Request for proposal RFP 022775 – ONCO-32 – DEVELOPMENT AND MANUFACTURE OF A SINGLE API IN GMP CONDITIONS

In connection with obtaining from the National Centre for Research and Development a grant for the project „Clinical development of an innovative anti-cancer drug using the mechanism of  reactivation of p53 protein” (project no. MAZOWSZE/0012/19) under R&D programme ,,Ścieżka dla Mazowsza”, acting on the basis of Article 10 of the financial project support contract Adamed Pharma S.A. invites to submit tenders for the below-defined service.

Object of the contract

1. Development and manufacture of a single API in GMP conditions - 1 kg of isomer S.The drug substance is an anti-cancer small molecule. The drug product is intended to be used in early-stage clinical trials.
2. The company stipulates that disclosure of the full details concerning the subject will be done after signing of confidentiality agreement (in case of contractors with whom such agreement have not yet been concluded) which is attached to this inquiry – Appendix 1.
3. Details are described in the Appendix 2 (available after signing the NDA). Sponsor will provide data for API as it relates to API properties, current best manufacturing process, specifications and testing methods (Appendix 2).Vendor will source all required raw materials and reagents and test them in conformance with cGMP requirements, including generating and approval of GMP related documents (e.g. specifications, test methods, MBR’s, validation protocols and reports, etc.).The following activities shall be conducted:
   1. Process transfer and optimization (manufacturing and analytical).Familiarization with the current best process following documentation from Adamed.Laboratory-scale process familiarization, development and safety evaluation.Manufacture of demonstration, non-GMP batch at maximum laboratory scale
   2. Analytical methods familiarization, development and validation.Establishment of analytic methods necessary for the product release, including the development of analytics for the key starting material, intermediates, and in-process controls required for GMP production
   3. Scale-Up, Delivery of cGMP batch at 1 kg of non-GMP.
   4. Production of one GMP batch of API at 1 kg GMP (isomer S). Preparation  for GMP Production / Scale-Up to cGMP Pilot Plant/kilo-lab, Production and SFC separationproduct purity of not less than 98% (preferably 99% or greater)
   5. Release testing
   6. Stability studies conduction of a forced degradation study and a stability study (12 months, 40 °C, 75% RH) on the material from 1 kg batch - in compliance with ICH guideline
   7. Complete documentation including all the data and information required to support regulatory filings in Europe and the USA should be provided to the sponsor as it becomes available.
4. Deliverables:
   1. Process optimization and fit for purpose in order to prepare the scalable, industrially applicable process to enable GMP production supporting Clinical Development Program of Adamed.
   2. Lab demonstration batch of API.
   3. Analytical methods validations allowing release testing of GMP batch.
   4. Tech Transfer and Development Report  - Executive summary of process and analytical methods familiarization, development and validations
   5. A safety evaluation report
   6. 1kg (+/- 20%) kg of API isomer S from GMP batch.
   7. Release testing covered in CoA against the DS specification
   8. Stability results for GMP batch
   9. Documents for the cGMP batch:Certificate of analysis, Certificate of GMP compliance, Certificate of origin (BSE/TSE), Copy of the executed batch records, Raw analytical data and testing documentation, Manufacturing campaign report
5. It is allowed to introduce small changes by Contracting Authority in the order regarding theamount of sample batches, scope of experiments or analytics, however the order will not extend the frames of this request for proposal.
6. Place of delivery: Adamed Pharma SA, Pieńków, Mariana Adamkiewicza 6A, 05-152 Czosnów, Poland.
7. Time of delivery: 28.04.2023

Conditions for participation in the proceedings:

