosis control: WHO report 2012

32 Kanamycin Capacity in patient treatments, all potential suppliers vs current GDF deliveries vs global cases expected to be enrolled 70,000 60,000 50,000 40,000 30,000 20,000 40% of treatments contain kanamycin Macleods Panpharma Meiji 10,000 0 GDF deliveries Capacity GDF deliveries Capacity GDF forecast Global report Capacity Global report Capacity Global report Capacity

33 Capreomycin Capacity in patient treatments, all potential suppliers vs current GDF deliveries vs global cases expected to be enrolled 90,000 80,000 70,000 60,000 50,000 40,000 30,000 20,000 50% of treatments contain capreomycin Macleods Hisun DP Aspen Akorn -IN Vianex Akorn -US Lilly 10,000 0 GDF deliveries Capacity GDF deliveries Capacity GDF forecast Global report Capacity Global report Capacity Global report Capacity

34 Cycloserine Capacity in patient treatments, all potential suppliers vs current GDF deliveries vs global cases expected to be enrolled 90,000 80,000 70, % of treatments contain cycloserine 60,000 50,000 40,000 30,000 20,000 Dong A Biocom Aspen TCC Macleods 10,000 - GDF deliveries Capacity GDF deliveries Capacity GDF forecast Global report Capacity Global report Capacity Global report Capacity

35 PAS sodium and acid formulations Capacity in patient treatments, all potential suppliers vs current GDF deliveries vs global cases expected to be enrolled % of treatments contain PAS Macleods Jacobus Olainfarm GDF deliveries Capacity GDF deliveries Capacity GDF forecast Global report Capacity Global report Capacity Global report Capacity

36 GDF initiatives

37 MDR-TB Public health problem of access Demand Side 1. SLD is a small market 2. Little incentive for manufacturers to enter the IQA SLD Market Half a million people are estimated to have MDR-TB today, with little progress in diagnosing and treating them The complexity of treating MDR-TB has limited rapid scale up and thus demand: Diagnosis is technically challenging, time consuming and relatively expensive: many countries fail to diagnose and enroll cases planned for their GF projects Treatment must be tailored to individual drug resistance profile, treatment lasts 2 years and can cause debilitating side effects Drug intake is very complex: 4-5 drugs have to be taken every day for 24 months, with one injectable to be used daily for 6-8 months Drugs are expensive and countries have insufficient funding to procure IQA SLDs from GDF MDR-TB expansion is slower than expected 38

38 MDR-TB Public health problem of access Supply Side 1. SLD is a small market 2. Little incentive for manufacturers to enter the IQA SLD Market Public market for IQA SLDs estimated for 2013, is just $ million (GDF projections) SLD orders are often small in scale and unpredictable sometimes come to GDF as emergency requests due to incountry capacity problems Manufacturing of API is limited to very few sites (monopoly) Combined global demand for IQA SLD is below the comfort level required for efficient and profitable manufacturing (full batch and continuous) Manufacturers must make significant investments, especially for QA certifications and in-country registration requirements. Supplier prequalification requires months or longer For most manufacturers, SLDs are just a small fraction of their total sales, which makes MDR-TB much less attractive 39

39 Two New Initiatives GDF worked with technical partners to develop following initiatives: 2 New initiatives (1) Global Strategic Stockpile (2) Flexible Procurement Fund Expected impact s Greatly reduce lead times (from 4-6 months to 4-6 weeks) Avoid unnecessary drug stockouts Maintain quality and supplier base for the FLD and SLD market Sustain, then further reduce prices, gradually Contribute to better global forecast of FLDs and SLDs with partners 40

40 With Donor Support to a New Paradigm The Global Strategic Stockpile (GSS) GDF would build on the existing stockpile for SLDs Flexibly manage supply of FLDs and SLDs Stabilize SLD market (e.g. APIs and prices) Larger stockpile would require at least FLD and up to SLD patient treatments The Flexible Procurement Fund (FPF): FPF would mitigate funding delays on the demand side Ensure procurement volume commitment to suppliers Increase availability of medicines Reduce threat of stockouts Promote efficiency of the reordering process Bridging gaps caused by funding delays from donors and clients GDF manufacturers will shift from a production to order to a production to stock paradigm allowing building of stocks in anticipation of firm orders with significantly lower lead times 41

41 Expected Impact of the Paradigm Shift 1. Public Health Impact - in one year s time: Increased number of countries served via the GSS and FPF Reduced risk of supply interruptions Reduced lead times for standard orders Growth in the IQA SLD market based on increased orders placed 2. Sustainable Market Impact in three years time. Reduction in the cost of overall SLD treatment regimens over 3 years vs costs, due to a reduction of the inefficiency, demand risk and monopoly premiums currently built into SLD prices Increased market share for GDF, allowing pooled procurement to function at its best Increased number of IQA suppliers available in the market 42

42 Additional Needed interventions Registration of medicines in countries: Problem: registration requirement and stringency differs by country: No registration required: (e.g. Mexico, Afghanistan); importation through waiver: (e.g. China); full registration (e.g. Russia, Kenya) Increasing trend is towards full registration; and harmonization among countries is rare Some requirements mean a large investment of resources (financial and time) compared with size of sales; cost of registration can range from a few hundred dollars to more than USD per product (e.g. Russia) Solution: Entity to be identified, which would incentivize manufacturers to enter smaller countries by: covering registration fees, translation services

43 Conclusion

44 GDF service is highly rated by its customers From 2008, 130 Feedback surveys were received from GDF customers as a systemic control of GDF quality of service and performance (ISO 9001) Live Report : d=gdfread1

45 GDF is the one-stop solution for quality assured anti-tb products GDF can respond to the current scale up plans for MDR-TB

46 Thank you!

47 Back up TB-specific medicines in the regimen contributing to 80% of the costs Item Form Dose Units per patient course, average =Units*days*months Proportion in the drug group Share of treatments required for total treatments Injectable Amikacin ampoules/vials 500 mg % 5,000 Capreomycin vials 1 g % 25,000 Kanamycin ampoules/vials 1 g % 20,000 Oral bacteriostatics Cycloserine capsules 250 mg % 50,000 PAS products combined sachets 4 g % 35,000