Tag Archives: FDA

Validation Project Plans

develop-project-plan-1200x480

Hello good people of the world! Today’s post is about Validation Project Plans, which is a specific type of project plan for projects in the pharmaceutical, biotechnology, and medical device regulated industries. This post covers Validation Project Plans for pharmaceutical/biotechnology industries in particular.

Often I’ve see Validation Project Plans contain a lot of fluff but little meat, making them of less value to the project team. A good project plan clearly documents the following, at a minimum:

  1. What facilities, systems, and equipment are in scope of the plan
  2. What are the expected activities and deliverables
  3. Who is responsible for what
  4. What is the validation approach and rationale for that approach
  5. What happens after the validation scope covered in the plan is completed (i.e. ongoing requirements)

Note I do not include project cost or schedule in a project plan, because these are often changing rapidly and should be maintained in a less controlled, more flexible manner, e.g. with scheduling software for a schedule.

The plan itself should be controlled (i.e. approved and revision controlled) as soon as possible in the project but early enough so that scope will not change (too much).

Additional things to think about when drafting your plan:

  1.  Commissioning versus Qualification versus Validation. If your project has multiple phases (and any decent-sized project should), be sure to clearly state responsibilities and deliverables at each stage.
  2. Include references to regulations, industry guidance, and site procedures that govern your plan. Make it clear to everyone who reads the plan what framework you are working inside.
  3. The purpose and scope of the document should be clear and up front.
  4. Get buy-in from all functional groups by having them approve the document.
  5. Like all controlled documents, the plan should have version/revision history.
  6. Use tables to clearly present information.

I put together a quick template here:

Validation Project Plan Template MWV

What do you feel is necessary in a Validation Project Plan? Comment below.

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Serialization Basics

vials
Hello good people of the world! Today’s post is high-level regarding serialization. Serialization is a process mandated by the world’s regulatory agencies to reduce counterfeit drug products in the market. Besides being costly to drug companies, counterfeit drug products are often less efficacious and less safe than the real drug they are purporting to be. Additionally, counterfeit drug products can be contaminated with other APIs and/or toxic excipients.
Continue reading Serialization Basics

Corrective Action / Preventive Action (CAPA)

CAPA Process
Hello good people of the world! Today’s post is about Corrective Action / Preventive Action, typically referred to as CAPA. CAPA is an integral part of any Quality System, and certainly one of the first things an agency will look at in any audit.

There is a ton of good information out there already on CAPA, including FDA’s own guidance from 2014.

I’ve personally used a few software packages for CAPA management, including MasterControl and Oracle’s Agile, among others, but have not seen any standouts.

The key points of the CAPA program are:

  1. Issue identification, i.e. ensuring the issue is truly understood and well documented
  2. Root cause analysis, i.e. identifying the root cause of the issue
  3. effectiveness check, i.e. verifying actions have actually resolved the issue

What tips have you learned from your CAPA program? Comment below.

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Free Offer! Get Your Org Chart Online and Organized

Portfolio10Hello good people of the world! As you probably know, one of the first things an agency is likely to ask for in an audit is your company’s organization chart. They want to know how the organization is structured, and particularly where the quality unit fits in.

If you have a SharePoint tenant, I have an offer for you. For a limited time, MWV, in conjunction with dikuw.com, is offering a free SharePoint Add-in for generating organization charts. This add-in integrates with your existing SharePoint On-Premise or Online service, and gives a secure, centralized location for your org chart. The custom interface makes it easy to navigate and update the chart in real-time.

Get all the details and download the add-in here: http://www.dikuw.com/OrgChart.html

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Environmental Control and Monitoring for Aseptic Processing

Petri dish

Hello good people of the world! Today’s post is an overview of environmental control and monitoring for aseptic processing.

Applicable references for the US are:

  • FDA Guideline for “Sterile Drug Products Produced by Aseptic Processing” September, 2004
  • FDA Guideline for the submission of “Documentation for Sterilization Process Validation in Applications for Human and Veterinary Drug Products”
  • 21 CFR Part 211 — Current Good Manufacturing Practices for Finished Pharmaceuticals

Purpose:

Environmental control is designed to prevent microbiological contamination of sterile products.

Environmental monitoring is designed to detect microbiological contamination in aseptic processing areas.

Scope: Environmental control and monitoring is a required part of aseptic processing, i.e. where “terminal” sterilization is not possible. Terminal sterilization means the finished drug product is sterilized at the last step of the process via heat, radiation or other. Many pharmaceuticals and most biologics do not tolerate terminal sterilization, thus the importance of aseptic processing.

Control Considerations:

  1. Air particle count: maintaining air particle counts is critical to aseptic processing, because particles themselves can be harmful, and likely carry microorganisms.
  2. Cleanroom design: for the aseptic core (where critical aseptic process steps occur, e.g. where product is open to the environment) the FDA recommends class 100. The core should surrounded by class 1,000 or class 10,000 areas.
  3. Air pressure differentials: the FDA recommends a 10-15 Pascal pressure differential between rooms of differing classification, with the higher pressure in higher-class rooms, so that air naturally flows outward to the lower class rooms.
  4. HEPA filtration: High Efficiency Particulate Air (HEPA) filters should be used in class 100 rooms to aid in particle removal
  5. Equipment: should be cleanable and non-shedding. Stainless steel is the preferred material of construction for equipment surfaces.
  6. Process design: processes should be designed with minimizing contaminate risks in mind (e.g. don’t force operators to reach over open product)
  7. Process Validation: media runs should be performed to demonstrate the process can run aseptically

Monitoring Considerations:

  1. Air quality measurements should look at viable and nonviable particulate levels
  2. Particle counting: ongoing monitoring should look at particle counts in critical areas
  3. Active sampling: devices such as impaction and membrane samplers should be used to evaluate aseptic processing areas
  4. Passive sampling: settling plates should be used to collect microbial information
  5. WFI and other excipients: should be routinely tested for microbial/particulate load
  6. Personnel: the greatest single contributor of particulates and microbes in a cleanroom. Steps (training, gowning, testing) must be taken to minimize risk

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