Containment Checklist for CDMO RFPs 2026

Selecting a Contract Development and Manufacturing Organisation (CDMO) for high-potency active pharmaceutical ingredient (HPAPI) small molecule formulation development requires a verification process that is fundamentally more rigorous than for standard compound programmes. The containment infrastructure, operator safety controls and Good Manufacturing Practice (GMP) evidence that HPAPI work demands cannot be assumed from a CDMO’s general quality credentials; they must be confirmed before any project is awarded.

This guide provides an end-to-end checklist for pharmaceutical and biotech development leaders building or refining their Request for Proposal (RFP) process for HPAPI-capable CDMO sourcing. It covers Occupational Exposure Band (OEB) classification, containment infrastructure requirements, Heating, Ventilation and Air Conditioning (HVAC) pressure cascade design, cleaning validation methodology and the GMP documentation every RFP should formally require.

What Is a High-Potency Active Pharmaceutical Ingredient?

A high-potency active pharmaceutical ingredient is a pharmacologically active compound characterised by significant biological activity at low doses, typically resulting in an Occupational Exposure Limit (OEL) set below 10 micrograms per cubic metre of air (µg/m³). At concentrations within this threshold, uncontrolled airborne exposure during manufacturing, weighing, transfer or cleaning operations presents a genuine and documented risk to operator health.

The HPAPI category encompasses a broad and growing range of compound types, including oncology agents, hormonal compounds and highly targeted therapies. As development pipelines skew increasingly towards high-potency chemistry, the ability of a CDMO partner to handle these compounds safely and in full compliance with regulatory expectations has become a primary sourcing criterion, not a secondary consideration.

Why Containment Strategy Is the First Filter in CDMO Selection

Before evaluating any other characteristic of a prospective CDMO partner, a development team must confirm that the facility’s containment infrastructure is appropriate for the OEB classification of their specific compound. A CDMO that cannot receive and handle the compound safely cannot progress the programme, regardless of its other strengths.

Proceeding without containment verification creates three distinct categories of risk. The first is operator health risk, where inadequate engineering controls expose personnel to pharmacologically active compounds above permissible airborne concentrations. The second is regulatory risk, where a facility operating beyond its certified containment capability is vulnerable to observations during competent authority inspections. The third is programme risk, where a mid-development CDMO change driven by a containment gap is both costly and time-consuming to remediate.

Containment verification is therefore the mandatory first gate in any HPAPI CDMO RFP process.

Understanding Occupational Exposure Band Classification

Q: What is OEB classification and how should it be applied when selecting a HPAPI-capable CDMO?

Occupational Exposure Band classification is a hazard banding system used to categorise pharmacologically active compounds by their airborne exposure risk. OEB banding is particularly useful at early programme stages, before a formally derived OEL has been established by a qualified industrial hygienist or toxicologist. It allows a development team to define the containment requirements of their compound and evaluate CDMO suitability before compound-specific toxicological data are complete.

The standard five-band classification system is as follows:

OEB Level	Occupational Exposure Limit Range	Hazard Level	Primary Containment Approach
OEB 1	Greater than 1,000 µg/m³	Low	Standard manufacturing with basic Personal Protective Equipment (PPE)
OEB 2	100 to 1,000 µg/m³	Moderate	Enhanced local ventilation and standard PPE programme
OEB 3	10 to 100 µg/m³	Moderate-High	Local exhaust ventilation, containment enclosures and respiratory protection
OEB 4	1 to 10 µg/m³	High	Dedicated pharmaceutical isolators and negative pressure containment suites
OEB 5	Below 1 µg/m³	Very High	Closed pharmaceutical isolators and fully dedicated HPAPI-only suites

Most compounds classified as HPAPIs fall within OEB 4 or OEB 5. Certain cytotoxic compounds used as payload components in antibody-drug conjugate programmes may require sub-band categorisation below OEB 5, and any CDMO handling such compounds should be evaluated accordingly.

Your RFP must state the OEB classification of your compound and request explicit confirmation that the CDMO’s certified containment capability covers that classification. Where a formal OEL has not yet been established, the CDMO should confirm the process by which compound-specific OEB banding will be conducted or commissioned prior to any handling operations commencing.

Containment Infrastructure Requirements by OEB Level

Q: What containment infrastructure should I expect from a CDMO handling OEB 4 or OEB 5 compounds?

