Oral Solid Dose – Unit Operations

Granulator at an OSD Plant in Vietnam

Hello good people of the world! Continuing the series on oral solid dosage forms, today we’re going to talk about unit operations typical in a oral solid dose manufacturing process.

Typical OSD processes may include some combination of weighing/dispensing, material transfer, blending, granulation, drying, milling/sieving, compression, encapsulation, and coating. Some considerations around each step may include:

1. Weighing/Dispensing: includes sampling for quality purposes. Materials to be sampled typically include: APIs, excipients, primary and secondary packaging, cleaning agents. Sampling areas must be protected from contamination.
2. Material Transfer: material flows should be documented and reviewed, with the intention of minimizing any contamination.
3. Blending: materials are typically blended to ensure a uniform composition, prior to downstream process steps. Many methods exist, including: tumble blending, bin blending, and agitator mixers.
4. Granulation: granulation is the process of combining particles into a granule. Many methods of granulation exist: wet massing/extrusion, high shear, spray, speronization, and hot melt extrusion, for example.
5. Drying: the purpose of the drying step is to remove any excess moisture from the drug product. Drying methods include: tray , fluidized bed, and spray drying.
6. Milling/Sieving: the purpose of this process step is to reduce granule size to conform to specification. Some methods include: impact/hammer mills, conical mills, and oscillating horizontal screens.
7. Compression: compression is used to create tablets.
8. Encapsulation: encapsulation is used to create capsules.
9. Coating: coating is used to apply a coat to tablets

In the next post we’ll cover supporting equipment and quality systems. What process steps do you use in your OSD process? Comment below!

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Validation Program Tenets

Hello good people of the world! What are the overarching tenets that you go to when making decisions related to your validation program? The regulations and guidance from industry only go so far and you will be regularly tasked with situations unique to your program. How do you know what is the right way to go in the grey areas? I like to keep these tenets in mind:

1. The manufacturing process should be the most complex process on the site. Reduce complexity everywhere else. Reduce the number of deliverables. Reduce the number of process steps.
2. Requirements feed specifications feed test protocols. Remember that you should always be able to trace a test case to a requirement through the specifications.
3. Compliance is not binary, you are accepting degrees of regulatory risk. Make sure you understand the risk and that you accept it.
4. Good Manufacturing Practices are not just from the CFRs. World-wide best practices need to be considered and applied where applicable.
5. It’s all about documentation. If it’s not documented it didn’t happen. Create a logical narrative, and you’re already mostly there.
6. Our primary purpose is to create documentation for agencies. Take any kind of writing class, and one of the first things you’ll learn is: know who your audience is and write for them. While it’s great the validation documentation can be used for commissioning, process improvement, etc. that must not come at the cost of it’s primary purpose.

What are some of your go-to tenets?  Comment below.

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Validation Project Plans

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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Corrective Action / Preventive Action (CAPA)

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

Hello 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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CSV Pre-Execution Checklist

Hello good people of the world! Today’s post is a short one covering things you should check before starting a Computer Systems Validation (CSV) package execution so you can hit the ground running! This list assumes you have an approved protocol, of course. 🙂

Start-Up Tip: Task Duration Buy-In

Hello good people of the world! Today’s post might be a bit of a rant, but this is something I’m seeing lately and is a good way to kill your project schedule. What I’m talking about is task duration buy-in. It is critical in a start-up project to get all stakeholders and especially responsible parties to buy in to the amount of time they are allotted for each task in the schedule.

And I mean formal buy in. Get it in writing. Have them sign their name to it.

Too often I have seen a schedule suffer due to this gross oversight. Yes, a schedule may say you have three days to complete a task, but if that duration feels arbitrary or not “owned”, it is not going to be met when other priorities come in to play. This is especially true with resources that are not used to working in start-up environments/come from steady-state situations.

Get buy in, have consequences for failing to meet dates, force resources to delegate when they are overwhelmed.

What’s your go-to method for getting buy-in on task durations and keeping that schedule moving along?

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