To evaluate a Contract Development and Manufacturing Organisation (CDMO) for Occupational Exposure Band 5 (OEB5) High Potency Active Pharmaceutical Ingredient (HPAPI) small molecule formulation, Chemistry, Manufacturing and Controls (CMC) and procurement teams should apply a five-domain weighted scorecard across written Request for Proposal (RFP) responses and then validate every score in person during a site visit. The five domains are: containment engineering and OEB5 capability (30%); integrated small molecule formulation development expertise (25%); Good Manufacturing Practice (GMP) quality systems and regulatory track record (20%); analytical and stability support (15%); and supply chain reliability and scalability (10%). This guide defines each domain, explains the scoring rationale, provides a live-calculation scorecard and identifies the questions that separate documented capability from stated intent.
What Is OEB5 and Why Does It Demand a Structured CDMO Evaluation?
An Occupational Exposure Band (OEB) is a standardised classification system that groups pharmaceutical compounds by their potency and associated inhalation hazard. There are five bands in total. OEB1 represents the least hazardous substances; OEB5 represents the most toxic. Compounds at OEB5 carry Occupational Exposure Limits (OEL) at or below the sub-microgram per cubic metre range, and include cytotoxic oncology agents, targeted hormonal therapies and certain immunosuppressants.
At OEB5, inadequate containment does not only create a worker safety risk. It can compromise product quality, introduce cross-contamination risk across manufacturing campaigns and impair the ability of a Qualified Person (QP) to certify a batch with confidence. A CDMO that lacks validated OEB5 infrastructure cannot offset that deficit with expertise in any other domain.
A formal, scored RFP process ensures the selection decision is auditable, reproducible and defensible to internal governance functions and regulatory reviewers examining supplier qualification records.
The Five Scoring Domains
The weightings below reflect the risk profile of a high-potency small molecule development programme. Teams approaching late-stage development may choose to increase the supply chain or quality systems weighting. Any adjustment must be documented and applied consistently across all CDMO candidates on the shortlist.
Containment Engineering and OEB5 Capability
Containment engineering carries the highest weighting because it represents a hard binary requirement: either the facility can safely contain the compound at the required OEL, or it cannot. No formulation expertise or regulatory history elsewhere compensates for an unvalidated containment environment. Evaluators should request documented evidence of the following:
- A defined OEB classification scheme with a confirmed upper handling capability at OEB5, expressed as a specific OEL threshold
- A dedicated, physically separated suite for high-potency operations, with documented engineering controls including pressure cascade management, interlocked access systems and continuous airborne monitoring
- Validated cleaning and decontamination procedures, with analytical detection limits appropriate to HPAPI residue verification
- A risk-based, compound-specific OEB classification process applied before each campaign begins
- GMP certification of the HPAPI suite by a recognised regulatory authority
The Adragos Athens Centre of Excellence operates a dedicated HPAPI laboratory, built in 2023 and certified as EU-GMP compliant by the Greek Regulatory Authorities in the same year. The facility is capable of handling high-potency compounds at OEB5, with an OEL not lower than 0.5 μg/m³ (equivalent to 0.0005 mg/m³). The dedicated suite accommodates lab-scale manufacturing for the research and development production of both solid and liquid pharmaceutical products containing HPAPI, alongside a fully equipped analytical laboratory. The suite was constructed in direct response to growing demand from oncology and other high-potency therapeutic areas.
- What is the lowest OEL your facility is validated to handle, and can you provide the relevant GMP certification documentation for your high-potency suite?
- Describe the engineering controls within your high-potency suite, including pressure cascade design and real-time monitoring systems.
- How do you classify each incoming compound for OEB assignment, and at what point in the project intake process does that classification occur?
- Can you share a containment logbook summary from the past 12 months, including any excursions and the corrective actions taken?
Integrated Small Molecule Formulation Development Expertise
High-potency small molecules frequently present formulation challenges including poor aqueous solubility, polymorphic instability and sensitivity to moisture, light or oxidative stress. A CDMO with genuine, integrated formulation development capability reduces the risk of reformulation mid-programme, which is one of the most common and most disruptive sources of delay in small molecule development. Evaluators should assess the following:
- Pre-formulation services including solid-state characterisation, polymorph screening and solubility profiling
- Dosage form breadth across oral solid dose, parenteral and modified-release formats
- Documented experience with New Chemical Entities (NCEs) and Value-Added Medicines
- Technology transfer protocols from development scale to clinical and commercial GMP manufacturing
- A track record of electronic Common Technical Dossier (eCTD) dossier preparation and submission across multiple regulatory jurisdictions
The Athens Centre of Excellence operates as the primary centre for galenic development within the Adragos network, functioning as a strategic profit centre within the business. A team of over 70 pharmaceutical research and development professionals supports development across all dosage forms, including HPAPI handling and controlled substances. The site has delivered over 150 eCTD dossier submissions with product approvals in more than 20 countries, supporting NCEs, Value-Added Medicines and generics.
