Process Management
- Basma Osman (Deactivated)
- Jean Marie Schiraldi
- Adrienne O'Reilly
Table of Contents
- 1 Overview
- 2 Video Tutorial - Overviews
- 3 Process Record Types
- 3.1 Unit Operations
- 3.2 Steps
- 3.3 Material Attributes
- 3.4 Process Components
- 3.5 Process Parameters
- 3.6 Input, Intermediate, and Output Materials
- 3.7 Intermediate Quality Attributes
- 3.7.1 Risk in IQAs
- 3.7.2 Acceptance Criteria in IQAs
- 3.8 Intermediate Performance Attributes
- 3.8.1 Risk in IPAs
- 3.8.2 Acceptance Criteria in IPAs
- 4 Frequently Asked Questions
Overview
Your Process will contain some or all of the following: Unit Operations, Steps, Process Components, Process Parameters, Materials, Material Attributes, Intermediate Process Attributes, Intermediate Quality Attributes, Intermediate Performance Attributes, and Samples. You may have one Process or multiple Processes in a Project for different scales or even different parts of a single Process (e.g. a buffer).
Video Tutorial - Overviews
Your Process will consist of layers. The top layer is your Process name; it holds the summary details of the process itself. The next layer consists of Unit Operations and Steps. Below that is Raw Materials, Process Components (equipment), Samples, Intermediate Quality Attributes, and Intermediate Performance Attributes. Lastly, are your Material Attributes and your Process Parameters.
Process Record Types
Unit Operations
Unit operations in pharmaceutical manufacturing are fundamental physical or chemical transformations, like mixing or drying, that are essential steps in creating a drug product or drug substance. They ensure quality and consistency by precisely controlling each stage of the manufacturing process.
Record Structure
When creating a new Unit Operation, you will list the name of the Unit Operation and the Description, and you can place the UO in the appropriate spot in your process by choosing the Previous Unit. You can also add a Supplier to your Unit Operation (the supplier does not need to be approved). The Risk captured here is the overall risk for this Unit Operation. It is not tied to the project’s risk management plan. Lastly, Source Documents may be added that support this Unit Operation.
Steps
A Step is an optional record that refers to a specific action or task within a Unit Operation.
Record Structure
In this section, you will list the name of the Step and the Description, and you can place the Step within a different Unit Operation and choose the appropriate Previous Step. Lastly, Source Documents may be added that support this Step.
Material Attributes
In pharmaceutical manufacturing, a material attribute plays a crucial role in ensuring the quality and performance of the final product. Material attributes refer to the specific characteristics or properties of raw materials, intermediates, or final products that can influence the manufacturing process and the quality of the end product. These attributes are crucial for evaluating the suitability, identity, purity, potency, and stability of materials used in pharmaceutical production.
Record Structure
When creating a new Material Attribute, you will fill in the name, Unit Operation, Material or Process Component the attribute is associated with, and if relevant, the Step and Type of the attribute. Type refers to whether it is a Physical, Chemical, Biological, or Microbiological type of attribute.
Risk in Material Attributes
In QbDVision, Material Attributes (and Process Parameters) are risk assessed because they play a critical role in determining the quality of the final product in pharmaceutical manufacturing. By assessing the risk associated with these factors, manufacturers can identify and prioritize critical material attributes (CMAs) and critical process parameters (CPPs) that have a significant impact on the final quality attributes (FQAs) and critical quality attributes (CQAs) of the product.
Click here for more information about Process Risk
Acceptance Criteria in Material Attributes
Acceptance criteria are essential in pharmaceutical manufacturing to ensure that the process, materials, and intermediate attributes meet the required quality standards. For material attributes, acceptance criteria are the specifications that define the quality and characteristics of the raw materials, excipients, or components used in the manufacturing process. These criteria are crucial in ensuring the identity, purity, strength, and quality of the materials, which directly impact the quality of the final product.
Click here for more information about Acceptance Criteria
Process Components
A Process Component refers to the equipment or physical components used in the manufacturing process. These components play a crucial role in determining the quality and performance attributes of the final product. By defining and monitoring Process Components, users can ensure consistency and efficiency in their manufacturing processes. Process Components can also be referred to as equipment.
