Good Documentation Practices of BMR & BPR, Processing & Packaging Instructions,Sampling ,Testing Procedures and Records.

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Good Documentation Practices of BMR & BPR, Processing & Packaging Instructions,Sampling ,Testing Procedures and records. (EudraLex  Volume-4)

Manufacturing Formula and Processing Instructions

Approved, written Manufacturing Formula and Processing Instructions should exist for each product and batch size to be manufactured.

The Manufacturing Formula should include:

a) The name of the product, with a product reference code relating to its specification;

b) A description of the pharmaceutical form, strength of the product and batch size;

c) A list of all starting materials to be used, with the amount of each, described; mention should be made of any substance that may disappear in the course of processing;

d) A statement of the expected final yield with the acceptable limits, and of relevant intermediate yields, where applicable 4.18 The Processing Instructions should include:

a) A statement of the processing location and the principal equipment to be used;

b) The methods, or reference to the methods, to be used for preparing the critical equipment (e.g. cleaning, assembling, calibrating, sterilising);

c) Checks that the equipment and work station are clear of previous products, documents or materials not required for the planned process, and that equipment is clean and suitable for use;

d) Detailed stepwise processing instructions [e.g. checks on materials, pre-treatments, sequence for adding materials, critical process parameters (time, temp etc)];

e) The instructions for any in-process controls with their limits;

f) Where necessary, the requirements for bulk storage of the products; including the container, labeling and special storage conditions where applicable;

g) Any special precautions to be observed.

 Packaging Instructions

Approved Packaging Instructions for each product, pack size and type should exist. These should include, or have a reference to, the following:

a) Name of the product; including the batch number of bulk and finished product

b) Description of its pharmaceutical form, and strength where applicable;

c) The pack size expressed in terms of the number, weight or volume of the product in the final container;

d) A complete list of all the packaging materials required, including quantities, sizes and types, with the code or reference number relating to the specifications of each packaging material;

e) Where appropriate, an example or reproduction of the relevant printed packaging materials, and specimens indicating where to apply batch number references, and shelf life of the product;

f) Checks that the equipment and work station are clear of previous products, documents or materials not required for the planned packaging operations (line clearance), and that equipment is clean and suitable for use.

g) Special precautions to be observed, including a careful examination of the area and equipment in order to ascertain the line clearance before operations begin;

h) A description of the packaging operation, including any significant subsidiary operations, and equipment to be used;

i) Details of in-process controls with instructions for sampling and acceptance limits.

 Batch Processing Record

A Batch Processing Record should be kept for each batch processed. It should be based on the relevant parts of the currently approved Manufacturing Formula and Processing Instructions, and should contain the following information:

a) The name and batch number of the product;

b) Dates and times of commencement, of significant intermediate stages and of completion of production;

c) Identification (initials) of the operator(s) who performed each significant step of the process and, where appropriate, the name of any person who checked these operations;

d) The batch number and/or analytical control number as well as the quantities of each starting material actually weighed (including the batch number and amount of any recovered or reprocessed material added);

e) Any relevant processing operation or event and major equipment used;

f) A record of the in-process controls and the initials of the person(s) carrying them out, and the results obtained;

g) The product yield obtained at different and pertinent stages of manufacture;

h) Notes on special problems including details, with signed authorisation for any deviation from the Manufacturing Formula and Processing Instructions;

i) Approval by the person responsible for the processing operations.

 Note: Where a validated process is continuously monitored and controlled, then automatically generated reports may be limited to compliance summaries and exception/ out-of specification (OOS) data reports.

 Batch Packaging Record

A Batch Packaging Record should be kept for each batch or part batch processed. It should be based on the relevant parts of the Packaging Instructions. The batch packaging record should contain the following information:

a) The name and batch number of the product,

b) The date(s) and times of the packaging operations;

c) Identification (initials) of the operator(s) who performed each significant step of the process and, where appropriate, the name of any person who checked these operations;

d) Records of checks for identity and conformity with the packaging instructions, including the results of in-process controls;

e) Details of the packaging operations carried out, including references to equipment and the packaging lines used;

f) Whenever possible, samples of printed packaging materials used, including specimens of the batch coding, expiry dating and any additional overprinting;

g) Notes on any special problems or unusual events including details, with signed authorisation for any deviation from the Packaging Instructions;

h) The quantities and reference number or identification of all printed packaging materials and bulk product issued, used, destroyed or returned to stock and the quantities of obtained product, in order to provide for an adequate reconciliation. Where there are there are robust electronic controls in place during packaging there may be justification for not including this information

i) Approval by the person responsible for the packaging operations

Procedures and records

Receipt

There should be written procedures and records for the receipt of each delivery of each starting material, (including bulk, intermediate or finished goods), primary, secondary and printed packaging materials.

The records of the receipts should include:

a) The name of the material on the delivery note and the containers;

b) The “in-house” name and/or code of material (if different from a);

c) Date of receipt; d) Supplier’s name and, manufacturer’s name;

e) Manufacturer’s batch or reference number;

f) Total quantity and number of containers received;

g) The batch number assigned after receipt;

h) Any relevant comment.

There should be written procedures for the internal labeling, quarantine and storage of starting materials, packaging materials and other materials, as appropriate.

 Sampling

There should be written procedures for sampling, which include the methods and equipment to be used, the amounts to be taken and any precautions to be observed to avoid contamination of the material or any deterioration in its quality.

Testing

There should be written procedures for testing materials and products at different stages of manufacture, describing the methods and equipment to be used. The tests performed should be recorded.

 Other

Written release and rejection procedures should be available for materials and products, and in particular for the certification for sale of the finished product by the Qualified Person(s). All records should be available to the Qualified Person. A system should be in place to indicate special observations and any changes to critical data.

Records should be maintained for the distribution of each batch of a product in order to facilitate recall of any batch, if necessary.

There should be written policies, procedures, protocols, reports and the associated records of actions taken or conclusions reached, where appropriate, for the following examples:

  • Validation and qualification of processes, equipment and systems;
  • Equipment assembly and calibration;
  • Technology transfer;

  • Maintenance, cleaning and sanitation;

  • Personnel matters including signature lists, training in GMP and technical matters, clothing and hygiene and verification of the effectiveness of training.

  • Environmental monitoring;

  • Pest control;

  • Complaints;

  • Recalls;

  • Returns;

  • Change control;

  • Investigations into deviations and non-conformances;

  • Internal quality/GMP compliance audits;

  • Summaries of records where appropriate (e.g. product quality review);

  • Supplier audits.

Clear operating procedures should be available for major items of manufacturing and test equipment.

Logbooks should be kept for major or critical analytical testing, production equipment, and areas where product has been processed. They should be used to record in chronological order, as appropriate, any use of the area, equipment/method, calibrations, maintenance, cleaning or repair operations, including the dates and identity of people who carried these operations out.

An inventory of documents within the Quality Management System should be maintained.

Reference: –

Volume 4
Good Manufacturing Practice
Medicinal Products for Human and Veterinary Use
Chapter 4: Documentation

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