- How many small molecule development projects involving HPAPI compounds have you completed in the past three years, and at what development stages?
- What pre-formulation services do you offer in-house, and how are they integrated with your containment-capable manufacturing suite?
- Describe your technology transfer process from development scale to GMP clinical manufacturing, including documentation standards and timeline expectations.
GMP Quality Systems and Regulatory Track Record
A CDMO’s regulatory inspection history is the most objective available signal of quality system robustness. Written self-assessments in RFP responses must be validated against independently verifiable records. Evaluators should request the following:
- The most recent GMP inspection outcomes from the European Medicines Agency (EMA), the United States Food and Drug Administration (FDA) or equivalent authority, including observation classifications and response documentation
- The scope and frequency of client quality audits and the CDMO’s standard audit hosting process
- The structure and documented independence of the Qualified Person function, particularly as it relates to HPAPI batch disposition
- Deviation management and Out-of-Specification (OOS) investigation procedures specific to high-potency operations
- Change control procedures governing modifications to containment infrastructure
Adragos Jura hosts 12 client audits per year and holds certifications from the EMA, the FDA and Swissmedic. The site produces approximately 200 clinical batches per year and has achieved five successful commercial launches, all under the EU-GMP framework. The Athens facility holds EU-GMP certification from the Greek Regulatory Authorities, including for the dedicated HPAPI suite certified in 2023.
- Which regulatory authorities have inspected your HPAPI-capable site in the past three years, what were the outcomes, and can you share the observation classifications?
- How many client audits does your site host per year, and how are HPAPI-specific elements of quality oversight structured within your quality management system?
- How does your Qualified Person function maintain documented independence from commercial and operational pressure during batch disposition decisions for high-potency programmes?
Analytical and Stability Support
Developing reliable analytical methods for OEB5 compounds requires sensitivity that extends well below standard pharmaceutical detection thresholds. For both product characterisation and cleaning verification, methods must be validated to detect residues at levels appropriate to the specific compound’s OEL. Evaluators should verify the following:
- Validated ultra-low detection analytical capability including High-Performance Liquid Chromatography (HPLC), Gas Chromatography (GC) and relevant spectrometric techniques, validated for HPAPI residue analysis
- In-house stability suite capacity under International Council for Harmonisation (ICH) climate zones, with alarm-controlled temperature and humidity monitoring and computer-aided data management
- Method transfer and cross-validation protocols for programmes transitioning between development and GMP manufacturing sites
- For injectable HPAPI programmes: sterility suitability testing, endotoxin suitability testing and bioburden suitability testing capacity
The Athens HPAPI laboratory incorporates a dedicated analytical laboratory within the certified suite, equipped to analyse both liquid and solid pharmaceutical products and active substances. Leipzig conducts stability testing for ICH climate areas II, IVa and IVb with alarm-controlled monitoring of temperature and humidity, computer-aided scheduling and data control, and method development and validation across HPLC, GC, GC-headspace, UV-VIS and titration. Jura provides stability studies under ICH long-term and intermediate conditions, HPLC validation, sterility suitability testing, endotoxin suitability testing and bioburden suitability testing as part of its standard clinical trial material service offering.
- What is the lowest detection limit your analytical methods have been validated to achieve for HPAPI residue verification, and which compound classes do you have prior method development experience with?
- Describe your stability suite infrastructure, including the ICH climate zones supported and your alarm and data management systems.
- How do you manage method transfer when a programme transitions from your development site to a separate clinical or commercial manufacturing site?
Supply Chain Reliability and Scalability
For OEB5 programmes, supply continuity carries implications beyond commercial risk. Interrupted supply of a high-potency oncology or hormonal compound during a clinical programme can have direct patient consequences. Evaluators should assess the following:
- Documented on-time delivery performance for clinical and commercial batch supply
- The ability to scale campaign size without triggering revalidation of containment infrastructure
- Raw material sourcing protocols for controlled, restricted or dual-use substances
- Existing GMP certification and dossier coverage across key markets including the European Union, the United States and Japan
Adragos operates seven GMP-certified facilities across Europe and Japan, with commercial supply reaching more than 60 countries. The network includes Athens for development, Jura for clinical and small-to-medium commercial sterile manufacturing, Leipzig for non-sterile liquids and semi-solids, and further sites supporting ampoules, suppositories, intravenous bags and prefilled syringes. This structure enables development-to-commercial continuity within a single accountable partner organisation.
- What is your documented on-time batch delivery performance for clinical trial material programmes over the past two years?
- If our programme scales from development to clinical to commercial volume, how does that progression interact with your containment validation status?
- How do you manage raw material sourcing for controlled or restricted compounds, and what is your approach to supply chain risk management?