1. Orders cannot be awarded to entities affiliated personally of financially with the Contracting Authority. Through financial or personal connection, we understand the interactions between the Contracting Authority or persons authorized to enter into commitments on behalf of the Contracting Authority or persons performing on behalf of the Contracting Party activities associated with the preparation and the procedure for selecting Suppliers and Supplier, in particular by:
   1. participation in the company as a partner or partnership,
   2. owning at least 10% of the shares,
   3. the functions of a member of the supervisory or management, proxy,
   4. remaining married in consanguinity or affinity in a straight line, second-degree consanguinity or affinity of the second degree in the collateral line or by adoption or guardianship.
      ​In order to fulfill this condition a tenderer is obliged to send with the offer signed statements about the lack of connections (Appendix 3).
2. It is required to sign a Confidentiality Agreement with Adamed Pharma S.A. before receiving any confidential information about the API (Appendix 1)
3. This offer is addressed to entities having aexperience in completion of similar services. Experience should be demonstrated by submission of appropriate documents/declaration confirming:
   1. At least 5 years of experience in Contract Manufacturing of commercial and clinical Drug Substance Batches according to GMP.
   2. A valid cGMP certification for drug substance manufacturing.The entity is obliged to send a scan of GMP certificate
   3. All resources to provide services required in Appendix 2 by submitting the list of infrastructural and personnel resources with a short description of works carried out with their involvement.
   4. The contractor should use a quality management system and the auditing system to ensure compliance with all required regulatory requirements.
   5. Manufacturing in the compliance with cGMP standards, approved by The European Medicines Agency (EMA) or US Food and Drug Administration (FDA).
   6. cGMP: Current Good Manufacturing Practice as defined in the rules governing medicinal products in the European Union. Volume 4 - Guidelines for good manufacturing practices for medicinal products for human and veterinary use. Part II – Basic Requirements for Active Substances used as Starting Materials and ICHQ7-2015 – as incorporated in the Federal Register volume 66 No 186 and those sections applicable within the FDA Regulations 21 CFR Part 210, 211, 600, 601 and 610.

Offer preparation

1. The title of each correspondence should include the number of the procedure RFP-022775 – DEVELOPMENT AND MANUFACTURE OF A SINGLE APIIN GMP CONDITIONS - Company Name
2. Deadline for submitting Offeris 04.11.2022 at 23:59 CET and visible in the system. The deadline for Answers submission may change, all Suppliers will be informed by e-mail from the Procurement System.
3. Questions of the inquiry may be submitted to the Adamed Procurement System at https://supplier.ariba.com or by e-mail: anna.klatkowska@adamed.com, in the form of a completed Appendix No.6  Late submission of questions may result in lack of time to provide the required answer. In order to ensure equal access to information to all Tenderers participating in the proceedings, questions and answers (with hiding the author's questions) will be sent to all Tenderers
4. The offer should be prepared on the excel spreadsheet which constitutes Appendix_4_RFP - 022775- Company Name.xlsx of this offerand should be submitted via Ariba system. If Appendix 4 is not filled out, the offer will not be considered
5. Offer along with the required attachments, may be submitted to the Adamed Procurement System at https://supplier.ariba.com or by e-mail: anna.klatkowska@adamed.
6. In addition, the Bidder may also prepare an offer in his own preferable format and uploaded into the system.
7. Access to the Procurement System the Supplier obtains through the registration to verify the existence of the company. Basic information such as country, tax identification number, postal code, contact details, etc. should be provided
8. The offer should include all required Appendices, statements and documents - please use the attached checklist (Appendix no.6) to confirm that all required documents will be delivered
9. Any Supplier may submit only one offer.
10. Partial bids are not allowed.
11. The offer should be prepared in English or Polish.
12. Prices in the offer should be expressed as net prices in Polish zlotych (PLN), or Euro (EUR).
13. If the prices in the offer are expressed in EUR they will be converted using the exchange rate of 4,4536 PLN/EUR, in accordance with the Notice of the President of the Public Procurement Office of 3 December 2021 on the current EU thresholds, their PLN equivalent, PLN equivalent of amounts expressed in EUR and the average PLN / EUR exchange rate constituting the basis for converting the value of public contracts or design contests.
14. Tenders submitted after the deadline will not be considered.
15. The Supplier before time-limit for receipt of tenders is entitled:
    1. to withdraw the offer by written notification by e-mail indicated for the submission of tenders,
    2. to change the offer – notification of the changes must be submitted by the same rules as the submitted offer, appropriately marked with the note "CHANGING THE OFFER".

