Premises and equipment (Chapter 3)
Starting material environment for sampling
The physical requirements for the area being used to sample non-sterile starting materials are described in clause 3.9. In order to protect the sampled material from contamination, this sampling would be expected to be carried out in an appropriately clean and controlled environment.
During sampling operations, consider the following:
- interior surfaces of the sampling area should permit easy and effective cleaning
- only one material at a time should be taken into the sampling area to prevent cross contamination back into any primary starting material container
- materials should only be opened in the controlled environment of the sampling area
- if sampled materials have fine particles and/or generate dust there should be adequate containment/dust extraction controls in place
- appropriate cleaning and area clearance should be in place
Sampling of starting materials in an open warehouse would not be allowed.
Primary packaging materials for non-sterile products environment for sampling
Physical requirements for the area being used to sample primary packaging material for non-sterile products are described in clause 3.9. As product-contact components, primary packaging materials should be sampled within an environment that adequately protects the packaging from contamination.
Sampling of primary packaging materials in an open warehouse would not be allowed
Air quality for sunscreen manufacture
The use of closed systems of processing and transfer in order to protect liquid, cream or ointment product from contamination are recommended (Annex 9). Production areas where the products, or open clean containers, are exposed should normally be effectively ventilated with filtered air.
The PIC/S Guide to GMP (PE009-13) does not reference a specific standard for air quality, or filtration, for non-sterile manufacturing areas and there are no Australian or ISO standards for air quality specific to sunscreen manufacture.
As a general guide, those areas used for manufacturing and packaging microbiologically sensitive sunscreen products should be supplied with air filtered to remove 85% of particles above 1 micron, or EU 7 standard. These areas should be at a positive pressure relative to the rest of the facility to ensure that the correct standard of air quality is maintained.
If you can demonstrate that closed systems are used, filtered air requirements can be reduced to only those areas where the product is exposed.
In all cases, it is your responsibility to ensure that adequate and appropriate qualification and monitoring processes are in place to justify the heating, ventilation and air conditioning (HVAC) design and to demonstrate that areas are effectively ventilated with adequately filtered air where sunscreen products, or open clean containers are exposed.
Give special attention to manufacturing environments that include the manufacture of products other than sunscreens.
Minimum air quality for microbiologically sensitive products
As a minimum expectation for areas where microbiologically sensitive products or open clean containers are exposed:
- air quality requirements (physical and microbiological) should be defined during system design and compliance demonstrated through qualification and on-going monitoring
- air filters used in manufacturing areas where product is exposed should be at least EU7 grade or equivalent
- air filters with a greater filter efficiency than EU7 may be required where adjacent products or processes, other than sunscreen manufacture, present a potential contamination risk
- room pressures and air flows must be defined and appropriate
For additional guidance in relation to recommended levels of air filtration, consult:
- WHO heating, ventilation and air-conditioning systems for non-sterile pharmaceutical dosage forms (Annex5, TRS 961)
Cleaning and sanitisation
The PIC/S Guide to GMP (PE009-13) contains limited detail on requirements for cleaning and sanitisation.
Cleaning of equipment with potable water is generally acceptable where equipment is:
- subjected to a final rinse with process (potable water that is appropriately treated to meet a designated specification for use) or purified water
- sanitised with an alcohol-based solution or similar
Annex 15 contains information about the validation of cleaning.
Premises and equipment definitions
Campaign manufacture is defined as being a separation in time of production (clause 5.19). That is, manufacturing a series of batches of the same product in sequence in a given period of time and/or maximum number of batches followed by an appropriate (validated) cleaning procedure.
A system should be in operation which ensures that cleaning and, where necessary, sanitisation has occurred after use and before re-use of equipment. However, where equipment is dedicated to one formulation only, or used for a run of batches of the same formulation, a partial clean would be acceptable, involving removal of as much as practicable of each batch before proceeding to the next batch. For example, manufacturing tanks and other product contact equipment are visibly clean but transfer pipes and pumps are not required to be stripped down for a complete clean between campaign batches.
In such cases, the maximum period of time or maximum number of batches that are permitted to elapse before complete cleaning is carried out, as well as detailed instructions for inter-batch campaign cleaning, should be specified in a standard procedure. Campaign lengths should be supported by cleaning and process validation data.
Warehouses and distribution centres
By definition, ‘manufacture' includes all steps in bringing the product to its final form with ‘release for supply' considered to be the last step in this process.
From a GMP point of view, warehousing and distribution after release for supply and after the product has left the manufacturer's control, is not currently regulated by the TGA. Hence, a facility that is used only for warehousing and distribution of fully finished and released products does not require a TGA manufacturing licence and is not required to comply with the PIC/S guide to GMP for medicinal products.
However, for an effective recall, cooperation from wholesalers and distributors is often essential. Wholesalers should have a procedure for conducting a recall at a sponsor's request. For more information, refer to:
There may be state or territory regulatory licensing requirements that are applicable, which should be checked with the relevant state or territory authority. The provisions of the Code of Good Wholesaling Practice for Medicines in Schedules 2, 3, 4 and 8 are applied through applicable state and territory therapeutic goods legislation or drugs and poisons legislation, and/or state or territory wholesaler licensing arrangements.