USP Draft General Chapters on Plastic Components and Systems Used in the Manufacturing of Drug Products

The USP General Chapters—Packaging and Distribution Expert Committee proposes two new general chapters to address the qualification of polymeric components used in the manufacture of both pharmaceutical and biopharmaceutical active pharmaceutical ingredients (APIs) and drug products (DPs):

• <665> Polymeric Components and Systems Used in the Manufacturing of Pharmaceutical and Biopharmaceutical Drug Products;
• <1665> Plastic Components and Systems Used to Manufacture Pharmaceutical Drug Products.

The drafts of these two chapters have been published for public comment in Pharmacopeial Forum (PF) 43(3) [May–Jun. 2017]. Deadline for comments is July 31, 2017.

Background:
Chapter <665> was initially published as Plastic Components and Systems Used in Pharmaceutical Manufacturing <661.3>  in PF 42(3) [May–June 2016]. The current proposals take into account comments received on the <661.3> proposal and from the USP Biocompatibility and Material Characterization Workshop held June 20–21, 2016. The chapter number <1665> was previously assigned to a proposed new general chapter Toxicological Safety Assessment of Extractables and Leachables (announced in the stimuli article "USP Plastic Packaging General Chapters: An Overview" in PF 39(6)). However, chapter number <1665> is now assigned to the proposed new general chapter Plastic Components and Systems Used to Manufacture Pharmaceutical Drug Products.

Chapter <665> is structured as follows:
 
1. INTRODUCTION  
2. SCOPE 
3. ASSESSMENT PROCESS
 
3.1 Initial Assessment:  

• Examines whether a polymeric material, component, or system is fit for its intended use (with respect to patient safety) without further characterization.
• The first and second steps consider whether there is contact between a component and a process stream and whether the process stream that contacts the polymeric material, component, or system is a liquid.
• The third step considers whether the material, component, or system is used to manufacture an approved and marketed API, DS, or DP. If a material, component, or system has been established to be acceptable, further characterization of the material, component or system is not required, providing this is justified.
• The last step considers whether the component or system under assessment is equivalent to a component or system that has already been established to be acceptable (a comparator). For example, a component that is used to manufacture an approved drug product could be a comparator for a second, but similar, component used to manufacture a different, but similar, drug product. In order to link a component or system to a comparator, reference is made to Plastic Components and Systems Used to Manufacture Pharmaceutical Drug Products <1665>.
• When a comparator has been established for the component under assessment, then further characterization of the material, component, or system is not required as long as a justification is provided. When a comparator cannot be established, proceed to 3.2 Risk Assessment to establish the appropriate and necessary level of material and component testing.

3.2 Risk Assessment:

• The testing of materials and components is driven by the risk that the material or component could be unsuited for its intended use. The greater the risk that the material or component could be unsuited for use, the greater the degree of required testing. Risk assessment is accomplished via application of a Risk Assessment Matrix detailed in Plastic Components and Systems Used to Manufacture Pharmaceutical Drug Products <1665>.
• The outcome of this assessment establishes three levels of risk: low (level A), moderate (level B), and high (level C). These levels are linked to the test requirements defined in section 4.2.1 and 4.2.2. 
• If a component has been tested according to this chapter and meets the specifications contained in this chapter, the component's materials of construction are deemed to be compliant with this chapter without having been tested according to <661.1>. 
• If the component meets the plastic class VI requirements according to USP general chapter <88>, it is not necessary to test the component according to <87>. 

4. POLYMERIC MATERIALS OF CONSTRUCTION 
4.1 Plastic Materials Not Addressed in  <661.1>   
4.2 Cured Polymeric Materials 
4.2.1 Test Methods  
4.2.2 Specifications  
     
5. POLYMERIC COMPONENTS AND SYSTEMS 
5.1 Test Methods  
5.2 Specifications:  

• Biological Reactivity:
  (Manufacturing components or systems that do not meet the requirements of the relevant biological reactivity tests (<87> and <88>, as appropriate) are not suitable as manufacturing components or systems for pharmaceutical and/or biopharmaceutical use);
• Extractable Metals;
• Organic Extractables Profile. 

Chapter  <1665> discusses material characterization and selection and safety qualifications of polymeric components and systems used to manufacture drug products (previously proposed to be incorporated in general chapter <1661> to support the use and understanding of the new general chapter <661.3>). The chapter is structured as follows:

1. INTRODUCTION  
2. SCOPE  

3. GENERAL PRINCIPLES 
3.1 Discussion  
3.2 Material Characterization and Selection  
3.3 Component Characterization and Selection  
  
CHARACTERIZATION PROCESS 
4.1 Initial Assessment  
4.2 Risk Assessment 
4.2.1 Risk evaluation matrix  
4.2.2 Application of the risk evaluation matrix  
4.2.3 Using the risk evaluation matrix  
4.2.4 Linking risk to characterization methodologies  
  
4.3 Establishing the Level of Characterization 
4.3.1 Baseline assessment  
4.3.2 Expanded baseline assessment  
4.3.3 Full testing (extractables profiling)  
  
4.4 Standard Extraction Protocol 
4.4.1 Extraction solvents  
4.4.2 Extraction temperature  
4.4.3 Extraction duration  
4.4.4 Accomplishing the extraction  
4.4.5 Non-standard extractions  
4.4.6 Accounting for conditioning and related steps employed in manufacturing  
  
4.5 Testing the Extracts and Generating the Extractables Profile  
4.6 Evaluation of the Extractables Profile Established by Implementing the Standard Extraction Protocol 
    
5. SAFETY QUALIFICATION 
5.1 General  
5.2 Chemical Safety Qualification  
5.3 Additional Safety Qualification   
     
GLOSSARY  

Following your registration on the Pharmacopeial Forum website you get access to the complete drafts of general chapters <665> and <1665>.