REQUEST FOR PROPOSAL (RFP) Title: Adult Darunavir /Ritonovir 400 mg /50mg tablets in a fixed dose combination. RFP Number: 0012-DRV/r Adult

Transcription

1 REQUEST FOR PROPOSAL (RFP) Title: Adult Darunavir /Ritonovir 400 mg /50mg tablets in a fixed dose combination RFP Number: 0012-DRV/r Adult Issue Date: 15 December, 2017 Deadline for Questions: 27 December, 2017 Closing Date: 17 January, 2018

2 [2] 1. Purpose This request for proposals (RFP) is for the award of subsidy incentive grants to accelerate commercialization of a darunavir /ritonovir 400mg/50 mg tablet (DRV/r 400/50) in generic accessible (GA) countries and to establish a DRV/r Ceiling Price. Responses to this RFP are due on at 5pm EST on 17 January, Upon receipt of the response, CHAI will assess each eligible application based on selection criteria, which will include the timeline for SRA filing and approval. CHAI anticipates that companies will be identified for further discussions to understand and refine the proposed Ceiling Price and potential grant. CHAI will perform a quality audit of each selected supplier. CHAI anticipates making grant decision in Q To be considered for the grant, a supplier must have a demonstrably viable plan to achieve SRA submission prior to December 31, 2018; and have an ability to manufacture and sell DRV/r at prices competitive to existing protease inhibitors atazanavir/ritonavir 300/100mg (ATV/r) and lopinavir/ritonavir 200/50mg (LPV/r). For the purpose of this RFP, Global Fund s Q4, 2017 published reference prices 1 for ATV/r ($15 per pack) and LPV/r ($18.41 per pack) serve as benchmarks prices for on-market protease inhibitors. 2. About CHAI The Clinton Health Access Initiative (CHAI) is a global health organization committed to catalyzing access to high-quality, low-cost drugs and diagnostics and strengthening integrated health systems in resourcelimited settings (RLS). CHAI and Unitaid are committed to increasing the affordability of and accelerating access to optimal ARV therapies in designated LMICs under a Unitaid funded project entitled Accelerating Patient Access to Optimal Antiretrovirals (Optimal ARV Project). This project is geared towards developing interventions that will: Accelerate time to market for innovative new products Achieve optimal pricing for innovative new products Generate early demand and rapid uptake through working with country HIV programs in a set of focus countries 3. About Unitaid Unitaid is an international organization that invests in new ways to prevent, diagnose and treat HIV/AIDS, hepatitis C, tuberculosis and malaria more quickly, more affordably and more effectively. It accelerates access to innovation so that critical health products can reach the people who most need them. Unitaid s work facilitates large-scale introduction of health products through funding by the Global Fund, the United States President s Emergency Plan for AIDS Relief (PEPFAR) and by governments. 1

3 [3] 4. Summary of Target Product The target product for this RFP is a fixed-dose combination (FDC) of Darunavir 400mg and Ritonavir 50mg (DRV/r 400/50mg). Prezista brand name for darunavir (DRV) was first approved by the United States Food and Drug Administration (FDA) over a decade ago at 800 mg once-daily (QD), in DRV in combination with ritonavir (RTV or r, 100mg QD) is a best-in-class protease inhibitor (PI) that has proven to be an effective antiretroviral therapy (ART) in both treatment-naïve and treatment-experienced human immunodeficiency virus (HIV) patients with multiple drug resistance. Superior clinical efficacy, favorable tolerability and toxicity profile, along with a high genetic barrier to the development of resistance makes DRV an optimal second-line antiretroviral (ARV) drug. DRV has been included in the World Health Organization (WHO), Center for Disease Control (CDC), and National Institute of Health (NIH) HIV treatment guidelines. In the case of the WHO 2016 treatment guidelines, DRV/r (400/50) was included as an alternative due to the absence of an affordable, generic, FDC product to the current standard of care second-line drugs in LMICs, LPV/r and ATV/r. Current market price, as indicated by Global Fund s Q4, 2017 reference prices, for ATV/r is $15 per pack and LPV/r is $18.41 per pack. The WHO also recommends DRV/r as a third-line regimen for adults and adolescents, as well as for pediatrics over the age of 3 years after failure on LPV/r, ATV/r, integrase strand transfer inhibitor (INSTI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) based secondline regimens Statement of Work The incentive grant funded by this RFP is designed to mitigate some of the commercialization and product uptake risks to the access markets associated with product pricing. These include the proposed financial support (Annex1) and the work on demand generation undertaken by CHAI. This scope of work will include the following activities: Preparation and submission of a regulatory dossier for the FDA PEPFAR Tentative Approval Program. Preparation and submission of a plan for regulatory filings in all additional countries on CHAI s priority list. Ensure capacity to supply-qualified orders with a lead time of not more than 90 days. The minimum size of a qualified order is to be determined as part of the incentive grant contract. For qualified orders, supply product at or below DRV/r Ceiling Price on a perpetual basis Supplier commits to maintaining proposed ceiling price for periods beyond incentive grant expiration on December 31, 2020, provided orders meet proposed supply conditions. Supply Conditions may include, among other things, conditions on minimum order size and lead times.

