{"id":7723,"date":"2026-09-16T16:03:47","date_gmt":"2026-09-16T14:03:47","guid":{"rendered":"https:\/\/www.airplan-sa.com\/?p=7723"},"modified":"2026-09-16T16:03:47","modified_gmt":"2026-09-16T14:03:47","slug":"key-considerations-in-the-design-of-facilities-handling-highly-potent-active-pharmaceutical-ingredients-hpapis","status":"publish","type":"post","link":"https:\/\/www.airplan-sa.com\/en\/key-considerations-in-the-design-of-facilities-handling-highly-potent-active-pharmaceutical-ingredients-hpapis\/","title":{"rendered":"Key Considerations in the Design of Facilities Handling Highly Potent Active Pharmaceutical Ingredients (HPAPIs)"},"content":{"rendered":"<p class=\"isSelectedEnd\"><strong>Keywords:<\/strong> Containment; Engineering; Pharmaceutical Manufacturing; Risk Assessment<\/p>\n<p class=\"isSelectedEnd\"><strong>Key Takeaways:<\/strong><\/p>\n<ul data-spread=\"false\">\n<li>In the event of conflicting criteria, personnel safety must always take precedence over GMP requirements.<\/li>\n<li>The most appropriate containment solution for each facility should be based on a holistic assessment.<\/li>\n<\/ul>\n<p class=\"isSelectedEnd\"><strong>Specific Characteristics of Highly Potent Substances<\/strong><\/p>\n<p class=\"isSelectedEnd\">Highly potent substances are potent active pharmaceutical ingredients (HPAPIs) \u2014 <em>High-Potency Active Pharmaceutical Ingredients<\/em> \u2014 used in pharmaceutical products. The definition of an HPAPI varies depending on the literature consulted; however, there is a general consensus that APIs are considered potent when they fall into one of the following categories <span class=\"text-token-text-primary cursor-text rounded-sm\" data-placeholder-token=\"true\">[1]<\/span>:<\/p>\n<ul data-spread=\"false\">\n<li>They exhibit biological activity at approximately 150 \u03bcg\/kg body weight or less in humans.<\/li>\n<li>They require a therapeutic daily dose (DDD) of 10 mg or less.<\/li>\n<li>They have an occupational exposure limit (OEL) of 10 \u03bcg\/m\u00b3 of air or less, based on an 8-hour time-weighted average (TWA).<\/li>\n<li>They exhibit high selectivity (the ability to bind to specific receptors or inhibit specific enzymes) and\/or have the potential, at low doses, to cause cancer, mutations, developmental effects or reproductive toxicity.<\/li>\n<li>Any novel compound of unknown potency and\/or toxicity.<\/li>\n<\/ul>\n<p>The harmful toxicological effects on health <span class=\"text-token-text-primary cursor-text rounded-sm\" data-placeholder-token=\"true\">[2]<\/span> that HPAPIs may cause are related to:<\/p>\n<p><img fetchpriority=\"high\" decoding=\"async\" class=\"alignnone size-medium wp-image-7663\" src=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-1.-Pictogramas-de-riesgo-550x309.jpg\" alt=\"\" width=\"550\" height=\"309\" srcset=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-1.-Pictogramas-de-riesgo-550x309.jpg 550w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-1.-Pictogramas-de-riesgo-1024x576.jpg 1024w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-1.-Pictogramas-de-riesgo-768x432.jpg 768w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-1.-Pictogramas-de-riesgo-1536x864.jpg 1536w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-1.-Pictogramas-de-riesgo.jpg 1920w\" sizes=\"(max-width: 550px) 100vw, 550px\" \/><\/p>\n<p class=\"isSelectedEnd\"><em>Figure 1. Hazard pictograms<\/em><\/p>\n<p>The relationship between the specific potency and toxicity values of the substances establishes a risk gradient associated with each substance:<\/p>\n<p><img decoding=\"async\" class=\"alignnone size-medium wp-image-7667\" src=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-2.-Matriz-de-riesgo-asociado-a-una-sustancia-550x309.jpg\" alt=\"\" width=\"550\" height=\"309\" srcset=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-2.-Matriz-de-riesgo-asociado-a-una-sustancia-550x309.jpg 550w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-2.-Matriz-de-riesgo-asociado-a-una-sustancia-1024x576.jpg 1024w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-2.-Matriz-de-riesgo-asociado-a-una-sustancia-768x432.jpg 768w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-2.-Matriz-de-riesgo-asociado-a-una-sustancia-1536x864.jpg 1536w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-2.