The Weighted Scorecard: Apply, Score and Calculate
Complete the scorecard in two stages. Stage one uses written RFP responses to generate an initial score. Stage two validates and adjusts each score based on direct observation during the in-person site visit. Enter a score between 1 and 5 in each field — weighted totals calculate automatically.
| Score | Definition |
|---|---|
| 5 | Fully validated, GMP-certified capability with documented third-party verification, regulatory inspection record and case study evidence provided |
| 4 | Established capability with supporting documentation; limited or no recent third-party verification of this specific capability |
| 3 | Capability claimed with partial documentation; gaps acknowledged by the CDMO and under active resolution |
| 2 | Partial capability with known, unresolved gaps; CDMO has acknowledged limitations |
| 1 | No documented capability at this time; aspirational or in planning only |
| Domain | Weight | Stage 1 Score | Stage 1 Weighted | Stage 2 Score | Stage 2 Weighted |
|---|---|---|---|---|---|
| Containment Engineering and OEB5 Capability | 30% | — | — | ||
| Integrated Small Molecule Formulation Development Expertise | 25% | — | — | ||
| GMP Quality Systems and Regulatory Track Record | 20% | — | — | ||
| Analytical and Stability Support | 15% | — | — | ||
| Supply Chain Reliability and Scalability | 10% | — | — | ||
| Total | 100% | — | — / 5.00 | — | — / 5.00 |
A minimum final weighted total of 3.50 out of 5.00 is recommended before advancing a CDMO to detailed due diligence.
Non-negotiable threshold: Any CDMO scoring below 3 in Domain 1 (Containment Engineering and OEB5 Capability) must not be advanced to the next stage, regardless of total scorecard performance.
A gap of more than 1.0 point between Stage 1 and Stage 2 scores in any single domain should trigger a formal explanation request to the CDMO before proceeding.
Conducting the Site Visit: Converting Written Responses into Verified Evidence
The site visit is not a procedural courtesy. It is the stage at which written RFP commitments are tested against physical reality. Structure the visit to include the following activity blocks:
Containment Verification
- Request a live walkthrough of the high-potency suite, including a demonstration of gowning procedures and observation of pressure monitoring systems in active operation
- Review the containment logbook for the preceding 12 months, specifically noting any excursions, near-miss events or corrective actions taken
- Observe waste decontamination and disposal procedures directly, not solely through written Standard Operating Procedures
Analytical and Stability Confirmation
- Physically inspect the stability suite, confirming that continuous temperature and humidity logging is active and that alarm records are current and maintained
- Request sight of at least two completed analytical method validation reports for HPAPI compounds, with detection limits confirmed and documented
Quality Culture Assessment
- Hold direct conversations with analytical chemistry and quality assurance staff, independently of the commercial account team
- Ask operational staff, without prompting, to describe the process that follows a containment excursion or documentation deviation
- Review at least two completed batch records from prior HPAPI campaigns to assess documentation standards and deviation management quality
Facilities where operational staff demonstrate unprompted awareness of containment protocols, deviation escalation paths and documentation requirements consistently outperform those where quality is managed solely at a senior level.
How Adragos Pharma Supports HPAPI Small Molecule Programmes
Adragos Pharma provides integrated small molecule formulation development and HPAPI handling capability across a network of seven GMP-certified sites in Europe and Japan, with commercial supply reaching more than 60 countries.
Athens, Greece
Formulation Development and HPAPI Handling
- EU-GMP certified HPAPI laboratory, built and certified in 2023
- OEB5 capability — OEL not lower than 0.5 μg/m³
- Lab-scale R&D production of solid and liquid HPAPI forms
- Dedicated in-suite analytical laboratory
- 70+ pharmaceutical research and development professionals
- 150+ eCTD submissions; approvals in 20+ countries
- NCEs, Value-Added Medicines and generics
Jura, Switzerland
Clinical Trial Material Manufacturing
- Aseptic fill-and-finish for liquid and lyophilised vials
- 200 clinical batches per year; no minimum batch size
- 3-month turnaround from order to batch
- Controlled drug handling; Restricted Access Barrier Systems (RABS) and single-use strategy
- EMA, FDA and Swissmedic certified
- 12 client audits per year; 5 commercial launches achieved
- ICH stability studies; sterility, endotoxin and bioburden suitability testing
Leipzig, Germany
Analytical, Stability and Non-Sterile Manufacturing
- EU-GMP certified; 100 years of production history
- Stability testing for ICH climate areas II, IVa and IVb
- Alarm-controlled temperature and humidity monitoring
- Method development and validation: HPLC, GC, GC-headspace, UV-VIS and titration
- Controlled drug handling
- Non-sterile liquids (up to 4,000 L) and semi-solids
Global Network
Commercial Supply and Market Access
- Seven GMP-certified sites across Europe and Japan
- Commercial supply to more than 60 countries
- Prefilled syringes and large-scale vials at Maisons-Alfort, France
- Ampoules and suppositories at Livron, France
- Intravenous bags and ampoules via BFS technology at Halden, Norway
- Visual inspection and packaging at Kawagoe, Japan
For CMC and procurement leaders building an HPAPI CDMO shortlist, Adragos provides a certified and operational OEB5 laboratory, documented formulation development expertise, a strong regulatory inspection record and clinical manufacturing capability within a single accountable partner organisation.
