Eye drops and other ophthalmic preparations are used by millions of individuals all over the world; in order to keep them safe and guarantee effectiveness, maintaining sterility is vital to proper ophthalmic manufacturing.
Ophthalmic manufacturing; that is, the manufacturing of any preparations or applications intended to be used directly on the conjunctiva or conjunctival sac or on the eyelids; requires careful oversight and accountability. The mucous membranes of the eye are susceptible to infection and disease if foreign elements are introduced via ophthalmic preparations, and because the eye is connected directly to the central nervous system, infections present serious concerns for the health of the subject.
Damage to the eye up to and including long-term loss of sight, or even more serious complications, can occur if ophthalmic manufacturing does not follow cGMP and other guidelines and doesn’t have the proper oversight to ensure sterility and accountability throughout the process.
While the most commonly-known ophthalmic products on the market are probably eye drops, ophthalmic manufacturing produces a range of preparations and products intended for use on and around the eyes, including liquid, semi-solid, and solid formulations. What all ophthalmic products have in common is the need for sterility and safety that ensures they are ready for use on or near the eye when the end-user is ready to deploy them.
Ophthalmic manufacturing safety begins with good manufacturing practices.
Cross-contamination is a particular concern in ophthalmic manufacturing, especially in facilities which also manufacture other chemical or pharmacological products. This is one reason why it is vital for ophthalmic manufacturing facilities to follow cGMP guidelines in every step of the process, from the filtration of water through filling and into packaging and storing of the final ophthalmic solution.
Most eye drops are emulsions, solutions, or suspensions in liquid, which means that most of the ophthalmic manufacturing process begins with water for injection (WFI). Some CMOs create their own WFI on-site by filtering water n a sterile environment, while others obtain sterile, filtered water from another source. Beginning as far back as securing the WFI, sterility is vital throughout every step of the manufacturing process, assuming that the end product cannot be sterilized via routine methods.
Appropriate in-process controls throughout the chain of manufacturing can help guarantee effectiveness, sterility, and traceability of the end product. These include the monitoring of environmental conditions, as well as checking for pyrogens, pH, and the clarity of the solution.
Packaging plays an important role in the ophthalmic manufacturing of eye drops and other solutions.
When it comes to eye drops, the container and applicator, if appropriate, is part of the end product, and needs to be manufactured, handled, and inspected with the same rigor used on the preparation itself. Contamination from the container is just as serious as contamination within the process of formulating the preparation, and can result in eye drops that are diluted, contaminated, or less effective.
An often-overlooked aspect of ophthalmic manufacturing is ensuring that the packaging is adequate to protect the product not only from potential contamination, but also from light, moisture, or damage due to handling in the CMO, at the warehouse, and on store shelves or wherever the product is ultimately headed.
Accountability doesn’t stop when the product leaves the ophthalmic manufacturing facility.
Most eye drops are designed to be used, a few drops at a time, over a course of days, weeks, or even longer, until the bottle is depleted. This means that ophthalmic manufacturers have a duty to ensure that the product is not only stable and effective when it leaves their facility, but that it will remain stable and effective throughout its intended shelf life.
At its most basic, this means including information like the expiration date, period of use, and date of manufacture on the label, along with all other FDA-required data. The label should also include batch or lot numbers, as well as directions for how to store and apply the product so that it retains its effectiveness for the duration of its intended use and shelf life.
This also means ensuring that the proper steps are being followed throughout the manufacturing process to guarantee the stability and effectiveness of the product, not to mention the traceability of all of its ingredients. Any deviation in the manufacturing process can potentially affect the product, not only at the point of manufacture but also during its later shelf life. All processes should follow cGMP and any other relevant guidelines, and should remain consistent throughout.
Eye drops and other ophthalmic preparations should be monitored for contamination, separation, agglomeration, discoloration, emulsion breakdown, crystal growth, or any other unexpected changes both during the manufacturing process and after.