-Matriz-de-riesgo-asociado-a-una-sustancia.jpg 1920w\" sizes=\"(max-width: 550px) 100vw, 550px\" \/><\/p>\n<p><em>Figure 2. Risk matrix associated with a substance<\/em><\/p>\n<p>Adicionalmente, las sustancias pueden tener otros riesgos asociados a sus caracter\u00edsticas f\u00edsicas (explosividad, inflamaci\u00f3n, corrosividad\u2026) o al riesgo que suponen para el medio ambiente.<\/p>\n<p>Dada la gran diversidad de sustancias HPAPI, sus riesgos y efectos asociados, nos encontramos con la necesidad de categorizarlas, con el fin de poder asociarles un nivel de riesgo para el cual podamos definir unas adecuadas soluciones de contenci\u00f3n, puesto que el coste econ\u00f3mico y las dificultades en la operatividad de la planta son aspectos muy variables en funci\u00f3n de la soluci\u00f3n t\u00e9cnica definida.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Panorama global de la producci\u00f3n farmac\u00e9utica con HPAPIs<\/strong><\/p>\n<p>La importancia de las sustancias de alta potencia en el mercado farmac\u00e9utico se incrementa a\u00f1o tras a\u00f1o, donde la b\u00fasqueda de tratamientos cada vez m\u00e1s enfocados y personalizados, impulsa el desarrollo y uso de sustancias de alta potencia que requieren cantidades muy reducidas para obtener efectos terap\u00e9uticos.<\/p>\n<p>Actualmente, una cuarta parte de la manufactura farmac\u00e9utica se destina a producciones que contienen HPAPIs [3], tambi\u00e9n un cuarto de los nuevos medicamentos corresponde a formulaciones con HPAPIs [4] y el 60% de los medicamentos en desarrollo incorporan dichas sustancias [3].<\/p>\n<p><img decoding=\"async\" class=\"alignnone size-medium wp-image-7671\" src=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-3.-Peso-de-los-HPAPIs-en-la-produccion-global-550x309.jpg\" alt=\"\" width=\"550\" height=\"309\" srcset=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-3.-Peso-de-los-HPAPIs-en-la-produccion-global-550x309.jpg 550w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-3.-Peso-de-los-HPAPIs-en-la-produccion-global-1024x576.jpg 1024w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-3.-Peso-de-los-HPAPIs-en-la-produccion-global-768x432.jpg 768w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-3.-Peso-de-los-HPAPIs-en-la-produccion-global-1536x864.jpg 1536w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-3.-Peso-de-los-HPAPIs-en-la-produccion-global.jpg 1920w\" sizes=\"(max-width: 550px) 100vw, 550px\" \/><\/p>\n<p><em>Figure 3. Share of HPAPIs in global pharmaceutical production<\/em><\/p>\n<p>When current pharmaceutical manufacturing processes involving highly potent substances are broken down by category, it can be seen that most HPAPIs used are produced through chemical synthesis, although a significant proportion are of biotechnological origin <span class=\"text-token-text-primary cursor-text rounded-sm\" data-placeholder-token=\"true\">[5]<\/span>. Likewise, most treatments for which these HPAPI-containing formulations are intended are focused on oncology, followed by hormonal treatments <span class=\"text-token-text-primary cursor-text rounded-sm\" data-placeholder-token=\"true\">[4]<\/span>. HPAPI-containing medicines are predominantly available in solid dosage forms (capsules, tablets and granules), followed by liquid\/injectable formulations and, to a lesser extent, semi-solid or other formats <span class=\"text-token-text-primary cursor-text rounded-sm\" data-placeholder-token=\"true\">[6]<\/span>.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-medium wp-image-7675\" src=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-4.-Tipologias-de-HPAPIs-y-desglose-producciones-550x309.jpg\" alt=\"\" width=\"550\" height=\"309\" srcset=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-4.-Tipologias-de-HPAPIs-y-desglose-producciones-550x309.jpg 550w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-4.-Tipologias-de-HPAPIs-y-desglose-producciones-1024x576.jpg 1024w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-4.-Tipologias-de-HPAPIs-y-desglose-producciones-768x432.jpg 768w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-4.-Tipologias-de-HPAPIs-y-desglose-producciones-1536x864.jpg 1536w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-4.