The physical infrastructure required for high-potency compound handling is determined by OEB classification and must be verified through documentation. It cannot be accepted on the basis of a CDMO’s self-declaration alone. The requirements below represent the minimum acceptable standard for HPAPI small molecule formulation development.

Requirements for OEB 4 Compounds

• Dedicated weighing and dispensing areas with pharmaceutical containment enclosures or isolator systems
• Continuous airborne monitoring at operator breathing zone level during all manufacturing operations
• Negative pressure room design with continuously monitored pressure differentials relative to adjacent zones
• High-Efficiency Particulate Air (HEPA)-filtered exhaust systems on all containment area extract air
• Interlocked airlock systems between the containment suite and adjacent general manufacturing or corridor areas
• Documented gowning and de-gowning procedures with operator competency verification records
• Dedicated process equipment or validated shared equipment with a cleaning validation programme based on health-based exposure limits

Requirements for OEB 5 Compounds

All OEB 4 requirements apply, with the following additional controls mandatory:

• Fully closed pharmaceutical isolator systems for all powder handling and inter-vessel transfer operations
• Secondary containment on all product transfer steps where the compound is in an open or uncontained state
• Continuous real-time airborne particle monitoring throughout all manufacturing activities
• Dedicated, campaign-specific or single-product suites, preventing any concurrent multi-product processing
• Documented Containment Performance Testing (CPT) data using surrogate compounds to verify that engineering controls achieve the claimed containment levels under realistic operational conditions

When evaluating RFP responses, request CPT data along with a description of the testing methodology and the surrogate compound used. CPT results provide objective, measurable evidence of containment performance independent of operator behaviour and are the clearest technical basis on which to assess an OEB 5 capability claim.

HVAC Pressure Cascade Requirements for High-Potency Compound Manufacturing

Q: What HVAC pressure cascade design is required for HPAPI manufacturing suites at a qualified CDMO?

Heating, Ventilation and Air Conditioning design for high-potency compound manufacturing is built on the principle of directional airflow control. Air must flow consistently from areas of lower hazard towards areas of higher containment, ensuring that any airborne compound generated during manufacturing operations remains within the boundary of the designated controlled zone.

The standard pressure cascade for an HPAPI containment suite operates across the following sequential zones:

1. General corridor or uncontrolled building area: Reference pressure baseline
2. Gowning anteroom: Transitional zone at slight positive pressure relative to the external building environment
3. Airlock: Transitional negative pressure zone, typically 10 to 15 Pascals below the anteroom
4. OEB 4 manufacturing suite: Typically a minimum of 15 Pascals negative relative to the airlock
5. OEB 5 manufacturing suite: Typically a minimum of 30 Pascals negative relative to the airlock, with additional containment provided by the isolator or enclosure system where applicable

These values represent typical industry guidance ranges. The CDMO’s validated and qualified HVAC specifications, documented in its qualification records, are the governing reference for confirming compliance with the compound’s specific requirements.

Your RFP should request evidence of the following HVAC controls in all cases:

• Independent HVAC systems for all HPAPI suites, fully segregated from general manufacturing HVAC circuits; shared systems across containment and general manufacturing areas are not acceptable for OEB 4 and above
• Continuous pressure differential monitoring with audible and visual alarm activation at defined alert and action limits for each zone transition
• HEPA filtration on all exhaust air exiting containment areas; H14 rated terminal HEPA filtration is widely specified for HPAPI suite exhaust
• Defined minimum air change rates documented in the room design specification and appropriate to the OEB level of compounds handled
• Validated pressure cascade mapping completed during initial commissioning and re-verified following any HVAC maintenance, modification or significant intervention
• Documented contingency and deviation procedures covering the management of pressure differential excursions occurring during active manufacturing operations

Request the full HVAC qualification package, comprising the Installation Qualification, Operational Qualification and Performance Qualification records, and confirm these are current and cover the active HPAPI suite configuration.

Cleaning Validation for High-Potency Active Pharmaceutical Ingredients

Q: How should cleaning validation for HPAPI compounds be approached in a shared-equipment CDMO setting?

Cleaning validation for high-potency active pharmaceutical ingredients must be based on health-based acceptance criteria derived from compound-specific toxicological data. The legacy approaches previously applied to standard compound cleaning validation programmes, specifically the ten parts per million criterion and the one-thousandth of the minimum therapeutic dose calculation, are not appropriate for compounds with OELs below 10 µg/m³ and are not consistent with current regulatory expectations for shared manufacturing facilities.