Record Structure
Users will complete this information by filling out the name of the Process Component, the Unit Operations, and the Steps. The Type of Process Component is a required field that denotes whether the component is Equipment, Instrument/Sensor, etc.
Other sections of information include Component Qualification, Unit Qualification, Component Risk, Integration Mappings, and References & Standards.
Process Parameters
A process parameter refers to a specific variable or factor that can affect the quality, performance, or safety of a pharmaceutical manufacturing process. These parameters are closely monitored and controlled to ensure the consistency and reliability of the final product. Examples of process parameters include temperature, pressure, flow rate, pH level, mixing speed, and many others. By identifying and defining critical process parameters (CPPs) within QbDVision, users can optimize their processes and improve overall product quality.
Record Structure
When creating a new Process Parameter, you will fill in the name, Unit Operation, Material or Process Component the Parameter is associated with, and if relevant, the Step and Type of Parameter. Type refers to whether it is a Design Parameter, Operating Parameter, or Control Parameter.
Risk in Process Parameters
In QbDVision, Process Parameters (and Material Attributes) are risk assessed because they play a critical role in determining the quality of the final product in pharmaceutical manufacturing. By assessing the risk associated with these factors, manufacturers can identify and prioritize critical process parameters (CPPs) and critical material attributes (CMAs) that have a significant impact on the final quality attributes (FQAs) and critical quality attributes (CQAs) of the product.
Click here for more information about Process Risk
Acceptance Criteria in Process Parameters
Acceptance criteria are essential in pharmaceutical manufacturing to ensure that the process, materials, and intermediate attributes meet the required quality standards. In the context of process parameters, acceptance criteria refer to the predetermined standards or limits that must be met during the manufacturing process to ensure the quality of the final product. These criteria are often established based on the critical process parameters (CPP) and help in monitoring and controlling the process to ensure consistency and quality throughout.
Click here for more information about Acceptance Criteria
Input, Intermediate, and Output Materials
When creating a Material, users will now specify if the Material is an Input, Intermediate, or Output Material using the Relationship to Process section in the record (shown below). Along with selecting the type of Material, users will complete the Process, Unit Operation, and Step fields to detail where the Material is consumed and/or produced from. Today, the Process field is filled out on behalf of users based on where the Material is created and cannot be changed.
For Input Materials, users will specify at least one “Input to” location. Users can then click “Add Input” and specify additional Unit Operations and Steps, which will create a Shared Material. It is important to note that Shared Materials are limited to multiple locations within the same Process. If the user wants to specify locations that exist in different Projects and Processes, they will need to use the Material Library. For this approach, users would first create a Library Material, add it to their Project, and then specify multiple Input locations by syncing or linking the Library Material to each location within the Process. Please refer to the Material Library for more information.
Users should select one of the two approaches because the system does not allow Project Materials that are used in multiple Input locations to be associated with the Library. Users will first be required to remove additional locations so that only one remains before associating the Project Material with the Library. Therefore, due to the constraints of Shared Materials, we recommend using Project Materials and Library Materials, specifically by associating them via syncing or linking.
In QbDVision, an Intermediate Material is defined as a Material that is first produced in a Process and then later consumed. To model this using the Relationship to Process section, users will specify one “Output of” location to detail where the Intermediate Material is produced from, and at least one “Input to” location to detail where the Intermediate Material is consumed. Another requirement for Intermediate Materials is that the “Output of” location must come before the “Input to” location(s) in the Process. These requirements are important to highlight because users will see error messages if they try to perform actions that invalidate them.
For Output Materials, users will specify one “Output of” location. Rules for each type of Material are summarized in the table below:
Type of Material | “Input to” locations | “Output of” locations |
|---|
Type of Material | “Input to” locations | “Output of” locations |
|---|---|---|
Input | One location is required, and multiple locations are allowed. | None allowed. |
Intermediate | One location is required, and multiple locations are allowed. The location must come after the “Output of” location. | One location is required. The location must come before the “Input to” location(s). |
Output | None allowed. | One location is required. |
Additional information in the Project Material record includes areas for Formulation Quantity, Qualification, Regulatory, Properties, Integration Mappings, and References & Standards.