4 [4] 6. Instructions to Interested Parties a. RFP responses i. All RFP responses should be submitted in English and should be signed by an authorized representative of the Responder. (Form A) ii. RFP responses should be submitted via with the subject line Request for RFP Adult DRV/r to: Sheetal Ghelani at cc: Sunil Panicker at cc: Ateen Paliwal at iii. RFP responses received after the stipulated closing date shall be invalid. b. Timeline and Information Session The timeline for the RFP process is described below. Proposals received after the deadline will not be considered. RFP Released 15 December, 2017 Information Session (details below) 20 December, :00AM EST Questions Deadline for Manufacturers (submission via 27 December, 2017 only) Q&A Response Document Released 3 January, 2018 Proposals Due* 17 January, :00PM EST *Late applications will not be accepted. Information webinar to discuss RFP process-related questions: Wednesday, December 20, :00 AM EST/3:30 PM IST Meeting details: Meeting ID: Online Login (for slide viewing): United States: Toll Free China: (010) (Premium Toll); (Toll Free) India: (Premium Toll); (Toll Free) Other International numbers available: c. Questions and answers i. As seen above, there will be a formal period during which questions regarding this RFP will be accepted. ii. Questions should be addressed to: Sheetal Ghelani at sghelani@clintonhealthaccess.org cc: Sunil Panicker at spanicker@clintonhealthaccess.org cc: Ateen Paliwal at apaliwal@clintonhealthaccess.org by the stipulated deadline above. Questions and answers will be published on the CHAI website: iii. Phone requests will not be honored.

5 [5] d. Eligibility The RFP is open to companies who meet the following criteria: Supplier should provide evidence of a filing with an SRA for DRV/r or provide evidence of a viable plan to submit DRV/r for SRA regulatory approval no later than December 31, 2018 Ability to manufacture and supply DRV/r at a price of $18.41 or lower per the terms of this RFP Supplier s production facility operates under current Good Manufacturing Practice (cgmp) as established by WHO (Geneva) or FDA Suppliers must agree to host and pass a quality audit if they are selected for the award. e. Costs of preparing documents All costs associated with preparing and submitting this RFP response will be borne by the Responder. f. Confidentiality Information which the Responder considers to be proprietary should be clearly marked as such. All such information will be treated as confidential and used for CHAI internal purposes only. g. Disclosure Information relating to the examination, clarification, and evaluation of responses shall not be disclosed to Responders or any other persons not officially concerned with such process. h. Terms and Conditions Although final terms and conditions for the contract will be finalized during the negotiation process after final supplier(s) have been chosen, CHAI s standard terms and conditions has been attached to this document for reference. 7. RFP response requirements Responders should provide the following information in response to this RFP: a. Completed forms: A (Response to RFP)and B (Quality Audit Agreement) b. A completed Annex 1 c. List of documents in Annex 2 CHAI reserves the right to request additional information; to arrange interviews with the Responder; to visit the Responder s premises and facilities; and to conduct an audit to verify the information provided. 8. Evaluation Criteria To be considered for an award, the manufacturer must demonstrate the necessary experience of commercializing HIV drugs and experience registering and supplying generic ARV drugs to low and middle income countries. CHAI will assess each eligible proposal based on selection criteria that includes the timeline for product commercialization, proposed ceiling price, and proposed estimated total subsidy. CHAI anticipates that a number of companies will be identified for further discussions to refine proposed ceiling price and subsidy amount and structure. CHAI reserves the right to perform a quality audit of each selected supplier. CHAI anticipates making a grant award to one or more suppliers in Q