Health-Based Acceptance Criteria

The Acceptable Daily Exposure (ADE), equivalent to the Permitted Daily Exposure (PDE) referenced in International Council for Harmonisation (ICH) guidance, is established by a qualified toxicologist for each compound handled in the HPAPI suite. The ADE represents the maximum quantity of residual compound that, if transferred to the next product manufactured on shared equipment, would not produce an adverse effect in any patient population.

The Maximum Allowable Carryover (MACO) translates the ADE into a surface residue limit:

MACO = ADE × (batch size of next product ÷ maximum daily dose of next product)

This MACO value sets the surface residue acceptance criterion against which cleaning validation sampling results are assessed.

Sampling Methods

Swab sampling is the primary verification method for HPAPI cleaning validation. Your RFP should request confirmation of the following from any CDMO under evaluation:

• Validated swab recovery studies conducted for the compound classes handled within the HPAPI suite
• Limit of Detection and Limit of Quantification values confirmed to be below the MACO-derived acceptance criterion for each compound or representative compound class
• Analytical methods validated in accordance with ICH Q2(R2) requirements for specificity, linearity, accuracy and precision
• Documented surface area calculations covering all product-contact surfaces, including filling heads, product vessels and transfer lines
• Rinse sampling available as a supplementary method for equipment areas where physical swab access is restricted

Dedicated versus Shared Equipment

Where dedicated equipment is used exclusively for HPAPI campaigns, cleaning validation requirements are reduced in scope, focusing on batch-to-batch carryover within the same compound rather than cross-product contamination. Where shared equipment is used, full cleaning validation in accordance with EU GMP Annex 15 and the European Medicines Agency (EMA) guideline on setting health-based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities is required in its entirety.

The Role of Single-Use Technology

For liquid formulation steps in clinical-phase HPAPI programmes, a single-use contact surface strategy eliminates the requirement to perform surface residue testing on those components. Single-use elements, including product contact tubing, product bags and single-use filtration assemblies, are discarded after each campaign. This removes the cross-contamination pathway for the liquid formulation phase entirely.

This approach materially reduces both the scope and the programme timeline associated with cleaning validation establishment. It is particularly advantageous for early clinical-phase HPAPI work where batch frequency is low and the time and resource investment of full dedicated equipment cleaning validation would be disproportionate to the programme stage.

Operator Safety Programme Requirements

Q: What operator safety programme must an HPAPI CDMO demonstrate for OEB 4 and OEB 5 compounds?

Engineering containment controls are the primary means of protecting operators in an HPAPI manufacturing environment. Personal Protective Equipment is a supplementary last-line-of-defence control and not a substitute for adequate engineering design. A CDMO whose HPAPI containment strategy relies primarily on PPE to achieve operator protection does not meet the expected standard for OEB 4 or OEB 5 compound handling.

Your RFP should request evidence of all of the following programme components:

Industrial Hygiene Programme

• Documented OEB or OEL classification for every compound handled, maintained or independently reviewed by a qualified industrial hygienist
• Routine air monitoring data from HPAPI manufacturing operations, including both real-time instrument readings and time-weighted average results
• Biological monitoring protocols where scientifically appropriate to the pharmacology of the compounds handled

Medical Surveillance

• Pre-placement health assessments for all operators assigned to HPAPI containment suite activities
• Periodic medical surveillance appropriate to the hazard classification of compounds handled at the site
• Documented incident and near-miss reporting and investigation procedures for any exposure events

Training and Competence

• HPAPI-specific training modules completed by all personnel entering containment areas
• Documented gowning and de-gowning competency verification records, not solely operator self-declaration
• Emergency response procedures specific to containment breaches or unanticipated exposure events

Personal Protective Equipment Programme

• PPE selection matrix aligned to the OEB classification for each compound handled
• Fit-testing records for respiratory protective equipment where required by the compound classification
• Documented PPE maintenance, inspection, replacement and disposal procedures

Request the CDMO’s most recent industrial hygiene monitoring report and confirm the frequency of routine air monitoring during active HPAPI manufacturing operations. Inconsistencies in monitoring frequency or extended gaps in monitoring records should be treated as a substantive evaluation concern.

GMP Evidence Your RFP Must Request

Q: What GMP documentation should an HPAPI-capable CDMO provide in an RFP response?

GMP compliance evidence for HPAPI manufacturing extends well beyond standard quality management system documentation. The following table identifies the minimum evidence set your RFP should formally request.