Intermediate Quality Attributes
Intermediate Quality Attributes (IQAs) are specific characteristics or properties of a product that are measured during intermediate stages of the manufacturing process in pharmaceutical manufacturing. These attributes are critical indicators of the product's quality and are essential for ensuring that the final product meets all necessary quality standards and specifications.
Monitoring and controlling IQAs throughout the manufacturing process is crucial for maintaining product quality, consistency, and compliance with regulatory requirements. By tracking and analyzing IQA data, manufacturers can identify any deviations or issues early on and take corrective actions to prevent quality issues in the final product.
Record Structure
When creating a new Intermediate Attribute, you will fill in the Name and Step (if applicable). The Process and Unit Operation will be preselected based on your current position in the Process. Select the Type, which could be: Physical, Biological, Microbiological, or Chemical
Risk in IQAs
Risk in intermediate quality attributes (IQA) is a critical aspect to consider in pharmaceutical manufacturing. IQAs are attributes of a material or product at an intermediate stage of production that can impact the final quality attributes (FQAs) of the finished product. Identifying and controlling IQAs is essential to ensuring product quality and compliance with regulatory requirements.
When assessing risk in intermediate quality attributes, it is important to consider the impact of variations in IQAs on the critical quality attributes (CQAs) of the final product. By understanding the relationship between IQAs and CQAs, manufacturers can implement appropriate control strategies to mitigate potential risks.
Risk assessment tools, such as Failure Mode and Effects Analysis (FMEA), can be used to identify and prioritize potential risks associated with IQAs. By conducting a comprehensive risk assessment, manufacturers can proactively identify and address potential issues, implementing appropriate controls to ensure product quality and patient safety.
Ultimately, managing risk in intermediate quality attributes requires a proactive and systematic approach to quality management throughout the manufacturing process. By identifying, monitoring, and controlling IQAs, manufacturers can optimize product quality, ensure regulatory compliance, and minimize the risk of product recalls or quality issues.
Click here for more information about Process Risk
Acceptance Criteria in IQAs
Acceptance criteria in intermediate quality attributes (IQA) are essential standards that define the acceptable range or limit for specific attributes of a material or product at an intermediate stage of production. These criteria are established based on scientific principles, regulatory requirements, and quality standards to ensure that the product meets the desired final quality attributes (FQAs) upon completion.
When setting acceptance criteria for intermediate quality attributes, manufacturers consider factors such as product specifications, critical quality attributes (CQA), and patient safety. The criteria are typically determined through a combination of historical data, risk assessments, and scientific knowledge to ensure that the product meets the required quality standards at each stage of manufacturing.
Acceptance criteria for intermediate quality attributes may be either quantitative (e.g., specific numerical values) or qualitative (e.g., visual inspection criteria), and they are designed to guide decision-making during the manufacturing process. These criteria serve as benchmarks for evaluating the quality of the product and determining whether it meets the necessary standards to progress to the next stage of production.
Monitoring and evaluating intermediate quality attributes against established acceptance criteria are crucial to identifying any deviations or trends that may indicate potential quality issues. By proactively addressing deviations and taking corrective actions as needed, manufacturers can ensure product quality, regulatory compliance, and patient safety throughout the manufacturing process.
Effective management of acceptance criteria in intermediate quality attributes involves ongoing monitoring, documentation, and communication across different functions within the organization. By adhering to established criteria and implementing robust quality control measures, manufacturers can optimize product quality, minimize risks, and deliver safe and effective products to customers.
Click here for more information about Acceptance Criteria
Intermediate Performance Attributes
Intermediate Performance Attributes (IPA) are specific characteristics or properties of a product that are measured during intermediate stages of the manufacturing process. These attributes are important indicators of the product's performance and can provide valuable insights into its quality and consistency. Monitoring IPA helps ensure that the product meets the desired specifications and performance standards.