-Tipologias-de-HPAPIs-y-desglose-producciones.jpg 1920w\" sizes=\"(max-width: 550px) 100vw, 550px\" \/><\/p>\n<p><em>Figure 4. HPAPI types and production breakdown<\/em><\/p>\n<p>&nbsp;<\/p>\n<p class=\"isSelectedEnd\"><strong>Risk Assessment Methodology<\/strong><\/p>\n<p>The methodology for conducting a containment risk assessment can be approached in several different ways. One approach is based on the principles established by the ICH <span class=\"text-token-text-primary cursor-text rounded-sm\" data-placeholder-token=\"true\">[7]<\/span> for quality risk management in pharmaceutical products, which the ISPE (<em>International Society for Pharmaceutical Engineering<\/em>) subsequently adapted for its Risk-MaPP methodology <span class=\"text-token-text-primary cursor-text rounded-sm\" data-placeholder-token=\"true\">[8]<\/span> and its later containment guideline <span class=\"text-token-text-primary cursor-text rounded-sm\" data-placeholder-token=\"true\">[9]<\/span>:<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-medium wp-image-7679\" src=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-5.-Metodologia-de-analisis-de-riesgos-de-contencion-550x309.jpg\" alt=\"\" width=\"550\" height=\"309\" srcset=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-5.-Metodologia-de-analisis-de-riesgos-de-contencion-550x309.jpg 550w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-5.-Metodologia-de-analisis-de-riesgos-de-contencion-1024x576.jpg 1024w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-5.-Metodologia-de-analisis-de-riesgos-de-contencion-768x432.jpg 768w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-5.-Metodologia-de-analisis-de-riesgos-de-contencion-1536x864.jpg 1536w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-5.-Metodologia-de-analisis-de-riesgos-de-contencion.jpg 1920w\" sizes=\"(max-width: 550px) 100vw, 550px\" \/><\/p>\n<p class=\"isSelectedEnd\"><em>Figure 5. Containment risk assessment methodology<\/em><\/p>\n<p>The risk associated with an operation is linked to the hazard posed by the substance being used, as well as the way in which it is handled:<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-medium wp-image-7683\" src=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-6.-Funcion-del-riesgo-550x309.jpg\" alt=\"\" width=\"550\" height=\"309\" srcset=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-6.-Funcion-del-riesgo-550x309.jpg 550w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-6.-Funcion-del-riesgo-1024x576.jpg 1024w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-6.-Funcion-del-riesgo-768x432.jpg 768w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-6.-Funcion-del-riesgo-1536x864.jpg 1536w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-6.-Funcion-del-riesgo.jpg 1920w\" sizes=\"(max-width: 550px) 100vw, 550px\" \/><\/p>\n<p class=\"isSelectedEnd\"><em>Figure 6. Risk Function<\/em><\/p>\n<p class=\"isSelectedEnd\">To control a risk, the first step is to consider whether the substance causing the hazard can be substituted or eliminated. If this is not possible, technical and operational measures should be implemented to reduce exposure to the hazard, with the aim of reducing the risk to acceptable levels.<\/p>\n<p>Therefore, the first step is to identify both the significant characteristics of the hazardous substances and the details of the process being assessed. The main variables to be collected during the risk identification phase are the physical characteristics of the substances and their exposure limit values, as well as the quantity of substance involved and the significant stages of the process, including their associated durations and the technology used in the operation:<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-medium wp-image-7687\" src=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-7.-Conceptos-principales-asociados-al-riesgo-550x309.jpg\" alt=\"\" width=\"550\" height=\"309\" srcset=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-7.-Conceptos-principales-asociados-al-riesgo-550x309.jpg 550w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-7.-Conceptos-principales-asociados-al-riesgo-1024x576.jpg 1024w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-7.-Conceptos-principales-asociados-al-riesgo-768x432.jpg 768w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-7.