GMP Document	Purpose	Verification Point
Site Master File	Site-level overview of HPAPI handling capabilities	Confirm certified OEB ceiling and containment classification
Containment Performance Testing Report	Engineering control verification under realistic operating conditions	CPT methodology, surrogate compound used and achieved containment levels
HVAC Qualification Package	Installation Qualification, Operational Qualification and Performance Qualification records for HPAPI suite	Pressure cascade maps, air change rates and filter specifications
Cleaning Validation Master Plan	Framework governing ADE/PDE-based cleaning validation	Methodology, responsibility matrix and ADE data source documentation
Compound-Specific Cleaning Validation Reports	Surface residue acceptance criteria and analytical verification	Recovery studies, MACO rationale and result summaries
Industrial Hygiene Monitoring Records	Operator exposure data from active HPAPI manufacturing operations	Monitoring frequency, historical results and defined action levels
Regulatory Inspection History	Competent authority assessment of HPAPI operations	Recent inspection outcomes and any HPAPI-specific observations or commitments
ADE/PDE Assessment Documents	Toxicologically derived exposure limit documentation	Qualified toxicologist sign-off and compound data sources cited

In addition to these documents, request the CDMO’s HPAPI standard operating procedures index. A CDMO with an established potent compound capability will maintain a comprehensive procedural framework developed specifically for HPAPI operations. A facility adapting generic quality procedures to cover HPAPI handling represents a materially higher technical and regulatory risk.

The Complete HPAPI Containment Checklist for Your RFP

The following checklist consolidates all requirements described in this guide into a structured format for direct use in CDMO RFP processes, organised by evaluation domain. It is intended for use as a formal RFP attachment or as an internal scoring framework during vendor assessment.

Section 1: OEB Classification and Compound Categorisation

• Confirm the CDMO’s maximum certified OEB handling level
• Request the classification methodology used (in-house industrial hygienist or qualified external specialist)
• Verify that the CDMO’s certified OEB ceiling covers your compound’s current classification
• Confirm the CDMO’s process for handling compounds without a formally established OEL

Section 2: Containment Infrastructure

• Dedicated HPAPI weighing and dispensing areas confirmed as in operation
• Appropriate containment technology verified for your compound’s OEB level (closed pharmaceutical isolator, Restricted Access Barrier System (RABS) or equivalent validated enclosure)
• Interlocked airlock systems present, qualified and in routine use
• Continuous airborne monitoring confirmed as operational during HPAPI manufacturing activities
• Containment Performance Testing data available, with methodology and date of testing confirmed
• Dedicated equipment confirmed, or validated shared equipment with health-based cleaning validation programme confirmed
• Single-use contact surface options available for liquid formulation steps where applicable

Section 3: HVAC Pressure Cascade

• Independent HVAC system for the HPAPI suite confirmed (no shared circuits with general manufacturing areas)
• Pressure differential specifications documented and appropriate to the compound’s OEB classification
• Continuous pressure differential monitoring with alarm systems at defined alert and action limits confirmed
• HEPA-filtered exhaust on all containment area extract air confirmed
• Air change rate specifications provided and verified against the room classification and OEB level
• Full HVAC qualification package available for technical and quality audit
• Contingency and deviation procedures for pressure excursions during manufacturing operations confirmed and documented

Section 4: Cleaning Validation

• ADE/PDE-based acceptance criteria confirmed as the governing methodology
• Qualified toxicologist responsible for ADE/PDE derivation identified
• Swab recovery studies conducted for the HPAPI compound classes handled at the site
• Analytical method Limit of Quantification confirmed to be below the MACO-derived acceptance criterion
• Cleaning validation methodology aligned to EU GMP Annex 15 and the EMA health-based exposure limits guideline confirmed
• Dedicated equipment programme or validated bracketing and matrixing strategy documented
• Single-use contact surface disposal strategy documented for liquid formulation steps

Section 5: Operator Safety Programme

• Industrial hygiene monitoring programme documented and actively maintained
• Air monitoring data from HPAPI operations available for prospective partner review
• Medical surveillance programme in place for all operators assigned to HPAPI containment areas
• HPAPI-specific training with documented competency verification records confirmed
• Gowning and de-gowning competency assessment process confirmed and records available
• PPE selection matrix based on OEB classification available for review
• Emergency response and exposure incident investigation procedures documented