In pharmaceutical manufacturing, intermediate performance attributes are critical for assessing the quality and performance of the product at various stages of the production process. By monitoring and controlling IPA, manufacturers can identify potential issues early on and make necessary adjustments to ensure the final product meets all requirements.
Record Structure
When creating a new Intermediate Attribute, you will fill in the Name and Step (if applicable). The Process and Unit Operation will be preselected based on your current position in the Process. Select the Type, which could be: Physical, Biological, Microbiological, or Chemical
Risk in IPAs
Risk in intermediate performance attributes (IPA) is another important consideration in pharmaceutical manufacturing. IPAs are attributes of a material or product at an intermediate stage of production that can impact the final performance attributes (FPA) of the finished product. Managing risk in IPAs is crucial to ensuring product efficacy, safety, and overall performance.
Similar to intermediate quality attributes (IQA), assessing risk in intermediate performance attributes involves understanding how variations in IPAs can affect the final performance of the product. By identifying critical IPAs and their potential impact on FPAs, manufacturers can implement control strategies to mitigate risks and ensure product quality.
Risk assessment tools such as Failure Mode and Effects Analysis (FMEA) can also be applied to evaluate and prioritize risks associated with IPAs. By conducting a thorough risk assessment, manufacturers can identify potential failure modes, assess the severity of their impact, and implement preventive measures to reduce the likelihood of performance issues.
Effective risk management in intermediate performance attributes requires collaboration across different functions within the organization, including quality assurance, research and development, and manufacturing. By establishing clear communication channels and implementing robust quality control measures, manufacturers can minimize the risk of performance-related issues and deliver high-quality products to customers.
Overall, managing risk in intermediate performance attributes is essential for ensuring product performance, patient safety, and regulatory compliance in pharmaceutical manufacturing. By proactively addressing potential risks and implementing appropriate controls, manufacturers can optimize product performance and enhance customer satisfaction.
Click here for more information about Process Risk
Acceptance Criteria in IPAs
Acceptance criteria in intermediate performance attributes (IPA) play a crucial role in ensuring the quality and performance of pharmaceutical products during the manufacturing process. Acceptance criteria define the range or limits within which an intermediate performance attribute must fall to meet quality standards and ultimately contribute to the desired final performance attributes (FPA) of the finished product.
When establishing acceptance criteria for intermediate performance attributes, manufacturers consider factors such as product specifications, regulatory requirements, and patient safety. These criteria are typically based on scientific knowledge, historical data, and risk assessments to ensure that the product will meet its intended performance characteristics.
Acceptance criteria for intermediate performance attributes are often defined in terms of specific numerical values, ranges, or qualitative characteristics that must be met at various stages of production. These criteria serve as benchmarks for evaluating the product's performance and determining whether it meets the necessary quality standards to proceed to the next stage of manufacturing.
It is essential for manufacturers to establish acceptance criteria that are relevant, achievable, and aligned with the overall quality objectives of the product. By setting clear and objective acceptance criteria for intermediate performance attributes, manufacturers can ensure consistency in product quality, facilitate decision-making during the manufacturing process, and ultimately deliver safe and effective products to patients.
Regular monitoring and evaluation of intermediate performance attributes against established acceptance criteria are critical to identifying any deviations or trends that may indicate potential quality issues. By proactively addressing deviations and taking corrective actions as needed, manufacturers can maintain product quality, ensure compliance with regulations, and consistently deliver customer satisfaction throughout the manufacturing process.
Click here for more information about Acceptance Criteria.
Frequently Asked Questions
How do I manage dynamic acceptance criteria that have different Measure requirements? E.g. Bioburden (IQA) has two Acceptance Criteria. Each uses a different Measure (Range and Conforms).
Today, you would create two separate Bioburden IQAs. Our recommendation would be to name them Bioburden (Control Method name 1 ) and Bioburden (Control Method name 2).
How can I define process times (e.g. cycle times, hold times, time on equipment, etc.)?