-Conceptos-principales-asociados-al-riesgo-1536x864.jpg 1536w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-7.-Conceptos-principales-asociados-al-riesgo.jpg 1920w\" sizes=\"(max-width: 550px) 100vw, 550px\" \/><\/p>\n<p><em>Ilustraci\u00f3n 7. Conceptos principales asociados al riesgo<\/em><\/p>\n<p>Existen varios sistemas para la evaluaci\u00f3n del riesgo de los productos y procesos a manejar, la mayor\u00eda de los cuales se basan en llegar a una categorizaci\u00f3n donde se establezcan medidas de contenci\u00f3n asociadas. Uno de los m\u00e9todos m\u00e1s extendidos para la categorizaci\u00f3n del riesgo de los productos son las bandas de exposici\u00f3n OEB (<em>Operational Exposure Bands<\/em>) [9] [10]:<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-medium wp-image-7691\" src=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-8.-Bandas-de-exposicion-OEB-550x309.jpg\" alt=\"\" width=\"550\" height=\"309\" srcset=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-8.-Bandas-de-exposicion-OEB-550x309.jpg 550w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-8.-Bandas-de-exposicion-OEB-1024x576.jpg 1024w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-8.-Bandas-de-exposicion-OEB-768x432.jpg 768w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-8.-Bandas-de-exposicion-OEB-1536x864.jpg 1536w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-8.-Bandas-de-exposicion-OEB.jpg 1920w\" sizes=\"(max-width: 550px) 100vw, 550px\" \/><\/p>\n<p class=\"isSelectedEnd\"><em>Figure 8. OEB Exposure Bands<\/em><\/p>\n<p>Following the methodology established by ISPE <span class=\"text-token-text-primary cursor-text rounded-sm\" data-placeholder-token=\"true\">[9]<\/span>, once the characteristics of the substances are known, they are classified according to their Spread Potential (SP). This value is then combined with the quantity and exposure time to determine the Exposure Potential (EP) involved. The EP is subsequently compared against the assigned Occupational Exposure Band (OEB) in a risk matrix, with the aim of determining the Primary Containment Strategy (PCS). This strategy defines the first level of containment required to protect the operator from the product.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-medium wp-image-7695\" src=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-9.-Metodologia-de-evaluacion-del-riesgo-relativo-a-la-contencion-primaria-550x309.jpg\" alt=\"\" width=\"550\" height=\"309\" srcset=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-9.-Metodologia-de-evaluacion-del-riesgo-relativo-a-la-contencion-primaria-550x309.jpg 550w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-9.-Metodologia-de-evaluacion-del-riesgo-relativo-a-la-contencion-primaria-1024x576.jpg 1024w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-9.-Metodologia-de-evaluacion-del-riesgo-relativo-a-la-contencion-primaria-768x432.jpg 768w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-9.-Metodologia-de-evaluacion-del-riesgo-relativo-a-la-contencion-primaria-1536x864.jpg 1536w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-9.-Metodologia-de-evaluacion-del-riesgo-relativo-a-la-contencion-primaria.jpg 1920w\" sizes=\"(max-width: 550px) 100vw, 550px\" \/><\/p>\n<p class=\"isSelectedEnd\"><em>Figure 9. Methodology for Assessing Primary Containment Risk<\/em><\/p>\n<p>Similarly, the Migration Potential (MP) will be determined by considering the likelihood of residual material from the substance dispersing after cleaning and decontamination, together with the potential quantity that could be dispersed. This value is then assessed in another risk matrix against the assigned Occupational Exposure Band (OEB) to determine the Secondary Containment Strategy (SCS). This strategy defines the second level of containment required to protect the facility from the product.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-medium wp-image-7699\" src=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-10.-Metodologia-de-evaluacion-del-riesgo-relativo-a-la-contencion-secundaria-550x309.jpg\" alt=\"\" width=\"550\" height=\"309\" srcset=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-10.-Metodologia-de-evaluacion-del-riesgo-relativo-a-la-contencion-secundaria-550x309.jpg 550w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-10.