Selection criteria and evaluation methods:

1. The Contracting Authority is entitled to reject the tender submitted by the Supplier who does not meet the conditions for participation in the proceedings, or if the offer is incomplete or incompatible with this request.
2. Selection criteria:
   1. Net price (PLN/EUR), the weight criterion - 60%, shall include all the associated costs.
   2. Delivery time 1kg API (declared time needed for delivery of the100 g API (from the date of signing the contract) - 40% of the overall assessment.
3. The Contracting Authority shall evaluate offers based on the result of the accumulated number of points calculated on the basis of above criteria and scores:

   Criteria	Weightcriterion [%]	Method of evaluation in accordance with the formula
   Price	60%	net price of the lowest offer/net price of tested offer x 100 x 60% = number of points,
   Delivery time 1000 g	40%	the shortest time / offer tested x 100 x40% = number of points

4. The amounts of points for each criterion after summing up will be the final number of points awarded by each tender. As the most advantageous offer will be considered that which obtains the highest number of points.
5. The results of the mathematical calculations carried out in the evaluation of tenders are rounded to the second decimal place. In case of equal scores for at least two offers the Contracting Authority will make the final choice of the offer more favorable when it comes to the impact on the environment (including the number of laboratory animals planned to use). For this purpose, the Contracting Authority shall have the right to call the Suppliers, whose tenders have obtained the highest final points, to complete the offer by giving indicated by the Contracting Authority information about an impact of the offer on the environment. The deadline to complete the offer will be determined by the Contracting Authority, but it cannot be less than 3 working days from receipt of the request.

The choice of Supplier and way of announcing:

1. The Contracting Authority will select the most advantageous offer on the basis of the selection criteria defined in this request for proposal.
2. The Contracting Authority will inform about the results of this request for proposal on website https://www.adamed.com/ and will send the information by the Procurement System SAP Ariba Sourcing to each Supplier which has submitted its offer.

General provisions

1. The Contracting Authority reserves the right to invalidated or terminate the procedure at each stage without giving any reason.
2. In the case of cancellation of the contract the Suppliers are not entitled to claim for reimbursement of the costs of participation in the proceedings.
3. Submission of the application for registration in the process or tender is implies acceptance without reservation all the conditions of the proceedings.
4. Withdrawal by the Contracting Authority from the conclusion of the contract after the notification the Supplier about the selecting the offer, cannot be the basis for claims of incurred costs of participation in the proceedings.
5. In the process of evaluating Offers the Contracting Authority may seek information from the contractors concerning the content of their documents.
6. If the application does not contain all the required elements, the Contracting Authority may in justified cases call the Supplier to complete it.
7. The Contracting Authority reserves the right to record sound during technical meetings with suppliers. Submission of the offer will be treated as giving consent to the recording of the meeting.
8. The Contracting Authority allows negotiations of the contract terms and conditions with the Tenderer.
9. The Contracting Authority reserves the right to negotiate the proposal with the Tenderer, whose bid has the highest number of points, especially when the price offered by the bidder exceeds the budget intended by the Contracting Authority to perform the order. Negotiations may have several consecutive  rounds with  the  possibility  to invite bidder to  submit the updated quotation after each round of negotiations
10. The Contracting Authority reserves the right to audit the Supplier before the conclusion of the contract. In case of obtaining not satisfactory results of the audit Sponsor may withdraw from signing the contract.
11. Terms of contract change: The contracting authority envisages the possibility of introducing significant changes to the contract concluded as a result of the conducted contract award procedure in relation to the content of the offer, on the basis of which the contractor was selected, in the event of the necessity to change the indicated scope of works specified in the offer:
    1. Necessary or justified changes in the design documentation resulting from unforeseeable reasons,
    2. The necessity or the technical-economic appropriateness of the use of equivalent materials and equipment,
    3. The necessity to make equivalent solutions resulting from technological or utility conditions,
    4. Financial constraints on the part of the Contracting Authority which cause the necessity to limit the scope of works included in the offer,
    5. Necessary or justified changes in the delivery time and conditions of the contract subject resulting from unforeseeable reasons

Any changes and additions to the contract concluded with the selected Supplier will be made in the form of written annexes to the contract signed by both parties, under rigor of invalidity.

Additional information about participation in the tender

1. Any questions should be submitted using Purchasing Platform according to attached instruction.

2. The person authorized to contact the bidders (Monday-Friday between 08:00-16:30) is: Anna Klatkowska [anna.klatkowska (at) adamed.com].

Appendix No 1  (download)

Appendix No 3  (download)

Appendix No 4  (download)

Appendix No 5  (download)

Appendix No 6  (download)

Supplier's instructions. Creating an offer on the Portal SAP Ariba Network (download)