Oral Solid Dose – Isolation and Containment

Hello good people of the world! Today we’re going to talk about isolation and containment considerations in oral solid dose manufacturing. The purpose of isolation and containment is to control the level of pharmaceutical ingredient exposure to personnel and the environment. It is typically not possible to eliminate all exposures, so we try to reduce it to a tolerable level, which must be defined.

The CFRs and other regulations require manufacturers to limit exposure to customers of any undesirable substance. Limits have been established by industry group and regulatory bodies, and quantify things such as Allowable Daily Exposure (ADE).

Things to look at when considering isolation and containment include:

• Material flow
• Personnel flow
• Operator interventions
• Sampling
• Waste flow
• Maintenance procedures
• Utility interactions

Isolation and containment risks must be evaluated and mitigated to get a solid handle on the implications. A multi-disciplinary approach must be used. Migations may include:

• Physical barriers
• Air control
• Cleaning procedures
• Disposables
• Training

What considerations come in to play in your isolation/containment strageties? Comment below!

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Oral Solid Dose – Equipment

Hello good people of the world! Today’s post is the third in the series covering the commissioning, qualification, and validation of facilities, systems, and equipment involved in the manufacture of oral solid dose (OSD) products. This post covers the equipment used to manufacture these products.

Considerations include: materials of construction, sampling, and cleanability.

1. Materials of Construction: it is critical that equipment materials do not react with or otherwise adulterate the product being manufactured. Materials of construction may be metals (e.g. 316L stainless steel), plastics, or elastomers. Other considerations include design documentation, surface finish including at welds, and any certification required.
2. Sampling: equipment must be designed so that sampling is facilitated where required. Sampling is typically a mitigation for product quality failure modes such as content uniformity in granulation, over/under drying in drying, failed particle size distribution in milling, leakage in encapsulation, and over spray in coating, among others.
3. Cleanability: automated clean-in-place (CIP) cleaning procedures are preferred where practical. Manual cleaning and sterilization may also be considerations.

What do you think about in terms of your OSD manufacturing equipment?

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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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