Pilot plant scale up techniques : overview || steps in scale-up || scale up of liquid dosage forms || semisolid dosage forms

 

PILOT PLANT SCALE UP

Definition

Objectives

Significance

Steps in scale-up

General considerations

Pilot plant uses

Scale up of liquid dosage forms

Scale up of semisolid dosage forms

Contract manufacturing

Definition

Plant

It is a location where the five production essentials—money, material, man, method, and machine—are brought together to create the goods.

Plant Pilot

It's the area of the pharmaceutical industry where a lab-scale recipe is turned into a marketable product by creating a reliable and efficient manufacturing process.

Scale-up

The practice of creating prototypes utilizing information from pilot plant models.

Objective

Before spending a significant amount of money on a manufacturing unit, test the process on a replica of the intended facility.

The formula is examined to see if it can resist changes in batch size and processing.

Process and equipment evaluation and validation.

Guidelines for production and process controls to identify the crucial aspects of the process.

To deliver manufacturing method instructions along with the master manufacturing formula.

To prevent scale-up issues.

SIGNIFICANCE OF PILOT PLANT

Formula examination.

Review of the many relevant processing tools.

Modifying the production rate.

Notion of the spatial requirements.

Suitable documentation and reports to support GMP.

Identification of essential characteristics to preserve quality.

STEPS IN SCALE UP

Describe the economics of the product based on the anticipated size of the market, the selling environment, and offer guidelines for the permissible manufacturing costs.

Do both scale-up planning and laboratory experiments simultaneously.

Describe the proposed process' essential rate-controlling phases.

To assist in plant design, do preliminary larger-than-laboratory experiments using the rate-controlling step's equipment.

Design and build a pilot plant that include features for process and environmental controls, cleaning and sanitizing systems, packaging and waste management systems, and compliance with regulatory agency standards.

Make any necessary modifications to the results of the pilot plant, including the process economy, and decide whether or not to move forward with the building of a full-scale plant.

Why conduct Pilot Plant Studies?

Pilot plant studies are conducted for several reasons, including:

Scale-up feasibility: Pilot plant studies help to determine the feasibility of scaling up a laboratory process to a larger industrial scale. This involves testing the process at a larger scale to identify any potential issues that may arise during full-scale production.

Process optimization: Pilot plant studies can also be used to optimize a process. By testing various operating conditions and process parameters, researchers can determine the most efficient and effective way to produce a product.

Quality control: Pilot plant studies can be used to establish quality control measures for a production process. This involves identifying key process parameters and establishing control limits to ensure that the final product meets the desired quality standards.

Cost analysis: Pilot plant studies can provide valuable data on the cost of production. This includes the cost of raw materials, energy, and labor, as well as the cost of equipment and facilities.

Regulatory compliance: Pilot plant studies can be used to demonstrate regulatory compliance. This involves testing the process under conditions that meet regulatory requirements and obtaining data to support compliance with relevant regulations and standards.

Overall, pilot plant studies are essential for assessing the technical and economic feasibility of a production process and for optimizing the process to achieve maximum efficiency and quality.

 

General considerations

1.   Reporting Responsibility

 R&D group with separate staffing.

The formulator who developed the product can take into the production and can provide support even after transition into production has been completed.

2. Personnel Requirement

The most ideal scientists are those who have worked in both actual production settings and pilot plant operations.

Thus they need to comprehend both the formulator's intention as well as the manufacturing staff's point of view.

The group has to have some engineers on staff because scaling up also uses engineering ideas.

3. Space Requirements

Administration and information processing

Physical testing area

Standard equipment floor space

Storage area

Administration and information processing:

Adequate office and desk space should be provided for both scientist and technicians.

The space should be adjacent to the working area.

Physical testing area:

This area should provide permanent bench top space for routinely used physical- testing equipment.

Storage area:

It ought to have two sections labelled approved and disapproved for active component and excipient, respectively.

Materials from the production's experimental scale-up batches, final bulk goods from the pilot plant, and in-process materials should all be stored in separate locations.

It should be possible to store the packing materials.

4. Review of the formula

It's crucial to analyse each component of formulation in depth.

It is important to comprehend the function of each component and how it contributes to the finished product produced using small-scale laboratory machinery.

The impact of scaling up employing machinery that might subject the product to stresses of various kinds and intensities can then be foreseen or identified more easily.

5. Equipment

The simplest, most cost-effective machinery that can produce goods that meet the requested standards is employed.

The equipment's size should be such that the experimental trials conducted are applicable to batches of the same size as those used for production.

The designed procedure won't scale up if the equipment is too tiny.

