As innovative drug development becomes increasingly specialized and refined, a growing number of pharmaceutical companies and biotechnology firms are opting to outsource the research, development, and manufacturing of active pharmaceutical ingredients (APIs) to specialized CDMO (contract development and manufacturing organization) partners.

Partnering with a CDMO to develop APIs not only leverages its state-of-the-art equipment and expert technical team to accelerate project timelines, but also helps effectively reduce capital expenditures and operational risks.

So, from initial engagement to final commercial-scale production, what steps are involved in collaborating with a CDMO to develop an active pharmaceutical ingredient (API)? This article will systematically outline the key milestones and critical considerations across five core phases: project evaluation and approval → small-scale R&D and process development → pilot-scale scale-up → trial production and process validation → commercial production and ongoing supply.

1. Project Evaluation and Approval: Laying the Foundation for Collaboration

Project evaluation and approval mark the starting point of the entire CDMO collaboration and constitute the foundational stage that determines the project’s success or failure. The primary objective of this phase is to validate the project’s technical feasibility, cost controllability, and the mutual commitment to collaboration.

• Business Liaison and Requirements Communication: Clients contact the CDMO’s business team via email, telephone, or other means to provide an overview of the project, including downstream drug information, indications, target markets, and whether the compound is a registration intermediate.

We recommend that clients provide as much detailed project information as possible in the Request for Proposal (RFP), including the molecular structure, process challenges, target timeline, and regulatory submission requirements, so that the CDMO can promptly assess the project and deliver an accurate quotation.

Feasibility Assessment and Cost Estimation: Cross-departmental collaboration among CDMO’s R&D, material control, analytical, and manufacturing teams. The R&D department reviews relevant literature and prepares purchase inquiries for raw materials based on project documentation; the Quality Control department assesses and analyzes costs, including consumables and personnel expenses; the Production department estimates production costs during the pilot‑run phase in the workshop. After consolidating information from all departments, the “Detailed Cost Assessment Form” and the “Inquiry Assessment Report” are prepared.

Project Approval and Task Assignment: Once the quotation is approved by the client, both parties sign a cooperation agreement, and CDMO internally issues the Project Charter, which clearly defines the project objectives, deliverables, and milestones, thereby officially launching the project.

Hengyuehe Tip: Shanghai Hengyuehe Biopharmaceutical Co., Ltd. boasts a dedicated project evaluation team that can swiftly conduct technical feasibility analyses and cost estimations, providing clients with transparent, efficient quotation and project initiation services.

2. Small-scale R&D and process development: validating the technical route

The small-scale stage is a core technical phase in API development, with the primary objectives of establishing the synthetic route, optimizing process parameters, and producing qualified samples at laboratory scale.

• Process route development: Based on the project task assignment, R&D personnel coordinate synthesis and analytical teams to carry out process development.

Developing the optimal synthetic route for a molecular drug is essential to ensuring a reliable supply throughout the entire pharmaceutical lifecycle. In this process, it is necessary to comprehensively consider multiple factors, including safety, efficiency and cost, scalability, intellectual property risks, the security of raw material supply, and environmental impact.

Method Development and Validation: The Analytical Department concurrently undertakes the development and validation of analytical methods for raw materials, intermediates, and finished products. The reliability of the analytical method is directly linked to the controllability of product quality.

Sample Preparation and Customer Confirmation: After preparing the qualified sample, the CDMO will ship it to the customer, and both parties will confirm the sample’s quality. After the customer confirms approval, the R&D department continues to optimize the process and validates the optimized small-scale pilot process, ultimately completing the Process Development Report.

Hengyuehe Note: Hengyuehe boasts a fully equipped synthesis laboratory and a quality-control testing center, enabling us to provide customers with end-to-end technical support—from route scouting to analytical-method development—during the small-scale trial phase.

3. Pilot-scale scale-up: verifying the industrial feasibility of the process

Pilot-scale scale-up is the key bridge connecting laboratory research and development with industrial production. Its primary objective is to, under conditions that simulate industrial-scale production, validate the reproducibility and stability of the laboratory-scale process when scaled up to large‑scale equipment.

