Procurement for the Supply of Active Pharmaceutical Ingredient - Physostigmine Free Base

The Chemical Biological Radiological and Nuclear Protection Delivery Team is inviting expressions of interest in respect of a proposed contract for the development, process validation, manufacture and supply of Physostigmine free base as an Active Pharmaceutical Ingredient (API) for use in a Ministry of Defence (MOD) final medicinal product currently under development. The Supplier will be required to develop, scale-up and validate the manufacturing method, define a detailed specification and full characterisation of the API, Physostigmine (also known as eserine; chemical name 1,2,3,3aβ,8,8aβ-hexahydro-1,3a,8-trimethylpyrrolo[2,3-b] indol-5-yl-methylcarbamate; chemical formula C15H21N3O2; molecular weight 275.36 g/mol) The Supplier will be required to supply the Authority with full information on the manufacture and control of the API as described in Annex I to Directive 2001/83/EC as amended (with particular reference to Part I, Section 3) and elaborated in the Notice to Applicants (Eudralex Volume 2: https://ec.europa.eu/health/documents/eudralex/vol-2_en). The specification should meet modern standards and best endeavours should be taken to remove processing impurities. The specification should align with current regulatory requirements for active pharmaceutical ingredients (including Ph.Eur). The Supplier will also be expected to analyse a sample (as much as is required) of the Authority's existing physostigmine API material, to assess the comparability of the two (to permit bridging between studies using old versus new material). The Authority will review the comparability and determine whether the specification of the new API is acceptable. The Supplier will be required to conduct appropriate stability studies as often as required as per the International Conference on Harmonisation (standard and accelerated), forced degradation and provide data in the form of a written report (including protocol(s)) to support the shelf life to be applied. A shelf life of at least 3 years under storage conditions 2-8°C is required. The Supplier will prepare a primary reference standard no later than the day of commencement of performance validation batches. This standard will be tested throughout its shelf life to maintain its usability and where necessary replaced with a new standard. This standard must be sufficient for all testing required throughout the life of the contract and the Authority reserves the right to request quantities on an ad-hoc basis.