6 [6] FORM A: RESPONSE TO REQUEST FOR PROPOSAL This form must be completed, signed and returned to CHAI. DECLARATION We, the undersigned, having read the Request for Proposal (RFP) Adult DRV/r 400/50 submit our response, which includes the information requested in Section 5. We confirm that all the information provided is true. We confirm that we are interested in entering into discussions for a possible collaboration with CHAI for the filing to SRA, and commercialization of Adult DRV/r 400/50 according to the terms of this RFP. We understand that issue of the RFP by CHAI and submission of our response is not a commitment by either party to enter into such discussions or such collaboration. We further understand that CHAI reserves the right to enter into collaboration discussions and a resulting collaboration with one or multiple parties, with no parties, or to cancel this RFP at its sole discretion. This RFP and any responses thereto shall be the property of CHAI. Name of authorized representative: Title: Signature: Date: Company name: Postal Address: Telephone No.: Address:

7 [7] FORM B: Quality Audit Agreement This form must be completed, signed and returned to CHAI. DECLARATION Responder agrees that if selected for RFP award, permission will be given to CHAI to conduct a quality audit, to assess that supplier operates under current Good Manufacturing Practice (cgmp) 1. This will be a general GMP and Quality Systems audit, likely performed by an independent third party consultant. This audit will be scheduled directly with the supplier. Name of authorized representative: Title: Signature: Date: Company name: 1 Valid cgmp authorities include SRAs and regulatory authorities participating in the Pharmaceutical Inspection Cooperation Scheme (PIC/S). For PIC/S, please refer to An SRA is defined as a regulatory authority which is (a) a Founding (USA, European Commission, Japan) or Standing (Canada, Switzerland) Regulatory Member of the International Conference on Harmonisation (ICH); or (b) a Standing Observer (WHO, The International Federation of Pharmaceutical Manufacturers and Associations (IFPMA)) as specified on In addition, countries with mutual recognition with one of the Founding Regulatory Members (e. g. EMA has mutual recognition with Australia and New Zealand.) are considered SRA

8 [8] Annexure 1 Proposed Incentive Grant Subsidy incentive grant of up to US$3M to the selected supplier(s) will be disbursed on a per pack subsidy basis based on actual volume sold by supplier in the market. We expect the Sales Volume Subsidy grant to gradually reduce as suppliers sell larger volumes into the market. Subsidy incentive grant will expire on December 31, Suppliers are requested to provide their proposal on DRV/r Ceiling Price along with associated Supply Conditions. Supply Conditions may include, among other things, conditions on minimum order size and lead times. Suppliers are requested to provide proposal on per pack subsidy in the below table to achieve their proposed DRV/r Ceiling Price. Total proposed subsidy should be capped at or below US$3M and should only be applicable for product sales made to generic accessible countries prior to December 31, Subsidy Proposals from Suppliers* Cumulative Packs Sold by Supplier* 0-100K 100K - 200K 200K + Proposed Subsidy per Pack (US$) * The volume brackets shown in above table are for illustrative purposes only. Suppliers may choose to propose a different set of volume brackets in their response to RFP. Suppliers are requested to provide a short statement on feasibility of achieving and maintaining proposed DRV/r Ceiling Price through December 31, 2021.

9 [9] Annexure 2 1) a. Copy of SRA approval or b. Copy of SRA dossier acceptance letter or c. Copy of documents to show completed development steps that demonstrate SRA submission is achievable by December 31, Such documents may include proof of SRA submission, ongoing BE, and stability studies 3) Written commitment to launch and supply the product on perpetual basis at or below DRV/r Ceiling Price in GA countries 4) Latest GMP (WHO Geneva)/FDA certificate of the facility where DRV/r will be manufactured