In contrast, if the equipment is overly large, valuable active chemicals would be wasted.

Easy to clean

the cleaning periods

6. Process Evaluation

Parameters:

Drying temperature and drying time

Order of mixing of components

Mixing speed

Screen size (solids)

Mixing time

Heating and cooling rates

Filters size (liquids)

Rate of addition of granulating agents, solvents, solutions of drug etc.

7. Product stability and uniformity

The physical and chemical stability of the products is the pilot plant's main goal.

Thus, stability testing should be done on each pilot batch that represents the final formulation and production process.

Completed packages should also undergo stability studies.

Pilot plant uses

A pilot plant is a small-scale version of a production plant used to test new processes, technologies, or equipment before full-scale implementation. Pilot plants are used in a variety of industries, including:

Chemicals: Pilot plants are used to develop new chemical processes or modify existing ones to improve efficiency, quality, and safety.

Pharmaceuticals: Pilot plants are used to test new drug formulations, production processes, and equipment before full-scale manufacturing.

Food and beverage: Pilot plants are used to test new recipes, improve processing methods, and develop new products.

Energy: Pilot plants are used to test new renewable energy technologies such as solar, wind, and geothermal power.

Environmental: Pilot plants are used to test new pollution control technologies, waste treatment methods, and sustainable energy solutions.

Biotechnology: Pilot plants are used to develop new bioprocesses, bioreactors, and fermentation systems for producing biologics and other biopharmaceuticals.

Overall, pilot plants are essential for reducing the risk of failure in new technology, optimizing manufacturing processes, and improving product quality while minimizing costs.

 

SCALE UP OF LIQUID ORALS

Liquid orals:

At normal temperature, a pharmacological product's pourable physical form exhibits Newtonian or pseudoplastic flow behavior and conforms to its container.

Liquid dosage forms might be solutions or dispersion systems.

There are two or more phases in dispersed systems, where one phase is scattered in another.

Any mixture of two or more components is referred to as a solution.

Steps of liquid manufacturing process:

Planning of material requirements

Liquid preparation

Filling and Packing

Quality assurance

Critical aspects of liquid manufacturing

Physical Plant:

Heating, ventilation, and air-conditioning systems:

It is important to take into account how long processing times at unfavorable temperatures may affect the physical or chemical stability of the ingredients as well as the final product.

Equipment’s

Mixer

Homogenizer

Filtration assembly

Bottling assembly

Quality assurance

Pharmaceutical evaporation from a solution

Suspension of pharmaceutical potency

Regularity of temperature in emulsions

Microbial regulation

Product similarity

Final volume

Stability

Scale-up of semisolid dosage forms

Semisolid dose forms typically have complex formulations with complex structural components.

They frequently consist of two phases—oil and water—with the exterior phase being continuous and the inside phase being scattered.

Although the medicine is occasionally partially soluble in the system and is disseminated in one or both phases, generating a three-phase system, the active ingredient is frequently dissolved in one phase.

The size of the dispersed particles, the interfacial tension between the phases, the partition coefficient of the active ingredient between the phases, and the product rheology are some of the variables that affect the physical properties of the dosage form.

These elements work together to influence the drug's release properties as well as other properties including viscosity.

General stability consideration

It is important to assess the potential impact of SUPAC alterations on the drug product's stability.

The FDA's guideline for submitting documentation for the stability of human medicines and biologics provides general instructions on conducting stability studies.

The upcoming considerations for SUPAC applications include:

1. The majority of times, with the exception of those containing scale-up stability data from pilot size batches, the suggested change will be supported.

2. It is advised to supply past accelerated stability data from a representative prior batch for comparison where stability data point to a trend of potency loss or degradant increase under accelerated settings.

3. There should be an agreement to carry out long-term stability studies on either the first three manufacturing batches or throughout the expiration dating period in accordance with the approved protocol and to report the findings in following yearly reports.

Contract manufacturing

One business will create unique components or other materials for their client as part of the arrangement.

As a result, in order to generate the final goods, the client does not need to maintain manufacturing facilities, buy raw materials, or employ labour.

An arrangement for contract manufacturing has a number of benefits.

The promise of consistent work is there for the manufacturer.

Furthermore, dealing with unsuccessful personnel does not cause any issues.

Also, dealing with absentee workers, malfunctioning machinery, or any of the other little issues that a manufacturing company must deal with on a daily basis is not a problem.

making goods under a label or brand owned by another business.

This service is provided by contract manufacturers to numerous companies based on their own designs, formulas, and specifications or those of the client. commonly referred to as private label manufacturing.

Contract manufacturing is a method of establishing a working relationship between two organisations.