OPHTHALMIC GENERIC

FORMULATIONSBY ADREA R. BENKOFF, M.D.

WHAT YOU NEED TO KNOW ABOUT OPHTHALMIC GENERICS

� GENERIC REQUIREMENTS

� WHO MAKES GENERIC OPHTHALMIC PRODUCTS

� DO THEY WORK AS WELL AS THE BRAND PRODUCT

� DO GENERICS SAVE MONEY FOR YOUR PATIENT

� ARE THERE ANY POTENTIAL DOWNSIDES TO USING OPHTHALMIC GENERICS

GENERIC REQUIREMENTS

� Are they the same?

� YES� The FDA requires generics to have “BIOEQUIVALENCE”� Equal in QUALITY, STRENGTH and THE WAY THEY

WORK to the brand drug

GENERIC REQUIREMENTS� GENERICS MUST:

� Contain the same active ingredient� Have the same use indications� Be identical in strength, dosage form, and route of

administration� Be manufactured according to FDA standards� Have a similar shelf life� Be bioequivalent: the rate and extent of drug absorption

should be the same

GENERIC REQUIREMENTS

� HOWEVER ---bioequivalence or efficacy to the brand are not required for ophthalmic generics

� Concentration of a SYSTEMIC generic drug in its target tissue can be determined by BLOOD levels at various time points

� In an OPHTHALMIC generic you DO NOT obtain aqueous fluid levels or corneal concentrations

� SO….. NO TRUE BIOEQUIVALENCE

GENERIC OPHTHALMIC REQUIREMENTS

� Ophthalmic generics must have same active ingredients in the same concentrations as the innovator product

� Excipients, or inactive ingredients, in generic ophthalmic medications are allowed to differ from those of the innovator product

� These include: preservatives, pH adjusters, antioxidant, thickening agents, buffers, and tonicity adjusters

GENERIC OPHTHALMIC REQUIREMENTS

� Formulations may differ by manufacturer and may be noticeable to patients

� Formulation differences may affect the safety or efficacy of the product

� Since no bioavailability data is required for ophthalmic generics, clinical studies are rarely done

WHO MAKES GENERIC OPHTHALMIC PRODUCTS?

� Some companies make only generics� Mylan, Hi-Tech, Apotex, Sun Pharmaglobal

� Some companies make brand and generic formulations� Bausch & Lomb, Alcon, Akorn

� Some companies that make the brand drug may have a generic arm also making the identical generic� Pfizer/Greenstone, Alcon/Falcon

DO GENERICS WORK AS WELL AS THE BRAND

PRODUCT?

� FDA consumer website:

� Generics are every bit as PURE, POTENT and SAFE as brands

DO GENERICS WORK AS WELL AS THE BRAND

PRODUCT?

� Generic versions of the following have had some concerns:

� Pred Forte� Branded 1% prednisolone acetate suspension is

milled into minute particles that achieve appropriate suspension prior to dispensing. Generic product particle size differences in the 1990s caused precipitation and associated administration difficulties due to plugging of the bottle dropper tip.

� Pred Forte cont.� This resulted in poor anti-inflammatory response

greater burning and stinging and higher rate of punctate keratopathy.

� Voltaren� Generic diclofenac had different preservatives and

excipients than the innovator product in the 1990s.� Significant increase in severe NSAID-related corneal

events, ranging from superficial punctate keratitis to full corneal melting, some patients required corneal transplants.

� This product was removed from the market.

� Timolol XE� IOP-lowering efficacy of the generic was inferior to that

of the brand product. � The generic product was shown to have shorter retention

time on the ocular surface due to differences in the extended-release gel vehicle.

� Cosopt� Anecdotal reports of IOP increase

� Xalatan� In a randomized crossover trial in India: IOP reductions

at week 12 were significantly less for the generic compared with branded product. IOP increased when patients were switched from the branded to the generic drug while IOP continued to decrease in patients switched to the branded drug. The generic product had higher levels of particulate matter and a higher pH compared with the branded product. These differences could possibly affect product stability as well as release of active compound in the eye.

� Gentamicin� A study in India showed that about 20% of generic

ciprofloxacin eye drop solutions contained less than the required active drug concentration.

� Generic gentamicin caused rebound conjunctivitis and conjunctival burns due to a change in osmotic gradient affecting conjunctival epithelial cells.

DO GENERICS WORK AS WELL AS THE BRAND

PRODUCT?

� Need to record the manufacturer if problems arise

� Report adverse reactions to the FDA

� There may be a need to further test generics for efficacy

DO GENERICS SAVE MONEY FOR YOUR PATIENT?

� In the U.S. generic cost, on average, is 80-85% lower than the brand name product.

� Generics medications usually offer patients lower co-pays.

� Generics are considered Tier 1 products. However, some managed care plans place generics in Tier 2 or 3 co-pay categories to avoid incurring financial losses.

DO GENERICS SAVE MONEY FOR YOUR PATIENT?

� In 2011, the Medicare Part D “donut hole” gap coverage plan discounted name brands 50%, meaning that generics did not always lead to the best cost saving for the patient.

� e.g. a patient buying branded Cosopt, with an average wholesale price of $139.82 would pay about $70 for 10mL. The generic product, with a wholesale cost of $122.60, would cost $114 at the 7% generic discount rate, or 60% more than the branded product.

DO GENERICS SAVE MONEY FOR YOUR PATIENT?

� Special Generic Plans are available from some discount pharmacies (e.g. Walgreens, Walmart, Target)

� The list for ophthalmics is very limited� Some have special pricing on brand products (Costco)

� Cash

� Cash pay for some generics may not differ much from branded products

� Be Alert For Pharmacy Chains That Provide Incentives To Pharmacists Who Switch Patients To A Generic Product When One Is Available

ARE THERE ANY POTENTIAL DOWNSIDES TO USING

GENERICS?� In 2011 40% of drugs listed in the FDA database had

generic counterparts.

� In 2009, 75% of prescriptions dispensed in the U.S. were filled using generics.

� Majority of drug dispensed under Medicare – 65% and Medicaid – 68% are now generics.

ARE THERE ANY POTENTIAL DOWNSIDES TO USING

OPHTHALMIC GENERICS?� Many generic companies make mostly systemic

products while producing very few ophthalmic products

� Most generic companies provide LITTLE or NO research in ocular drug development

� Bottle design, drop flow and labeling varies

� Differences in pH or other formulation affects tolerability, solubility, and compliance

CONSIDERATIONS FOR BRAND vs. GENERIC

OPHTHALMICS

� GENERAL CONSIDERATIONS� Systemic generics may save money but there are limited

ophthalmic generics on the pharmacy generic savings lists

� MANAGED CARE CONSIDERATIONS� Not all generics are Tier 1� If a larger size is available in the branded product and

for a single copay, the patient may save money with the branded product

CONSIDERATIONS FOR BRAND vs. GENERIC

OPHTHALMICS

� CASH CONSIDERATIONS

� Patients need to shop different pharmacies for generic or branded products since prices can vary significantly

CONSIDERATIONS FOR BRAND vs. GENERIC

OPHTHALMICS� CLINICAL CONSIDERATIONS

� Most patients DO NOT have adverse effects or reduced treatment effectiveness with generics

� However, actual complication rates are not known because of lack of safety and efficacy data

� Generics are NOT available as NO-COST samples� Samples save money for the patient, allow initial trial to

determine effectiveness, and allow the patient to start medications as soon as possible

� Practitioners may not know if pharmacists switch generic brands which complicates patient progress, outcome and compliance