In the 2010–2015 cycle, the Packaging, Storage, and Distribution Expert Committee determined the need to update general chapters that focus on the quality of the packaging systems used to store drug products. The Expert Committee's initial focus was on the final packaging systems; however, it has been extended to include packaging systems components and their materials of construction.  

The suitability of a pharmaceutical packaging system for a drug product can be assessed by extractables and leachables testing. Out of these characterization studies, specific controls for a packaging system, its components, or its materials of construction can be established. 

The suite of general chapters for packaging systems begins with Plastic Materials of Construction 661.1 , which is used to characterize the materials of construction, and Plastic Packaging Systems for Pharmaceutical Use 661.2 , which is used to characterize the final packaging system and/or component. 

Other chapters that will be proposed in the future will address the characterization of plastic materials used in the manufacturing process and medical devices, Plastic Systems Used for Manufacturing Pharmaceutical Products 661.3 and Plastic Medical Devices Used to Deliver or Administer Pharmaceutical Products 661.4 .  

As part of this continuation, the Packaging, Storage, and Distribution Expert Committee is proposing Assessment of Extractables Associated with Pharmaceutical Packaging/Delivery Systems 1663 , which presents a framework for the design, justification, and execution of an extractables assessment for pharmaceutical packaging and delivery systems. A workshop will be held on December 9 and 10, 2013, at USP in Rockville, Maryland to discuss comments on the suite of packaging general chapters and potential future revisions.

Safety Thresholds and Best Demonstrated Practices for Extractables and Leachables 

in Parenteral Drug Products (Intravenous, Subcutaneous, and Intramuscular)

28 October 2021

Part 3. Best Practices for Extractables and Leachables Assessment in PDP

II. Material/Component Characterization and Selection


PDP general recommendation #3 emphasizes materials of construction, finished components and complete packaging systems. The pharmaceutical product manufacturer typically has responsibility for establishing a comprehensive understanding of the requirements for manufacturing, packaging, storage and delivery of a unique pharmaceutical product safely and effectively to an intended patient population. The pharmaceutical product manufacturer may work collaboratively with specific suppliers to enable selection of an appropriate materials or components that will ultimately satisfy the pharmaceutical product manufacturer’s unique manufacturing, packaging storage and delivery requirements.

The type of information that is required for material/component selection varies depending on the route of administration and dosage form. The level of concern associated with a particular material/component is directly related to the type of interaction with the dosage form [7].

Therefore, critical components are those that have high concern because of potential interaction with the dosage form (e.g., liquids) and those that have negligible interaction with the dosage form (e.g., powders) have low concern. Critical components require comprehensive information that may include extractables and other charterization information. The OINDP recommendations recognized high concern components as critical. In a follow-on effort by IPAC-RS, “Baseline Requirements for OINDP” was published in 2011 and updated in 2017 (https://www.ipacrs.org/publications), and took into consideration the level of concern not only for components but also for materials of construction, and finished packaging/delivery systems. Likewise, PDP has taken a risk-based approach to characterization and selection of materials of construction, components and finished systems.

The OINDP recommendations regarding material/component selection can thus be broadened as follows:

  • The pharmaceutical product development and manufacturing team should obtain any/all available information on the composition and manufacturing/fabrication processes for each material of construction and finished component utilized in a complete packaging system (i.e., container closure/delivery system).

  • The information thus obtained, augmented with appropriate testing of the materials of construction and finished components (see Table 3-1), should drive material/component selection.

  • Material and component selection should be based on an assessment of potential risk of patient leachables exposure or formulation compatibility issues, which should consider the criticality with consideration of the material, finished component or complete system in which it is used.

The PDP recommendations for materials/component selection is based on the OINDP recommendations while widening them to include consideration of materials of construction, drug product dosage form and route of administration, with the recognition that selection may be facilitated by performing extractables assessments and other relevant testing.

II. 재료/구성요소 특성화 및 선택

주사제 일반 권장 사항 #3은 용기재료, 완성된구성요소 및 완전한 포장 시스템을 강조합니다. 제약 제품 제조업체는 일반적으로 제조, 포장, 저장 및 고유한 제약 제품을 안전하고 효과적으로 의도된 환자 집단에 전달하는 요구사항에 대한 포괄적인 이해를 설정하는 책임이 있습니다. 제약 제품 제조업체는 제조업체의 고유한 제조, 포장, 저장 및 전달 요구 사항을 만족시키기 위해 적절한 재료 또는 구성요소를 선택하도록 특정 공급 업체와 협력적으로 작업할 수 있습니다.

재료/구성요소 선택에 필요한 정보의 유형은 투여 경로와 투여 형태에 따라 다릅니다. 특정 재료/구성요소와 관련된 우려의 수준은 투여 형태와의 상호 작용 유형과 직접 관련이 있습니다 [7].

따라서, 중요한 구성요소는 투여 형태(예: 액체)와의 잠재적 상호 작용으로 인해 높은 우려를 가진 것들과 투여 형태(예: 분말)와의 무시할 수 있는 상호 작용을 가진 것들은 우려가 적습니다. 중요한 구성요소는 추출물 및 기타 특성화 정보를 포함할 수 있는 포괄적인 정보를 필요로 합니다. 구강흡입 및 비강제품 권장 사항은 높은 우려 구성요소를 중요하게 인식했습니다. IPAC-RS에 의한 후속 노력에서는 2011년에 발표되고 2017년에 업데이트 된 "구강흡입 및 비강제품의 기본 요구사항"(https://www.ipacrs.org/publications)이 있으며, 구성재료 및 완성 포장/전달 시스템에 대한 우려 수준을 고려했습니다. 마찬가지로, 주사제는 구성재료, 구성요소 및 완성 시스템의 특성화 및 선택에 위험 기반 접근법을 채택했습니다.

구강흡입 및 비강제품에 대한 재료/구성요소 선택에 대한 권장 사항은 다음과 같이 확대될 수 있습니다:

• 제약 제품 개발 및 제조 팀은 완전한 포장 시스템(즉, 컨테이너 폐쇄/전달 시스템)에서 사용되는 각 구성재료 및 완성 구성요소의 구성 및 제조/제작 공정에 대한 모든/모든 사용 가능한 정보를 얻어야 합니다.

• 따라서 얻은 정보는 구성재료 및 완성 구성요소의 적절한 시험(표 3-1 참조)과 함께 재료/구성요소 선택을 주도해야 합니다.

• 재료 및 구성요소 선택은 환자의 침출물 노출 또는 제형 호환성 문제에 대한 잠재적 위험의 평가를 기반으로 해야 하며, 사용되는 재료, 완성 구성요소 또는 완전한 시스템의 중요성을 고려해야 합니다.

주사제의 재료/구성요소 선택에 대한 권장 사항은 구강흡입 및 비강제품의 권장 사항을 기반으로 하면서도 구성재료, 약제 투여 형태 및 투여 경로를 고려하여 확대되었으며, 추출물평가 및 기타 관련 시험을 수행하여 선택을 용이하게 할 수 있음을 인식하고 있습니다.