10 [10] CHAI s Standard Terms and Conditions The Supplier will come to an agreement with CHAI on the terms of the commercialization support and the milestones to be reached for funding to be provided by CHAI. This will include regular financial and Product specific milestone reporting requirements. CHAI will determine disbursement requirements. In addition to the terms and conditions of the Project Plan relating to the product for which they are receiving commercialization support (the Product ), representations and warranties on the quality, safety and compliance of the Product, confidentiality and other standard terms and conditions, the Commercialization Support Agreement between CHAI and Supplier will include these sample terms, substantially in the form below: 1. Supplier agrees that it shall meet the following qualifications at all times during the Term of the Agreement and for the duration of its participation in the Project: a) Manufacturing Quality. Compliance with WHO GMP standards applicable to the manufacture or supply of the Product, including, but not limited to, adherence to certain minimum manufacturing and quality control standards necessary for Supplier to manufacture and supply the Product, and possession of all applicable certifications and approvals from any certifying industry organizations or national regulatory authority. b) Financial Stability. Maintenance, on a financial basis, of positive net worth and adequate cash flow to ensure that Supplier is capable of paying for the resources necessary for Supplier to manufacture and supply the Products. c) Compliance with Laws. Compliance with all applicable laws, regulations and conditions, relevant to Supplier s operations and performance under the Commercialization Support Agreement. d) Compliance with Labor Codes. Compliance with its Internal Code of Conduct which is compliant with the International Labor Organization s Standards and Fundamental Principles and Rights at Work and the Fair Labor Association s Workplace Code of Conduct. 2. Indemnification. Supplier agrees to indemnify, defend and hold Unitaid, WHO and CHAI (the Indemnified Parties ) harmless from and against any claims, losses, liability, obligations, lawsuits, deficiencies, damages or expense of whatever nature, whether known or unknown, accrued, absolute, contingent or otherwise, including, without limitation, interest, penalties, attorney's fees, costs of investigation and all amounts paid in defense or settlement of the foregoing (collectively, Loss ), suffered or incurred by the Indemnified Parties as a result of the occurrence of, or arising out of, any breach of this Agreement by Supplier, including, but not limited to, any of Supplier s representations and warranties contained herein. a) Supplier also agrees to indemnify, defend and hold the Indemnified Parties harmless from and against any Loss suffered or incurred by the Indemnified Parties arising out of or relating to (i) any third Party product liability claim against any Product, (ii) any defects in any Product supplied; or (iii) any noncompliance by such manufacturer or supplier with any technical requirements applicable to any Products supplied. b) Supplier also agrees to indemnify, defend and hold the Indemnified Parties from and against all claims, damages, losses, costs and expenses arising out of the alleged infringement of a patent, design, trade-name or trade-mark arising under or relating to the Commercialization Agreement. 3. Dispute Resolution. Any dispute arising out of or relating to the Commercialization Support Agreement or the transactions contemplated hereby, or any breach of the same shall be settled by final

11 [11] and binding arbitration. Any arbitration conducted pursuant to this provision shall be conducted in New York, New York, USA, and shall be conducted in the English language in accordance with the International Arbitration Rules established by the American Arbitration Association. 4. Loss, Fraud, Bribery, Corruption and Conflicts of Interest a) The Parties confirm that no official, employee or officer of the other Party has received or will be offered any individual benefit arising from this Agreement. b) The Supplier will take all measures to prevent conflicts of interest arising which may have an impact on the implementation of the Project and will promptly declare to CHAI and proactively manage any such conflicts of interest. c) The following may be deemed by CHAI to be a material breach of this Agreement: (i) failure by the Grantee to report to CHAI any known or suspected cases of loss, bribery, fraud or other corrupt practice; (ii) confirmed serious or repeated instances of loss, bribery, fraud or other corrupt practices; (iii) failure to declare and/ or proactively manage any conflicts of interest; (iv) the giving to or receiving by an official, employee or officer of the Supplier of any individual benefit in connection with this Agreement. 5. Marks. a) This Agreement shall not be construed to grant Partner any license to use CHAI s name or logo, both current and future, in any format (the CHAI Marks ). Any requests for use of CHAI Marks shall be submitted in writing to CHAI. CHAI shall have the right, in its sole discretion, to grant Partner any usage rights in the CHAI Marks. An authorized CHAI representative must document such a grant in writing for it to be valid. b) CHAI exists as a separate entity from the Bill, Hillary & Chelsea Clinton Foundation (the Foundation ) to carry on and expand the projects previously conducted through the Clinton HIV/AIDS Initiative. This Agreement shall not be construed to grant Partner any license to use the name, logo, or other marks owned by the Foundation (the Foundation Marks ), in any format, including any quote, image or likeness, in any form, of President Clinton, Secretary Clinton, or Chelsea Clinton (the Clintons ). All requests for use of Foundation Marks shall be submitted in writing to CHAI. CHAI shall refer any such requests to the Clinton Foundation, which shall have sole discretion in granting any usage rights in Foundation Marks to Partner. 6. This Agreement shall be governed by and construed in accordance with the laws of the state of New York, without giving effect to applicable conflict of laws provisions.