{"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":"2026-10-02T12:25:38","modified_gmt":"2026-10-02T10:25:38","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\"><em><strong>Keywords:<\/strong> Containment; Engineering; Pharmaceutical Manufacturing; Risk Assessment<\/em><\/p>\n<p class=\"isSelectedEnd\"><em><strong>Key Takeaways:<\/strong><\/em><\/p>\n<ul data-spread=\"false\">\n<li><em>In the event of conflicting criteria, personnel safety must always take precedence over GMP requirements.<\/em><\/li>\n<li><em>The most appropriate containment solution for each facility should be based on a holistic assessment.<br \/>\n<\/em><\/li>\n<\/ul>\n<h2 class=\"isSelectedEnd\"><strong><br \/>\nSpecific Characteristics of Highly Potent Substances<\/strong><\/h2>\n<p class=\"isSelectedEnd\">Highly potent substances, or HPAPIs, are pharmaceutical ingredients that exert a biological or therapeutic effect at very low doses and may cause significant adverse effects. The definition of an HPAPI varies depending on the literature consulted. WHO <span class=\"text-token-text-primary cursor-text rounded-sm\" data-placeholder-token=\"true\">[1]<\/span> and ISPE <span class=\"text-token-text-primary cursor-text rounded-sm\" data-placeholder-token=\"true\">[2]<\/span> define potent APIs as substances that pose a substantial risk of harm to human health, other organisms, or the environment, even at very low exposure levels.<\/p>\n<p>Some of the conditions that define an HPAPI based on the substantial risk it poses include the following <span class=\"text-token-text-primary cursor-text rounded-sm\" data-placeholder-token=\"true\">[3]<\/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><em><strong><img fetchpriority=\"high\" decoding=\"async\" class=\"alignnone size-medium wp-image-7749\" src=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/2-550x309.jpg\" alt=\"\" width=\"550\" height=\"309\" srcset=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/2-550x309.jpg 550w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/2-1024x576.jpg 1024w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/2-768x432.jpg 768w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/2-1536x864.jpg 1536w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/2.jpg 1920w\" sizes=\"(max-width: 550px) 100vw, 550px\" \/><\/strong><\/em><\/p>\n<p class=\"isSelectedEnd\"><em>Figure 1. Hazard pictograms<br \/>\nSource: Prepared by the authors<br \/>\n<\/em><\/p>\n<p>The relationship between the specific potency and toxicity values of the substances [4] establishes a risk gradient associated with each substance:<\/p>\n<p><img decoding=\"async\" class=\"alignnone size-medium wp-image-7753\" src=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/4-550x309.jpg\" alt=\"\" width=\"550\" height=\"309\" srcset=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/4-550x309.jpg 550w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/4-1024x576.jpg 1024w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/4-768x432.jpg 768w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/4-1536x864.jpg 1536w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/4.jpg 1920w\" sizes=\"(max-width: 550px) 100vw, 550px\" \/><\/p>\n<p><em>Figure 2. Risk matrix associated with a substance<br \/>\nSource: Prepared by the authors<br \/>\n<\/em><\/p>\n<p>&nbsp;<\/p>\n<p class=\"isSelectedEnd\">Additionally, substances may present other hazards associated with their physical properties (explosivity, flammability, corrosivity, etc.) or with the risks they pose to the environment.<\/p>\n<p class=\"isSelectedEnd\">Given the wide variety of HPAPIs and their associated hazards and effects, these substances need to be categorized in order to assign an appropriate risk level and define suitable containment solutions. This is particularly important because both the economic impact and the operational complexity of the plant can vary significantly depending on the technical solution selected.<\/p>\n<p class=\"isSelectedEnd\"><strong>Global Overview of Pharmaceutical Manufacturing with HPAPIs<\/strong><\/p>\n<p class=\"isSelectedEnd\">The importance of highly potent substances in the pharmaceutical market continues to grow year after year. The increasing focus on more targeted and personalized treatments is driving the development and use of highly potent substances that require only very small quantities to achieve therapeutic effects.