-Metodologia-de-evaluacion-del-riesgo-relativo-a-la-contencion-secundaria-1024x576.jpg 1024w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-10.-Metodologia-de-evaluacion-del-riesgo-relativo-a-la-contencion-secundaria-768x432.jpg 768w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-10.-Metodologia-de-evaluacion-del-riesgo-relativo-a-la-contencion-secundaria-1536x864.jpg 1536w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-10.-Metodologia-de-evaluacion-del-riesgo-relativo-a-la-contencion-secundaria.jpg 1920w\" sizes=\"(max-width: 550px) 100vw, 550px\" \/><\/p>\n<p class=\"isSelectedEnd\"><em>Figure 10. Methodology for Assessing Secondary Containment Risk<\/em><\/p>\n<p>The boundary of the secondary containment system defines the perimeter of the containment area.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-medium wp-image-7703\" src=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-11.-Conceptos-de-contencion-primaria-y-secundaria-550x309.jpg\" alt=\"\" width=\"550\" height=\"309\" srcset=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-11.-Conceptos-de-contencion-primaria-y-secundaria-550x309.jpg 550w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-11.-Conceptos-de-contencion-primaria-y-secundaria-1024x576.jpg 1024w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-11.-Conceptos-de-contencion-primaria-y-secundaria-768x432.jpg 768w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-11.-Conceptos-de-contencion-primaria-y-secundaria-1536x864.jpg 1536w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-11.-Conceptos-de-contencion-primaria-y-secundaria.jpg 1920w\" sizes=\"(max-width: 550px) 100vw, 550px\" \/><\/p>\n<p class=\"isSelectedEnd\"><em>Figure 11. Primary and Secondary Containment Concepts<\/em><\/p>\n<p class=\"isSelectedEnd\">The strategy for directly protecting operators within the containment area through the use of personal protective equipment (PPE) will be determined once the quantity of hazardous substance present in the room has been calculated, taking into account the leakage rate of the primary containment equipment, the dilution capacity of the room\u2019s HVAC (Heating, Ventilation and Air Conditioning) system, and the operator\u2019s exposure over the defined period. The objective is to ensure that the applicable exposure limits are not exceeded, including NOEL values, daily\/shift exposure limits (OEL, TWA, PDE, HBEL, etc.), and short-term exposure limits (STEL).<\/p>\n<p>&nbsp;<\/p>\n<p class=\"isSelectedEnd\"><strong>Design Process for a High-Containment Facility<\/strong><\/p>\n<p class=\"isSelectedEnd\">Once the risks present in the facility have been identified, assessed and characterised, the most appropriate solutions for the facility must be conceptualised. A layout will be defined that meets both GMP (<em>Good Manufacturing Practices<\/em>) and HSE (<em>Health, Safety and Environment<\/em>) requirements, taking into account that, in the event of conflicting criteria, personnel safety requirements must always take precedence over GMP requirements.<\/p>\n<p>The primary objective of GMP criteria for pharmaceutical manufacturing areas is to prevent the environment from contaminating the product. Once the containment area has been defined, the first step is to establish the most appropriate pressure and airlock criteria to also ensure that nothing can escape from the containment area. For this reason, negative pressure is maintained in the highest-risk areas, with pressure cascades, bubbles, pressure sinks, or combinations thereof established in adjacent airlocks, depending on the planned gowning procedures and the required criticality of the containment strategy.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-medium wp-image-7707\" src=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-12.-Ejemplo-de-definicion-de-esclusas-de-personal-de-un-area-de-contencion-1-550x309.jpg\" alt=\"\" width=\"550\" height=\"309\" srcset=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-12.-Ejemplo-de-definicion-de-esclusas-de-personal-de-un-area-de-contencion-1-550x309.jpg 550w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-12.-Ejemplo-de-definicion-de-esclusas-de-personal-de-un-area-de-contencion-1-1024x576.jpg 1024w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-12.