Pharma Manufacturing Premises – Risk classification guide for drug good manufacturing practices observations

Risk 1 (critical) observations in Pharma Industry

• There was no air filtration system to eliminate airborne contaminants likely to be generated during fabrication or packaging.
• There was generalized malfunctioning of the ventilation system(s), with evidence of widespread cross-contamination.
• Segregation of manufacturing or testing areas from other manufacturing areas was inadequate for higher risk products.

Risk 2 (major) observations in Pharma Industry

• Maintenance and scheduled verification (e.g. air filter replacement and monitoring of
  pressure differentials) were not done. (↑).
• The establishment’s heat, ventilation and air conditioning (HVAC) and/or purified water systems were not qualified. (↑).
• Unsealed porous finish in manufacturing areas showed evidence of contamination (e.g.mildew, mould or powder from previous productions). (↑).
• There was insufficient manufacturing space, which could lead to mix-ups. (↑).
• Physical or electrical quarantine areas were not adequately controlled, identified, well marked and/or not respected when used. (↑).
• There was malfunctioning of the ventilation system that could result in localized or occasional cross-contamination.
• Accessory supplies (e.g. steam, air, nitrogen and dust collection) were not qualified.
• Temperature and humidity were not controlled or monitored when necessary (i.e. products were not stored according to labelling requirements).
• Holes, cracks, peeling paint or other damages to walls and/or ceilings were observed immediately adjacent to or above:

• manufacturing areas in which products were exposed.
• equipment that handled products.

• The placement of pipes, fixtures or ducts directly above products or manufacturing
  equipment created surfaces that could not be cleaned.
• The finish of surfaces such as floors, walls and ceilings did not permit effective cleaning.
• Unauthorized staff had access to physical and electronic quarantine areas.
• A separate area was not assigned for raw material sampling.
• Proper precautions were not taken to prevent contamination or cross-contamination
  during raw material sampling.

Risk 3 (other) observations in Pharma Industry

• Personnel used doors with direct access to the exterior from manufacturing and packaging areas.
• Floor drains were not screened and/or trapped.
• Outlets for liquids and gases were not identified.
• Permanent pipeline installations in production areas were not identified appropriately.
• Damage was noted on surfaces not directly adjacent to or above exposed products.
• Non-production activities were performed in production areas.
• Rest, change, wash-up and/or toilet facilities were inadequate.

Reference: Risk classification guide for drug good manufacturing practices observations (GUI-0023)

Process Validation: General Principles (USFDA)