Hazard and risk analysis in Pharmaceutical Products

Application of hazard analysis and critical control point (HACCP) methodology to pharmaceuticals.

Any circumstance in the production, control, and distribution of a pharmaceutical which can cause an adverse health effect.
Hazard analysis:-
The process of collecting and evaluating information on hazards which should be addressed in the HACCP plan.

Traditionally, the Hazard Analysis and Critical Control Point (HACCP) the methodology has been considered to be a food safety management system. It aims to prevent known hazards and to reduce the risks that they will occur at specific points in the food chain. The same principles are also increasingly being applied in other industries, such as the car industry, aviation, and the chemical industry.
This text provides general guidance on the use of the HACCP system to ensure the quality of pharmaceuticals while recognizing that the details of its application may vary depending on the circumstances (see Appendix 1). It does not provide detailed information on major hazards.
Hazards affecting quality are controlled to a certain extent through the validation of critical operations and processes in the manufacture of finished pharmaceutical products in accordance with Good Manufacturing Practices (GMP).
However, GMP does not cover the safety of the personnel engaged in the manufacture, while both aspects are covered by HACCP.
Procedures, including GMP, address operational conditions and provide the basis for HACCP. HACCP is a systematic method for the identification, assessment, and control of safety hazards. Such hazards are defined as biological, chemical, or physical agents or operations that are reasonably likely to cause illness or injury if not controlled. In the manufacture of pharmaceuticals,2 these may include the manufacture of certain antibiotics, hormones, cytotoxic substances or other highly active pharmaceuticals, together with operations such as fluid-bed drying and granulation, which are examples of hazard unit operations.
The use of inflammable solvents (solutions) and certain laboratory operations may also constitute hazards.

The following elements of the HACCP methodology are integral parts of the validation master file:
— development of a flow diagram of the process;
— verification of the flow diagram on site.
In addition, HACCP will extend this concept to include an analysis of the critical quality variables as well as the assessment of hazards affecting the safety of workers and environmental pollution hazards directly related to the process (in particular in open systems) concerned.
GMP for pharmaceutical products requires the validation of critical processes as well as of changes in the manufacturing process which may affect the quality of the final product. Experience shows that most manufacturing processes contain steps that are “critical” from the point of view of variations in final product quality.
The HACCP system is based on seven principles. In applying these principles, 12 stages are recommended and are discussed in section 7. Some stages are linked to specific principles while others serve as an introduction to the concept.
The seven principles are:

  1. Conduct a hazard analysis.
  2. Determine the critical control points (CCPs).
  3. Establish target levels and critical limit(s).
  4. Establish a system to monitor the CCPs.
  5. Establish the corrective action to be taken when monitoring indicates that
    a particular CCP is not under control.
  6. Establish procedures to verify that the HACCP system is working
  7. Establish documentation concerning all procedures and keep records
    appropriate to these principles and their application.

Guidelines for the application of the HACCP system

The following guidelines will be found useful in applying the HACCP system:
• Before HACCP is applied to any sector, that sector should be operating in accordance with the principles of good practices and the relevant legislation.
• Management commitment is necessary if an effective HACCP system is to be implemented.
• HACCP should be applied to each specific operation separately.
• CCPs identified in any given example in any referenced document (including GMP guidelines) may not be the only ones identified for a specific application or may be of a different nature.
• The HACCP application should be reviewed and necessary changes made when any modification is made in the product or process, or in any step.
• It is important when applying HACCP, to take into account the nature and
size of the operation.
• There should be a HACCP plan. The format of such plans may vary, but they
should preferably be specific to a particular product, process or operation.
Generic HACCP plans can serve as useful guides in the development of
product and process HACCP plans; however, it is essential that the unique
conditions within each facility are considered during the development of all
components of the HACCP plan.

Potential hazards in relation to at least the following should be considered:
— materials and ingredients;
— physical characteristics and composition of the product;
— processing procedures;
— microbial limits, where applicable;
— premises;
— equipment;
— packaging;
— sanitation and hygiene;
— personnel;
— risk of explosions;
— mix-ups.


Reference :- Quality Assurance of Pharmaceuticals Vol2

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