• Equipment scaling and process adjustment: As the scale is ramped up from gram-level small-scale trials to kilogram‑ or even hundred‑kilogram‑level pilot production, the heat and mass transfer characteristics of the reactor change, necessitating the adaptation and optimization of process parameters to suit the equipment configuration.
• Determination of Critical Process Parameters (CPPs): Through pilot-scale scale-up studies, identify the critical process parameters that influence product quality and establish their acceptable ranges.
• Risk Assessment: Employ tools such as FMEA (Failure Mode and Effects Analysis) and HAZOP (Hazard and Operability Study) to systematically identify potential risks in the amplification process.

Hengyuehe advises: Hengyuehe boasts scalable production capabilities ranging from the kilogram to the ton level, with extensive experience in pilot-scale scale-up, enabling effective mitigation of technical and quality risks during process scaling.

4. Pilot Production and Process Validation: Ensuring Process Robustness

After the process validation has been confirmed through pilot-scale testing, the next phase begins: pilot production and further process validation. The objective of this phase is to demonstrate, through a validated validation batch, that the process can consistently and reliably produce products that meet quality specifications at commercial scale.

• Pre‑production plan and batch record preparation: The R&D department prepares the pre‑production plan and the corresponding batch records, facilitates the technical transfer of the project to the Production Department, and coordinates related tasks such as equipment modifications, document handover, and production training.

Process validation batches: Typically, three consecutive successful process validation batches must be completed to establish process reproducibility.

Stability Studies: Stability studies are conducted on the validation batches to provide data support for the product’s shelf life and storage conditions.

Trial Production Summary and Document Revision: Following the completion of trial production, prepare the Trial Production Summary Report, process procedures, and batch production records, and conduct ongoing stability studies on the product.

Hengyuehe Note: Hengyuehe operates multiple GMP-compliant production facilities, enabling customers to conduct robust process validation and stability studies, and providing comprehensive technical documentation to support product registration submissions.

5. Commercial Production and Sustained Supply: Ensuring Long-Term, Stable Delivery

After process validation is completed, the project enters the commercial production phase. The primary objective of this phase is to ensure the long-term stable supply of the product while continuously optimizing processes and reducing costs.

• Scale-up production: Based on customer requirements, we provide commercial-scale API manufacturing ranging from hundreds of kilograms to metric tons.
• Supply Chain Management: Establish a robust supply chain system to ensure a stable supply of critical raw materials and maintain appropriate safety stock levels.
• Continued Process Verification (CPV): Commercial-scale batches are continuously monitored and evaluated to ensure that the process remains in a state of control.
• Full Lifecycle Management: Covers post‑market process and operational improvements, yield optimization, and any potential quality- or production-related investigations. The two parties may also establish a full-lifecycle strategic partnership encompassing process development, technology transfer, commercial-scale production, and continuous improvement.

Hengyuehe Tip: Shanghai Hengyuehe Biopharmaceutical Co., Ltd. has been deeply engaged in the industry for more than a decade and has established long-term strategic partnerships with over 120 renowned pharmaceutical companies both domestically and internationally. Its robust supply-chain capabilities and consistent delivery performance have been thoroughly validated.

Collaborating with CDMO companies to develop APIs is a complex, multidisciplinary, multi‑departmental, and multi‑phase systems engineering project. From **project evaluation and approval, small-scale R&D, pilot-scale scale-up, trial production and process validation to commercial manufacturing**, every stage is tightly linked; any oversight at a single step can lead to project delays or even failure. Partnering with a CDMO that boasts end-to-end service capabilities, a robust quality management system, and extensive scale-up expertise can not only significantly accelerate the API development pipeline from the lab to market but also lay a solid foundation for the product’s long‑term commercial success. Shanghai Hengyuehe Biopharmaceutical Co., Ltd., backed by a state-of-the-art GMP manufacturing facility, a dedicated R&D team, and a robust supply chain, is committed to providing global pharmaceutical and biotechnology companies with end-to‑end CDMO services—spanning from early-stage development to commercial-scale production. We look forward to becoming your trusted long-term partner.