<\/p>\n<p>Currently, approximately one quarter of pharmaceutical manufacturing involves products containing HPAPIs <span class=\"text-token-text-primary cursor-text rounded-sm\" data-placeholder-token=\"true\">[5]<\/span>. Likewise, around one quarter of new drugs are HPAPI-based formulations <span class=\"text-token-text-primary cursor-text rounded-sm\" data-placeholder-token=\"true\">[6]<\/span>, while 60% of drugs currently in development incorporate these substances <span class=\"text-token-text-primary cursor-text rounded-sm\" data-placeholder-token=\"true\">[5]<\/span>.<\/p>\n<p><img decoding=\"async\" class=\"alignnone size-medium wp-image-7757\" src=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/7-550x309.jpg\" alt=\"\" width=\"550\" height=\"309\" srcset=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/7-550x309.jpg 550w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/7-1024x576.jpg 1024w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/7-768x432.jpg 768w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/7-1536x864.jpg 1536w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/7.jpg 1920w\" sizes=\"(max-width: 550px) 100vw, 550px\" \/><\/p>\n<p><em>Figure 3. Share of HPAPIs in global pharmaceutical production<br \/>\nSource: Prepared by the authors based on data from [5] and [6]<br \/>\n<\/em><\/p>\n<p>&nbsp;<\/p>\n<p>When looking at current pharmaceutical manufacturing involving highly potent substances, most HPAPIs 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\">[7]<\/span>. Most HPAPI-containing formulations are intended for oncology treatments, followed by hormonal therapies <span class=\"text-token-text-primary cursor-text rounded-sm\" data-placeholder-token=\"true\">[6]<\/span>. In terms of dosage forms, HPAPI-containing medicines are predominantly solids (capsules, tablets, and granules), followed by liquids\/injectables, with semisolids and other dosage forms representing only a small proportion <span class=\"text-token-text-primary cursor-text rounded-sm\" data-placeholder-token=\"true\">[8]<\/span>.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-medium wp-image-7761\" src=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/9-550x309.jpg\" alt=\"\" width=\"550\" height=\"309\" srcset=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/9-550x309.jpg 550w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/9-1024x576.jpg 1024w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/9-768x432.jpg 768w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/9-1536x864.jpg 1536w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/9.jpg 1920w\" sizes=\"(max-width: 550px) 100vw, 550px\" \/><\/p>\n<p><em>Figure 4. HPAPI types and production breakdown<br \/>\nSource: Prepared by the authors based on data from [6], [7] and [8]<br \/>\n<\/em><\/p>\n<p>&nbsp;<\/p>\n<p class=\"isSelectedEnd\"><strong>Risk Assessment Methodology<\/strong><\/p>\n<p>Containment risk assessment can be approached using a variety of methodologies. One approach follows principles similar to those established by ICH <span class=\"text-token-text-primary cursor-text rounded-sm\" data-placeholder-token=\"true\">[9]<\/span> for quality risk management in pharmaceutical products. These principles were subsequently adapted by ISPE for its <em>Risk-MaPP methodology<\/em> <span class=\"text-token-text-primary cursor-text rounded-sm\" data-placeholder-token=\"true\">[10]<\/span> and later incorporated into its containment guidance <span class=\"text-token-text-primary cursor-text rounded-sm\" data-placeholder-token=\"true\">[2]<\/span>:<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-medium wp-image-7765\" src=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/11-550x309.jpg\" alt=\"\" width=\"550\" height=\"309\" srcset=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/11-550x309.jpg 550w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/11-1024x576.jpg 1024w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/11-768x432.jpg 768w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/11-1536x864.jpg 1536w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/11.jpg 1920w\" sizes=\"(max-width: 550px) 100vw, 550px\" \/><\/p>\n<p class=\"isSelectedEnd\"><em>Figure 5. Containment risk assessment methodology<br \/>\n<\/em><em>Source: ISPE [2]<\/em><\/p>\n<p class=\"isSelectedEnd\"><em>\u00a0<\/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-7769\" src=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/13-550x309.jpg\" alt=\"\" width=\"550\" height=\"309\" srcset=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/13-550x309.jpg 