-Ejemplo-de-definicion-de-esclusas-de-personal-de-un-area-de-contencion-1-768x432.jpg 768w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-12.-Ejemplo-de-definicion-de-esclusas-de-personal-de-un-area-de-contencion-1-1536x864.jpg 1536w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-12.-Ejemplo-de-definicion-de-esclusas-de-personal-de-un-area-de-contencion-1.jpg 1920w\" sizes=\"(max-width: 550px) 100vw, 550px\" \/> <img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-medium wp-image-7711\" src=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-12.-Ejemplo-de-definicion-de-esclusas-de-personal-de-un-area-de-contencion-2-550x309.jpg\" alt=\"\" width=\"550\" height=\"309\" srcset=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-12.-Ejemplo-de-definicion-de-esclusas-de-personal-de-un-area-de-contencion-2-550x309.jpg 550w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-12.-Ejemplo-de-definicion-de-esclusas-de-personal-de-un-area-de-contencion-2-1024x576.jpg 1024w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-12.-Ejemplo-de-definicion-de-esclusas-de-personal-de-un-area-de-contencion-2-768x432.jpg 768w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-12.-Ejemplo-de-definicion-de-esclusas-de-personal-de-un-area-de-contencion-2-1536x864.jpg 1536w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Ilustracion-12.-Ejemplo-de-definicion-de-esclusas-de-personal-de-un-area-de-contencion-2.jpg 1920w\" sizes=\"(max-width: 550px) 100vw, 550px\" \/><\/p>\n<p class=\"isSelectedEnd\"><em>Figure 12. Example of personnel airlock layout for a containment area<\/em><\/p>\n<p>With regard to room classifications, all applicable GMP requirements will be complied with, depending on the type of facility and manufacturing process under consideration. Annexes 1 and 2 of the European GMP guidelines for the manufacture of sterile medicinal products and biological medicinal products, respectively <span class=\"text-token-text-primary cursor-text rounded-sm\" data-placeholder-token=\"true\">[11]<\/span> <span class=\"text-token-text-primary cursor-text rounded-sm\" data-placeholder-token=\"true\">[12]<\/span>, are the main reference documents.<\/p>\n<p>&nbsp;<\/p>\n<p class=\"isSelectedEnd\"><strong>Technologies and Equipment Associated with Containment Strategies<\/strong><\/p>\n<p>Once the primary (PCS) and secondary (SCS) containment strategies identified through the risk assessment have been established, the most appropriate solutions must be defined to ensure the required level of containment for the processes to be carried out. Some of the most commonly used technologies are described below:<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-medium wp-image-7715\" src=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Captura-de-pantalla-2026-09-16-153718-376x400.png\" alt=\"\" width=\"376\" height=\"400\" srcset=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Captura-de-pantalla-2026-09-16-153718-376x400.png 376w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Captura-de-pantalla-2026-09-16-153718.png 546w\" sizes=\"(max-width: 376px) 100vw, 376px\" \/><\/p>\n<p>Figure 13. Primary Containment Strategies and Associated Equipment<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-medium wp-image-7719\" src=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/22-388x400.png\" alt=\"\" width=\"388\" height=\"400\" srcset=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/22-388x400.png 388w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/22.png 582w\" sizes=\"(max-width: 388px) 100vw, 388px\" \/><\/p>\n<p data-pm-slice=\"1 1 []\"><em>Figure 14 \u2013 Secondary Containment Strategies and Associated Operational Considerations<\/em><\/p>\n<p>The selection of the most appropriate containment solution for each facility should be based on a holistic assessment that considers all the factors involved and the specific characteristics of the process, such as the particular requirements of multiproduct facilities, the desired production intensity, the available budget, the impact on personnel availability and operational flexibility, the level of redundancy defined for critical utilities, etc.