Tag Archives: CFR

Oral Solid Dose – Material Handling

Hello good people of the world! Continuing the series on oral solid dosage forms, today we’re going to talk about material handling. Oral solid dose manufacturing is typically a batch process, which means materials need to be transferred from step-to-step. Sometimes there is direct conveyance between steps, but often transfer is performed via Intermediate Bulk Container (IBC).

In terms of design, IBCs should be able to handle the worst-case (lowest) density material in the process. IBCs should be cleanable, especially if a single container will support many product manufacturing processes. IBCs should be designed in such a way that they drain easily. Charging/discharging must be considered.

IBCs may be transported on wheels, or by a pallet truck.

Discharging may be facilitated by applying vibrations to the IBC, either internally or externally.

For direct conveyance, gravity, pneumatic conveyance, and mechanical conveyors are options.

What considerations around material handling do you have in your OSD lines? Comment below!

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Oral Solid Dose – Critical Properties

Hello good people of the world! Today’s post is the first in a series covering considerations around the commissioning, qualification, and validation of facilities, systems, and equipment involved in the manufacture of oral solid dose (OSD) products. OSD is a wide-spread method of pharmaceutical delivery, including well known medicines such as aspirin, Viagra, and many antibiotics. Solid doses can take the form of powders, tablets, capsules, pills, lozenges, granules and more.

Here we’re going to cover the physical and chemical properties that should be considered in equipment design.

First, environmental factors:

  1. Temperature and Humidity: temperature and humidity should be controlled even if the product is not sensitive, as most processes are susceptible to flow issues in the extreme temperature and/or humidity ranges.
  2. Light: some OSD products are light (especially UV light) sensitive and must be protected from sunlight and even indoor light in some cases.
  3. Oxygen: some products may also be sensitive to oxygen exposure.

Second, process factors:

  1. Particle size and size distribution: powders inevitably have some variation in particle size that must be understood and controlled
  2. Particle shape: similarly to size, particles will have variation in shape
  3. Surface properties: are the particles smooth or rough? Do they stick together? Do they readily absorb moisture? Surface properties must be understood
  4. Particle strength: particles will break down under enough force. Particle strength must be understood and undue stress avoided in manufacturing processes.
  5. Density, porosity, and packing: how does a particle pack? Things like minimum bulk density, poured bulk density, and tapped bulk density should be understood.
  6. Cohesion in powders: related to surface properties, how to particles stick together? Magnetic, electrostatic, and intermolecular forces may be in play and should be understood.

What factors do you consider in your OSD manufacturing process?

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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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