Section 6: GMP Evidence and Regulatory History

• Site Master File includes HPAPI capability statement and confirmed OEB handling ceiling
• Regulatory inspection history reviewed; no critical or major observations relating to HPAPI containment controls
• Cleaning Validation Master Plan and compound-specific validation reports available for review
• ADE/PDE assessment documentation available for compound classes previously handled at the site
• HPAPI standard operating procedures index provided to confirm procedural framework scope
• HVAC qualification package available for technical audit
• Containment Performance Testing report including methodology, surrogate compound details and quantified results available

How Adragos Pharma Supports High-Potency Small Molecule Development

Adragos Pharma operates as a global Contract Development and Manufacturing Organisation with confirmed high-potency active pharmaceutical ingredient handling capabilities at two sites within its network: Jura in Switzerland and Athens in Greece.

Adragos Jura, Switzerland

The Jura site is Adragos Pharma’s primary location for drug development of small molecules, including HPAPI handling. With over 25 years of specialisation in aseptic fill-and-finish for liquid and lyophilised vials, the facility holds certification from the European Medicines Agency, the US Food and Drug Administration and Swissmedic. It supports Clinical Trial Material production through to small-to-medium scale commercial manufacturing, serving client profiles ranging from large pharmaceutical companies to biotech start-ups.

Capabilities directly relevant to high-potency small molecule development programmes include:

• Aseptic processing via RABS technology, supporting formulation through closed systems or open handling within a dedicated Restricted Access Barrier System environment, providing the contained aseptic conditions required for liquid HPAPI formulation
• Single-use contact surface strategy, which minimises cleaning validation scope and reduces the risk of cross-contamination between consecutive campaigns; a critical operational advantage for HPAPI development where health-based surface residue limits are inherently stringent
• Controlled drug handling integrated within a three-month turnaround from order to first batch
• No minimum batch size, with fill capacity of up to 74,000 vials per batch, supporting early-phase programmes where compound quantities are limited and overage cannot be justified
• 200 clinical batches produced per year and five successful commercial launches, supporting assessment of manufacturing reliability and regulatory readiness
• 12 client audits per year, providing a practical indicator of the facility’s transparent approach to quality oversight

The single-use strategy at Jura is of particular technical value to development teams working with potent compounds at clinical stage. By eliminating product carryover risk from liquid formulation contact surfaces, it removes a significant element of cleaning validation scope while reducing the cross-contamination risk that would otherwise require extensive analytical verification between campaigns.

Adragos Athens, Greece

The Athens site has been upgraded with HPAPI capabilities and handles both high-potency active pharmaceutical ingredients and controlled substances within its pharmaceutical development operations. Athens functions as Adragos Pharma’s centre of excellence for galenic development and supports the development of all dosage forms.

The team at Athens comprises more than 70 pharmaceutical research and development professionals and operates under EU-GMP and in compliance with US Food and Drug Administration regulations. The site has submitted more than 150 electronic Common Technical Document (eCTD) dossiers, with resulting product approvals across more than 20 countries. This regulatory dossier track record is directly relevant to development teams progressing HPAPI small molecule programmes through to market authorisation submission.

Integrated Small Molecule Development Pathway

The combination of HPAPI-capable galenic and formulation development at Athens with Jura’s aseptic HPAPI manufacturing and clinical supply capability creates an integrated development pathway for potent compound programmes. Development teams sourcing a single CDMO partner for formulation development, clinical trial material production and GMP-compliant batch manufacture can engage Adragos Pharma across multiple programme stages within a single contractual relationship and connected quality management system.

Frequently Asked Questions

Summary

Selecting a Contract Development and Manufacturing Organisation for high-potency active pharmaceutical ingredient small molecule formulation development requires a structured, evidence-led evaluation process from the first stage of vendor engagement. The containment checklist in this guide covers the six domains that define HPAPI CDMO competence: OEB classification, containment infrastructure, HVAC pressure cascade design, cleaning validation methodology, operator safety programme and GMP documentation.

Development teams that embed this checklist formally into their RFP process establish a factual and comparable basis for assessing CDMO responses, reduce the risk of selecting a facility whose containment capability does not match the compound’s hazard classification and create a documented baseline for ongoing technical oversight of the manufacturing partnership.

Adragos Pharma’s network, with confirmed HPAPI handling capability at Jura, Switzerland and Athens, Greece, supports the integrated formulation development and clinical supply requirements of potent compound programmes across multiple development stages. To discuss your HPAPI programme requirements and assess site suitability, contact the Adragos Pharma team at Adragos Pharma.