Good Manufacturing Practices Questions and Answers
Health Canada / Health Products and Food Branch Inspectorate
Sanitation - C.02.007 & C.02.008
Q.1 Is fumigation a requirement under sanitation?
A.1 The written sanitation program should include procedures for pest control as well as precautions required to prevent contamination of a drug when fumigating agents are used.
Fumigation is not a requirement per se. Infestation should be monitored and controlled. Where fumigation is used, appropriate precautions should be taken.
Methods of sanitary control that satisfy the requirements of Sections 8 and 11 of the Food and Drugs Act would be considered to be acceptable.
Q.2 What limits are acceptable on product residues regarding sanitation?
A.2 Guidance for the establishment of limits can be obtained from the “Cleaning Validation Guidelines (GUI-0028)”.
(http://www.hc-sc.gc.ca/dhp-mps/compli-conform/gmp-bpf/validation/gui-0028_cleaning-nettoyage_ltr-doc- eng.php).
Q.3 Are gowning rooms required even in pilot plant operations?
A.3 Even in a pilot plant consisting of a small laminar flow area where the apparatus for filter sterilization of solutions are set up, it is an unacceptable practice to gown in there. A change room should be available besides their sterile pilot plant production area.
Based on the assumption that the pilot plant will produce drugs for sale - including clinical studies - then the same principles and considerations that apply to full scale production operations must also be utilized in pilot plant facilities.
Q.4 What are considered as being acceptable limits for cross-contamination when performing cleaning validation?
A.4 Guidance for the establishment of limits can be obtained from the “Cleaning Validation Guidelines (GUI-0028)”.
(http://www.hc-sc.gc.ca/dhp-mps/compli-conform/gmp-bpf/validation/gui-0028_cleaning-nettoyage_ltr-doc- eng.php).
Q.5 In terms of cleaning, what would be the frequency and type of cleaning for equipment and premises for successive manufacturing of batches of the same product? And for different strengths of the same product?
A.5 Interpretation 3.5 under Section C.02.007 Sanitation specifies that “a cleaning procedure requiring complete product removal may not be necessary between batches of the same drug”. The frequency and type of cleaning for equipment and premises must address the length of time between consecutive lots with the ultimate goal that a particular lot won’t be contaminated by the previous lot or the environment. It must also ensure that residual quantities of the previous lot won’t impact on the quality of the following lot. Thus, a partial cleaning would be required between two lots of the same product, especially for forms such as liquids or suspensions, in order to prevent a few units at the beginning of a new lot from being filled with residual quantities from the previous lot that may be located in equipment such as hoses or pumps. A procedure should be established to ensure adequate removal of residual quantities from the previous lot and validation available for the maximum period of time between two successive lots in order to avoid problems such as microbial contamination, accumulation of residue, or degradation of product. The number of lots of the same product which could be manufactured before a complete/full cleaning should be determined.
Q.6 Clothing: Is it acceptable to have two levels of clothing in the non-sterile manufacturing areas, i.e., one level for operators with full gowning and coveralls and another level for QA auditors and visitors? What environmental monitoring data is required?
A.6 Yes. There are basic clothing requirements for any person entering the manufacturing areas, such as hair, mustache and beard covering, as well as protective garments. However, a firm may decide to apply more stringent requirements for operators, such as dedicated shoes and garments providing a higher level of protection. There are no specific environmental monitoring requirements for clothing worn in the non- sterile manufacturing areas.
Q.7 Can the sampling for the microbial monitoring of air in non-sterile areas where susceptible products are produced be conducted when there are no manufacturing packaging activities?
A.7 The sampling should occur during actual manufacturing or packaging in order to reflect the conditions to which the products being produced are really exposed. Monitoring between production runs is also advisable in order to detect potential problems before they arise.
Q.8 Must written procedures be available to prevent objectionable microorganisms in drug products not required to be sterile?
A.8 Yes. Appropriate written procedures, designed to prevent objectionable microorganisms in drug products not required to be sterile, should be established and followed. This means that even though a drug product is not sterile, a firm must follow written procedures that pro-actively prevent contamination and proliferation of microorganisms that are objectionable.