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Pilot Plant

Presented By-

Md. Mizanur Rahman

Assistant Professor

Pharmacy Dept. DIU

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Definition

The pilot program is a scale up techniques, conducted to the product and its process,

-leaving the development laboratory.

- accepted by the full production manufacturing unit.

The pilot plant is intermediate sized equipment in between the laboratory & commercial scale. The drug dosage forms are developed in a medium-sized pilot plant with-

    • Exact formulation specification
    • Guaranteed adequate physical & chemical stability
    • Routine processing in a full scale production facility

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Primary function/Scopes/ Objectives/Importance of Pilot Plant:

  • To formulate a viable, robust product with exact formulation specification
  • To determine the compatibility of relevant processing equipment with the formulation
  • To determine whether the formulation parameters are economic, simple & reliable in producing the product
  • To determine the availability of the raw materials
  • To evaluate the production rate to meet the market demand
  • Validation and evaluation of production & process controls
  • Evaluation of training, reporting relationships, responsibilities of personnel
  • Appropriate records & reports are issued to support GMP’s
  • Development & validation of management product reprocessing procedures
  • Identification of the critical features of a process

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General Consideration

  • Reporting responsibilities
  • Personnel requirements
  • Space requirements
  • Review of the formula
  • Raw materials
  • Relevant processing equipment
  • Production rates
  • Process evaluation
  • Preparation of master manufacturing procedures.

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1. Reporting responsibilities

Pilot plant function is a part of research & development group with separate staffing. This arrangement is designed to provide a hierarchy of responsibility to scale-up formulations that have been development by research & development group. The goal of a pilot plant is to facilitate of a product from laboratory scale to production scale.

And this can be achieved by is good relationship exists between pilot plant group & other group-

  • Research & Development
  • Manufacturing
  • Packaging
  • Engineering
  • Marketing
  • Administration
  • QA/QC

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2. Personnel requirements:

a. Qualification

-Have good theoretical, practical & technical knowledge of Pharmaceuticals

-Ability to communicate well in speaking & writing

b. Type & level of education

Pharmaceutically trained scientists who play role on physical, chemical, biochemical & medical attributes of dosage forms.

c. No. of personnel

It’s depends on number of products.

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3. Space requirements:

A pilot plant has the following 4 types of space requirements-

  • Administration & information processing-
  • Adequate office & desk space ( for scientist , technicians)
  • An area where 3-4 people can meet and discuss.
  • Space for computer terminal ( for conventional data entry)
  • Retrieval and archives for stability data protocols and historical files.

b. Physical testing area-

-Adequate working area in which samples can be laid out and examined.

- Permanent bench- top space for physical testing equipment’s (balance, pH meter, viscometer)

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c. Standard pilot plant equipment’s for space-

- Separate plant space where equipment’s needed for manufacturing of all types dosage forms located (semi solid, solid, liquid, sterile products)

d. Storage area-

- Separate areas according to GMP for

API, excipient, packaging materials, retained samples, experimental production batches, shell room, bottles, closure, tubes, vials, ampoules.

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4. Review of the formula:

A thorough review of each aspect of the formulation should be carried out early in the scale up process. The purpose of each ingredient & the continuation to the final product manufactured on small scale laboratory equipment should be understood.

5. Raw materials:

An important role of the pilot plant is to approve and validate the raw materials used as active ingredients and excipients in pharmaceutical products. Due to the possibility that big volume shipments of the raw materials utilized in large-scale production may not be indicative of those used in large-scale formulation trials. The evaluation of alternative suppliers is based on numerous batches of products made from alternative materials and how well they function in terms of formulation and finished product stability when compared to the conventional product.

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6. Relevant processing equipment’s:

Based on the known processing characteristics of the product, the equipment that seems to the most economical. The most efficient and the most capable of regularly producing product within the proposed specifications should be evaluated.

The size of this equipment should be such that experimental trials can be run that are meaningful & relevant to the production sized batches that will finally be made.

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7. Production rates:

The immediate & future market requirements must be considered when determining the production rates & the type & size of production equipment needed.

The size of this equipment should be such that it is properly utilized. The equipment & process should be chosen so as to produce batches at a frequency that takes in to consideration

-Product loss in the equipment during manufacture

-The time required to clean the equipment between batches

-The number of batches needs to be tested before release

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8. Process evaluation:

The purpose of process validation is to confirm that the selected manufacturing procedure assures the quality of the product at various critical stages in the process and in the finished product.

The following points should be examined-

  • Order of addition of materials (amount)
  • Mixing speed
  • Mixing time
  • Rate of addition of granulating agents(solvents, solution of drugs, slurries etc)
  • Heating and cooling rates
  • Filter sizes(Liquids)
  • Screen sizes (solids)
  • Drying temperature
  • Drying time

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9. Preparation of master manufacturing procedure:

Criteria/basis

-Chemical weigh sheet (MO/PO: manufacturing order)

-Manufacturing directions (BMR/BPR)

- Standard operating procedure (SOP)

MO/PO should contain

- Product name, -Batch no

-Identifications of chemicals

  • Dispensing dates, -Batch size

-Amount of chemicals

-Sign of responsible people (IPC)

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-BMR/BPR

-It should be precise

-Language should be easy (Understand by production operators)

- Each and every step of manufacturing should be clearly specified

Should contain-

-Product name

-Batch number &

-Batch size

-Identification of chemicals

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BMR…..

-Amounts of chemicals

-Order of mixing & time of mixing

-Speed of mixing (RMP-Rotation per minute)

-Sampling direction

-In process and finished product specification

In case of coated tablet-

-Type of coating

-Coating material (name, amount & volume of coating solution)

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BMR…..

-Order of mixing

-Spray rate

-Machine RPM

-Drying temperature and time

-Exhaust and inlet air temperature

- Inlet Humidity

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SOP(Standard Operating Procedure)

- How to operate the instrument

- It should be precise

- Language should be easy

- Every step of should be clearly mentioned