550w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/13-1024x576.jpg 1024w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/13-768x432.jpg 768w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/13-1536x864.jpg 1536w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/13.jpg 1920w\" sizes=\"(max-width: 550px) 100vw, 550px\" \/><\/p>\n<p class=\"isSelectedEnd\"><em>Figure 6. Risk Function<br \/>\nSource: ISPE [2]<\/em><\/p>\n<p>&nbsp;<\/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-7773\" src=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/15-550x309.jpg\" alt=\"\" width=\"550\" height=\"309\" srcset=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/15-550x309.jpg 550w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/15-1024x576.jpg 1024w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/15-768x432.jpg 768w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/15-1536x864.jpg 1536w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/15.jpg 1920w\" sizes=\"(max-width: 550px) 100vw, 550px\" \/><\/p>\n<p><em>Figure 7.\u00a0<\/em>Key Concepts Associated with Risk<br \/>\n<em>Source: Prepared by the authors<\/em><\/p>\n<p>Several systems are available for assessing the risks associated with the products and processes involved. Most of these systems are based on establishing categories linked to specific containment measures. One of the most widely used methods for categorizing product risk is the OEB (<em>Occupational Exposure Band<\/em>) system [2] [11]:<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-medium wp-image-7777\" src=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/17-550x309.jpg\" alt=\"\" width=\"550\" height=\"309\" srcset=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/17-550x309.jpg 550w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/17-1024x576.jpg 1024w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/17-768x432.jpg 768w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/17-1536x864.jpg 1536w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/17.jpg 1920w\" sizes=\"(max-width: 550px) 100vw, 550px\" \/><\/p>\n<p class=\"isSelectedEnd\"><em>Figure 8. OEB Exposure Bands<br \/>\nSource: ISPE [2]<br \/>\n<\/em><\/p>\n<p>&nbsp;<\/p>\n<p>Following the methodology established by ISPE <span class=\"text-token-text-primary cursor-text rounded-sm\" data-placeholder-token=\"true\">[2]<\/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-7781\" src=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/19-550x309.jpg\" alt=\"\" width=\"550\" height=\"309\" srcset=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/19-550x309.jpg 550w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/19-1024x576.jpg 1024w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/19-768x432.jpg 768w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/19-1536x864.jpg 1536w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/19.jpg 1920w\" sizes=\"(max-width: 550px) 100vw, 550px\" \/><\/p>\n<p class=\"isSelectedEnd\"><em>Figure 9. Methodology for Assessing Primary Containment Risk<br \/>\nSource: ISPE [2]<\/em><\/p>\n<p>&nbsp;<\/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-7785\" src=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/21-550x309.jpg\" alt=\"\" width=\"550\" height=\"309\" srcset=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/21-550x309.jpg 550w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/21-1024x576.jpg 1024w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/21-768x432.jpg 768w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/21-1536x864.jpg 1536w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/21.jpg 1920w\" sizes=\"(max-width: 550px) 100vw, 550px\" \/><\/p>\n<p class=\"isSelectedEnd\"><em>Figure 10. Methodology for Assessing Secondary Containment Risk<br \/>\nSource: ISPE [2]<\/em><\/p>\n<p>&nbsp;<\/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-7789\" src=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/23-550x309.jpg\" alt=\"\" width=\"550\" height=\"309\" srcset=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/23-550x309.jpg 550w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/23-1024x576.jpg 1024w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/23-768x432.jpg 768w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/23-1536x864.jpg 1536w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/23.jpg 1920w\" sizes=\"(max-width: 550px) 100vw, 550px\" \/><\/p>\n<p class=\"isSelectedEnd\"><em>Figure 11. Primary