We recommend creating Process Parameter records to define times for each part of the Process. The Acceptance Criteria Range section can be used to capture the specifications for each time. Additionally, we recommend setting up aggregate times (e.g. total cycle time, total UO time, etc.) as calculated values so that they are automatically calculated and updated as changes are made. Instructions on how to set up calculations are explained here in the Calculated Parameters page.
For example, for a chromatography operation, users will create a Process Parameter under each Step to specify phase durations (e.g. “Load Time” under the “Load” step, “Wash Time” under the “Wash” step, etc.). Then, create another Process Parameter at the Unit Operation level for total cycle time (e.g. “AEX Cycle Time” under the “AEX” operation). In the “AEX Cycle Time” record, use the calculator to define the Acceptance Crtieria Range fields as the sum of all the Step times (e.g. AEX Cycle Time = Load Time + Wash Time + …).
Once these records are created, users can use Dynamic Tables and filters to view multiple times across Unit Operations and Steps.
How should a user set up a branching process in QbDVision today? For example, during the Cleaning Process, you might clean the column immediately after the batch is made or save it for a couple of days and clean it later before it goes into the cabinet. The Parameters are the same but in one case it will move through Cleaning and in the other, it won't.
We recommend setting up all these steps in serial order, as they are all part of the longest form of the process.
This will allow you to assess the risk of inputs to outputs and further evaluate how each input CAN affect each output even if all the steps are not run. Taking this approach, you can also track all related information such as acceptance criteria, control strategies, etc., for each variable.
Why don’t we allow sharing of process parameters or material attributes?
In QbDVision, each parameter or attribute has a different meaning based on where it is positioned within a process. For example, a process parameter for “Flow Rate” may be in two different Unit Operations, however, its definition, acceptance criteria, risk, etc., can vary substantially based on where it’s used.
The specific reasons include:
Each process parameter or material attribute will have its criticality assessment associated with the relevant Unit Operation or Step. Doing this ensures that each process requirement (IQAs, IPAs, MAs, PPs) has been ranked for risk in the necessary step/unit operation against intermediate or final product quality.
The Acceptance Criteria for each material attribute, process parameter, and intermediate attribute (IQA/IPA) are different.
Measurement Data is different based on where the record is within the process, e.g., the flow rate in UO 1 compared to UO 2.
What happens when two users are editing the same record?
In the (rare) event that two different people are editing the same record, the first person to save the record wins. Meaning their updates will be recorded. When the other person tries to save the record, they will get an error message that says the record has been modified.
How do I bring in a Certificate of Analysis (CoA)?
See this Video Tutorial: Import a CoA
How do I find comments made by approvers when they approve or reject a record?
Approve/Reject comments are logged in the History widget.
Does QbDVision perform raw material risk assessment?
Material risk assessments are conducted on the Material Attributes. For example, let’s say you have a Material, sodium citrate, that has a high particle size distribution (PSD). The risk assessment would be completed in the Material Attribute record for PSD, which is a separate record from the Material.
How can I quickly find and load an existing record?
One of the most efficient ways to locate an existing record (ex. Document, Material, Process Component, General Attribute) is by directly typing its ID into the URL of your browser. You can do this by opening any other record of that type (ex. any Process Parameter record, if you’re trying to find the Process Parameter with ID PP-255), and editing the URL. A video tutorial and instructions for an example, Process Parameter, ID: PP-255, are shown below:
Instructions
Open any record of the same type as the record you’re looking for. For example, if you’re trying to find Process Parameter PP-255, you can open any other Process Parameter record (ex. PP-2735).
Open the record in the full-page browser view.
Modify the URL: in the address bar, replace the current record ID with the desired record ID (e.g. "255").
For example, if the current URL is https://any_environment.qbdvision.com/processExplorer/processParameters/viewEdit.html?operation=View&id=2735, change the ID (the last digits of the URL) from ”2735” to “255”.
Press Enter to load PP-255 on the page.
The number of records in my Process's tree view and Dynamic Table differs.
The Process Explorer tree view shows the Process record and all the DS/DP records associated with that Process; the Table view does not. Comparing record counts between those two views will not match if you have DS/DP records related to the Process.