Introduction
This document provides guidance for the prevention of cross contamination in production processes, warehousing, material transfer, and distribution.
Facility Design should include consideration of, and not be limited to, the following items:
- Room and equipment layouts that minimize potential cross contamination of products (e.g., use of airlocks);
- Use of closed processing equipment;
- Air quality, airflow requirements, and air recirculation controls;
- Product and material flow;
- Personnel flow and gowning requirements;
- Collection, transportation, and storage of waste;
- Drainage systems; and
Cleanable continuous, smooth, and non-porous floors, walls, doors, and ceilings with surfaces able to withstand repeated application of cleaning agents.
In Cases Where Product or Components are Exposed, Material Flow should be designed to avoid cross flow of exposed materials and to minimize activities that increase the potential for cross contamination.
Products Requiring Special Containment Measures should be classified as follows:
Special Precautions Required: Occupational Exposure Band (OEB) classification 4 or classification 5 products (e.g., corticosteroids) that are not beta-lactams, cytotoxics or sex hormones.
For these products, the requirements should be established as the operational (e.g., procedures, material flows) and design principles (e.g., air handling, airlock use) for containment and prevention of cross contamination. In addition, Environmental Health and Safety guidelines should define containment measures that provide additional assurance to prevent cross contamination;
Dedicated Manufacturing Suite Required: cytotoxics and sex hormones classified as OEB 4 or 5 products. Dedicated Manufacturing Suite Specifications include, but are not limited to:
- Processing areas at negative pressure with respect to adjacent rooms;
- Air handling systems designed to prevent cross contamination;
- Suite dedicated equipment;
- Suite dedicated sampling/dispensing area;
- Use of airlocks;
- Suite dedicated clothing and shoes; and
- Decontamination of containers and other articles prior to removal from isolated area; and
- Dedicated building with dedicated entrances and exits for personnel and materials;
- Dedicated utility systems, including air handling;
- Dedicated personnel (i.e., no cross flow with other personnel after entry to the area);
- Dedicated materials (i.e., no cross flow after entry to the area); and
- Dedicated laboratories.
- Booth or canopy over tank hatch openings;
- Isolators (e.g., glove boxes);
- SOPs defining conditions under which vessels can be opened;
- Periodic inspection of overhead piping and ducts to ensure that there are no leaks, condensation, flaking of paint and/or insulation that might fall into vessel openings;
Drip pans under HVAC units or cold surfaces to collect or contain condensation; and Facilities designed with minimal overhead ducts and piping.
Equipment should be located so that cross contamination between production operations undertaken in a common area is prevented.
Ovens, Dryers, Autoclaves and Similar Equipment should contain only one open, exposed RM, API, intermediate, in-process material, medical device or drug product at a time.
Airflow Patterns should not present a cross contamination risk. Air handling systems should be designed to prevent cross contamination of exposed product, components, or production areas.
Raw Material (RM) Sampling should be performed in an area dedicated to sampling (e.g., sampling booth).
In-Process Sampling should be conducted according to SOPs designed to prevent cross contamination of the sampled material and other materials, intermediates, APIs, in-process materials, drug products, or medical devices.
Where Dust is Generated (e.g., during sampling, weighing, mixing and processing operations, packaging of dry products), dust collection or containment systems should be used to avoid cross contamination and to facilitate cleaning.
Dust Collectors of any type should not exhaust into any storage or production areas.
Air Filtration Systems, Including Pre-Filters and Terminal Filters should be used when required on air supplies to production areas. Air recirculated to production areas should be controlled to prevent recirculation of dust from production. In areas where air contamination occurs during production, there should be exhaust systems or other systems to control contaminants.
Air should not be recirculated from production areas handling live pathogenic organisms.
A Certificate of Cleaning is required for all bulk deliveries made in non-dedicated bulk carriers (e.g., tankers, railcars). Additional assurances that there will be no cross contamination from the bulk carriers should include consideration of, but are not limited to, the following:
- Testing for trace impurities (e.g., nonspecific volatile and/or nonvolatile impurity testing);
- Audit of the supply chain (supplier, carrier); and
- Use of dedicated transfer lines.