Medicines are commonly administered to the eye by topical application as eye drops. Most are licensed products or medical devices, but certain eye drops are prepared aseptically from materials supplied for injection. These products are available as “Specials” from UK Manufacturers Specials (MS) licence holders.
It is recognised that there may be clinical circumstances where urgent treatment will be required in the best interests of the patient, e.g. in order to potentially save sight when a licensed eye drop or “special” is not available. The alternative may be to return preparation to the clinical area which would increase the risk of error and contamination.
Aseptic Preparation in the UK is only exempt from the licensing requirements of the Medicines Act 1968 providing five criteria listed in the NHSE guidance “Assurance of aseptic preparation of medicines” are met.
Criteria 2 states that for aseptic units operating under section 10 exemption, “preparation uses only closed systems with the exception that emergency eye drop preparation is allowed under defined circumstances”.
Defined circumstances under Section 10
Emergency eye drop preparation is allowed under Section 10 exemption providing the following circumstances are considered and met, where applicable.
Licensed product is unavailable
Clinical guidance on the use of eye drops and other eye preparations has been issued jointly by the Royal College of Ophthalmologists and the UK Ophthalmology Pharmacist Group. The guidance is written for primary care but the essential principles apply to the hospital setting and the recommendations are in line with the requirements of the Special Needs section in MHRA Guidance Note 14:
- “A licensed medicinal product obtainable from normal distribution channels in a reasonable time should be considered available for use. If a licensed product becomes unavailable, it may be necessary for an unlicensed equivalent to be supplied. This should be seen as a temporary expedient and should not be taken as justification for long term supply. Supply in these circumstances should cease as soon as is practicable, following reinstatement of the licensed product.”
Emergency preparation in an open system
The MHRA Guidance for Specials Manufacturer’s specifies the requirements for the manufacture of eye drops using open systems in manufacturing units. This guidance should also be applied to the preparation of eye drops using open systems under Section 10.
A higher risk is assigned to the preparation of aseptic products using “open” systems and an increased level of environmental control is required to assure the quality of products prepared in this way. The risks and controls required vary depending on whether the process takes place in an open fronted Laminar Air Flow Cabinet (LAFC) or in a pharmaceutical isolator.
Laminar Air Flow Cabinet (LAFC)
In an LAFC, full compliance with Annex 1 (EU Guidance on Good Manufacturing Practice) is required. This would entail:
- continuous particle monitoring during operations
- full gowning with no facial exposure
- sterile goggles are the preferred option, but other types of protection may be used so long as they are completely sealed to the head dress to prevent any egress of contamination
- visors that are open at the side are not acceptable
In an isolator, Annex 1 requirements must be met at rest and the isolator integrity must be checked prior to undertaking eye drop preparation. Goggles or other face protection are not required for open system manufacture in an isolator.
Guidance is provided for Accountable Pharmacists on the circumstances and potential risks that should be considered before the preparation of eye drops is undertaken under Section 10.
Assessing patient need
Ensure the need for preparation of an eye drop under Section 10 exemption is defined and aligns with the requirements in Guidance note 14.
Using an open system
Before preparing an eye drop using an open system, the Accountable Pharmacist should ensure that:
- the clinical situation requires urgent treatment and is clinically justified
- a suitable eye drop prepared in a licensed unit is not available OR there will be an unacceptable delay in the commencement of treatment by obtaining a product from a licensed unit
- the required medication cannot be delivered in an alternative presentation using closed system techniques
- supply is a temporary expedient and must cease as soon as is practicable, i.e. as soon as a product prepared under licence is available
- the procedure is undertaken in a pharmaceutical isolator, the integrity of which is demonstrated prior to commencing filling i.e. a compliant leak test has been completed and passed
A deviation should be raised in the Pharmaceutical Quality System for each preparation episode.
Assigning a shelf life
The labelled shelf life of the eye drops prepared under these circumstances should be based on a knowledgeable assessment of the formulation of the preparation and the microbiological risk to the product, balanced against the expiry period required to meet the patient’s needs until a product prepared under licence can be obtained.
The shortest possible practical expiry period should be assigned to the eye drop product. This would not normally exceed 72 hours.
In use, the eye drops should be assigned a 24-hour maximum expiry period after first opening.
Preparing eye drops in an LAFC is a higher risk option and a short shelf life not exceeding 24 hours is recommended for eye drops prepared in this way.
The process of preparing eye drops in Section 10 units should be subject to validation. The following validation approach is suggested:
- prepare an additional bottle in each “batch” and send for sterility testing
- complete an end of session broth fill at the end of the process