<\/p>\n<p>All these factors will influence and determine the selection of certain solutions over others. This selection and elimination process should be carried out by a multidisciplinary working group together with the Client, in order to ensure that the facility\u2019s containment design is fully aligned with the expected operational requirements and capabilities.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Conclusions<\/strong><\/p>\n<p>The design of pharmaceutical manufacturing facilities handling products that pose a certain level of risk and require containment measures is becoming increasingly standardised, largely due to the growing use of HPAPIs in pharmaceutical formulations.<\/p>\n<p>Only through a systematic risk assessment during the engineering phase, based on reliable data on the substances and formulations involved and tailored to the parameters of the intended manufacturing process, can the containment area and its appropriate treatment be properly determined.<\/p>\n<p>The main objective is to adopt a global approach that takes into account all the operational particularities of the facility, enabling the successful completion of the design process for a high-containment facility with appropriate technical and operational solutions that ensure both the safety of personnel involved in production and the quality of the pharmaceutical products manufactured.<\/p>\n<p>The success of a facility design incorporating containment solutions lies in identifying the precise solution that meets the needs of the process, addressing the safety requirements of this type of facility while also ensuring the economic and operational sustainability of the project.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Lista de abreviaturas<\/strong><\/p>\n<p>(indicadas en el orden de aparici\u00f3n)<\/p>\n<p>HPAPI: Ingrediente farmac\u00e9utico activo de alta potencia (<em>High-Potency Active Pharmaceutical Ingredient<\/em>)<\/p>\n<p>API: Ingrediente farmac\u00e9utico activo (<em>Active Pharmaceutical Ingredient<\/em>)<\/p>\n<p>DDD: Dosis diaria definida (<em>Defined Daily Dose<\/em>)<\/p>\n<p>OEL: L\u00edmite de exposici\u00f3n ocupacional (<em>Occupational Exposure Limit<\/em>)<\/p>\n<p>TWA: Promedio ponderado en el tiempo (<em>Time-Weighted Average<\/em>)<\/p>\n<p>ICH: <em>International Council for Harmonisation of technical requirements for pharmaceuticals for human use<\/em><\/p>\n<p>ISPE: <em>International Society for Pharmaceutical Engineering<\/em><\/p>\n<p>Risk-MaPP: <em>Risk-based Manufacture of Pharmaceutical Products<\/em><\/p>\n<p>STEL: L\u00edmite de exposici\u00f3n a corto plazo (<em>Short-Term Exposure L\u00edmit<\/em>)<\/p>\n<p>NOEL: Nivel sin efecto observable (<em>No Observed Effect Level<\/em>)<\/p>\n<p>PDE: Exposici\u00f3n diaria permitida (<em>Permitted Daily Exposure<\/em>)<\/p>\n<p>HBEL: L\u00edmite de exposici\u00f3n basado en la salud (<em>Health-Based Exposure L\u00edmit<\/em>)<\/p>\n<p>OEB: Banda de exposici\u00f3n operacional (Operational exposure band)<\/p>\n<p>SP: Potencial de dispersi\u00f3n (<em>Spread potential<\/em>)<\/p>\n<p>EP: Potencial de exposici\u00f3n (<em>Exposure potential<\/em>)<\/p>\n<p>PCS: Estrategia de contenci\u00f3n primaria (<em>Primary containment strategy<\/em>)<\/p>\n<p>MP: Potencial de migraci\u00f3n MP (<em>Migration potential<\/em>)<\/p>\n<p>SCS: Estrategia de contenci\u00f3n secundaria (<em>Secondary containment strategy<\/em>)<\/p>\n<p>PPE: Equipos de protecci\u00f3n personal (<em>Personal protective equipment<\/em>)<\/p>\n<p>HVAC: Calefacci\u00f3n, ventilaci\u00f3n y aire acondicionado (<em>Heating, Ventilating and Air Conditioning<\/em>)<\/p>\n<p>GMP: Buenas pr\u00e1cticas de fabricaci\u00f3n (<em>Good Manufacturing Practices<\/em>)<\/p>\n<p>HSE: Seguridad, salud y medioambiente (<em>Health, Safety and Environment<\/em>)<\/p>\n<p>EMA: <em>European Medicines Agency<\/em><\/p>\n<p>LEV: Extracci\u00f3n localizada (<em>Local Exhaust Ventilation<\/em>)<\/p>\n<p>HEPA: Filtro de aire de alta eficiencia (<em>High Efficiency Particulate Air<\/em>)<\/p>\n<p>RABS: Sistemas de barrera con acceso restringido (<em>Restricted Access Barrier Systems<\/em>)<\/p>\n<p><strong>\u00a0<\/strong><\/p>\n<p><strong>Ilustaciones <\/strong><\/p>\n<p>Ilustraci\u00f3n 1. Pictogramas de riesgo<\/p>\n<p>Ilustraci\u00f3n 2. Matriz de riesgo asociado a una sustancia<\/p>\n<p>Ilustraci\u00f3n 3. Peso de los HPAPIs en la producci\u00f3n global<\/p>\n<p>Ilustraci\u00f3n 4. Tipolog\u00edas