Industry: Drug Development and Manufacturing

Evaluating Process Deviations


Background

Within the pharmaceutical industry, a Contract Development and Manufacturing Organization (CDMO) is a biotechnology organization that provides clients with services such as drug development and drug manufacturing. For example, a cell culture development CDMO specifically focuses on the production of cell lines and media. This type of CDMO also commonly offers clients analytical services to analyze their cell environments to ensure optimal growth. 

Process engineers play an important role in CDMOs. The main function of a process engineer within this type of company is to oversee manufacturing protocols known as master batch records (MBR) to be used in manufacturing. An MBR documents the entire manufacturing process and the history of a product batch. MBRs provide detailed instruction on how a product is made (including equipment, product amount, temperature, time, etc), and records each step that happens for each batch. Utilization of the MBR helps to ensure that products are being produced safely, efficiently, and consistently by the scientists directly involved. MBRs are authored by the process engineers, which are reviewed by a cross functional team including quality assurance, quality control, manufacturing, process development, and the customer. These protocols are executed by manufacturing scientists who make the products. 

Process engineers then provide oversight of the manufacturing process, which typically involves the daily review of process data, review of MBRs  to determine that every step outlined is followed and identify areas for process improvement. When the paperwork reveals a deviation in the MBR, the event is documented and management is notified. A deviation is any unwanted event that differs from the approved processes, procedures, instructions, or specifications. A thorough investigation is completed to determine if the deviation resulted in any issues with product quality. Process engineers are a critical member of the investigative team to provide insight into how the deviation impacts the process and (if applicable) the product.At other times, deviations can be discovered through other paths such as changes in product quality. In situations such as this, a process engineer is asked to step in and investigate the manufacturing practices to determine the cause. 

Apart from a strong technical background and knowledge of regulatory guidelines, good communication skills are essential to be a process engineer. When deviations are the fault of personnel, it is their responsibility to discuss the problem and provide training. They are also the primary point of contact between the facility and its customers where they are involved in ensuring that stakeholder expectations are met while ensuring the manufacturability of the process.

The Process

The process below includes information that is necessary to evaluate process deviations.

  1. Quality Review – check documentation from standard operating procedures, MBRs, and logbooks to ensure consistent execution and manufacture of the drug substance
  2. Deviation Discovery – identify and assist in remediating manufacturing challenges
  3. Communication – working in interdisciplinary teams and engage with external stakeholders
  4. Investigation – identify source of deviation as man, machine (equipment), material, method, measurement or milieu (environment)
  5. Criticality assessment – determine the level of severity, assess changes in product quality and if is it still acceptable for client use
  6. Corrective action – develop a course of action to resolve the current problem and prevent the recurrence of similar issues (e.g., train relevant personnel)
  7. Client communication – communicate with the customer during the investigative process, its findings, and possible remediative actions

The Exercise

For this exercise, you are a process engineer at a cell culture development CDMO. You will be evaluating two different manufacturing deviations and using the details to determine whether there was a product quality impact.


Task 1: Deviation Discovery

Read the example of a deviation that could occur in cell culture manufacturing. Write a brief summary (4-5 sentences) describing how the deviation was discovered, what went wrong, and how the deviation may have impacted the product quality. Refer to the Resources section for more information on deviations and industry cell culture protocols.

Task 2: Identify Performance Indicators

Using the deviations in the example, make a list of cell culture performance indicators that could be used to assess cell culture viability (and therefore product quality) in response to the deviations.

Task 3 (advanced): Determine possible personnel actions

Based on the problems that occurred during the deviation, determine what, if any, correct action would be suggested for the personnel and staff involved. Note: Corrective actions ensure proper training of personnel involved in the affected processes.


Sample Deliverable

View Sample Deliverable with summary of deviations, identification of performance indicators, and possible corrective actions.


Resources

Skills Used to Perform These Tasks

  • Root cause analysis
  • Research
  • Problem solving
  • Critical thinking

Skills Needed for This Career

  • Knowledge of Good Manufacturing Practice and regulatory guidelines
  • Attention to detail
  • Collaboration
  • Communication skills
  • Technical knowledge (statistics, bioprocessing, chemistry, cell biology)

Additional Responsibilities

A professional in the field of Drug Development and Manufacturing may also perform these activities:

  • Process validation (statistical evaluation of processes to ensure that the parameters deliver a consistent product)
  • Technology transfer (process scale-up and facility fit)
  • Equipment qualification and commissioning (identifying new equipment and ensuring that it is suitable/usable for manufacturing use)
  • Floor support (support the technicians from a technical/troubleshooting standpoint)
  • Project management (manage and drive projects – typically process improvement initiatives – apart from customer programs)

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Simulation authors – Sophia Isis, PhD candidate at UT Austin
Job simulation vetted by professionals from CDMOs in the greater St. Louis area