Oral Solid Dose – Architectural Considerations

Hello good people of the world! Today we’re talking about architectural considerations in the design of oral solid dose (OSD) manufacturing facilities.

In addition to normal architectural standards, the following must be considered for OSD manufacturing facilities:

• Manufacturing process flow
• Personnel flow
• Equipment flow (clean and dirty)
• Waste flow

Risks to consider when mapping flows include:

• Risk of contamination from outside contaminates
• Risk of cross-contamination
• Risk of mix-up

Risk mitigations should consider:

• Process containment
• Isolators
• Environmental controls
• Room size
• Transition spaces and airlocks
• Personnel controls such as gowning
• Administrative controls such as frequency of operation

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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 – Supporting Equipment and Systems

Hello good people of the world! Continuing the series on oral solid dosage forms, today we’re going to talk about supporting equipment and systems. The main equipment in unit operations get the spotlight when it comes to manufacturing Oral Solid Dosage forms, but they cannot work without supporting equipment and systems.

Supporting Equipment:
Typical supporting equipment in a OSD manufacturing process includes:

1. Air Systems: all modern manufacturing processes use air systems for process, instruments, and environment. HVAC helps control environmental conditions, including particulate (viable and nonviable) counts, temperature, and humidity. Compressed air systems may be used in the process to cool or cover product, such as with nitrogen, or operate unit operation steps, such as in fluid bed drying. Automated systems will use compressed air to pneumatically control valves and other components.
2. Dust Collection: compared to biotech and other pharmacuetical processes, OSD processes have the added complication of dust collection. OSD material movement and processes can create a lot of dust, which can be a risk from a product quality point-of-view, but also a safety point-of-view, since dust can lead to fires and even explosions. Dust collection equipment must be employed to minimize and control dust.
3. Vacuum Systems: vacuum systems may be used for cleaning, dust collection, and also in process steps such as vacuum drying.

Supporting Systems:
Typical supporting systems include:

1. Change Control: it is expected that engineering changes are controlled with quality oversight through a formal process.
2. Preventive Maintenance: it is expected that regular preventive maintenance be performed and documented formally.
3. Calibration: it is expected that “critical” instruments are calibrated at regular intervals traceable to an international standard. Calibration procedures and results must be formally documented. The method to determine and results of the determination of critical instruments must be documented.

What supporting equipment and/or systems do you use in your OSD manufacturing process? Comment below!

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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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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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Oral Solid Dose – Quality Risk Management Considerations

Hello good people of the world! Today’s post is the second 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 quality risk management.

Quality Risk Management is performed per the principles outlined in ICH Q9. The management process may then be divided up into six (6) steps:

1. Determine risk areas. These are typically safety, product quality, schedule, cost, etc.
2. Identify the risks for each area defined in step 1. For example, microbiological contamination may be a risk to product quality, APIs may be a risk to personnel safety.
3. Identify the failure modes which contribute to the risks identified in step 2. For example, pests contribute to microbiological contamination risk, and HVAC failure could be a vector by which personnel are exposed to an API.
4. Analyze failure modes and identify mitigations. In our examples procedures around pest control and qualification of HVAC systems could be mitigation to the failure modes identified.
5. Implement monitoring and CAPA (corrective and preventative action) processes.
6. Apply a continuous improvement plan to periodically review risks, risk assessments, and mitigation.

There are many tools which may be used to document the process, such as: FMEA, HAZOP, PHA, etc.

How do you execute your quality risk management process?

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