Category Archives: Cleaning Validation

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 – Equipment Cleaning

Hello good people of the world! Continuing the series on oral solid dosage forms, today we’re going to talk about equipment cleaning. OSD manufacturing equipment can be notoriously hard to clean, and manual cleaning procedures introduce high risk of contamination and carryover. It is recommended that any new or existing process equipment be cleaned with automated processes wherever possible.

The three automated cleaning processes typically used in industry are:

  • Clean-in-Place (CIP)
  • Wash-in-Place (WIP)
  • Clean-out-of-Place (COP)

CIP is done without moving the equipment, as the name implies, and uses a CIP skid to deliver cleaning and rinse solutions. CIP should not require any manual operations.

WIP is done in-place as well, but may include some manual operations, such as removing filters.

COP requires equipment to be moved to a wash station. Tanks and vessels are typically COP’d.

Some specific concerns related to cleaning OSD equipment include:

  • Dry Granulator/Roller Compactor cannot typically be CIP’d. Particularly the auger must be removed and COP’d.
  • Fluid Bed Dryers a large and complex, making cleaning difficult. Modern dryers will include CIP/WIP but typically still require manual cleaning of some parts.
  • Milling equipment typically requires the screen to be manually removed before any CIP/WIP.
  • Tablet presses can be difficult to clean, requiring many manual interventions prior to washing.
  • Capsule filling machines should be wettable to allow cleaning.
  • Tablet coaters should include WIP

Of course, cleaning processes, whether automated or not, need to be validated. Riboflavin tests may be performed to verify wash coverage, and swabbing can verify lack of residual API and cleaning solutions.

What challenges have you run into in cleaning your OSD manufacturing equipment? Comment below!

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Cleaning Validation: Detergent Removal

Detergents

Hello good people of the world! Today’s blog post is about verification of detergent removal in cleaning validation. As we know, cleaning validation is concerned with leaving process equipment clean; that means not residual API, excipients, or detergents. One unique problem with detergents is that, while we typically know in detail the composition of APIs and excipients, detergent composition may be proprietary and not available to the end-user. Continue reading Cleaning Validation: Detergent Removal

Recovery Studies – What the Heck?!

Recovery

Hello, good people of the world! Recovery studies are studies to support surface swab processes. They typically involve “spiking” a “coupon” made from a particular material with a known amount of the contaminate you’re interested in, and then systematically quantifying the amount recovered via the swab process.

You’ll need to perform recovery studies for all product-contact materials you have in your manufacturing process. These typically include 316L stainless steel, PTFE, glass, etc.

Parts Washer Qualification – PQ

Parts Washer

This post is about Parts Washer qualification. This covers any manner of automated system that cleans parts out-of-place (Clean-out-of-place = COP). This includes process parts washers, glassware  washers, laboratory parts washers, etc. all of which may be termed COP washers.

The scope of a performance qualification of a washer is the performance of the equipment with defined recipe(s) and load(s). Be sure to capture the recipe and load configuration in the protocol prior to execution or as part of the execution itself. This is how the recipe and load configuration become “validated.” The recipe includes all steps and parameter values, and the load includes what parts or components will be washed and how they will be arranged. You’ll need to include a picture or diagram. Continue reading Parts Washer Qualification – PQ

Cleaning Validation – Visual Inspection

Visual Inspection

Visual inspection is actually a method used to collect data against an acceptance criterion.

Per PDA’s Technical Report 29 “Cleaning Validation” (2012) you only need a quantitative visual limit if visual examination is the only method used and visually clean is the only acceptance criterion. According to the report, if you are using visually clean as an acceptance criterion in conjunction with swab or rinse sampling, you do not need to quantify the visual limit and what “visually clean” means.
If you do need to quantify the visual limit, you can do so by spiking coupons with solutions at different surface densities (e.g. microgram/cm2 or ppm) and having a panel of qualified personnel determine at which level the residue ceases to be clearly visible. Distance, lighting, and viewing angle need to be considered.