and Secondary Containment Concepts<br \/>\nSource: Prepared by the authors<br \/>\n<\/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 plant have been identified, assessed, and characterized, the most appropriate solutions for the facility must be defined. The layout should comply both with GMP criteria for pharmaceutical manufacturing areas, aimed at preventing contamination of the product by the surrounding environment, and with occupational health and safety and environmental protection requirements. In the event of a conflict, HSE criteria should always take precedence over GMP requirements, while maintaining the protection of the general population as the highest priority.<\/p>\n<p>Once the containment area has been defined, the first step is to establish the most appropriate pressure regime and airlock configuration to ensure that contaminants cannot escape from the containment area. Negative pressure is therefore maintained in the highest-risk areas, with pressure cascades, bubbles, sinks, or combinations of these established in adjacent airlocks, depending on the required gowning steps and the criticality of the containment strategy to be achieved.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-medium wp-image-7793\" src=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/25-550x309.jpg\" alt=\"\" width=\"550\" height=\"309\" srcset=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/25-550x309.jpg 550w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/25-1024x576.jpg 1024w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/25-768x432.jpg 768w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/25-1536x864.jpg 1536w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/25.jpg 1920w\" sizes=\"(max-width: 550px) 100vw, 550px\" \/> <img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-medium wp-image-7797\" src=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/27-550x309.jpg\" alt=\"\" width=\"550\" height=\"309\" srcset=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/27-550x309.jpg 550w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/27-1024x576.jpg 1024w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/27-768x432.jpg 768w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/27-1536x864.jpg 1536w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/27.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<br \/>\nSource: Prepared by the authors<br \/>\n<\/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\">[12]<\/span> <span class=\"text-token-text-primary cursor-text rounded-sm\" data-placeholder-token=\"true\">[13]<\/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 [2][14][15][16][17]:<\/p>\n<p>&nbsp;<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-7744 size-medium\" src=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Captura-de-pantalla-2026-10-02-093128-e1790930918258-332x400.png\" alt=\"\" width=\"332\" height=\"400\" srcset=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Captura-de-pantalla-2026-10-02-093128-e1790930918258-332x400.png 332w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Captura-de-pantalla-2026-10-02-093128-e1790930918258.png 564w\" sizes=\"(max-width: 332px) 100vw, 332px\" \/><\/p>\n<p>Figure 13. Primary Containment Strategies and Associated Equipment. <em>References: ISPE [2 y 14], EMA [15] y INSHT [16 y 17]<br \/>\n<\/em>Sources: ISPE [2] [14] EMA [15] y INSHT [16][17]<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-7740 size-medium\" src=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Captura-de-pantalla-2026-10-02-093145-e1790930943843-306x400.png\" alt=\"\" width=\"306\" height=\"400\" srcset=\"https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Captura-de-pantalla-2026-10-02-093145-e1790930943843-306x400.png 306w, https:\/\/www.airplan-sa.com\/wp-content\/uploads\/2026\/09\/Captura-de-pantalla-2026-10-02-093145-e1790930943843.png 592w\" sizes=\"(max-width: 306px) 100vw, 306px\" \/><\/p>\n<p data-pm-slice=\"1 1 []\"><em>Figure 14 \u2013 Secondary Containment Strategies and Associated Operational Considerations<br \/>\n<\/em><em>Fuentes: ISPE [2] [14] EMA [15] y INSHT [16][17]<\/em><\/p>\n<p data-pm-slice=\"1 1 []\"><em>\u00a0<\/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 class=\"isSelectedEnd\"><strong>List of Abbreviations<\/strong><\/p>\n<p class=\"isSelectedEnd\">(listed in order of appearance)<\/p>\n<p class=\"isSelectedEnd\">HPAPI: High-Potency Active Pharmaceutical Ingredient<\/p>\n<p class=\"isSelectedEnd\">WHO: World Health Organization<\/p>\n<p class=\"isSelectedEnd\">ISPE: International Society for Pharmaceutical Engineering<\/p>\n<p class=\"isSelectedEnd\">API: Active Pharmaceutical Ingredient<\/p>\n<p class=\"isSelectedEnd\">DDD: Defined Daily Dose<\/p>\n<p class=\"isSelectedEnd\">OEL: Occupational Exposure Limit<\/p>\n<p class=\"isSelectedEnd\">TWA: Time-Weighted Average<\/p>\n<p class=\"isSelectedEnd\">ICH: International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use<\/p>\n<p class=\"isSelectedEnd\">Risk-MaPP: Risk-Based Manufacture of Pharmaceutical Products<\/p>\n<p class=\"isSelectedEnd\">STEL: Short-Term Exposure Limit<\/p>\n<p class=\"isSelectedEnd\">NOEL: No Observed Effect Level<\/p>\n<p class=\"isSelectedEnd\">PDE: Permitted Daily Exposure<\/p>\n<p class=\"isSelectedEnd\">HBEL: Health-Based Exposure Limit<\/p>\n<p class=\"isSelectedEnd\">OEB: Occupational Exposure Band<\/p>\n<p class=\"isSelectedEnd\">SP: Spread Potential<\/p>\n<p class=\"isSelectedEnd\">EP: Exposure Potential<\/p>\n<p class=\"isSelectedEnd\">PCS: Primary Containment Strategy<\/p>\n<p class=\"isSelectedEnd\">MP: Migration Potential<\/p>\n<p class=\"isSelectedEnd\">SCS: Secondary Containment Strategy<\/p>\n<p class=\"isSelectedEnd\">PPE: Personal Protective Equipment<\/p>\n<p class=\"isSelectedEnd\">HVAC: Heating, Ventilation and Air Conditioning<\/p>\n<p class=\"isSelectedEnd\">GMP: Good Manufacturing Practices<\/p>\n<p class=\"isSelectedEnd\">HSE: Health, Safety and Environment<\/p>\n<p class=\"isSelectedEnd\">EMA: European Medicines Agency<\/p>\n<p class=\"isSelectedEnd\">LEV: Local Exhaust Ventilation<\/p>\n<p class=\"isSelectedEnd\">HEPA: High-Efficiency Particulate Air<\/p>\n<p>RABS: Restricted Access Barrier Systems<\/p>\n<p>&nbsp;<\/p>\n<p class=\"isSelectedEnd\"><strong>Figures<\/strong><\/p>\n<p class=\"isSelectedEnd\">Figure 1. Hazard pictograms<\/p>\n<p class=\"isSelectedEnd\">Figure 2. Risk matrix associated with a substance<\/p>\n<p class=\"isSelectedEnd\">Figure 3. Share of HPAPIs in global pharmaceutical manufacturing<\/p>\n<p class=\"isSelectedEnd\">Figure 4. HPAPI types and manufacturing breakdown<\/p>\n<p class=\"isSelectedEnd\">Figure 5. Containment risk assessment methodology<\/p>\n<p class=\"isSelectedEnd\">Figure 6. Risk function<\/p>\n<p class=\"isSelectedEnd\">Figure 7. Key concepts associated with risk<\/p>\n<p class=\"isSelectedEnd\">Figure 8. OEB exposure bands<\/p>\n<p class=\"isSelectedEnd\">Figure 9. Primary containment risk assessment methodology<\/p>\n<p class=\"isSelectedEnd\">Figure 10. Secondary containment risk assessment methodology<\/p>\n<p class=\"isSelectedEnd\">Figure 11. Primary and secondary containment concepts<\/p>\n<p class=\"isSelectedEnd\">Figure 12. Example of personnel airlock configuration for a containment area<\/p>\n<p class=\"isSelectedEnd\">Figure 13. Primary containment strategies and associated equipment<\/p>\n<p>Figure 14. Secondary containment strategies and associated operational considerations<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Sources<\/strong><\/p>\n<ol>\n<li>WHO, 2010, \u201cTechnical Report Series, No. 957 &#8211; Annex 3 WHO good manufacturing practices for pharmaceutical products containing hazardous substances\u201d.<\/li>\n<li>ISPE, 2022, \u201cGood Practice Guide: Containment for potent compounds\u201d.<\/li>\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>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<li>ISPE D\/A\/CH Affiliate, 2016, \u201cContainment manual\u201d.<\/li>\n<li>European Commission &#8211; Directorate-general for employment, social affairs and inclusion, 2023 \u201cGuidance for the safe management of hazardous medicinal products at work\u201d.<\/li>\n<li>INSHT, 2008, \u201cNotas T\u00e9cnicas de prevenci\u00f3n &#8211; NTP 798 Industria farmac\u00e9utica: medidas preventivas de la exposici\u00f3n a principios activos\u201d.<\/li>\n<li>INSHT, 2018, \u201cNotas T\u00e9cnicas de prevenci\u00f3n &#8211; NTP 1105 Industria farmac\u00e9utica: medidas para la prevenci\u00f3n de la exposici\u00f3n a principios activos\u201d.<\/li>\n<\/ol>\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, or HPAPIs, are pharmaceutical ingredients that exert [&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":9,"href":"https:\/\/www.airplan-sa.com\/en\/wp-json\/wp\/v2\/posts\/7723\/revisions"}],"predecessor-version":[{"id":7801,"href":"https:\/\/www.airplan-sa.com\/en\/wp-json\/wp\/v2\/posts\/7723\/revisions\/7801"}],"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}]}}