de HPAPIs y desglose producciones<\/p>\n<p>Ilustraci\u00f3n 5. Metodolog\u00eda de an\u00e1lisis de riesgos de contenci\u00f3n<\/p>\n<p>Ilustraci\u00f3n 6. Funci\u00f3n del riesgo<\/p>\n<p>Ilustraci\u00f3n 7. Conceptos principales asociados al riesgo<\/p>\n<p>Ilustraci\u00f3n 8. Bandas de exposici\u00f3n OEB<\/p>\n<p>Ilustraci\u00f3n 9. Metodolog\u00eda de evaluaci\u00f3n del riesgo relativo a la contenci\u00f3n primaria<\/p>\n<p>Ilustraci\u00f3n 10. Metodolog\u00eda de evaluaci\u00f3n del riesgo relativo a la contenci\u00f3n secundaria<\/p>\n<p>Ilustraci\u00f3n 11. Conceptos de contenci\u00f3n primaria y secundaria<\/p>\n<p>Ilustraci\u00f3n 12. Ejemplo de definici\u00f3n de esclusas de personal de un \u00e1rea de contenci\u00f3n<\/p>\n<p>Ilustraci\u00f3n 13. Estrategias de contenci\u00f3n primaria y equipamiento asociado<\/p>\n<p>Ilustraci\u00f3n 14 \u2013 Estrategias de contenci\u00f3n secundaria y asuntos operativos asociados<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Bibliograf\u00eda<\/strong><\/p>\n<ul>\n<li>Bormett, D., 2008. \u201cHigh-potency APIs: Containment and handling issues\u201d. Pharmaceutical Technology Vol 2008 Supplement, Issue 4.<\/li>\n<li>WHO, 2025, \u201cGlobally Harmonized System of classification and labelling of chemicals (GHS)\u201d, Rev. 11<\/li>\n<li>Website European Pharmaceutical Manufacturer &#8211; Understanding the HPAPI sector<\/li>\n<li>McCleary, K., 2019 \u201cManufacturing of highly potent APIs with best-practice safety and containment control procedures\u201d, American Pharmaceutical Review 2019 (September\/October):144<\/li>\n<li>Website Grand View Research &#8211; High potency active pharmaceutical ingredients market (2026 &#8211; 2033)<\/li>\n<li>Website Roots analysis &#8211; Cytotoxic drugs and HPAPI manufacturing market<\/li>\n<li>ICH, 2025, \u201cGuideline &#8211; Q9 (R1) Quality risk management\u201d, Step 5 &#8211; Revision 2.<\/li>\n<li>ISPE, 2017, \u201cBaseline Guide Vol 7: Risk-based Manufacture of Pharma Products (Risk-MaPP)\u201d, 2nd Ed.<\/li>\n<li>ISPE, 2022, \u201cGood Practice Guide: Containment for potent compounds\u201d.<\/li>\n<li>Lentz, TJ et al., 2019, \u201cNIOSH Technical report &#8211; Occupational exposure banding process for chemical risk management\u201d. DHHS (NIOSH) Publication No. 2019-132<\/li>\n<li>EMA, 2022, \u201cEudraLex vol. 4 &#8211; Annex 1 Manufacture of sterile medicinal products\u201d.<\/li>\n<li>EMA, 2022, \u201cEudraLex vol. 4 &#8211; Annex 2 Manufacture of biological active substances and medicinal products for human use\u201d.<\/li>\n<\/ul>\n","protected":false},"excerpt":{"rendered":"<p>Keywords: Containment; Engineering; Pharmaceutical Manufacturing; Risk Assessment Key Takeaways: In the event of conflicting criteria, personnel safety must always take precedence over GMP requirements. The most appropriate containment solution for each facility should be based on a holistic assessment. Specific Characteristics of Highly Potent Substances Highly potent substances are potent active pharmaceutical ingredients (HPAPIs) \u2014 [&hellip;]<\/p>\n","protected":false},"author":15,"featured_media":7659,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[56],"class_list":["post-7723","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-uncategorized"],"acf":[],"_links":{"self":[{"href":"https:\/\/www.airplan-sa.com\/en\/wp-json\/wp\/v2\/posts\/7723"}],"collection":[{"href":"https:\/\/www.airplan-sa.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.airplan-sa.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.airplan-sa.com\/en\/wp-json\/wp\/v2\/users\/15"}],"replies":[{"embeddable":true,"href":"https:\/\/www.airplan-sa.com\/en\/wp-json\/wp\/v2\/comments?post=7723"}],"version-history":[{"count":1,"href":"https:\/\/www.airplan-sa.com\/en\/wp-json\/wp\/v2\/posts\/7723\/revisions"}],"predecessor-version":[{"id":7724,"href":"https:\/\/www.airplan-sa.com\/en\/wp-json\/wp\/v2\/posts\/7723\/revisions\/7724"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.airplan-sa.com\/en\/wp-json\/wp\/v2\/media\/7659"}],"wp:attachment":[{"href":"https:\/\/www.airplan-sa.com\/en\/wp-json\/wp\/v2\/media?parent=7723"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.airplan-sa.com\/en\/wp-json\/wp\/v2\/categories?post=7723"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}